Testing hierarchical pathway kinetics with residue data on cyantraniliprole • mkin

+ + + + +

Introduction +

The purpose of this document is to test demonstrate how nonlinear +hierarchical models (NLHM) based on the parent degradation models SFO, +FOMC, DFOP and HS, with serial formation of two or more metabolites can +be fitted with the mkin package.

It was assembled in the course of work package 1.2 of Project Number +173340 (Application of nonlinear hierarchical models to the kinetic +evaluation of chemical degradation data) of the German Environment +Agency carried out in 2022 and 2023.

The mkin package is used in version 1.2.2 which is currently under +development. The newly introduced functionality that is used here is a +simplification of excluding random effects for a set of fits based on a +related set of fits with a reduced model, and the documentation of the +starting parameters of the fit, so that all starting parameters of +saem fits are now listed in the summary. The +saemix package is used as a backend for fitting the NLHM, +but is also loaded to make the convergence plot function available.

This document is processed with the knitr package, which +also provides the kable function that is used to improve +the display of tabular data in R markdown documents. For parallel +processing, the parallel package is used.

+library(mkin)
+library(knitr)
+library(saemix)
+library(parallel)
+n_cores <- detectCores()
+if (Sys.info()["sysname"] == "Windows") {
+  cl <- makePSOCKcluster(n_cores)
+} else {
+  cl <- makeForkCluster(n_cores)
+}

Test data +

The example data are taken from the final addendum to the DAR from +2014 and are distributed with the mkin package. Residue data and time +step normalisation factors are read in using the function +read_spreadsheet from the mkin package. This function also +performs the time step normalisation.

+data_file <- system.file(
+  "testdata", "cyantraniliprole_soil_efsa_2014.xlsx",
+  package = "mkin")
+cyan_ds <- read_spreadsheet(data_file, parent_only = FALSE)

The following tables show the covariate data and the 5 datasets that +were read in from the spreadsheet file.

+pH <- attr(cyan_ds, "covariates")
+kable(pH, caption = "Covariate data")

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + +

Covariate data
	pH
Nambsheim	7.90
Tama	6.20
Gross-Umstadt	7.04
Sassafras	4.62
Lleida	8.05

+for (ds_name in names(cyan_ds)) {
+  print(
+    kable(mkin_long_to_wide(cyan_ds[[ds_name]]),
+      caption = paste("Dataset", ds_name),
+      booktabs = TRUE, row.names = FALSE))
+    cat("\n\\clearpage\n")
+}

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +

Dataset Nambsheim
time	cyan	JCZ38	J9C38	JSE76	J9Z38
0.000000	105.79	NA	NA	NA	NA
3.210424	77.26	7.92	11.94	5.58	9.12
7.490988	57.13	15.46	16.58	12.59	11.74
17.122259	37.74	15.98	13.36	26.05	10.77
23.543105	31.47	6.05	14.49	34.71	4.96
43.875788	16.74	6.07	7.57	40.38	6.52
67.418893	8.85	10.34	6.39	30.71	8.90
107.014116	5.19	9.61	1.95	20.41	12.93
129.487080	3.45	6.18	1.36	21.78	6.99
195.835832	2.15	9.13	0.95	16.29	7.69
254.693596	1.92	6.92	0.20	13.57	7.16
321.042348	2.26	7.02	NA	11.12	8.66
383.110535	NA	5.05	NA	10.64	5.56
0.000000	105.57	NA	NA	NA	NA
3.210424	78.88	12.77	11.94	5.47	9.12
7.490988	59.94	15.27	16.58	13.60	11.74
17.122259	39.67	14.26	13.36	29.44	10.77
23.543105	30.21	16.07	14.49	35.90	4.96
43.875788	18.06	9.44	7.57	42.30	6.52
67.418893	8.54	5.78	6.39	34.70	8.90
107.014116	7.26	4.54	1.95	23.33	12.93
129.487080	3.60	4.22	1.36	23.56	6.99
195.835832	2.84	3.05	0.95	16.21	7.69
254.693596	2.00	2.90	0.20	15.53	7.16
321.042348	1.79	0.94	NA	9.80	8.66
383.110535	NA	1.82	NA	9.49	5.56

Dataset Tama
time	cyan	JCZ38	J9Z38	JSE76
0.000000	106.14	NA	NA	NA
2.400833	93.47	6.46	2.85	NA
5.601943	88.39	10.86	4.65	3.85
12.804442	72.29	11.97	4.91	11.24
17.606108	65.79	13.11	6.63	13.79
32.811382	53.16	11.24	8.90	23.40
50.417490	44.01	11.34	9.98	29.56
80.027761	33.23	8.82	11.31	35.63
96.833591	40.68	5.94	8.32	29.09
146.450803	20.65	4.49	8.72	36.88
190.466072	17.71	4.66	11.10	40.97
240.083284	14.86	2.27	11.62	40.11
286.499386	12.02	NA	10.73	42.58
0.000000	109.11	NA	NA	NA
2.400833	96.84	5.52	2.04	2.02
5.601943	85.29	9.65	2.99	4.39
12.804442	73.68	12.48	5.05	11.47
17.606108	64.89	12.44	6.29	15.00
32.811382	52.27	10.86	7.65	23.30
50.417490	42.61	10.54	9.37	31.06
80.027761	34.29	10.02	9.04	37.87
96.833591	30.50	6.34	8.14	33.97
146.450803	19.21	6.29	8.52	26.15
190.466072	17.55	5.81	9.89	32.08
240.083284	13.22	5.99	10.79	40.66
286.499386	11.09	6.05	8.82	42.90

Dataset Gross-Umstadt
time	cyan	JCZ38	J9Z38	JSE76
0.0000000	103.03	NA	NA	NA
2.1014681	87.85	4.79	3.26	0.62
4.9034255	77.35	8.05	9.89	1.32
10.5073404	69.33	9.74	12.32	4.74
21.0146807	55.65	14.57	13.59	9.84
31.5220211	49.03	14.66	16.71	12.32
42.0293615	41.86	15.97	13.64	15.53
63.0440422	34.88	18.20	14.12	22.02
84.0587230	28.26	15.64	14.06	25.60
0.0000000	104.05	NA	NA	NA
2.1014681	85.25	2.68	7.32	0.69
4.9034255	77.22	7.28	8.37	1.45
10.5073404	65.23	10.73	10.93	4.74
21.0146807	57.78	12.29	14.80	9.05
31.5220211	54.83	14.05	12.01	11.05
42.0293615	45.17	12.12	17.89	15.71
63.0440422	34.83	12.90	15.86	22.52
84.0587230	26.59	14.28	14.91	28.48
0.0000000	104.62	NA	NA	NA
0.8145225	97.21	NA	4.00	NA
1.9005525	89.64	3.59	5.24	NA
4.0726125	87.90	4.10	9.58	NA
8.1452251	86.90	5.96	9.45	NA
12.2178376	74.74	7.83	15.03	5.33
16.2904502	74.13	8.84	14.41	5.10
24.4356753	65.26	11.84	18.33	6.71
32.5809004	57.70	12.74	19.93	9.74
0.0000000	101.94	NA	NA	NA
0.8145225	99.94	NA	NA	NA
1.9005525	94.87	NA	4.56	NA
4.0726125	86.96	6.75	6.90	NA
8.1452251	80.51	10.68	7.43	2.58
12.2178376	78.38	10.35	9.46	3.69
16.2904502	70.05	13.73	9.27	7.18
24.4356753	61.28	12.57	13.28	13.19
32.5809004	52.85	12.67	12.95	13.69

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +

Dataset Sassafras
time	cyan	JCZ38	J9Z38	JSE76
0.000000	102.17	NA	NA	NA
2.216719	95.49	1.11	0.10	0.83
5.172343	83.35	6.43	2.89	3.30
11.083593	78.18	10.00	5.59	0.81
22.167186	70.44	17.21	4.23	1.09
33.250779	68.00	20.45	5.86	1.17
44.334371	59.64	24.64	3.17	2.72
66.501557	50.73	27.50	6.19	1.27
88.668742	45.65	32.77	5.69	4.54
0.000000	100.43	NA	NA	NA
2.216719	95.34	3.21	0.14	0.46
5.172343	84.38	5.73	4.75	0.62
11.083593	78.50	11.89	3.99	0.73
22.167186	71.17	17.28	4.39	0.66
33.250779	59.41	18.73	11.85	2.65
44.334371	64.57	22.93	5.13	2.01
66.501557	49.08	33.39	5.67	3.63
88.668742	40.41	39.60	5.93	6.17

Dataset Lleida
time	cyan	JCZ38	J9Z38	JSE76
0.000000	102.71	NA	NA	NA
2.821051	79.11	5.70	8.07	0.97
6.582451	70.03	7.17	11.31	4.72
14.105253	50.93	10.25	14.84	9.95
28.210505	33.43	10.40	14.82	24.06
42.315758	24.69	9.75	16.38	29.38
56.421010	22.99	10.06	15.51	29.25
84.631516	14.63	5.63	14.74	31.04
112.842021	12.43	4.17	13.53	33.28
0.000000	99.31	NA	NA	NA
2.821051	82.07	6.55	5.60	1.12
6.582451	70.65	7.61	8.01	3.21
14.105253	53.52	11.48	10.82	12.24
28.210505	35.60	11.19	15.43	23.53
42.315758	34.26	11.09	13.26	27.42
56.421010	21.79	4.80	18.30	30.20
84.631516	14.06	6.30	16.35	32.32
112.842021	11.51	5.57	12.64	32.51

Parent only evaluations +

As the pathway fits have very long run times, evaluations of the +parent data are performed first, in order to determine for each +hierarchical parent degradation model which random effects on the +degradation model parameters are ill-defined.

+cyan_sep_const <- mmkin(c("SFO", "FOMC", "DFOP", "SFORB", "HS"),
+  cyan_ds, quiet = TRUE, cores = n_cores)
+cyan_sep_tc <- update(cyan_sep_const, error_model = "tc")
+cyan_saem_full <- mhmkin(list(cyan_sep_const, cyan_sep_tc))
+status(cyan_saem_full) |> kable()

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +

	const	tc
SFO	OK	OK
FOMC	OK	OK
DFOP	OK	OK
SFORB	OK	OK
HS	OK	OK

All fits converged successfully.

+illparms(cyan_saem_full) |> kable()

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +

	const	tc
SFO	sd(cyan_0)	sd(cyan_0)
FOMC	sd(log_beta)	sd(cyan_0)
DFOP	sd(cyan_0)	sd(cyan_0), sd(log_k1)
SFORB	sd(cyan_free_0)	sd(cyan_free_0), sd(log_k_cyan_free_bound)
HS	sd(cyan_0)	sd(cyan_0)

In almost all models, the random effect for the initial concentration +of the parent compound is ill-defined. For the biexponential models DFOP +and SFORB, the random effect of one additional parameter is ill-defined +when the two-component error model is used.

+anova(cyan_saem_full) |> kable(digits = 1)

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +

	npar	AIC	BIC	Lik
SFO const	5	833.9	832.0	-412.0
SFO tc	6	831.6	829.3	-409.8
FOMC const	7	709.1	706.4	-347.6
FOMC tc	8	689.2	686.1	-336.6
DFOP const	9	703.0	699.5	-342.5
SFORB const	9	701.3	697.8	-341.7
HS const	9	718.6	715.1	-350.3
DFOP tc	10	703.1	699.2	-341.6
SFORB tc	10	700.1	696.2	-340.1
HS tc	10	716.7	712.8	-348.3

Model comparison based on AIC and BIC indicates that the +two-component error model is preferable for all parent models with the +exception of DFOP. The lowest AIC and BIC values are are obtained with +the FOMC model, followed by SFORB and DFOP.

Pathway fits +

Evaluations with pathway established previously +

To test the technical feasibility of coupling the relevant parent +degradation models with different transformation pathway models, a list +of mkinmod models is set up below. As in the EU evaluation, +parallel formation of metabolites JCZ38 and J9Z38 and secondary +formation of metabolite JSE76 from JCZ38 is used.

+if (!dir.exists("cyan_dlls")) dir.create("cyan_dlls")
+cyan_path_1 <- list(
+  sfo_path_1 = mkinmod(
+    cyan = mkinsub("SFO", c("JCZ38", "J9Z38")),
+    JCZ38 = mkinsub("SFO", "JSE76"),
+    J9Z38 = mkinsub("SFO"),
+    JSE76 = mkinsub("SFO"), quiet = TRUE,
+    name = "sfo_path_1", dll_dir = "cyan_dlls", overwrite = TRUE),
+  fomc_path_1 = mkinmod(
+    cyan = mkinsub("FOMC", c("JCZ38", "J9Z38")),
+    JCZ38 = mkinsub("SFO", "JSE76"),
+    J9Z38 = mkinsub("SFO"),
+    JSE76 = mkinsub("SFO"), quiet = TRUE,
+    name = "fomc_path_1", dll_dir = "cyan_dlls", overwrite = TRUE),
+  dfop_path_1 = mkinmod(
+    cyan = mkinsub("DFOP", c("JCZ38", "J9Z38")),
+    JCZ38 = mkinsub("SFO", "JSE76"),
+    J9Z38 = mkinsub("SFO"),
+    JSE76 = mkinsub("SFO"), quiet = TRUE,
+    name = "dfop_path_1", dll_dir = "cyan_dlls", overwrite = TRUE),
+  sforb_path_1 = mkinmod(
+    cyan = mkinsub("SFORB", c("JCZ38", "J9Z38")),
+    JCZ38 = mkinsub("SFO", "JSE76"),
+    J9Z38 = mkinsub("SFO"),
+    JSE76 = mkinsub("SFO"), quiet = TRUE,
+    name = "sforb_path_1", dll_dir = "cyan_dlls", overwrite = TRUE),
+  hs_path_1 = mkinmod(
+    cyan = mkinsub("HS", c("JCZ38", "J9Z38")),
+    JCZ38 = mkinsub("SFO", "JSE76"),
+    J9Z38 = mkinsub("SFO"),
+    JSE76 = mkinsub("SFO"), quiet = TRUE,
+    name = "hs_path_1", dll_dir = "cyan_dlls", overwrite = TRUE)
+)

To obtain suitable starting values for the NLHM fits, separate +pathway fits are performed for all datasets.

+f_sep_1_const <- mmkin(
+  cyan_path_1,
+  cyan_ds,
+  error_model = "const",
+  cluster = cl,
+  quiet = TRUE)
+status(f_sep_1_const) |> kable()

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +

	Nambsheim	Tama	Gross-Umstadt	Sassafras	Lleida
sfo_path_1	OK	OK	OK	OK	OK
fomc_path_1	OK	OK	OK	OK	OK
dfop_path_1	OK	OK	OK	OK	OK
sforb_path_1	OK	OK	OK	OK	OK
hs_path_1	C	C	C	C	C

+f_sep_1_tc <- update(f_sep_1_const, error_model = "tc")
+status(f_sep_1_tc) |> kable()

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +

	Nambsheim	Tama	Gross-Umstadt	Sassafras	Lleida
sfo_path_1	OK	OK	OK	OK	OK
fomc_path_1	OK	OK	OK	OK	C
dfop_path_1	OK	OK	OK	OK	OK
sforb_path_1	OK	C	OK	OK	OK
hs_path_1	C	OK	C	OK	OK

Most separate fits converged successfully. The biggest convergence +problems are seen when using the HS model with constant variance.

For the hierarchical pathway fits, those random effects that could +not be quantified in the corresponding parent data analyses are +excluded.

In the code below, the output of the illparms function +for the parent only fits is used as an argument +no_random_effect to the mhmkin function. The +possibility to do so was introduced in mkin version 1.2.2 +which is currently under development.

+f_saem_1 <- mhmkin(list(f_sep_1_const, f_sep_1_tc),
+  no_random_effect = illparms(cyan_saem_full),
+  cluster = cl)

+status(f_saem_1) |> kable()

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +

	const	tc
sfo_path_1	Fth, FO	Fth, FO
fomc_path_1	OK	Fth, FO
dfop_path_1	Fth, FO	Fth, FO
sforb_path_1	Fth, FO	Fth, FO
hs_path_1	Fth, FO	Fth, FO

The status information from the individual fits shows that all fits +completed successfully. The matrix entries Fth and FO indicate that the +Fisher Information Matrix could not be inverted for the fixed effects +(theta) and the random effects (Omega), respectively. For the affected +fits, ill-defined parameters cannot be determined using the +illparms function, because it relies on the Fisher +Information Matrix.

+illparms(f_saem_1) |> kable()

+ +++++ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +

	const	tc
sfo_path_1	NA	NA
fomc_path_1	sd(log_k_J9Z38), sd(f_cyan_ilr_2), +sd(f_JCZ38_qlogis)	NA
dfop_path_1	NA	NA
sforb_path_1	NA	NA
hs_path_1	NA	NA

The model comparison below suggests that the pathway fits using DFOP +or SFORB for the parent compound provide the best fit.

+anova(f_saem_1) |> kable(digits = 1)

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +

	npar	AIC	BIC	Lik
sfo_path_1 const	16	2692.8	2686.6	-1330.4
sfo_path_1 tc	17	2657.7	2651.1	-1311.9
fomc_path_1 const	18	2427.8	2420.8	-1195.9
fomc_path_1 tc	19	2423.4	2416.0	-1192.7
dfop_path_1 const	20	2403.2	2395.4	-1181.6
sforb_path_1 const	20	2401.4	2393.6	-1180.7
hs_path_1 const	20	2427.3	2419.5	-1193.7
dfop_path_1 tc	20	2398.0	2390.2	-1179.0
sforb_path_1 tc	20	2399.8	2392.0	-1179.9
hs_path_1 tc	21	2422.3	2414.1	-1190.2

For these two parent model, successful fits are shown below. Plots of +the fits with the other parent models are shown in the Appendix.

+plot(f_saem_1[["dfop_path_1", "tc"]])

+DFOP pathway fit with two-component error +

+plot(f_saem_1[["sforb_path_1", "tc"]])

+SFORB pathway fit with two-component error +

A closer graphical analysis of these Figures shows that the residues +of transformation product JCZ38 in the soils Tama and Nambsheim observed +at later time points are strongly and systematically underestimated.

Alternative pathway fits +

To improve the fit for JCZ38, a back-reaction from JSE76 to JCZ38 was +introduced in an alternative version of the transformation pathway, in +analogy to the back-reaction from K5A78 to K5A77. Both pairs of +transformation products are pairs of an organic acid with its +corresponding amide (Addendum 2014, p. 109). As FOMC provided the best +fit for the parent, and the biexponential models DFOP and SFORB provided +the best initial pathway fits, these three parent models are used in the +alternative pathway fits.

+cyan_path_2 <- list(
+  fomc_path_2 = mkinmod(
+    cyan = mkinsub("FOMC", c("JCZ38", "J9Z38")),
+    JCZ38 = mkinsub("SFO", "JSE76"),
+    J9Z38 = mkinsub("SFO"),
+    JSE76 = mkinsub("SFO", "JCZ38"),
+    name = "fomc_path_2", quiet = TRUE,
+    dll_dir = "cyan_dlls",
+    overwrite = TRUE
+  ),
+  dfop_path_2 = mkinmod(
+    cyan = mkinsub("DFOP", c("JCZ38", "J9Z38")),
+    JCZ38 = mkinsub("SFO", "JSE76"),
+    J9Z38 = mkinsub("SFO"),
+    JSE76 = mkinsub("SFO", "JCZ38"),
+    name = "dfop_path_2", quiet = TRUE,
+    dll_dir = "cyan_dlls",
+    overwrite = TRUE
+  ),
+  sforb_path_2 = mkinmod(
+    cyan = mkinsub("SFORB", c("JCZ38", "J9Z38")),
+    JCZ38 = mkinsub("SFO", "JSE76"),
+    J9Z38 = mkinsub("SFO"),
+    JSE76 = mkinsub("SFO", "JCZ38"),
+    name = "sforb_path_2", quiet = TRUE,
+    dll_dir = "cyan_dlls",
+    overwrite = TRUE
+  )
+)
+f_sep_2_const <- mmkin(
+  cyan_path_2,
+  cyan_ds,
+  error_model = "const",
+  cluster = cl,
+  quiet = TRUE)
+
+status(f_sep_2_const) |> kable()

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +

	Nambsheim	Tama	Gross-Umstadt	Sassafras	Lleida
fomc_path_2	OK	OK	OK	C	OK
dfop_path_2	OK	OK	OK	C	OK
sforb_path_2	OK	OK	OK	C	OK

Using constant variance, separate fits converge with the exception of +the fits to the Sassafras soil data.

+f_sep_2_tc <- update(f_sep_2_const, error_model = "tc")
+status(f_sep_2_tc) |> kable()

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +

	Nambsheim	Tama	Gross-Umstadt	Sassafras	Lleida
fomc_path_2	OK	C	OK	C	OK
dfop_path_2	OK	OK	OK	C	OK
sforb_path_2	OK	OK	OK	OK	OK

Using the two-component error model, all separate fits converge with +the exception of the alternative pathway fit with DFOP used for the +parent and the Sassafras dataset.

+f_saem_2 <- mhmkin(list(f_sep_2_const, f_sep_2_tc),
+  no_random_effect = illparms(cyan_saem_full[2:4, ]),
+  cluster = cl)

+status(f_saem_2) |> kable()

+ + + + + + + + + + + + + + + + + + + + + + + +

	const	tc
fomc_path_2	OK	FO
dfop_path_2	OK	OK
sforb_path_2	OK	OK

The hierarchical fits for the alternative pathway completed +successfully.

+illparms(f_saem_2) |> kable()

+ +++++ + + + + + + + + + + + + + + + + + + + + + + +

	const	tc
fomc_path_2	sd(f_JCZ38_qlogis), sd(f_JSE76_qlogis)	NA
dfop_path_2	sd(f_JCZ38_qlogis), sd(f_JSE76_qlogis)	sd(f_JCZ38_qlogis), sd(f_JSE76_qlogis)
sforb_path_2	sd(f_JCZ38_qlogis), sd(f_JSE76_qlogis)	sd(f_JCZ38_qlogis), sd(f_JSE76_qlogis)

In both fits, the random effects for the formation fractions for the +pathways from JCZ38 to JSE76, and for the reverse pathway from JSE76 to +JCZ38 are ill-defined.

+anova(f_saem_2) |> kable(digits = 1)

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +

	npar	AIC	BIC	Lik
fomc_path_2 const	20	2308.3	2300.5	-1134.2
fomc_path_2 tc	21	2248.3	2240.1	-1103.2
dfop_path_2 const	22	2289.6	2281.0	-1122.8
sforb_path_2 const	22	2284.1	2275.5	-1120.0
dfop_path_2 tc	22	2234.4	2225.8	-1095.2
sforb_path_2 tc	22	2240.4	2231.8	-1098.2

The variants using the biexponential models DFOP and SFORB for the +parent compound and the two-component error model give the lowest AIC +and BIC values and are plotted below. Compared with the original +pathway, the AIC and BIC values indicate a large improvement. This is +confirmed by the plots, which show that the metabolite JCZ38 is fitted +much better with this model.

+plot(f_saem_2[["fomc_path_2", "tc"]])

+FOMC pathway fit with two-component error, alternative pathway +

+plot(f_saem_2[["dfop_path_2", "tc"]])

+DFOP pathway fit with two-component error, alternative pathway +

+plot(f_saem_2[["sforb_path_2", "tc"]])

+SFORB pathway fit with two-component error, alternative pathway +

+ +

All ill-defined random effects that were identified in the parent +only fits and in the above pathway fits, are excluded for the final +evaluations below. For this purpose, a list of character vectors is +created below that can be indexed by row and column indices, and which +contains the degradation parameter names for which random effects should +be excluded for each of the hierarchical fits contained in +f_saem_2.

+no_ranef <- matrix(list(), nrow = 3, ncol = 2, dimnames = dimnames(f_saem_2))
+no_ranef[["fomc_path_2", "const"]] <- c("log_beta", "f_JCZ38_qlogis", "f_JSE76_qlogis")
+no_ranef[["fomc_path_2", "tc"]] <- c("cyan_0", "f_JCZ38_qlogis", "f_JSE76_qlogis")
+no_ranef[["dfop_path_2", "const"]] <- c("cyan_0", "f_JCZ38_qlogis", "f_JSE76_qlogis")
+no_ranef[["dfop_path_2", "tc"]] <- c("cyan_0", "log_k1", "f_JCZ38_qlogis", "f_JSE76_qlogis")
+no_ranef[["sforb_path_2", "const"]] <- c("cyan_free_0",
+  "f_JCZ38_qlogis", "f_JSE76_qlogis")
+no_ranef[["sforb_path_2", "tc"]] <- c("cyan_free_0", "log_k_cyan_free_bound",
+  "f_JCZ38_qlogis", "f_JSE76_qlogis")
+clusterExport(cl, "no_ranef")
+
+f_saem_3 <- update(f_saem_2,
+  no_random_effect = no_ranef,
+  cluster = cl)

+status(f_saem_3) |> kable()

+ + + + + + + + + + + + + + + + + + + + + + + +

	const	tc
fomc_path_2	E	Fth
dfop_path_2	Fth	Fth
sforb_path_2	Fth	Fth

With the exception of the FOMC pathway fit with constant variance, +all updated fits completed successfully. However, the Fisher Information +Matrix for the fixed effects (Fth) could not be inverted, so no +confidence intervals for the optimised parameters are available.

+illparms(f_saem_3) |> kable()

+ + + + + + + + + + + + + + + + + + + + + + + +

	const	tc
fomc_path_2	E
dfop_path_2
sforb_path_2

+anova(f_saem_3) |> kable(digits = 1)

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +

	npar	AIC	BIC	Lik
fomc_path_2 tc	19	2250.9	2243.5	-1106.5
dfop_path_2 const	20	2281.7	2273.9	-1120.8
sforb_path_2 const	20	2279.5	2271.7	-1119.7
dfop_path_2 tc	20	2231.5	2223.7	-1095.8
sforb_path_2 tc	20	2235.7	2227.9	-1097.9

While the AIC and BIC values of the best fit (DFOP pathway fit with +two-component error) are lower than in the previous fits with the +alternative pathway, the practical value of these refined evaluations is +limited as no confidence intervals are obtained.

Conclusion +

It was demonstrated that a relatively complex transformation pathway +with parallel formation of two primary metabolites and one secondary +metabolite can be fitted even if the data in the individual datasets are +quite different and partly only cover the formation phase.

The run times of the pathway fits were several hours, limiting the +practical feasibility of iterative refinements based on ill-defined +parameters and of alternative checks of parameter identifiability based +on multistart runs.

Acknowledgements +

The helpful comments by Janina Wöltjen of the German Environment +Agency are gratefully acknowledged.

Appendix +

Plots of fits that were not refined further +

+plot(f_saem_1[["sfo_path_1", "tc"]])

+SFO pathway fit with two-component error +

+plot(f_saem_1[["fomc_path_1", "tc"]])

+FOMC pathway fit with two-component error +

+plot(f_saem_1[["sforb_path_1", "tc"]])

+HS pathway fit with two-component error +

Hierarchical fit listings +

Pathway 1 +

+ +Hierarchical SFO path 1 fit with constant variance + +


+saemix version used for fitting:      3.2 
+mkin version used for pre-fitting:  1.2.2 
+R version used for fitting:         4.2.2 
+Date of fit:     Sat Jan 28 10:07:38 2023 
+Date of summary: Sat Jan 28 11:22:29 2023 
+
+Equations:
+d_cyan/dt = - k_cyan * cyan
+d_JCZ38/dt = + f_cyan_to_JCZ38 * k_cyan * cyan - k_JCZ38 * JCZ38
+d_J9Z38/dt = + f_cyan_to_J9Z38 * k_cyan * cyan - k_J9Z38 * J9Z38
+d_JSE76/dt = + f_JCZ38_to_JSE76 * k_JCZ38 * JCZ38 - k_JSE76 * JSE76
+
+Data:
+433 observations of 4 variable(s) grouped in 5 datasets
+
+Model predictions using solution type deSolve 
+
+Fitted in 1088.473 s
+Using 300, 100 iterations and 10 chains
+
+Variance model: Constant variance 
+
+Starting values for degradation parameters:
+        cyan_0     log_k_cyan    log_k_JCZ38    log_k_J9Z38    log_k_JSE76 
+       95.3304        -3.8459        -3.1305        -5.0678        -5.3196 
+  f_cyan_ilr_1   f_cyan_ilr_2 f_JCZ38_qlogis 
+        0.8158        22.5404        10.4289 
+
+Fixed degradation parameter values:
+None
+
+Starting values for random effects (square root of initial entries in omega):
+               cyan_0 log_k_cyan log_k_JCZ38 log_k_J9Z38 log_k_JSE76
+cyan_0          4.797     0.0000       0.000       0.000      0.0000
+log_k_cyan      0.000     0.9619       0.000       0.000      0.0000
+log_k_JCZ38     0.000     0.0000       2.139       0.000      0.0000
+log_k_J9Z38     0.000     0.0000       0.000       1.639      0.0000
+log_k_JSE76     0.000     0.0000       0.000       0.000      0.7894
+f_cyan_ilr_1    0.000     0.0000       0.000       0.000      0.0000
+f_cyan_ilr_2    0.000     0.0000       0.000       0.000      0.0000
+f_JCZ38_qlogis  0.000     0.0000       0.000       0.000      0.0000
+               f_cyan_ilr_1 f_cyan_ilr_2 f_JCZ38_qlogis
+cyan_0               0.0000        0.000           0.00
+log_k_cyan           0.0000        0.000           0.00
+log_k_JCZ38          0.0000        0.000           0.00
+log_k_J9Z38          0.0000        0.000           0.00
+log_k_JSE76          0.0000        0.000           0.00
+f_cyan_ilr_1         0.7714        0.000           0.00
+f_cyan_ilr_2         0.0000        8.684           0.00
+f_JCZ38_qlogis       0.0000        0.000          13.48
+
+Starting values for error model parameters:
+a.1 
+  1 
+
+Results:
+
+Likelihood computed by importance sampling
+   AIC  BIC logLik
+  2693 2687  -1330
+
+Optimised parameters:
+                     est. lower upper
+cyan_0            95.0946    NA    NA
+log_k_cyan        -3.8544    NA    NA
+log_k_JCZ38       -3.0402    NA    NA
+log_k_J9Z38       -5.0109    NA    NA
+log_k_JSE76       -5.2857    NA    NA
+f_cyan_ilr_1       0.8069    NA    NA
+f_cyan_ilr_2      16.6623    NA    NA
+f_JCZ38_qlogis     1.3602    NA    NA
+a.1                4.8326    NA    NA
+SD.log_k_cyan      0.5842    NA    NA
+SD.log_k_JCZ38     1.2680    NA    NA
+SD.log_k_J9Z38     0.3626    NA    NA
+SD.log_k_JSE76     0.5244    NA    NA
+SD.f_cyan_ilr_1    0.2752    NA    NA
+SD.f_cyan_ilr_2    2.3556    NA    NA
+SD.f_JCZ38_qlogis  0.2400    NA    NA
+
+Correlation is not available
+
+Random effects:
+                    est. lower upper
+SD.log_k_cyan     0.5842    NA    NA
+SD.log_k_JCZ38    1.2680    NA    NA
+SD.log_k_J9Z38    0.3626    NA    NA
+SD.log_k_JSE76    0.5244    NA    NA
+SD.f_cyan_ilr_1   0.2752    NA    NA
+SD.f_cyan_ilr_2   2.3556    NA    NA
+SD.f_JCZ38_qlogis 0.2400    NA    NA
+
+Variance model:
+     est. lower upper
+a.1 4.833    NA    NA
+
+Backtransformed parameters:
+                      est. lower upper
+cyan_0           95.094581    NA    NA
+k_cyan            0.021186    NA    NA
+k_JCZ38           0.047825    NA    NA
+k_J9Z38           0.006665    NA    NA
+k_JSE76           0.005063    NA    NA
+f_cyan_to_JCZ38   0.757885    NA    NA
+f_cyan_to_J9Z38   0.242115    NA    NA
+f_JCZ38_to_JSE76  0.795792    NA    NA
+
+Resulting formation fractions:
+                   ff
+cyan_JCZ38  7.579e-01
+cyan_J9Z38  2.421e-01
+cyan_sink   5.877e-10
+JCZ38_JSE76 7.958e-01
+JCZ38_sink  2.042e-01
+
+Estimated disappearance times:
+        DT50   DT90
+cyan   32.72 108.68
+JCZ38  14.49  48.15
+J9Z38 103.99 345.46
+JSE76 136.90 454.76
+
+

+ +Hierarchical SFO path 1 fit with two-component error + +


+saemix version used for fitting:      3.2 
+mkin version used for pre-fitting:  1.2.2 
+R version used for fitting:         4.2.2 
+Date of fit:     Sat Jan 28 10:08:17 2023 
+Date of summary: Sat Jan 28 11:22:29 2023 
+
+Equations:
+d_cyan/dt = - k_cyan * cyan
+d_JCZ38/dt = + f_cyan_to_JCZ38 * k_cyan * cyan - k_JCZ38 * JCZ38
+d_J9Z38/dt = + f_cyan_to_J9Z38 * k_cyan * cyan - k_J9Z38 * J9Z38
+d_JSE76/dt = + f_JCZ38_to_JSE76 * k_JCZ38 * JCZ38 - k_JSE76 * JSE76
+
+Data:
+433 observations of 4 variable(s) grouped in 5 datasets
+
+Model predictions using solution type deSolve 
+
+Fitted in 1127.552 s
+Using 300, 100 iterations and 10 chains
+
+Variance model: Two-component variance function 
+
+Starting values for degradation parameters:
+        cyan_0     log_k_cyan    log_k_JCZ38    log_k_J9Z38    log_k_JSE76 
+       96.0039        -3.8907        -3.1276        -5.0069        -4.9367 
+  f_cyan_ilr_1   f_cyan_ilr_2 f_JCZ38_qlogis 
+        0.7937        20.0030        15.1336 
+
+Fixed degradation parameter values:
+None
+
+Starting values for random effects (square root of initial entries in omega):
+               cyan_0 log_k_cyan log_k_JCZ38 log_k_J9Z38 log_k_JSE76
+cyan_0          4.859      0.000        0.00        0.00      0.0000
+log_k_cyan      0.000      0.962        0.00        0.00      0.0000
+log_k_JCZ38     0.000      0.000        2.04        0.00      0.0000
+log_k_J9Z38     0.000      0.000        0.00        1.72      0.0000
+log_k_JSE76     0.000      0.000        0.00        0.00      0.9076
+f_cyan_ilr_1    0.000      0.000        0.00        0.00      0.0000
+f_cyan_ilr_2    0.000      0.000        0.00        0.00      0.0000
+f_JCZ38_qlogis  0.000      0.000        0.00        0.00      0.0000
+               f_cyan_ilr_1 f_cyan_ilr_2 f_JCZ38_qlogis
+cyan_0               0.0000        0.000           0.00
+log_k_cyan           0.0000        0.000           0.00
+log_k_JCZ38          0.0000        0.000           0.00
+log_k_J9Z38          0.0000        0.000           0.00
+log_k_JSE76          0.0000        0.000           0.00
+f_cyan_ilr_1         0.7598        0.000           0.00
+f_cyan_ilr_2         0.0000        7.334           0.00
+f_JCZ38_qlogis       0.0000        0.000          11.78
+
+Starting values for error model parameters:
+a.1 b.1 
+  1   1 
+
+Results:
+
+Likelihood computed by importance sampling
+   AIC  BIC logLik
+  2658 2651  -1312
+
+Optimised parameters:
+                      est. lower upper
+cyan_0            94.72923    NA    NA
+log_k_cyan        -3.91670    NA    NA
+log_k_JCZ38       -3.12917    NA    NA
+log_k_J9Z38       -5.06070    NA    NA
+log_k_JSE76       -5.09254    NA    NA
+f_cyan_ilr_1       0.81116    NA    NA
+f_cyan_ilr_2      39.97850    NA    NA
+f_JCZ38_qlogis     3.09728    NA    NA
+a.1                3.95044    NA    NA
+b.1                0.07998    NA    NA
+SD.log_k_cyan      0.58855    NA    NA
+SD.log_k_JCZ38     1.29753    NA    NA
+SD.log_k_J9Z38     0.62851    NA    NA
+SD.log_k_JSE76     0.37235    NA    NA
+SD.f_cyan_ilr_1    0.37346    NA    NA
+SD.f_cyan_ilr_2    1.41667    NA    NA
+SD.f_JCZ38_qlogis  1.81467    NA    NA
+
+Correlation is not available
+
+Random effects:
+                    est. lower upper
+SD.log_k_cyan     0.5886    NA    NA
+SD.log_k_JCZ38    1.2975    NA    NA
+SD.log_k_J9Z38    0.6285    NA    NA
+SD.log_k_JSE76    0.3724    NA    NA
+SD.f_cyan_ilr_1   0.3735    NA    NA
+SD.f_cyan_ilr_2   1.4167    NA    NA
+SD.f_JCZ38_qlogis 1.8147    NA    NA
+
+Variance model:
+       est. lower upper
+a.1 3.95044    NA    NA
+b.1 0.07998    NA    NA
+
+Backtransformed parameters:
+                      est. lower upper
+cyan_0           94.729229    NA    NA
+k_cyan            0.019907    NA    NA
+k_JCZ38           0.043754    NA    NA
+k_J9Z38           0.006341    NA    NA
+k_JSE76           0.006142    NA    NA
+f_cyan_to_JCZ38   0.758991    NA    NA
+f_cyan_to_J9Z38   0.241009    NA    NA
+f_JCZ38_to_JSE76  0.956781    NA    NA
+
+Resulting formation fractions:
+                 ff
+cyan_JCZ38  0.75899
+cyan_J9Z38  0.24101
+cyan_sink   0.00000
+JCZ38_JSE76 0.95678
+JCZ38_sink  0.04322
+
+Estimated disappearance times:
+        DT50   DT90
+cyan   34.82 115.67
+JCZ38  15.84  52.63
+J9Z38 109.31 363.12
+JSE76 112.85 374.87
+
+

+ +Hierarchical FOMC path 1 fit with constant variance + +


+saemix version used for fitting:      3.2 
+mkin version used for pre-fitting:  1.2.2 
+R version used for fitting:         4.2.2 
+Date of fit:     Sat Jan 28 10:09:12 2023 
+Date of summary: Sat Jan 28 11:22:29 2023 
+
+Equations:
+d_cyan/dt = - (alpha/beta) * 1/((time/beta) + 1) * cyan
+d_JCZ38/dt = + f_cyan_to_JCZ38 * (alpha/beta) * 1/((time/beta) + 1) *
+           cyan - k_JCZ38 * JCZ38
+d_J9Z38/dt = + f_cyan_to_J9Z38 * (alpha/beta) * 1/((time/beta) + 1) *
+           cyan - k_J9Z38 * J9Z38
+d_JSE76/dt = + f_JCZ38_to_JSE76 * k_JCZ38 * JCZ38 - k_JSE76 * JSE76
+
+Data:
+433 observations of 4 variable(s) grouped in 5 datasets
+
+Model predictions using solution type deSolve 
+
+Fitted in 1182.258 s
+Using 300, 100 iterations and 10 chains
+
+Variance model: Constant variance 
+
+Starting values for degradation parameters:
+        cyan_0    log_k_JCZ38    log_k_J9Z38    log_k_JSE76   f_cyan_ilr_1 
+      101.2314        -3.3680        -5.1108        -5.9416         0.7144 
+  f_cyan_ilr_2 f_JCZ38_qlogis      log_alpha       log_beta 
+        7.3870        15.7604        -0.1791         2.9811 
+
+Fixed degradation parameter values:
+None
+
+Starting values for random effects (square root of initial entries in omega):
+               cyan_0 log_k_JCZ38 log_k_J9Z38 log_k_JSE76 f_cyan_ilr_1
+cyan_0          5.416       0.000         0.0       0.000       0.0000
+log_k_JCZ38     0.000       2.439         0.0       0.000       0.0000
+log_k_J9Z38     0.000       0.000         1.7       0.000       0.0000
+log_k_JSE76     0.000       0.000         0.0       1.856       0.0000
+f_cyan_ilr_1    0.000       0.000         0.0       0.000       0.7164
+f_cyan_ilr_2    0.000       0.000         0.0       0.000       0.0000
+f_JCZ38_qlogis  0.000       0.000         0.0       0.000       0.0000
+log_alpha       0.000       0.000         0.0       0.000       0.0000
+log_beta        0.000       0.000         0.0       0.000       0.0000
+               f_cyan_ilr_2 f_JCZ38_qlogis log_alpha log_beta
+cyan_0                 0.00           0.00    0.0000   0.0000
+log_k_JCZ38            0.00           0.00    0.0000   0.0000
+log_k_J9Z38            0.00           0.00    0.0000   0.0000
+log_k_JSE76            0.00           0.00    0.0000   0.0000
+f_cyan_ilr_1           0.00           0.00    0.0000   0.0000
+f_cyan_ilr_2          12.33           0.00    0.0000   0.0000
+f_JCZ38_qlogis         0.00          20.42    0.0000   0.0000
+log_alpha              0.00           0.00    0.4144   0.0000
+log_beta               0.00           0.00    0.0000   0.5077
+
+Starting values for error model parameters:
+a.1 
+  1 
+
+Results:
+
+Likelihood computed by importance sampling
+   AIC  BIC logLik
+  2428 2421  -1196
+
+Optimised parameters:
+                      est.     lower    upper
+cyan_0            101.0225 98.306270 103.7387
+log_k_JCZ38        -3.3786 -4.770657  -1.9866
+log_k_J9Z38        -5.2603 -5.902085  -4.6186
+log_k_JSE76        -6.1427 -7.318336  -4.9671
+f_cyan_ilr_1        0.7437  0.421215   1.0663
+f_cyan_ilr_2        0.9108  0.267977   1.5537
+f_JCZ38_qlogis      2.0487  0.524897   3.5724
+log_alpha          -0.2268 -0.618049   0.1644
+log_beta            2.8986  2.700701   3.0964
+a.1                 3.4058  3.169913   3.6416
+SD.cyan_0           2.5279  0.454190   4.6016
+SD.log_k_JCZ38      1.5636  0.572824   2.5543
+SD.log_k_J9Z38      0.5316 -0.004405   1.0677
+SD.log_k_JSE76      0.9903  0.106325   1.8742
+SD.f_cyan_ilr_1     0.3464  0.112066   0.5807
+SD.f_cyan_ilr_2     0.2804 -0.393900   0.9546
+SD.f_JCZ38_qlogis   0.9416 -0.152986   2.0362
+SD.log_alpha        0.4273  0.161044   0.6936
+
+Correlation: 
+               cyan_0  l__JCZ3 l__J9Z3 l__JSE7 f_cy__1 f_cy__2 f_JCZ38 log_lph
+log_k_JCZ38    -0.0156                                                        
+log_k_J9Z38    -0.0493  0.0073                                                
+log_k_JSE76    -0.0329  0.0018  0.0069                                        
+f_cyan_ilr_1   -0.0086  0.0180 -0.1406  0.0012                                
+f_cyan_ilr_2   -0.2629  0.0779  0.2826  0.0274  0.0099                        
+f_JCZ38_qlogis  0.0713 -0.0747 -0.0505  0.1169 -0.1022 -0.4893                
+log_alpha      -0.0556  0.0120  0.0336  0.0193  0.0036  0.0840 -0.0489        
+log_beta       -0.2898  0.0460  0.1305  0.0768  0.0190  0.4071 -0.1981  0.2772
+
+Random effects:
+                    est.     lower  upper
+SD.cyan_0         2.5279  0.454190 4.6016
+SD.log_k_JCZ38    1.5636  0.572824 2.5543
+SD.log_k_J9Z38    0.5316 -0.004405 1.0677
+SD.log_k_JSE76    0.9903  0.106325 1.8742
+SD.f_cyan_ilr_1   0.3464  0.112066 0.5807
+SD.f_cyan_ilr_2   0.2804 -0.393900 0.9546
+SD.f_JCZ38_qlogis 0.9416 -0.152986 2.0362
+SD.log_alpha      0.4273  0.161044 0.6936
+
+Variance model:
+     est. lower upper
+a.1 3.406  3.17 3.642
+
+Backtransformed parameters:
+                      est.     lower     upper
+cyan_0           1.010e+02 9.831e+01 1.037e+02
+k_JCZ38          3.409e-02 8.475e-03 1.372e-01
+k_J9Z38          5.194e-03 2.734e-03 9.867e-03
+k_JSE76          2.149e-03 6.633e-04 6.963e-03
+f_cyan_to_JCZ38  6.481e-01        NA        NA
+f_cyan_to_J9Z38  2.264e-01        NA        NA
+f_JCZ38_to_JSE76 8.858e-01 6.283e-01 9.727e-01
+alpha            7.971e-01 5.390e-01 1.179e+00
+beta             1.815e+01 1.489e+01 2.212e+01
+
+Resulting formation fractions:
+                ff
+cyan_JCZ38  0.6481
+cyan_J9Z38  0.2264
+cyan_sink   0.1255
+JCZ38_JSE76 0.8858
+JCZ38_sink  0.1142
+
+Estimated disappearance times:
+        DT50    DT90 DT50back
+cyan   25.15  308.01    92.72
+JCZ38  20.33   67.54       NA
+J9Z38 133.46  443.35       NA
+JSE76 322.53 1071.42       NA
+
+

+ +Hierarchical FOMC path 1 fit with two-component error + +


+saemix version used for fitting:      3.2 
+mkin version used for pre-fitting:  1.2.2 
+R version used for fitting:         4.2.2 
+Date of fit:     Sat Jan 28 10:09:18 2023 
+Date of summary: Sat Jan 28 11:22:29 2023 
+
+Equations:
+d_cyan/dt = - (alpha/beta) * 1/((time/beta) + 1) * cyan
+d_JCZ38/dt = + f_cyan_to_JCZ38 * (alpha/beta) * 1/((time/beta) + 1) *
+           cyan - k_JCZ38 * JCZ38
+d_J9Z38/dt = + f_cyan_to_J9Z38 * (alpha/beta) * 1/((time/beta) + 1) *
+           cyan - k_J9Z38 * J9Z38
+d_JSE76/dt = + f_JCZ38_to_JSE76 * k_JCZ38 * JCZ38 - k_JSE76 * JSE76
+
+Data:
+433 observations of 4 variable(s) grouped in 5 datasets
+
+Model predictions using solution type deSolve 
+
+Fitted in 1188.041 s
+Using 300, 100 iterations and 10 chains
+
+Variance model: Two-component variance function 
+
+Starting values for degradation parameters:
+        cyan_0    log_k_JCZ38    log_k_J9Z38    log_k_JSE76   f_cyan_ilr_1 
+     101.13827       -3.32493       -5.08921       -5.93478        0.71330 
+  f_cyan_ilr_2 f_JCZ38_qlogis      log_alpha       log_beta 
+      10.05989       12.79248       -0.09621        3.10646 
+
+Fixed degradation parameter values:
+None
+
+Starting values for random effects (square root of initial entries in omega):
+               cyan_0 log_k_JCZ38 log_k_J9Z38 log_k_JSE76 f_cyan_ilr_1
+cyan_0          5.643       0.000       0.000        0.00       0.0000
+log_k_JCZ38     0.000       2.319       0.000        0.00       0.0000
+log_k_J9Z38     0.000       0.000       1.731        0.00       0.0000
+log_k_JSE76     0.000       0.000       0.000        1.86       0.0000
+f_cyan_ilr_1    0.000       0.000       0.000        0.00       0.7186
+f_cyan_ilr_2    0.000       0.000       0.000        0.00       0.0000
+f_JCZ38_qlogis  0.000       0.000       0.000        0.00       0.0000
+log_alpha       0.000       0.000       0.000        0.00       0.0000
+log_beta        0.000       0.000       0.000        0.00       0.0000
+               f_cyan_ilr_2 f_JCZ38_qlogis log_alpha log_beta
+cyan_0                 0.00           0.00    0.0000   0.0000
+log_k_JCZ38            0.00           0.00    0.0000   0.0000
+log_k_J9Z38            0.00           0.00    0.0000   0.0000
+log_k_JSE76            0.00           0.00    0.0000   0.0000
+f_cyan_ilr_1           0.00           0.00    0.0000   0.0000
+f_cyan_ilr_2          12.49           0.00    0.0000   0.0000
+f_JCZ38_qlogis         0.00          20.19    0.0000   0.0000
+log_alpha              0.00           0.00    0.3142   0.0000
+log_beta               0.00           0.00    0.0000   0.7331
+
+Starting values for error model parameters:
+a.1 b.1 
+  1   1 
+
+Results:
+
+Likelihood computed by importance sampling
+   AIC  BIC logLik
+  2423 2416  -1193
+
+Optimised parameters:
+                       est. lower upper
+cyan_0            100.57649    NA    NA
+log_k_JCZ38        -3.46250    NA    NA
+log_k_J9Z38        -5.24442    NA    NA
+log_k_JSE76        -5.75229    NA    NA
+f_cyan_ilr_1        0.68480    NA    NA
+f_cyan_ilr_2        0.61670    NA    NA
+f_JCZ38_qlogis     87.97407    NA    NA
+log_alpha          -0.15699    NA    NA
+log_beta            3.01540    NA    NA
+a.1                 3.11518    NA    NA
+b.1                 0.04445    NA    NA
+SD.log_k_JCZ38      1.40732    NA    NA
+SD.log_k_J9Z38      0.56510    NA    NA
+SD.log_k_JSE76      0.72067    NA    NA
+SD.f_cyan_ilr_1     0.31199    NA    NA
+SD.f_cyan_ilr_2     0.36894    NA    NA
+SD.f_JCZ38_qlogis   6.92892    NA    NA
+SD.log_alpha        0.25662    NA    NA
+SD.log_beta         0.35845    NA    NA
+
+Correlation is not available
+
+Random effects:
+                    est. lower upper
+SD.log_k_JCZ38    1.4073    NA    NA
+SD.log_k_J9Z38    0.5651    NA    NA
+SD.log_k_JSE76    0.7207    NA    NA
+SD.f_cyan_ilr_1   0.3120    NA    NA
+SD.f_cyan_ilr_2   0.3689    NA    NA
+SD.f_JCZ38_qlogis 6.9289    NA    NA
+SD.log_alpha      0.2566    NA    NA
+SD.log_beta       0.3585    NA    NA
+
+Variance model:
+       est. lower upper
+a.1 3.11518    NA    NA
+b.1 0.04445    NA    NA
+
+Backtransformed parameters:
+                      est. lower upper
+cyan_0           1.006e+02    NA    NA
+k_JCZ38          3.135e-02    NA    NA
+k_J9Z38          5.277e-03    NA    NA
+k_JSE76          3.175e-03    NA    NA
+f_cyan_to_JCZ38  5.991e-01    NA    NA
+f_cyan_to_J9Z38  2.275e-01    NA    NA
+f_JCZ38_to_JSE76 1.000e+00    NA    NA
+alpha            8.547e-01    NA    NA
+beta             2.040e+01    NA    NA
+
+Resulting formation fractions:
+                ff
+cyan_JCZ38  0.5991
+cyan_J9Z38  0.2275
+cyan_sink   0.1734
+JCZ38_JSE76 1.0000
+JCZ38_sink  0.0000
+
+Estimated disappearance times:
+        DT50   DT90 DT50back
+cyan   25.50 281.29    84.68
+JCZ38  22.11  73.44       NA
+J9Z38 131.36 436.35       NA
+JSE76 218.28 725.11       NA
+
+

+ +Hierarchical DFOP path 1 fit with constant variance + +


+saemix version used for fitting:      3.2 
+mkin version used for pre-fitting:  1.2.2 
+R version used for fitting:         4.2.2 
+Date of fit:     Sat Jan 28 10:10:30 2023 
+Date of summary: Sat Jan 28 11:22:29 2023 
+
+Equations:
+d_cyan/dt = - ((k1 * g * exp(-k1 * time) + k2 * (1 - g) * exp(-k2 *
+           time)) / (g * exp(-k1 * time) + (1 - g) * exp(-k2 * time)))
+           * cyan
+d_JCZ38/dt = + f_cyan_to_JCZ38 * ((k1 * g * exp(-k1 * time) + k2 * (1 -
+           g) * exp(-k2 * time)) / (g * exp(-k1 * time) + (1 - g) *
+           exp(-k2 * time))) * cyan - k_JCZ38 * JCZ38
+d_J9Z38/dt = + f_cyan_to_J9Z38 * ((k1 * g * exp(-k1 * time) + k2 * (1 -
+           g) * exp(-k2 * time)) / (g * exp(-k1 * time) + (1 - g) *
+           exp(-k2 * time))) * cyan - k_J9Z38 * J9Z38
+d_JSE76/dt = + f_JCZ38_to_JSE76 * k_JCZ38 * JCZ38 - k_JSE76 * JSE76
+
+Data:
+433 observations of 4 variable(s) grouped in 5 datasets
+
+Model predictions using solution type deSolve 
+
+Fitted in 1260.905 s
+Using 300, 100 iterations and 10 chains
+
+Variance model: Constant variance 
+
+Starting values for degradation parameters:
+        cyan_0    log_k_JCZ38    log_k_J9Z38    log_k_JSE76   f_cyan_ilr_1 
+      102.0644        -3.4008        -5.0024        -5.8613         0.6855 
+  f_cyan_ilr_2 f_JCZ38_qlogis         log_k1         log_k2       g_qlogis 
+        1.2365        13.7245        -1.8641        -4.5063        -0.6468 
+
+Fixed degradation parameter values:
+None
+
+Starting values for random effects (square root of initial entries in omega):
+               cyan_0 log_k_JCZ38 log_k_J9Z38 log_k_JSE76 f_cyan_ilr_1
+cyan_0          4.466       0.000       0.000       0.000       0.0000
+log_k_JCZ38     0.000       2.382       0.000       0.000       0.0000
+log_k_J9Z38     0.000       0.000       1.595       0.000       0.0000
+log_k_JSE76     0.000       0.000       0.000       1.245       0.0000
+f_cyan_ilr_1    0.000       0.000       0.000       0.000       0.6852
+f_cyan_ilr_2    0.000       0.000       0.000       0.000       0.0000
+f_JCZ38_qlogis  0.000       0.000       0.000       0.000       0.0000
+log_k1          0.000       0.000       0.000       0.000       0.0000
+log_k2          0.000       0.000       0.000       0.000       0.0000
+g_qlogis        0.000       0.000       0.000       0.000       0.0000
+               f_cyan_ilr_2 f_JCZ38_qlogis log_k1 log_k2 g_qlogis
+cyan_0                 0.00           0.00 0.0000 0.0000    0.000
+log_k_JCZ38            0.00           0.00 0.0000 0.0000    0.000
+log_k_J9Z38            0.00           0.00 0.0000 0.0000    0.000
+log_k_JSE76            0.00           0.00 0.0000 0.0000    0.000
+f_cyan_ilr_1           0.00           0.00 0.0000 0.0000    0.000
+f_cyan_ilr_2           1.28           0.00 0.0000 0.0000    0.000
+f_JCZ38_qlogis         0.00          16.11 0.0000 0.0000    0.000
+log_k1                 0.00           0.00 0.9866 0.0000    0.000
+log_k2                 0.00           0.00 0.0000 0.5953    0.000
+g_qlogis               0.00           0.00 0.0000 0.0000    1.583
+
+Starting values for error model parameters:
+a.1 
+  1 
+
+Results:
+
+Likelihood computed by importance sampling
+   AIC  BIC logLik
+  2403 2395  -1182
+
+Optimised parameters:
+                      est. lower upper
+cyan_0            102.6079    NA    NA
+log_k_JCZ38        -3.4855    NA    NA
+log_k_J9Z38        -5.1686    NA    NA
+log_k_JSE76        -5.6697    NA    NA
+f_cyan_ilr_1        0.6714    NA    NA
+f_cyan_ilr_2        0.4986    NA    NA
+f_JCZ38_qlogis     55.4760    NA    NA
+log_k1             -1.8409    NA    NA
+log_k2             -4.4915    NA    NA
+g_qlogis           -0.6403    NA    NA
+a.1                 3.2387    NA    NA
+SD.log_k_JCZ38      1.4524    NA    NA
+SD.log_k_J9Z38      0.5151    NA    NA
+SD.log_k_JSE76      0.6514    NA    NA
+SD.f_cyan_ilr_1     0.3023    NA    NA
+SD.f_cyan_ilr_2     0.2959    NA    NA
+SD.f_JCZ38_qlogis   1.9984    NA    NA
+SD.log_k1           0.5188    NA    NA
+SD.log_k2           0.3894    NA    NA
+SD.g_qlogis         0.8579    NA    NA
+
+Correlation is not available
+
+Random effects:
+                    est. lower upper
+SD.log_k_JCZ38    1.4524    NA    NA
+SD.log_k_J9Z38    0.5151    NA    NA
+SD.log_k_JSE76    0.6514    NA    NA
+SD.f_cyan_ilr_1   0.3023    NA    NA
+SD.f_cyan_ilr_2   0.2959    NA    NA
+SD.f_JCZ38_qlogis 1.9984    NA    NA
+SD.log_k1         0.5188    NA    NA
+SD.log_k2         0.3894    NA    NA
+SD.g_qlogis       0.8579    NA    NA
+
+Variance model:
+     est. lower upper
+a.1 3.239    NA    NA
+
+Backtransformed parameters:
+                      est. lower upper
+cyan_0           1.026e+02    NA    NA
+k_JCZ38          3.064e-02    NA    NA
+k_J9Z38          5.692e-03    NA    NA
+k_JSE76          3.449e-03    NA    NA
+f_cyan_to_JCZ38  5.798e-01    NA    NA
+f_cyan_to_J9Z38  2.243e-01    NA    NA
+f_JCZ38_to_JSE76 1.000e+00    NA    NA
+k1               1.587e-01    NA    NA
+k2               1.120e-02    NA    NA
+g                3.452e-01    NA    NA
+
+Resulting formation fractions:
+                ff
+cyan_JCZ38  0.5798
+cyan_J9Z38  0.2243
+cyan_sink   0.1958
+JCZ38_JSE76 1.0000
+JCZ38_sink  0.0000
+
+Estimated disappearance times:
+        DT50   DT90 DT50back DT50_k1 DT50_k2
+cyan   25.21 167.73    50.49   4.368   61.87
+JCZ38  22.62  75.15       NA      NA      NA
+J9Z38 121.77 404.50       NA      NA      NA
+JSE76 200.98 667.64       NA      NA      NA
+
+

+ +Hierarchical DFOP path 1 fit with two-component error + +


+saemix version used for fitting:      3.2 
+mkin version used for pre-fitting:  1.2.2 
+R version used for fitting:         4.2.2 
+Date of fit:     Sat Jan 28 10:16:28 2023 
+Date of summary: Sat Jan 28 11:22:29 2023 
+
+Equations:
+d_cyan/dt = - ((k1 * g * exp(-k1 * time) + k2 * (1 - g) * exp(-k2 *
+           time)) / (g * exp(-k1 * time) + (1 - g) * exp(-k2 * time)))
+           * cyan
+d_JCZ38/dt = + f_cyan_to_JCZ38 * ((k1 * g * exp(-k1 * time) + k2 * (1 -
+           g) * exp(-k2 * time)) / (g * exp(-k1 * time) + (1 - g) *
+           exp(-k2 * time))) * cyan - k_JCZ38 * JCZ38
+d_J9Z38/dt = + f_cyan_to_J9Z38 * ((k1 * g * exp(-k1 * time) + k2 * (1 -
+           g) * exp(-k2 * time)) / (g * exp(-k1 * time) + (1 - g) *
+           exp(-k2 * time))) * cyan - k_J9Z38 * J9Z38
+d_JSE76/dt = + f_JCZ38_to_JSE76 * k_JCZ38 * JCZ38 - k_JSE76 * JSE76
+
+Data:
+433 observations of 4 variable(s) grouped in 5 datasets
+
+Model predictions using solution type deSolve 
+
+Fitted in 1617.774 s
+Using 300, 100 iterations and 10 chains
+
+Variance model: Two-component variance function 
+
+Starting values for degradation parameters:
+        cyan_0    log_k_JCZ38    log_k_J9Z38    log_k_JSE76   f_cyan_ilr_1 
+      101.3964        -3.3626        -4.9792        -5.8727         0.6814 
+  f_cyan_ilr_2 f_JCZ38_qlogis         log_k1         log_k2       g_qlogis 
+        6.7799        13.7245        -1.9222        -4.5035        -0.7172 
+
+Fixed degradation parameter values:
+None
+
+Starting values for random effects (square root of initial entries in omega):
+               cyan_0 log_k_JCZ38 log_k_J9Z38 log_k_JSE76 f_cyan_ilr_1
+cyan_0          5.317       0.000       0.000       0.000       0.0000
+log_k_JCZ38     0.000       2.272       0.000       0.000       0.0000
+log_k_J9Z38     0.000       0.000       1.633       0.000       0.0000
+log_k_JSE76     0.000       0.000       0.000       1.271       0.0000
+f_cyan_ilr_1    0.000       0.000       0.000       0.000       0.6838
+f_cyan_ilr_2    0.000       0.000       0.000       0.000       0.0000
+f_JCZ38_qlogis  0.000       0.000       0.000       0.000       0.0000
+log_k1          0.000       0.000       0.000       0.000       0.0000
+log_k2          0.000       0.000       0.000       0.000       0.0000
+g_qlogis        0.000       0.000       0.000       0.000       0.0000
+               f_cyan_ilr_2 f_JCZ38_qlogis log_k1 log_k2 g_qlogis
+cyan_0                 0.00           0.00 0.0000 0.0000    0.000
+log_k_JCZ38            0.00           0.00 0.0000 0.0000    0.000
+log_k_J9Z38            0.00           0.00 0.0000 0.0000    0.000
+log_k_JSE76            0.00           0.00 0.0000 0.0000    0.000
+f_cyan_ilr_1           0.00           0.00 0.0000 0.0000    0.000
+f_cyan_ilr_2          11.77           0.00 0.0000 0.0000    0.000
+f_JCZ38_qlogis         0.00          16.11 0.0000 0.0000    0.000
+log_k1                 0.00           0.00 0.9496 0.0000    0.000
+log_k2                 0.00           0.00 0.0000 0.5846    0.000
+g_qlogis               0.00           0.00 0.0000 0.0000    1.719
+
+Starting values for error model parameters:
+a.1 b.1 
+  1   1 
+
+Results:
+
+Likelihood computed by importance sampling
+   AIC  BIC logLik
+  2398 2390  -1179
+
+Optimised parameters:
+                      est. lower upper
+cyan_0            100.8076    NA    NA
+log_k_JCZ38        -3.4684    NA    NA
+log_k_J9Z38        -5.0844    NA    NA
+log_k_JSE76        -5.5743    NA    NA
+f_cyan_ilr_1        0.6669    NA    NA
+f_cyan_ilr_2        0.7912    NA    NA
+f_JCZ38_qlogis     84.1825    NA    NA
+log_k1             -2.1671    NA    NA
+log_k2             -4.5447    NA    NA
+g_qlogis           -0.5631    NA    NA
+a.1                 2.9627    NA    NA
+b.1                 0.0444    NA    NA
+SD.log_k_JCZ38      1.4044    NA    NA
+SD.log_k_J9Z38      0.6410    NA    NA
+SD.log_k_JSE76      0.5391    NA    NA
+SD.f_cyan_ilr_1     0.3203    NA    NA
+SD.f_cyan_ilr_2     0.5038    NA    NA
+SD.f_JCZ38_qlogis   3.5865    NA    NA
+SD.log_k2           0.3119    NA    NA
+SD.g_qlogis         0.8276    NA    NA
+
+Correlation is not available
+
+Random effects:
+                    est. lower upper
+SD.log_k_JCZ38    1.4044    NA    NA
+SD.log_k_J9Z38    0.6410    NA    NA
+SD.log_k_JSE76    0.5391    NA    NA
+SD.f_cyan_ilr_1   0.3203    NA    NA
+SD.f_cyan_ilr_2   0.5038    NA    NA
+SD.f_JCZ38_qlogis 3.5865    NA    NA
+SD.log_k2         0.3119    NA    NA
+SD.g_qlogis       0.8276    NA    NA
+
+Variance model:
+      est. lower upper
+a.1 2.9627    NA    NA
+b.1 0.0444    NA    NA
+
+Backtransformed parameters:
+                      est. lower upper
+cyan_0           1.008e+02    NA    NA
+k_JCZ38          3.117e-02    NA    NA
+k_J9Z38          6.193e-03    NA    NA
+k_JSE76          3.794e-03    NA    NA
+f_cyan_to_JCZ38  6.149e-01    NA    NA
+f_cyan_to_J9Z38  2.395e-01    NA    NA
+f_JCZ38_to_JSE76 1.000e+00    NA    NA
+k1               1.145e-01    NA    NA
+k2               1.062e-02    NA    NA
+g                3.628e-01    NA    NA
+
+Resulting formation fractions:
+                ff
+cyan_JCZ38  0.6149
+cyan_J9Z38  0.2395
+cyan_sink   0.1456
+JCZ38_JSE76 1.0000
+JCZ38_sink  0.0000
+
+Estimated disappearance times:
+        DT50   DT90 DT50back DT50_k1 DT50_k2
+cyan   26.26 174.32    52.47   6.053   65.25
+JCZ38  22.24  73.88       NA      NA      NA
+J9Z38 111.93 371.82       NA      NA      NA
+JSE76 182.69 606.88       NA      NA      NA
+
+

+ +Hierarchical SFORB path 1 fit with constant variance + +


+saemix version used for fitting:      3.2 
+mkin version used for pre-fitting:  1.2.2 
+R version used for fitting:         4.2.2 
+Date of fit:     Sat Jan 28 10:10:49 2023 
+Date of summary: Sat Jan 28 11:22:29 2023 
+
+Equations:
+d_cyan_free/dt = - k_cyan_free * cyan_free - k_cyan_free_bound *
+           cyan_free + k_cyan_bound_free * cyan_bound
+d_cyan_bound/dt = + k_cyan_free_bound * cyan_free - k_cyan_bound_free *
+           cyan_bound
+d_JCZ38/dt = + f_cyan_free_to_JCZ38 * k_cyan_free * cyan_free - k_JCZ38
+           * JCZ38
+d_J9Z38/dt = + f_cyan_free_to_J9Z38 * k_cyan_free * cyan_free - k_J9Z38
+           * J9Z38
+d_JSE76/dt = + f_JCZ38_to_JSE76 * k_JCZ38 * JCZ38 - k_JSE76 * JSE76
+
+Data:
+433 observations of 4 variable(s) grouped in 5 datasets
+
+Model predictions using solution type deSolve 
+
+Fitted in 1279.472 s
+Using 300, 100 iterations and 10 chains
+
+Variance model: Constant variance 
+
+Starting values for degradation parameters:
+          cyan_free_0       log_k_cyan_free log_k_cyan_free_bound 
+             102.0643               -2.8987               -2.7077 
+log_k_cyan_bound_free           log_k_JCZ38           log_k_J9Z38 
+              -3.4717               -3.4008               -5.0024 
+          log_k_JSE76          f_cyan_ilr_1          f_cyan_ilr_2 
+              -5.8613                0.6855                1.2366 
+       f_JCZ38_qlogis 
+              13.7418 
+
+Fixed degradation parameter values:
+None
+
+Starting values for random effects (square root of initial entries in omega):
+                      cyan_free_0 log_k_cyan_free log_k_cyan_free_bound
+cyan_free_0                 4.466          0.0000                 0.000
+log_k_cyan_free             0.000          0.6158                 0.000
+log_k_cyan_free_bound       0.000          0.0000                 1.463
+log_k_cyan_bound_free       0.000          0.0000                 0.000
+log_k_JCZ38                 0.000          0.0000                 0.000
+log_k_J9Z38                 0.000          0.0000                 0.000
+log_k_JSE76                 0.000          0.0000                 0.000
+f_cyan_ilr_1                0.000          0.0000                 0.000
+f_cyan_ilr_2                0.000          0.0000                 0.000
+f_JCZ38_qlogis              0.000          0.0000                 0.000
+                      log_k_cyan_bound_free log_k_JCZ38 log_k_J9Z38 log_k_JSE76
+cyan_free_0                           0.000       0.000       0.000       0.000
+log_k_cyan_free                       0.000       0.000       0.000       0.000
+log_k_cyan_free_bound                 0.000       0.000       0.000       0.000
+log_k_cyan_bound_free                 1.058       0.000       0.000       0.000
+log_k_JCZ38                           0.000       2.382       0.000       0.000
+log_k_J9Z38                           0.000       0.000       1.595       0.000
+log_k_JSE76                           0.000       0.000       0.000       1.245
+f_cyan_ilr_1                          0.000       0.000       0.000       0.000
+f_cyan_ilr_2                          0.000       0.000       0.000       0.000
+f_JCZ38_qlogis                        0.000       0.000       0.000       0.000
+                      f_cyan_ilr_1 f_cyan_ilr_2 f_JCZ38_qlogis
+cyan_free_0                 0.0000         0.00           0.00
+log_k_cyan_free             0.0000         0.00           0.00
+log_k_cyan_free_bound       0.0000         0.00           0.00
+log_k_cyan_bound_free       0.0000         0.00           0.00
+log_k_JCZ38                 0.0000         0.00           0.00
+log_k_J9Z38                 0.0000         0.00           0.00
+log_k_JSE76                 0.0000         0.00           0.00
+f_cyan_ilr_1                0.6852         0.00           0.00
+f_cyan_ilr_2                0.0000         1.28           0.00
+f_JCZ38_qlogis              0.0000         0.00          16.14
+
+Starting values for error model parameters:
+a.1 
+  1 
+
+Results:
+
+Likelihood computed by importance sampling
+   AIC  BIC logLik
+  2401 2394  -1181
+
+Optimised parameters:
+                             est. lower upper
+cyan_free_0              102.7803    NA    NA
+log_k_cyan_free           -2.8068    NA    NA
+log_k_cyan_free_bound     -2.5714    NA    NA
+log_k_cyan_bound_free     -3.4426    NA    NA
+log_k_JCZ38               -3.4994    NA    NA
+log_k_J9Z38               -5.1148    NA    NA
+log_k_JSE76               -5.6335    NA    NA
+f_cyan_ilr_1               0.6597    NA    NA
+f_cyan_ilr_2               0.5132    NA    NA
+f_JCZ38_qlogis            37.2090    NA    NA
+a.1                        3.2367    NA    NA
+SD.log_k_cyan_free         0.3161    NA    NA
+SD.log_k_cyan_free_bound   0.8103    NA    NA
+SD.log_k_cyan_bound_free   0.5554    NA    NA
+SD.log_k_JCZ38             1.4858    NA    NA
+SD.log_k_J9Z38             0.5859    NA    NA
+SD.log_k_JSE76             0.6195    NA    NA
+SD.f_cyan_ilr_1            0.3118    NA    NA
+SD.f_cyan_ilr_2            0.3344    NA    NA
+SD.f_JCZ38_qlogis          0.5518    NA    NA
+
+Correlation is not available
+
+Random effects:
+                           est. lower upper
+SD.log_k_cyan_free       0.3161    NA    NA
+SD.log_k_cyan_free_bound 0.8103    NA    NA
+SD.log_k_cyan_bound_free 0.5554    NA    NA
+SD.log_k_JCZ38           1.4858    NA    NA
+SD.log_k_J9Z38           0.5859    NA    NA
+SD.log_k_JSE76           0.6195    NA    NA
+SD.f_cyan_ilr_1          0.3118    NA    NA
+SD.f_cyan_ilr_2          0.3344    NA    NA
+SD.f_JCZ38_qlogis        0.5518    NA    NA
+
+Variance model:
+     est. lower upper
+a.1 3.237    NA    NA
+
+Backtransformed parameters:
+                          est. lower upper
+cyan_free_0          1.028e+02    NA    NA
+k_cyan_free          6.040e-02    NA    NA
+k_cyan_free_bound    7.643e-02    NA    NA
+k_cyan_bound_free    3.198e-02    NA    NA
+k_JCZ38              3.022e-02    NA    NA
+k_J9Z38              6.007e-03    NA    NA
+k_JSE76              3.576e-03    NA    NA
+f_cyan_free_to_JCZ38 5.787e-01    NA    NA
+f_cyan_free_to_J9Z38 2.277e-01    NA    NA
+f_JCZ38_to_JSE76     1.000e+00    NA    NA
+
+Estimated Eigenvalues of SFORB model(s):
+cyan_b1 cyan_b2  cyan_g 
+0.15646 0.01235 0.33341 
+
+Resulting formation fractions:
+                    ff
+cyan_free_JCZ38 0.5787
+cyan_free_J9Z38 0.2277
+cyan_free_sink  0.1936
+cyan_free       1.0000
+JCZ38_JSE76     1.0000
+JCZ38_sink      0.0000
+
+Estimated disappearance times:
+        DT50  DT90 DT50back DT50_cyan_b1 DT50_cyan_b2
+cyan   24.48 153.7    46.26         4.43        56.15
+JCZ38  22.94  76.2       NA           NA           NA
+J9Z38 115.39 383.3       NA           NA           NA
+JSE76 193.84 643.9       NA           NA           NA
+
+

+ +Hierarchical SFORB path 1 fit with two-component error + +


+saemix version used for fitting:      3.2 
+mkin version used for pre-fitting:  1.2.2 
+R version used for fitting:         4.2.2 
+Date of fit:     Sat Jan 28 10:17:00 2023 
+Date of summary: Sat Jan 28 11:22:29 2023 
+
+Equations:
+d_cyan_free/dt = - k_cyan_free * cyan_free - k_cyan_free_bound *
+           cyan_free + k_cyan_bound_free * cyan_bound
+d_cyan_bound/dt = + k_cyan_free_bound * cyan_free - k_cyan_bound_free *
+           cyan_bound
+d_JCZ38/dt = + f_cyan_free_to_JCZ38 * k_cyan_free * cyan_free - k_JCZ38
+           * JCZ38
+d_J9Z38/dt = + f_cyan_free_to_J9Z38 * k_cyan_free * cyan_free - k_J9Z38
+           * J9Z38
+d_JSE76/dt = + f_JCZ38_to_JSE76 * k_JCZ38 * JCZ38 - k_JSE76 * JSE76
+
+Data:
+433 observations of 4 variable(s) grouped in 5 datasets
+
+Model predictions using solution type deSolve 
+
+Fitted in 1649.941 s
+Using 300, 100 iterations and 10 chains
+
+Variance model: Two-component variance function 
+
+Starting values for degradation parameters:
+          cyan_free_0       log_k_cyan_free log_k_cyan_free_bound 
+             101.3964               -2.9881               -2.7949 
+log_k_cyan_bound_free           log_k_JCZ38           log_k_J9Z38 
+              -3.4376               -3.3626               -4.9792 
+          log_k_JSE76          f_cyan_ilr_1          f_cyan_ilr_2 
+              -5.8727                0.6814                6.8139 
+       f_JCZ38_qlogis 
+              13.7419 
+
+Fixed degradation parameter values:
+None
+
+Starting values for random effects (square root of initial entries in omega):
+                      cyan_free_0 log_k_cyan_free log_k_cyan_free_bound
+cyan_free_0                 5.317          0.0000                 0.000
+log_k_cyan_free             0.000          0.7301                 0.000
+log_k_cyan_free_bound       0.000          0.0000                 1.384
+log_k_cyan_bound_free       0.000          0.0000                 0.000
+log_k_JCZ38                 0.000          0.0000                 0.000
+log_k_J9Z38                 0.000          0.0000                 0.000
+log_k_JSE76                 0.000          0.0000                 0.000
+f_cyan_ilr_1                0.000          0.0000                 0.000
+f_cyan_ilr_2                0.000          0.0000                 0.000
+f_JCZ38_qlogis              0.000          0.0000                 0.000
+                      log_k_cyan_bound_free log_k_JCZ38 log_k_J9Z38 log_k_JSE76
+cyan_free_0                           0.000       0.000       0.000       0.000
+log_k_cyan_free                       0.000       0.000       0.000       0.000
+log_k_cyan_free_bound                 0.000       0.000       0.000       0.000
+log_k_cyan_bound_free                 1.109       0.000       0.000       0.000
+log_k_JCZ38                           0.000       2.272       0.000       0.000
+log_k_J9Z38                           0.000       0.000       1.633       0.000
+log_k_JSE76                           0.000       0.000       0.000       1.271
+f_cyan_ilr_1                          0.000       0.000       0.000       0.000
+f_cyan_ilr_2                          0.000       0.000       0.000       0.000
+f_JCZ38_qlogis                        0.000       0.000       0.000       0.000
+                      f_cyan_ilr_1 f_cyan_ilr_2 f_JCZ38_qlogis
+cyan_free_0                 0.0000         0.00           0.00
+log_k_cyan_free             0.0000         0.00           0.00
+log_k_cyan_free_bound       0.0000         0.00           0.00
+log_k_cyan_bound_free       0.0000         0.00           0.00
+log_k_JCZ38                 0.0000         0.00           0.00
+log_k_J9Z38                 0.0000         0.00           0.00
+log_k_JSE76                 0.0000         0.00           0.00
+f_cyan_ilr_1                0.6838         0.00           0.00
+f_cyan_ilr_2                0.0000        11.84           0.00
+f_JCZ38_qlogis              0.0000         0.00          16.14
+
+Starting values for error model parameters:
+a.1 b.1 
+  1   1 
+
+Results:
+
+Likelihood computed by importance sampling
+   AIC  BIC logLik
+  2400 2392  -1180
+
+Optimised parameters:
+                              est. lower upper
+cyan_free_0              100.69983    NA    NA
+log_k_cyan_free           -3.11584    NA    NA
+log_k_cyan_free_bound     -3.15216    NA    NA
+log_k_cyan_bound_free     -3.65986    NA    NA
+log_k_JCZ38               -3.47811    NA    NA
+log_k_J9Z38               -5.08835    NA    NA
+log_k_JSE76               -5.55514    NA    NA
+f_cyan_ilr_1               0.66764    NA    NA
+f_cyan_ilr_2               0.78329    NA    NA
+f_JCZ38_qlogis            25.35245    NA    NA
+a.1                        2.99088    NA    NA
+b.1                        0.04346    NA    NA
+SD.log_k_cyan_free         0.48797    NA    NA
+SD.log_k_cyan_bound_free   0.27243    NA    NA
+SD.log_k_JCZ38             1.42450    NA    NA
+SD.log_k_J9Z38             0.63496    NA    NA
+SD.log_k_JSE76             0.55951    NA    NA
+SD.f_cyan_ilr_1            0.32687    NA    NA
+SD.f_cyan_ilr_2            0.48056    NA    NA
+SD.f_JCZ38_qlogis          0.43818    NA    NA
+
+Correlation is not available
+
+Random effects:
+                           est. lower upper
+SD.log_k_cyan_free       0.4880    NA    NA
+SD.log_k_cyan_bound_free 0.2724    NA    NA
+SD.log_k_JCZ38           1.4245    NA    NA
+SD.log_k_J9Z38           0.6350    NA    NA
+SD.log_k_JSE76           0.5595    NA    NA
+SD.f_cyan_ilr_1          0.3269    NA    NA
+SD.f_cyan_ilr_2          0.4806    NA    NA
+SD.f_JCZ38_qlogis        0.4382    NA    NA
+
+Variance model:
+       est. lower upper
+a.1 2.99088    NA    NA
+b.1 0.04346    NA    NA
+
+Backtransformed parameters:
+                          est. lower upper
+cyan_free_0          1.007e+02    NA    NA
+k_cyan_free          4.434e-02    NA    NA
+k_cyan_free_bound    4.276e-02    NA    NA
+k_cyan_bound_free    2.574e-02    NA    NA
+k_JCZ38              3.087e-02    NA    NA
+k_J9Z38              6.168e-03    NA    NA
+k_JSE76              3.868e-03    NA    NA
+f_cyan_free_to_JCZ38 6.143e-01    NA    NA
+f_cyan_free_to_J9Z38 2.389e-01    NA    NA
+f_JCZ38_to_JSE76     1.000e+00    NA    NA
+
+Estimated Eigenvalues of SFORB model(s):
+cyan_b1 cyan_b2  cyan_g 
+0.10161 0.01123 0.36636 
+
+Resulting formation fractions:
+                       ff
+cyan_free_JCZ38 6.143e-01
+cyan_free_J9Z38 2.389e-01
+cyan_free_sink  1.468e-01
+cyan_free       1.000e+00
+JCZ38_JSE76     1.000e+00
+JCZ38_sink      9.763e-12
+
+Estimated disappearance times:
+        DT50  DT90 DT50back DT50_cyan_b1 DT50_cyan_b2
+cyan   25.91 164.4    49.49        6.822        61.72
+JCZ38  22.46  74.6       NA           NA           NA
+J9Z38 112.37 373.3       NA           NA           NA
+JSE76 179.22 595.4       NA           NA           NA
+
+

+ +Hierarchical HS path 1 fit with constant variance + +


+saemix version used for fitting:      3.2 
+mkin version used for pre-fitting:  1.2.2 
+R version used for fitting:         4.2.2 
+Date of fit:     Sat Jan 28 10:11:04 2023 
+Date of summary: Sat Jan 28 11:22:29 2023 
+
+Equations:
+d_cyan/dt = - ifelse(time <= tb, k1, k2) * cyan
+d_JCZ38/dt = + f_cyan_to_JCZ38 * ifelse(time <= tb, k1, k2) * cyan -
+           k_JCZ38 * JCZ38
+d_J9Z38/dt = + f_cyan_to_J9Z38 * ifelse(time <= tb, k1, k2) * cyan -
+           k_J9Z38 * J9Z38
+d_JSE76/dt = + f_JCZ38_to_JSE76 * k_JCZ38 * JCZ38 - k_JSE76 * JSE76
+
+Data:
+433 observations of 4 variable(s) grouped in 5 datasets
+
+Model predictions using solution type deSolve 
+
+Fitted in 1294.259 s
+Using 300, 100 iterations and 10 chains
+
+Variance model: Constant variance 
+
+Starting values for degradation parameters:
+        cyan_0    log_k_JCZ38    log_k_J9Z38    log_k_JSE76   f_cyan_ilr_1 
+      102.8738        -3.4490        -4.9348        -5.5989         0.6469 
+  f_cyan_ilr_2 f_JCZ38_qlogis         log_k1         log_k2         log_tb 
+        1.2854         9.7193        -2.9084        -4.1810         1.7813 
+
+Fixed degradation parameter values:
+None
+
+Starting values for random effects (square root of initial entries in omega):
+               cyan_0 log_k_JCZ38 log_k_J9Z38 log_k_JSE76 f_cyan_ilr_1
+cyan_0          5.409        0.00        0.00       0.000       0.0000
+log_k_JCZ38     0.000        2.33        0.00       0.000       0.0000
+log_k_J9Z38     0.000        0.00        1.59       0.000       0.0000
+log_k_JSE76     0.000        0.00        0.00       1.006       0.0000
+f_cyan_ilr_1    0.000        0.00        0.00       0.000       0.6371
+f_cyan_ilr_2    0.000        0.00        0.00       0.000       0.0000
+f_JCZ38_qlogis  0.000        0.00        0.00       0.000       0.0000
+log_k1          0.000        0.00        0.00       0.000       0.0000
+log_k2          0.000        0.00        0.00       0.000       0.0000
+log_tb          0.000        0.00        0.00       0.000       0.0000
+               f_cyan_ilr_2 f_JCZ38_qlogis log_k1 log_k2 log_tb
+cyan_0                0.000           0.00 0.0000 0.0000 0.0000
+log_k_JCZ38           0.000           0.00 0.0000 0.0000 0.0000
+log_k_J9Z38           0.000           0.00 0.0000 0.0000 0.0000
+log_k_JSE76           0.000           0.00 0.0000 0.0000 0.0000
+f_cyan_ilr_1          0.000           0.00 0.0000 0.0000 0.0000
+f_cyan_ilr_2          2.167           0.00 0.0000 0.0000 0.0000
+f_JCZ38_qlogis        0.000          10.22 0.0000 0.0000 0.0000
+log_k1                0.000           0.00 0.7003 0.0000 0.0000
+log_k2                0.000           0.00 0.0000 0.8928 0.0000
+log_tb                0.000           0.00 0.0000 0.0000 0.6774
+
+Starting values for error model parameters:
+a.1 
+  1 
+
+Results:
+
+Likelihood computed by importance sampling
+   AIC  BIC logLik
+  2427 2420  -1194
+
+Optimised parameters:
+                       est. lower upper
+cyan_0            101.84849    NA    NA
+log_k_JCZ38        -3.47365    NA    NA
+log_k_J9Z38        -5.10562    NA    NA
+log_k_JSE76        -5.60318    NA    NA
+f_cyan_ilr_1        0.66127    NA    NA
+f_cyan_ilr_2        0.60283    NA    NA
+f_JCZ38_qlogis     45.06408    NA    NA
+log_k1             -3.10124    NA    NA
+log_k2             -4.39028    NA    NA
+log_tb              2.32256    NA    NA
+a.1                 3.32683    NA    NA
+SD.log_k_JCZ38      1.41427    NA    NA
+SD.log_k_J9Z38      0.54767    NA    NA
+SD.log_k_JSE76      0.62147    NA    NA
+SD.f_cyan_ilr_1     0.30189    NA    NA
+SD.f_cyan_ilr_2     0.34960    NA    NA
+SD.f_JCZ38_qlogis   0.04644    NA    NA
+SD.log_k1           0.39534    NA    NA
+SD.log_k2           0.43468    NA    NA
+SD.log_tb           0.60781    NA    NA
+
+Correlation is not available
+
+Random effects:
+                     est. lower upper
+SD.log_k_JCZ38    1.41427    NA    NA
+SD.log_k_J9Z38    0.54767    NA    NA
+SD.log_k_JSE76    0.62147    NA    NA
+SD.f_cyan_ilr_1   0.30189    NA    NA
+SD.f_cyan_ilr_2   0.34960    NA    NA
+SD.f_JCZ38_qlogis 0.04644    NA    NA
+SD.log_k1         0.39534    NA    NA
+SD.log_k2         0.43468    NA    NA
+SD.log_tb         0.60781    NA    NA
+
+Variance model:
+     est. lower upper
+a.1 3.327    NA    NA
+
+Backtransformed parameters:
+                      est. lower upper
+cyan_0           1.018e+02    NA    NA
+k_JCZ38          3.100e-02    NA    NA
+k_J9Z38          6.063e-03    NA    NA
+k_JSE76          3.686e-03    NA    NA
+f_cyan_to_JCZ38  5.910e-01    NA    NA
+f_cyan_to_J9Z38  2.320e-01    NA    NA
+f_JCZ38_to_JSE76 1.000e+00    NA    NA
+k1               4.499e-02    NA    NA
+k2               1.240e-02    NA    NA
+tb               1.020e+01    NA    NA
+
+Resulting formation fractions:
+               ff
+cyan_JCZ38  0.591
+cyan_J9Z38  0.232
+cyan_sink   0.177
+JCZ38_JSE76 1.000
+JCZ38_sink  0.000
+
+Estimated disappearance times:
+        DT50   DT90 DT50back DT50_k1 DT50_k2
+cyan   29.09 158.91    47.84   15.41   55.91
+JCZ38  22.36  74.27       NA      NA      NA
+J9Z38 114.33 379.80       NA      NA      NA
+JSE76 188.04 624.66       NA      NA      NA
+
+

+ +Hierarchical HS path 1 fit with two-component error + +


+saemix version used for fitting:      3.2 
+mkin version used for pre-fitting:  1.2.2 
+R version used for fitting:         4.2.2 
+Date of fit:     Sat Jan 28 10:11:24 2023 
+Date of summary: Sat Jan 28 11:22:29 2023 
+
+Equations:
+d_cyan/dt = - ifelse(time <= tb, k1, k2) * cyan
+d_JCZ38/dt = + f_cyan_to_JCZ38 * ifelse(time <= tb, k1, k2) * cyan -
+           k_JCZ38 * JCZ38
+d_J9Z38/dt = + f_cyan_to_J9Z38 * ifelse(time <= tb, k1, k2) * cyan -
+           k_J9Z38 * J9Z38
+d_JSE76/dt = + f_JCZ38_to_JSE76 * k_JCZ38 * JCZ38 - k_JSE76 * JSE76
+
+Data:
+433 observations of 4 variable(s) grouped in 5 datasets
+
+Model predictions using solution type deSolve 
+
+Fitted in 1313.805 s
+Using 300, 100 iterations and 10 chains
+
+Variance model: Two-component variance function 
+
+Starting values for degradation parameters:
+        cyan_0    log_k_JCZ38    log_k_J9Z38    log_k_JSE76   f_cyan_ilr_1 
+       101.168         -3.358         -4.941         -5.794          0.676 
+  f_cyan_ilr_2 f_JCZ38_qlogis         log_k1         log_k2         log_tb 
+         5.740         13.863         -3.147         -4.262          2.173 
+
+Fixed degradation parameter values:
+None
+
+Starting values for random effects (square root of initial entries in omega):
+               cyan_0 log_k_JCZ38 log_k_J9Z38 log_k_JSE76 f_cyan_ilr_1
+cyan_0           5.79       0.000       0.000       0.000       0.0000
+log_k_JCZ38      0.00       2.271       0.000       0.000       0.0000
+log_k_J9Z38      0.00       0.000       1.614       0.000       0.0000
+log_k_JSE76      0.00       0.000       0.000       1.264       0.0000
+f_cyan_ilr_1     0.00       0.000       0.000       0.000       0.6761
+f_cyan_ilr_2     0.00       0.000       0.000       0.000       0.0000
+f_JCZ38_qlogis   0.00       0.000       0.000       0.000       0.0000
+log_k1           0.00       0.000       0.000       0.000       0.0000
+log_k2           0.00       0.000       0.000       0.000       0.0000
+log_tb           0.00       0.000       0.000       0.000       0.0000
+               f_cyan_ilr_2 f_JCZ38_qlogis log_k1 log_k2 log_tb
+cyan_0                0.000           0.00 0.0000 0.0000  0.000
+log_k_JCZ38           0.000           0.00 0.0000 0.0000  0.000
+log_k_J9Z38           0.000           0.00 0.0000 0.0000  0.000
+log_k_JSE76           0.000           0.00 0.0000 0.0000  0.000
+f_cyan_ilr_1          0.000           0.00 0.0000 0.0000  0.000
+f_cyan_ilr_2          9.572           0.00 0.0000 0.0000  0.000
+f_JCZ38_qlogis        0.000          19.19 0.0000 0.0000  0.000
+log_k1                0.000           0.00 0.8705 0.0000  0.000
+log_k2                0.000           0.00 0.0000 0.9288  0.000
+log_tb                0.000           0.00 0.0000 0.0000  1.065
+
+Starting values for error model parameters:
+a.1 b.1 
+  1   1 
+
+Results:
+
+Likelihood computed by importance sampling
+   AIC  BIC logLik
+  2422 2414  -1190
+
+Optimised parameters:
+                      est. lower upper
+cyan_0            100.9521    NA    NA
+log_k_JCZ38        -3.4629    NA    NA
+log_k_J9Z38        -5.0346    NA    NA
+log_k_JSE76        -5.5722    NA    NA
+f_cyan_ilr_1        0.6560    NA    NA
+f_cyan_ilr_2        0.7983    NA    NA
+f_JCZ38_qlogis     42.7949    NA    NA
+log_k1             -3.1721    NA    NA
+log_k2             -4.4039    NA    NA
+log_tb              2.3994    NA    NA
+a.1                 3.0586    NA    NA
+b.1                 0.0380    NA    NA
+SD.log_k_JCZ38      1.3754    NA    NA
+SD.log_k_J9Z38      0.6703    NA    NA
+SD.log_k_JSE76      0.5876    NA    NA
+SD.f_cyan_ilr_1     0.3272    NA    NA
+SD.f_cyan_ilr_2     0.5300    NA    NA
+SD.f_JCZ38_qlogis   6.4465    NA    NA
+SD.log_k1           0.4135    NA    NA
+SD.log_k2           0.4182    NA    NA
+SD.log_tb           0.6035    NA    NA
+
+Correlation is not available
+
+Random effects:
+                    est. lower upper
+SD.log_k_JCZ38    1.3754    NA    NA
+SD.log_k_J9Z38    0.6703    NA    NA
+SD.log_k_JSE76    0.5876    NA    NA
+SD.f_cyan_ilr_1   0.3272    NA    NA
+SD.f_cyan_ilr_2   0.5300    NA    NA
+SD.f_JCZ38_qlogis 6.4465    NA    NA
+SD.log_k1         0.4135    NA    NA
+SD.log_k2         0.4182    NA    NA
+SD.log_tb         0.6035    NA    NA
+
+Variance model:
+     est. lower upper
+a.1 3.059    NA    NA
+b.1 0.038    NA    NA
+
+Backtransformed parameters:
+                      est. lower upper
+cyan_0           1.010e+02    NA    NA
+k_JCZ38          3.134e-02    NA    NA
+k_J9Z38          6.509e-03    NA    NA
+k_JSE76          3.802e-03    NA    NA
+f_cyan_to_JCZ38  6.127e-01    NA    NA
+f_cyan_to_J9Z38  2.423e-01    NA    NA
+f_JCZ38_to_JSE76 1.000e+00    NA    NA
+k1               4.191e-02    NA    NA
+k2               1.223e-02    NA    NA
+tb               1.102e+01    NA    NA
+
+Resulting formation fractions:
+                ff
+cyan_JCZ38  0.6127
+cyan_J9Z38  0.2423
+cyan_sink   0.1449
+JCZ38_JSE76 1.0000
+JCZ38_sink  0.0000
+
+Estimated disappearance times:
+        DT50   DT90 DT50back DT50_k1 DT50_k2
+cyan   29.94 161.54    48.63   16.54   56.68
+JCZ38  22.12  73.47       NA      NA      NA
+J9Z38 106.50 353.77       NA      NA      NA
+JSE76 182.30 605.60       NA      NA      NA
+
+

Pathway 2 +

+ +Hierarchical FOMC path 2 fit with constant variance + +


+saemix version used for fitting:      3.2 
+mkin version used for pre-fitting:  1.2.2 
+R version used for fitting:         4.2.2 
+Date of fit:     Sat Jan 28 10:34:28 2023 
+Date of summary: Sat Jan 28 11:22:29 2023 
+
+Equations:
+d_cyan/dt = - (alpha/beta) * 1/((time/beta) + 1) * cyan
+d_JCZ38/dt = + f_cyan_to_JCZ38 * (alpha/beta) * 1/((time/beta) + 1) *
+           cyan - k_JCZ38 * JCZ38 + f_JSE76_to_JCZ38 * k_JSE76 * JSE76
+d_J9Z38/dt = + f_cyan_to_J9Z38 * (alpha/beta) * 1/((time/beta) + 1) *
+           cyan - k_J9Z38 * J9Z38
+d_JSE76/dt = + f_JCZ38_to_JSE76 * k_JCZ38 * JCZ38 - k_JSE76 * JSE76
+
+Data:
+433 observations of 4 variable(s) grouped in 5 datasets
+
+Model predictions using solution type deSolve 
+
+Fitted in 1030.246 s
+Using 300, 100 iterations and 10 chains
+
+Variance model: Constant variance 
+
+Starting values for degradation parameters:
+        cyan_0    log_k_JCZ38    log_k_J9Z38    log_k_JSE76   f_cyan_ilr_1 
+      101.8173        -1.8998        -5.1449        -2.5415         0.6705 
+  f_cyan_ilr_2 f_JCZ38_qlogis f_JSE76_qlogis      log_alpha       log_beta 
+        4.4669        16.1281        13.3327        -0.2314         2.8738 
+
+Fixed degradation parameter values:
+None
+
+Starting values for random effects (square root of initial entries in omega):
+               cyan_0 log_k_JCZ38 log_k_J9Z38 log_k_JSE76 f_cyan_ilr_1
+cyan_0          5.742       0.000       0.000        0.00       0.0000
+log_k_JCZ38     0.000       1.402       0.000        0.00       0.0000
+log_k_J9Z38     0.000       0.000       1.718        0.00       0.0000
+log_k_JSE76     0.000       0.000       0.000        3.57       0.0000
+f_cyan_ilr_1    0.000       0.000       0.000        0.00       0.5926
+f_cyan_ilr_2    0.000       0.000       0.000        0.00       0.0000
+f_JCZ38_qlogis  0.000       0.000       0.000        0.00       0.0000
+f_JSE76_qlogis  0.000       0.000       0.000        0.00       0.0000
+log_alpha       0.000       0.000       0.000        0.00       0.0000
+log_beta        0.000       0.000       0.000        0.00       0.0000
+               f_cyan_ilr_2 f_JCZ38_qlogis f_JSE76_qlogis log_alpha log_beta
+cyan_0                 0.00           0.00           0.00    0.0000   0.0000
+log_k_JCZ38            0.00           0.00           0.00    0.0000   0.0000
+log_k_J9Z38            0.00           0.00           0.00    0.0000   0.0000
+log_k_JSE76            0.00           0.00           0.00    0.0000   0.0000
+f_cyan_ilr_1           0.00           0.00           0.00    0.0000   0.0000
+f_cyan_ilr_2          10.56           0.00           0.00    0.0000   0.0000
+f_JCZ38_qlogis         0.00          12.04           0.00    0.0000   0.0000
+f_JSE76_qlogis         0.00           0.00          15.26    0.0000   0.0000
+log_alpha              0.00           0.00           0.00    0.4708   0.0000
+log_beta               0.00           0.00           0.00    0.0000   0.4432
+
+Starting values for error model parameters:
+a.1 
+  1 
+
+Results:
+
+Likelihood computed by importance sampling
+   AIC  BIC logLik
+  2308 2301  -1134
+
+Optimised parameters:
+                      est.    lower     upper
+cyan_0            101.9586 99.22024 104.69700
+log_k_JCZ38        -2.4861 -3.17661  -1.79560
+log_k_J9Z38        -5.3926 -6.08842  -4.69684
+log_k_JSE76        -3.1193 -4.12904  -2.10962
+f_cyan_ilr_1        0.7368  0.42085   1.05276
+f_cyan_ilr_2        0.6196  0.06052   1.17861
+f_JCZ38_qlogis      4.8970 -4.68003  14.47398
+f_JSE76_qlogis      4.4066 -1.02087   9.83398
+log_alpha          -0.3021 -0.68264   0.07838
+log_beta            2.7438  2.57970   2.90786
+a.1                 2.9008  2.69920   3.10245
+SD.cyan_0           2.7081  0.64216   4.77401
+SD.log_k_JCZ38      0.7043  0.19951   1.20907
+SD.log_k_J9Z38      0.6248  0.05790   1.19180
+SD.log_k_JSE76      1.0750  0.33157   1.81839
+SD.f_cyan_ilr_1     0.3429  0.11688   0.56892
+SD.f_cyan_ilr_2     0.4774  0.09381   0.86097
+SD.f_JCZ38_qlogis   1.5565 -7.83970  10.95279
+SD.f_JSE76_qlogis   1.6871 -1.25577   4.63000
+SD.log_alpha        0.4216  0.15913   0.68405
+
+Correlation: 
+               cyan_0  l__JCZ3 l__J9Z3 l__JSE7 f_cy__1 f_cy__2 f_JCZ38 f_JSE76
+log_k_JCZ38    -0.0167                                                        
+log_k_J9Z38    -0.0307  0.0057                                                
+log_k_JSE76    -0.0032  0.1358  0.0009                                        
+f_cyan_ilr_1   -0.0087  0.0206 -0.1158 -0.0009                                
+f_cyan_ilr_2   -0.1598  0.0690  0.1770  0.0002 -0.0007                        
+f_JCZ38_qlogis  0.0966 -0.1132 -0.0440  0.0182 -0.1385 -0.4583                
+f_JSE76_qlogis -0.0647  0.1157  0.0333 -0.0026  0.1110  0.3620 -0.8586        
+log_alpha      -0.0389  0.0113  0.0209  0.0021  0.0041  0.0451 -0.0605  0.0412
+log_beta       -0.2508  0.0533  0.0977  0.0098  0.0220  0.2741 -0.2934  0.1999
+               log_lph
+log_k_JCZ38           
+log_k_J9Z38           
+log_k_JSE76           
+f_cyan_ilr_1          
+f_cyan_ilr_2          
+f_JCZ38_qlogis        
+f_JSE76_qlogis        
+log_alpha             
+log_beta        0.2281
+
+Random effects:
+                    est.    lower   upper
+SD.cyan_0         2.7081  0.64216  4.7740
+SD.log_k_JCZ38    0.7043  0.19951  1.2091
+SD.log_k_J9Z38    0.6248  0.05790  1.1918
+SD.log_k_JSE76    1.0750  0.33157  1.8184
+SD.f_cyan_ilr_1   0.3429  0.11688  0.5689
+SD.f_cyan_ilr_2   0.4774  0.09381  0.8610
+SD.f_JCZ38_qlogis 1.5565 -7.83970 10.9528
+SD.f_JSE76_qlogis 1.6871 -1.25577  4.6300
+SD.log_alpha      0.4216  0.15913  0.6840
+
+Variance model:
+     est. lower upper
+a.1 2.901 2.699 3.102
+
+Backtransformed parameters:
+                      est.     lower     upper
+cyan_0           101.95862 99.220240 1.047e+02
+k_JCZ38            0.08323  0.041727 1.660e-01
+k_J9Z38            0.00455  0.002269 9.124e-03
+k_JSE76            0.04419  0.016098 1.213e-01
+f_cyan_to_JCZ38    0.61318        NA        NA
+f_cyan_to_J9Z38    0.21630        NA        NA
+f_JCZ38_to_JSE76   0.99259  0.009193 1.000e+00
+f_JSE76_to_JCZ38   0.98795  0.264857 9.999e-01
+alpha              0.73924  0.505281 1.082e+00
+beta              15.54568 13.193194 1.832e+01
+
+Resulting formation fractions:
+                  ff
+cyan_JCZ38  0.613182
+cyan_J9Z38  0.216298
+cyan_sink   0.170519
+JCZ38_JSE76 0.992586
+JCZ38_sink  0.007414
+JSE76_JCZ38 0.987950
+JSE76_sink  0.012050
+
+Estimated disappearance times:
+         DT50   DT90 DT50back
+cyan   24.157 334.68    100.7
+JCZ38   8.328  27.66       NA
+J9Z38 152.341 506.06       NA
+JSE76  15.687  52.11       NA
+
+

+ +Hierarchical FOMC path 2 fit with two-component error + +


+saemix version used for fitting:      3.2 
+mkin version used for pre-fitting:  1.2.2 
+R version used for fitting:         4.2.2 
+Date of fit:     Sat Jan 28 10:37:36 2023 
+Date of summary: Sat Jan 28 11:22:29 2023 
+
+Equations:
+d_cyan/dt = - (alpha/beta) * 1/((time/beta) + 1) * cyan
+d_JCZ38/dt = + f_cyan_to_JCZ38 * (alpha/beta) * 1/((time/beta) + 1) *
+           cyan - k_JCZ38 * JCZ38 + f_JSE76_to_JCZ38 * k_JSE76 * JSE76
+d_J9Z38/dt = + f_cyan_to_J9Z38 * (alpha/beta) * 1/((time/beta) + 1) *
+           cyan - k_J9Z38 * J9Z38
+d_JSE76/dt = + f_JCZ38_to_JSE76 * k_JCZ38 * JCZ38 - k_JSE76 * JSE76
+
+Data:
+433 observations of 4 variable(s) grouped in 5 datasets
+
+Model predictions using solution type deSolve 
+
+Fitted in 1217.619 s
+Using 300, 100 iterations and 10 chains
+
+Variance model: Two-component variance function 
+
+Starting values for degradation parameters:
+        cyan_0    log_k_JCZ38    log_k_J9Z38    log_k_JSE76   f_cyan_ilr_1 
+      101.9028        -1.9055        -5.0249        -2.5646         0.6807 
+  f_cyan_ilr_2 f_JCZ38_qlogis f_JSE76_qlogis      log_alpha       log_beta 
+        4.8883        16.0676         9.3923        -0.1346         3.0364 
+
+Fixed degradation parameter values:
+None
+
+Starting values for random effects (square root of initial entries in omega):
+               cyan_0 log_k_JCZ38 log_k_J9Z38 log_k_JSE76 f_cyan_ilr_1
+cyan_0          6.321       0.000       0.000       0.000       0.0000
+log_k_JCZ38     0.000       1.392       0.000       0.000       0.0000
+log_k_J9Z38     0.000       0.000       1.561       0.000       0.0000
+log_k_JSE76     0.000       0.000       0.000       3.614       0.0000
+f_cyan_ilr_1    0.000       0.000       0.000       0.000       0.6339
+f_cyan_ilr_2    0.000       0.000       0.000       0.000       0.0000
+f_JCZ38_qlogis  0.000       0.000       0.000       0.000       0.0000
+f_JSE76_qlogis  0.000       0.000       0.000       0.000       0.0000
+log_alpha       0.000       0.000       0.000       0.000       0.0000
+log_beta        0.000       0.000       0.000       0.000       0.0000
+               f_cyan_ilr_2 f_JCZ38_qlogis f_JSE76_qlogis log_alpha log_beta
+cyan_0                 0.00           0.00           0.00    0.0000   0.0000
+log_k_JCZ38            0.00           0.00           0.00    0.0000   0.0000
+log_k_J9Z38            0.00           0.00           0.00    0.0000   0.0000
+log_k_JSE76            0.00           0.00           0.00    0.0000   0.0000
+f_cyan_ilr_1           0.00           0.00           0.00    0.0000   0.0000
+f_cyan_ilr_2          10.41           0.00           0.00    0.0000   0.0000
+f_JCZ38_qlogis         0.00          12.24           0.00    0.0000   0.0000
+f_JSE76_qlogis         0.00           0.00          15.13    0.0000   0.0000
+log_alpha              0.00           0.00           0.00    0.3701   0.0000
+log_beta               0.00           0.00           0.00    0.0000   0.5662
+
+Starting values for error model parameters:
+a.1 b.1 
+  1   1 
+
+Results:
+
+Likelihood computed by importance sampling
+   AIC  BIC logLik
+  2248 2240  -1103
+
+Optimised parameters:
+                       est.      lower      upper
+cyan_0            101.55545  9.920e+01  1.039e+02
+log_k_JCZ38        -2.37354 -2.928e+00 -1.819e+00
+log_k_J9Z38        -5.14736 -5.960e+00 -4.335e+00
+log_k_JSE76        -3.07802 -4.243e+00 -1.913e+00
+f_cyan_ilr_1        0.71263  3.655e-01  1.060e+00
+f_cyan_ilr_2        0.95202  2.701e-01  1.634e+00
+f_JCZ38_qlogis      3.58473  1.251e+00  5.919e+00
+f_JSE76_qlogis     19.03623 -1.037e+07  1.037e+07
+log_alpha          -0.15297 -4.490e-01  1.431e-01
+log_beta            2.99230  2.706e+00  3.278e+00
+a.1                 2.04816         NA         NA
+b.1                 0.06886         NA         NA
+SD.log_k_JCZ38      0.56174         NA         NA
+SD.log_k_J9Z38      0.86509         NA         NA
+SD.log_k_JSE76      1.28450         NA         NA
+SD.f_cyan_ilr_1     0.38705         NA         NA
+SD.f_cyan_ilr_2     0.54153         NA         NA
+SD.f_JCZ38_qlogis   1.65311         NA         NA
+SD.f_JSE76_qlogis   7.51468         NA         NA
+SD.log_alpha        0.31586         NA         NA
+SD.log_beta         0.24696         NA         NA
+
+Correlation is not available
+
+Random effects:
+                    est. lower upper
+SD.log_k_JCZ38    0.5617    NA    NA
+SD.log_k_J9Z38    0.8651    NA    NA
+SD.log_k_JSE76    1.2845    NA    NA
+SD.f_cyan_ilr_1   0.3870    NA    NA
+SD.f_cyan_ilr_2   0.5415    NA    NA
+SD.f_JCZ38_qlogis 1.6531    NA    NA
+SD.f_JSE76_qlogis 7.5147    NA    NA
+SD.log_alpha      0.3159    NA    NA
+SD.log_beta       0.2470    NA    NA
+
+Variance model:
+       est. lower upper
+a.1 2.04816    NA    NA
+b.1 0.06886    NA    NA
+
+Backtransformed parameters:
+                      est.    lower    upper
+cyan_0           1.016e+02 99.20301 103.9079
+k_JCZ38          9.315e-02  0.05349   0.1622
+k_J9Z38          5.815e-03  0.00258   0.0131
+k_JSE76          4.605e-02  0.01436   0.1477
+f_cyan_to_JCZ38  6.438e-01       NA       NA
+f_cyan_to_J9Z38  2.350e-01       NA       NA
+f_JCZ38_to_JSE76 9.730e-01  0.77745   0.9973
+f_JSE76_to_JCZ38 1.000e+00  0.00000   1.0000
+alpha            8.582e-01  0.63824   1.1538
+beta             1.993e+01 14.97621  26.5262
+
+Resulting formation fractions:
+                   ff
+cyan_JCZ38  6.438e-01
+cyan_J9Z38  2.350e-01
+cyan_sink   1.212e-01
+JCZ38_JSE76 9.730e-01
+JCZ38_sink  2.700e-02
+JSE76_JCZ38 1.000e+00
+JSE76_sink  5.403e-09
+
+Estimated disappearance times:
+         DT50   DT90 DT50back
+cyan   24.771 271.70    81.79
+JCZ38   7.441  24.72       NA
+J9Z38 119.205 395.99       NA
+JSE76  15.052  50.00       NA
+
+

+ +Hierarchical DFOP path 2 fit with constant variance + +


+saemix version used for fitting:      3.2 
+mkin version used for pre-fitting:  1.2.2 
+R version used for fitting:         4.2.2 
+Date of fit:     Sat Jan 28 10:38:34 2023 
+Date of summary: Sat Jan 28 11:22:29 2023 
+
+Equations:
+d_cyan/dt = - ((k1 * g * exp(-k1 * time) + k2 * (1 - g) * exp(-k2 *
+           time)) / (g * exp(-k1 * time) + (1 - g) * exp(-k2 * time)))
+           * cyan
+d_JCZ38/dt = + f_cyan_to_JCZ38 * ((k1 * g * exp(-k1 * time) + k2 * (1 -
+           g) * exp(-k2 * time)) / (g * exp(-k1 * time) + (1 - g) *
+           exp(-k2 * time))) * cyan - k_JCZ38 * JCZ38 +
+           f_JSE76_to_JCZ38 * k_JSE76 * JSE76
+d_J9Z38/dt = + f_cyan_to_J9Z38 * ((k1 * g * exp(-k1 * time) + k2 * (1 -
+           g) * exp(-k2 * time)) / (g * exp(-k1 * time) + (1 - g) *
+           exp(-k2 * time))) * cyan - k_J9Z38 * J9Z38
+d_JSE76/dt = + f_JCZ38_to_JSE76 * k_JCZ38 * JCZ38 - k_JSE76 * JSE76
+
+Data:
+433 observations of 4 variable(s) grouped in 5 datasets
+
+Model predictions using solution type deSolve 
+
+Fitted in 1276.128 s
+Using 300, 100 iterations and 10 chains
+
+Variance model: Constant variance 
+
+Starting values for degradation parameters:
+        cyan_0    log_k_JCZ38    log_k_J9Z38    log_k_JSE76   f_cyan_ilr_1 
+      102.4358        -2.3107        -5.3123        -3.7120         0.6753 
+  f_cyan_ilr_2 f_JCZ38_qlogis f_JSE76_qlogis         log_k1         log_k2 
+        1.1462        12.4095        12.3630        -1.9317        -4.4557 
+      g_qlogis 
+       -0.5648 
+
+Fixed degradation parameter values:
+None
+
+Starting values for random effects (square root of initial entries in omega):
+               cyan_0 log_k_JCZ38 log_k_J9Z38 log_k_JSE76 f_cyan_ilr_1
+cyan_0          4.594      0.0000       0.000         0.0       0.0000
+log_k_JCZ38     0.000      0.7966       0.000         0.0       0.0000
+log_k_J9Z38     0.000      0.0000       1.561         0.0       0.0000
+log_k_JSE76     0.000      0.0000       0.000         0.8       0.0000
+f_cyan_ilr_1    0.000      0.0000       0.000         0.0       0.6349
+f_cyan_ilr_2    0.000      0.0000       0.000         0.0       0.0000
+f_JCZ38_qlogis  0.000      0.0000       0.000         0.0       0.0000
+f_JSE76_qlogis  0.000      0.0000       0.000         0.0       0.0000
+log_k1          0.000      0.0000       0.000         0.0       0.0000
+log_k2          0.000      0.0000       0.000         0.0       0.0000
+g_qlogis        0.000      0.0000       0.000         0.0       0.0000
+               f_cyan_ilr_2 f_JCZ38_qlogis f_JSE76_qlogis log_k1 log_k2
+cyan_0                0.000           0.00            0.0  0.000 0.0000
+log_k_JCZ38           0.000           0.00            0.0  0.000 0.0000
+log_k_J9Z38           0.000           0.00            0.0  0.000 0.0000
+log_k_JSE76           0.000           0.00            0.0  0.000 0.0000
+f_cyan_ilr_1          0.000           0.00            0.0  0.000 0.0000
+f_cyan_ilr_2          1.797           0.00            0.0  0.000 0.0000
+f_JCZ38_qlogis        0.000          13.85            0.0  0.000 0.0000
+f_JSE76_qlogis        0.000           0.00           14.1  0.000 0.0000
+log_k1                0.000           0.00            0.0  1.106 0.0000
+log_k2                0.000           0.00            0.0  0.000 0.6141
+g_qlogis              0.000           0.00            0.0  0.000 0.0000
+               g_qlogis
+cyan_0            0.000
+log_k_JCZ38       0.000
+log_k_J9Z38       0.000
+log_k_JSE76       0.000
+f_cyan_ilr_1      0.000
+f_cyan_ilr_2      0.000
+f_JCZ38_qlogis    0.000
+f_JSE76_qlogis    0.000
+log_k1            0.000
+log_k2            0.000
+g_qlogis          1.595
+
+Starting values for error model parameters:
+a.1 
+  1 
+
+Results:
+
+Likelihood computed by importance sampling
+   AIC  BIC logLik
+  2290 2281  -1123
+
+Optimised parameters:
+                      est.     lower    upper
+cyan_0            102.6903 101.44420 103.9365
+log_k_JCZ38        -2.4018  -2.98058  -1.8230
+log_k_J9Z38        -5.1865  -5.92931  -4.4437
+log_k_JSE76        -3.0784  -4.25226  -1.9045
+f_cyan_ilr_1        0.7157   0.37625   1.0551
+f_cyan_ilr_2        0.7073   0.20136   1.2132
+f_JCZ38_qlogis      4.6797   0.43240   8.9269
+f_JSE76_qlogis      5.0080  -1.01380  11.0299
+log_k1             -1.9620  -2.62909  -1.2949
+log_k2             -4.4894  -4.94958  -4.0292
+g_qlogis           -0.4658  -1.34443   0.4129
+a.1                 2.7158   2.52576   2.9059
+SD.log_k_JCZ38      0.5818   0.15679   1.0067
+SD.log_k_J9Z38      0.7421   0.16751   1.3167
+SD.log_k_JSE76      1.2841   0.43247   2.1356
+SD.f_cyan_ilr_1     0.3748   0.13040   0.6192
+SD.f_cyan_ilr_2     0.4550   0.08396   0.8261
+SD.f_JCZ38_qlogis   2.0862  -0.73390   4.9062
+SD.f_JSE76_qlogis   1.9585  -3.14773   7.0647
+SD.log_k1           0.7389   0.25761   1.2201
+SD.log_k2           0.5132   0.18143   0.8450
+SD.g_qlogis         0.9870   0.35773   1.6164
+
+Correlation: 
+               cyan_0  l__JCZ3 l__J9Z3 l__JSE7 f_cy__1 f_cy__2 f_JCZ38 f_JSE76
+log_k_JCZ38    -0.0170                                                        
+log_k_J9Z38    -0.0457  0.0016                                                
+log_k_JSE76    -0.0046  0.1183  0.0005                                        
+f_cyan_ilr_1    0.0079  0.0072 -0.0909  0.0003                                
+f_cyan_ilr_2   -0.3114  0.0343  0.1542  0.0023 -0.0519                        
+f_JCZ38_qlogis  0.0777 -0.0601 -0.0152  0.0080 -0.0520 -0.2524                
+f_JSE76_qlogis -0.0356  0.0817  0.0073  0.0051  0.0388  0.1959 -0.6236        
+log_k1          0.0848 -0.0028  0.0010 -0.0010 -0.0014 -0.0245  0.0121 -0.0177
+log_k2          0.0274 -0.0001  0.0075  0.0000 -0.0023 -0.0060  0.0000 -0.0130
+g_qlogis        0.0159  0.0002 -0.0095  0.0002  0.0029 -0.0140 -0.0001  0.0149
+               log_k1  log_k2 
+log_k_JCZ38                   
+log_k_J9Z38                   
+log_k_JSE76                   
+f_cyan_ilr_1                  
+f_cyan_ilr_2                  
+f_JCZ38_qlogis                
+f_JSE76_qlogis                
+log_k1                        
+log_k2          0.0280        
+g_qlogis       -0.0278 -0.0310
+
+Random effects:
+                    est.    lower  upper
+SD.log_k_JCZ38    0.5818  0.15679 1.0067
+SD.log_k_J9Z38    0.7421  0.16751 1.3167
+SD.log_k_JSE76    1.2841  0.43247 2.1356
+SD.f_cyan_ilr_1   0.3748  0.13040 0.6192
+SD.f_cyan_ilr_2   0.4550  0.08396 0.8261
+SD.f_JCZ38_qlogis 2.0862 -0.73390 4.9062
+SD.f_JSE76_qlogis 1.9585 -3.14773 7.0647
+SD.log_k1         0.7389  0.25761 1.2201
+SD.log_k2         0.5132  0.18143 0.8450
+SD.g_qlogis       0.9870  0.35773 1.6164
+
+Variance model:
+     est. lower upper
+a.1 2.716 2.526 2.906
+
+Backtransformed parameters:
+                      est.     lower     upper
+cyan_0           1.027e+02 1.014e+02 103.93649
+k_JCZ38          9.056e-02 5.076e-02   0.16154
+k_J9Z38          5.591e-03 2.660e-03   0.01175
+k_JSE76          4.603e-02 1.423e-02   0.14890
+f_cyan_to_JCZ38  6.184e-01        NA        NA
+f_cyan_to_J9Z38  2.248e-01        NA        NA
+f_JCZ38_to_JSE76 9.908e-01 6.064e-01   0.99987
+f_JSE76_to_JCZ38 9.934e-01 2.662e-01   0.99998
+k1               1.406e-01 7.214e-02   0.27393
+k2               1.123e-02 7.086e-03   0.01779
+g                3.856e-01 2.068e-01   0.60177
+
+Resulting formation fractions:
+                  ff
+cyan_JCZ38  0.618443
+cyan_J9Z38  0.224770
+cyan_sink   0.156787
+JCZ38_JSE76 0.990803
+JCZ38_sink  0.009197
+JSE76_JCZ38 0.993360
+JSE76_sink  0.006640
+
+Estimated disappearance times:
+         DT50   DT90 DT50back DT50_k1 DT50_k2
+cyan   21.674 161.70    48.68   4.931   61.74
+JCZ38   7.654  25.43       NA      NA      NA
+J9Z38 123.966 411.81       NA      NA      NA
+JSE76  15.057  50.02       NA      NA      NA
+
+

+ +Hierarchical DFOP path 2 fit with two-component error + +


+saemix version used for fitting:      3.2 
+mkin version used for pre-fitting:  1.2.2 
+R version used for fitting:         4.2.2 
+Date of fit:     Sat Jan 28 10:45:32 2023 
+Date of summary: Sat Jan 28 11:22:29 2023 
+
+Equations:
+d_cyan/dt = - ((k1 * g * exp(-k1 * time) + k2 * (1 - g) * exp(-k2 *
+           time)) / (g * exp(-k1 * time) + (1 - g) * exp(-k2 * time)))
+           * cyan
+d_JCZ38/dt = + f_cyan_to_JCZ38 * ((k1 * g * exp(-k1 * time) + k2 * (1 -
+           g) * exp(-k2 * time)) / (g * exp(-k1 * time) + (1 - g) *
+           exp(-k2 * time))) * cyan - k_JCZ38 * JCZ38 +
+           f_JSE76_to_JCZ38 * k_JSE76 * JSE76
+d_J9Z38/dt = + f_cyan_to_J9Z38 * ((k1 * g * exp(-k1 * time) + k2 * (1 -
+           g) * exp(-k2 * time)) / (g * exp(-k1 * time) + (1 - g) *
+           exp(-k2 * time))) * cyan - k_J9Z38 * J9Z38
+d_JSE76/dt = + f_JCZ38_to_JSE76 * k_JCZ38 * JCZ38 - k_JSE76 * JSE76
+
+Data:
+433 observations of 4 variable(s) grouped in 5 datasets
+
+Model predictions using solution type deSolve 
+
+Fitted in 1693.767 s
+Using 300, 100 iterations and 10 chains
+
+Variance model: Two-component variance function 
+
+Starting values for degradation parameters:
+        cyan_0    log_k_JCZ38    log_k_J9Z38    log_k_JSE76   f_cyan_ilr_1 
+      101.7523        -1.5948        -5.0119        -2.2723         0.6719 
+  f_cyan_ilr_2 f_JCZ38_qlogis f_JSE76_qlogis         log_k1         log_k2 
+        5.1681        12.8238        12.4130        -2.0057        -4.5526 
+      g_qlogis 
+       -0.5805 
+
+Fixed degradation parameter values:
+None
+
+Starting values for random effects (square root of initial entries in omega):
+               cyan_0 log_k_JCZ38 log_k_J9Z38 log_k_JSE76 f_cyan_ilr_1
+cyan_0          5.627       0.000       0.000       0.000       0.0000
+log_k_JCZ38     0.000       2.327       0.000       0.000       0.0000
+log_k_J9Z38     0.000       0.000       1.664       0.000       0.0000
+log_k_JSE76     0.000       0.000       0.000       4.566       0.0000
+f_cyan_ilr_1    0.000       0.000       0.000       0.000       0.6519
+f_cyan_ilr_2    0.000       0.000       0.000       0.000       0.0000
+f_JCZ38_qlogis  0.000       0.000       0.000       0.000       0.0000
+f_JSE76_qlogis  0.000       0.000       0.000       0.000       0.0000
+log_k1          0.000       0.000       0.000       0.000       0.0000
+log_k2          0.000       0.000       0.000       0.000       0.0000
+g_qlogis        0.000       0.000       0.000       0.000       0.0000
+               f_cyan_ilr_2 f_JCZ38_qlogis f_JSE76_qlogis log_k1 log_k2
+cyan_0                  0.0           0.00           0.00 0.0000 0.0000
+log_k_JCZ38             0.0           0.00           0.00 0.0000 0.0000
+log_k_J9Z38             0.0           0.00           0.00 0.0000 0.0000
+log_k_JSE76             0.0           0.00           0.00 0.0000 0.0000
+f_cyan_ilr_1            0.0           0.00           0.00 0.0000 0.0000
+f_cyan_ilr_2           10.1           0.00           0.00 0.0000 0.0000
+f_JCZ38_qlogis          0.0          13.99           0.00 0.0000 0.0000
+f_JSE76_qlogis          0.0           0.00          14.15 0.0000 0.0000
+log_k1                  0.0           0.00           0.00 0.8452 0.0000
+log_k2                  0.0           0.00           0.00 0.0000 0.5968
+g_qlogis                0.0           0.00           0.00 0.0000 0.0000
+               g_qlogis
+cyan_0            0.000
+log_k_JCZ38       0.000
+log_k_J9Z38       0.000
+log_k_JSE76       0.000
+f_cyan_ilr_1      0.000
+f_cyan_ilr_2      0.000
+f_JCZ38_qlogis    0.000
+f_JSE76_qlogis    0.000
+log_k1            0.000
+log_k2            0.000
+g_qlogis          1.691
+
+Starting values for error model parameters:
+a.1 b.1 
+  1   1 
+
+Results:
+
+Likelihood computed by importance sampling
+   AIC  BIC logLik
+  2234 2226  -1095
+
+Optimised parameters:
+                       est.      lower      upper
+cyan_0            101.10667  9.903e+01  103.18265
+log_k_JCZ38        -2.49437 -3.297e+00   -1.69221
+log_k_J9Z38        -5.08171 -5.875e+00   -4.28846
+log_k_JSE76        -3.20072 -4.180e+00   -2.22163
+f_cyan_ilr_1        0.71059  3.639e-01    1.05727
+f_cyan_ilr_2        1.15398  2.981e-01    2.00984
+f_JCZ38_qlogis      3.18027  1.056e+00    5.30452
+f_JSE76_qlogis      5.61578 -2.505e+01   36.28077
+log_k1             -2.38875 -2.517e+00   -2.26045
+log_k2             -4.67246 -4.928e+00   -4.41715
+g_qlogis           -0.28231 -1.135e+00    0.57058
+a.1                 2.08190  1.856e+00    2.30785
+b.1                 0.06114  5.015e-02    0.07214
+SD.log_k_JCZ38      0.84622  2.637e-01    1.42873
+SD.log_k_J9Z38      0.84564  2.566e-01    1.43464
+SD.log_k_JSE76      1.04385  3.242e-01    1.76351
+SD.f_cyan_ilr_1     0.38568  1.362e-01    0.63514
+SD.f_cyan_ilr_2     0.68046  7.166e-02    1.28925
+SD.f_JCZ38_qlogis   1.25244 -4.213e-02    2.54700
+SD.f_JSE76_qlogis   0.28202 -1.515e+03 1515.87968
+SD.log_k2           0.25749  7.655e-02    0.43843
+SD.g_qlogis         0.94535  3.490e-01    1.54174
+
+Correlation: 
+               cyan_0  l__JCZ3 l__J9Z3 l__JSE7 f_cy__1 f_cy__2 f_JCZ38 f_JSE76
+log_k_JCZ38    -0.0086                                                        
+log_k_J9Z38    -0.0363 -0.0007                                                
+log_k_JSE76     0.0015  0.1210 -0.0017                                        
+f_cyan_ilr_1   -0.0048  0.0095 -0.0572  0.0030                                
+f_cyan_ilr_2   -0.4788  0.0328  0.1143  0.0027 -0.0316                        
+f_JCZ38_qlogis  0.0736 -0.0664 -0.0137  0.0145 -0.0444 -0.2175                
+f_JSE76_qlogis -0.0137  0.0971  0.0035  0.0009  0.0293  0.1333 -0.6767        
+log_k1          0.2345 -0.0350 -0.0099 -0.0113 -0.0126 -0.1652  0.1756 -0.2161
+log_k2          0.0440 -0.0133  0.0199 -0.0040 -0.0097 -0.0119  0.0604 -0.1306
+g_qlogis        0.0438  0.0078 -0.0123  0.0029  0.0046 -0.0363 -0.0318  0.0736
+               log_k1  log_k2 
+log_k_JCZ38                   
+log_k_J9Z38                   
+log_k_JSE76                   
+f_cyan_ilr_1                  
+f_cyan_ilr_2                  
+f_JCZ38_qlogis                
+f_JSE76_qlogis                
+log_k1                        
+log_k2          0.3198        
+g_qlogis       -0.1666 -0.0954
+
+Random effects:
+                    est.      lower     upper
+SD.log_k_JCZ38    0.8462  2.637e-01    1.4287
+SD.log_k_J9Z38    0.8456  2.566e-01    1.4346
+SD.log_k_JSE76    1.0439  3.242e-01    1.7635
+SD.f_cyan_ilr_1   0.3857  1.362e-01    0.6351
+SD.f_cyan_ilr_2   0.6805  7.166e-02    1.2893
+SD.f_JCZ38_qlogis 1.2524 -4.213e-02    2.5470
+SD.f_JSE76_qlogis 0.2820 -1.515e+03 1515.8797
+SD.log_k2         0.2575  7.655e-02    0.4384
+SD.g_qlogis       0.9453  3.490e-01    1.5417
+
+Variance model:
+       est.   lower   upper
+a.1 2.08190 1.85595 2.30785
+b.1 0.06114 0.05015 0.07214
+
+Backtransformed parameters:
+                      est.     lower     upper
+cyan_0           1.011e+02 9.903e+01 103.18265
+k_JCZ38          8.255e-02 3.701e-02   0.18411
+k_J9Z38          6.209e-03 2.809e-03   0.01373
+k_JSE76          4.073e-02 1.530e-02   0.10843
+f_cyan_to_JCZ38  6.608e-01        NA        NA
+f_cyan_to_J9Z38  2.419e-01        NA        NA
+f_JCZ38_to_JSE76 9.601e-01 7.419e-01   0.99506
+f_JSE76_to_JCZ38 9.964e-01 1.322e-11   1.00000
+k1               9.174e-02 8.070e-02   0.10430
+k2               9.349e-03 7.243e-03   0.01207
+g                4.299e-01 2.432e-01   0.63890
+
+Resulting formation fractions:
+                  ff
+cyan_JCZ38  0.660808
+cyan_J9Z38  0.241904
+cyan_sink   0.097288
+JCZ38_JSE76 0.960085
+JCZ38_sink  0.039915
+JSE76_JCZ38 0.996373
+JSE76_sink  0.003627
+
+Estimated disappearance times:
+         DT50   DT90 DT50back DT50_k1 DT50_k2
+cyan   24.359 186.18    56.05   7.555   74.14
+JCZ38   8.397  27.89       NA      NA      NA
+J9Z38 111.631 370.83       NA      NA      NA
+JSE76  17.017  56.53       NA      NA      NA
+
+

+ +Hierarchical SFORB path 2 fit with constant variance + +


+saemix version used for fitting:      3.2 
+mkin version used for pre-fitting:  1.2.2 
+R version used for fitting:         4.2.2 
+Date of fit:     Sat Jan 28 10:38:37 2023 
+Date of summary: Sat Jan 28 11:22:29 2023 
+
+Equations:
+d_cyan_free/dt = - k_cyan_free * cyan_free - k_cyan_free_bound *
+           cyan_free + k_cyan_bound_free * cyan_bound
+d_cyan_bound/dt = + k_cyan_free_bound * cyan_free - k_cyan_bound_free *
+           cyan_bound
+d_JCZ38/dt = + f_cyan_free_to_JCZ38 * k_cyan_free * cyan_free - k_JCZ38
+           * JCZ38 + f_JSE76_to_JCZ38 * k_JSE76 * JSE76
+d_J9Z38/dt = + f_cyan_free_to_J9Z38 * k_cyan_free * cyan_free - k_J9Z38
+           * J9Z38
+d_JSE76/dt = + f_JCZ38_to_JSE76 * k_JCZ38 * JCZ38 - k_JSE76 * JSE76
+
+Data:
+433 observations of 4 variable(s) grouped in 5 datasets
+
+Model predictions using solution type deSolve 
+
+Fitted in 1279.102 s
+Using 300, 100 iterations and 10 chains
+
+Variance model: Constant variance 
+
+Starting values for degradation parameters:
+          cyan_free_0       log_k_cyan_free log_k_cyan_free_bound 
+             102.4394               -2.7673               -2.8942 
+log_k_cyan_bound_free           log_k_JCZ38           log_k_J9Z38 
+              -3.6201               -2.3107               -5.3123 
+          log_k_JSE76          f_cyan_ilr_1          f_cyan_ilr_2 
+              -3.7120                0.6754                1.1448 
+       f_JCZ38_qlogis        f_JSE76_qlogis 
+              13.2672               13.3538 
+
+Fixed degradation parameter values:
+None
+
+Starting values for random effects (square root of initial entries in omega):
+                      cyan_free_0 log_k_cyan_free log_k_cyan_free_bound
+cyan_free_0                 4.589          0.0000                  0.00
+log_k_cyan_free             0.000          0.4849                  0.00
+log_k_cyan_free_bound       0.000          0.0000                  1.62
+log_k_cyan_bound_free       0.000          0.0000                  0.00
+log_k_JCZ38                 0.000          0.0000                  0.00
+log_k_J9Z38                 0.000          0.0000                  0.00
+log_k_JSE76                 0.000          0.0000                  0.00
+f_cyan_ilr_1                0.000          0.0000                  0.00
+f_cyan_ilr_2                0.000          0.0000                  0.00
+f_JCZ38_qlogis              0.000          0.0000                  0.00
+f_JSE76_qlogis              0.000          0.0000                  0.00
+                      log_k_cyan_bound_free log_k_JCZ38 log_k_J9Z38 log_k_JSE76
+cyan_free_0                           0.000      0.0000       0.000         0.0
+log_k_cyan_free                       0.000      0.0000       0.000         0.0
+log_k_cyan_free_bound                 0.000      0.0000       0.000         0.0
+log_k_cyan_bound_free                 1.197      0.0000       0.000         0.0
+log_k_JCZ38                           0.000      0.7966       0.000         0.0
+log_k_J9Z38                           0.000      0.0000       1.561         0.0
+log_k_JSE76                           0.000      0.0000       0.000         0.8
+f_cyan_ilr_1                          0.000      0.0000       0.000         0.0
+f_cyan_ilr_2                          0.000      0.0000       0.000         0.0
+f_JCZ38_qlogis                        0.000      0.0000       0.000         0.0
+f_JSE76_qlogis                        0.000      0.0000       0.000         0.0
+                      f_cyan_ilr_1 f_cyan_ilr_2 f_JCZ38_qlogis f_JSE76_qlogis
+cyan_free_0                 0.0000        0.000           0.00           0.00
+log_k_cyan_free             0.0000        0.000           0.00           0.00
+log_k_cyan_free_bound       0.0000        0.000           0.00           0.00
+log_k_cyan_bound_free       0.0000        0.000           0.00           0.00
+log_k_JCZ38                 0.0000        0.000           0.00           0.00
+log_k_J9Z38                 0.0000        0.000           0.00           0.00
+log_k_JSE76                 0.0000        0.000           0.00           0.00
+f_cyan_ilr_1                0.6349        0.000           0.00           0.00
+f_cyan_ilr_2                0.0000        1.797           0.00           0.00
+f_JCZ38_qlogis              0.0000        0.000          13.84           0.00
+f_JSE76_qlogis              0.0000        0.000           0.00          14.66
+
+Starting values for error model parameters:
+a.1 
+  1 
+
+Results:
+
+Likelihood computed by importance sampling
+   AIC  BIC logLik
+  2284 2275  -1120
+
+Optimised parameters:
+                             est.      lower      upper
+cyan_free_0              102.7730  1.015e+02  1.041e+02
+log_k_cyan_free           -2.8530 -3.167e+00 -2.539e+00
+log_k_cyan_free_bound     -2.7326 -3.543e+00 -1.922e+00
+log_k_cyan_bound_free     -3.5582 -4.126e+00 -2.990e+00
+log_k_JCZ38               -2.3810 -2.921e+00 -1.841e+00
+log_k_J9Z38               -5.2301 -5.963e+00 -4.497e+00
+log_k_JSE76               -3.0286 -4.286e+00 -1.771e+00
+f_cyan_ilr_1               0.7081  3.733e-01  1.043e+00
+f_cyan_ilr_2               0.5847  7.846e-03  1.162e+00
+f_JCZ38_qlogis             9.5676 -1.323e+03  1.342e+03
+f_JSE76_qlogis             3.7042  7.254e-02  7.336e+00
+a.1                        2.7222  2.532e+00  2.913e+00
+SD.log_k_cyan_free         0.3338  1.086e-01  5.589e-01
+SD.log_k_cyan_free_bound   0.8888  3.023e-01  1.475e+00
+SD.log_k_cyan_bound_free   0.6220  2.063e-01  1.038e+00
+SD.log_k_JCZ38             0.5221  1.334e-01  9.108e-01
+SD.log_k_J9Z38             0.7104  1.371e-01  1.284e+00
+SD.log_k_JSE76             1.3837  4.753e-01  2.292e+00
+SD.f_cyan_ilr_1            0.3620  1.248e-01  5.992e-01
+SD.f_cyan_ilr_2            0.4259  8.145e-02  7.704e-01
+SD.f_JCZ38_qlogis          3.5332 -1.037e+05  1.037e+05
+SD.f_JSE76_qlogis          1.6990 -2.771e-01  3.675e+00
+
+Correlation: 
+                      cyn_f_0 lg_k_c_ lg_k_cyn_f_ lg_k_cyn_b_ l__JCZ3 l__J9Z3
+log_k_cyan_free        0.2126                                                
+log_k_cyan_free_bound  0.0894  0.0871                                        
+log_k_cyan_bound_free  0.0033  0.0410  0.0583                                
+log_k_JCZ38           -0.0708 -0.0280 -0.0147      0.0019                    
+log_k_J9Z38           -0.0535 -0.0138  0.0012      0.0148      0.0085        
+log_k_JSE76           -0.0066 -0.0030 -0.0021     -0.0005      0.1090  0.0010
+f_cyan_ilr_1          -0.0364 -0.0157 -0.0095     -0.0015      0.0458 -0.0960
+f_cyan_ilr_2          -0.3814 -0.1104 -0.0423      0.0146      0.1540  0.1526
+f_JCZ38_qlogis         0.2507  0.0969  0.0482     -0.0097     -0.2282 -0.0363
+f_JSE76_qlogis        -0.1648 -0.0710 -0.0443     -0.0087      0.2002  0.0226
+                      l__JSE7 f_cy__1 f_cy__2 f_JCZ38
+log_k_cyan_free                                      
+log_k_cyan_free_bound                                
+log_k_cyan_bound_free                                
+log_k_JCZ38                                          
+log_k_J9Z38                                          
+log_k_JSE76                                          
+f_cyan_ilr_1           0.0001                        
+f_cyan_ilr_2           0.0031  0.0586                
+f_JCZ38_qlogis         0.0023 -0.1867 -0.6255        
+f_JSE76_qlogis         0.0082  0.1356  0.4519 -0.7951
+
+Random effects:
+                           est.      lower     upper
+SD.log_k_cyan_free       0.3338  1.086e-01 5.589e-01
+SD.log_k_cyan_free_bound 0.8888  3.023e-01 1.475e+00
+SD.log_k_cyan_bound_free 0.6220  2.063e-01 1.038e+00
+SD.log_k_JCZ38           0.5221  1.334e-01 9.108e-01
+SD.log_k_J9Z38           0.7104  1.371e-01 1.284e+00
+SD.log_k_JSE76           1.3837  4.753e-01 2.292e+00
+SD.f_cyan_ilr_1          0.3620  1.248e-01 5.992e-01
+SD.f_cyan_ilr_2          0.4259  8.145e-02 7.704e-01
+SD.f_JCZ38_qlogis        3.5332 -1.037e+05 1.037e+05
+SD.f_JSE76_qlogis        1.6990 -2.771e-01 3.675e+00
+
+Variance model:
+     est. lower upper
+a.1 2.722 2.532 2.913
+
+Backtransformed parameters:
+                          est.     lower     upper
+cyan_free_0          1.028e+02 1.015e+02 104.06475
+k_cyan_free          5.767e-02 4.213e-02   0.07894
+k_cyan_free_bound    6.505e-02 2.892e-02   0.14633
+k_cyan_bound_free    2.849e-02 1.614e-02   0.05028
+k_JCZ38              9.246e-02 5.390e-02   0.15859
+k_J9Z38              5.353e-03 2.572e-03   0.01114
+k_JSE76              4.838e-02 1.376e-02   0.17009
+f_cyan_free_to_JCZ38 6.011e-01 5.028e-01   0.83792
+f_cyan_free_to_J9Z38 2.208e-01 5.028e-01   0.83792
+f_JCZ38_to_JSE76     9.999e-01 0.000e+00   1.00000
+f_JSE76_to_JCZ38     9.760e-01 5.181e-01   0.99935
+
+Estimated Eigenvalues of SFORB model(s):
+cyan_b1 cyan_b2  cyan_g 
+0.13942 0.01178 0.35948 
+
+Resulting formation fractions:
+                       ff
+cyan_free_JCZ38 6.011e-01
+cyan_free_J9Z38 2.208e-01
+cyan_free_sink  1.780e-01
+cyan_free       1.000e+00
+JCZ38_JSE76     9.999e-01
+JCZ38_sink      6.996e-05
+JSE76_JCZ38     9.760e-01
+JSE76_sink      2.403e-02
+
+Estimated disappearance times:
+         DT50   DT90 DT50back DT50_cyan_b1 DT50_cyan_b2
+cyan   23.390 157.60    47.44        4.971        58.82
+JCZ38   7.497  24.90       NA           NA           NA
+J9Z38 129.482 430.13       NA           NA           NA
+JSE76  14.326  47.59       NA           NA           NA
+
+

+ +Hierarchical SFORB path 2 fit with two-component error + +


+saemix version used for fitting:      3.2 
+mkin version used for pre-fitting:  1.2.2 
+R version used for fitting:         4.2.2 
+Date of fit:     Sat Jan 28 10:46:02 2023 
+Date of summary: Sat Jan 28 11:22:29 2023 
+
+Equations:
+d_cyan_free/dt = - k_cyan_free * cyan_free - k_cyan_free_bound *
+           cyan_free + k_cyan_bound_free * cyan_bound
+d_cyan_bound/dt = + k_cyan_free_bound * cyan_free - k_cyan_bound_free *
+           cyan_bound
+d_JCZ38/dt = + f_cyan_free_to_JCZ38 * k_cyan_free * cyan_free - k_JCZ38
+           * JCZ38 + f_JSE76_to_JCZ38 * k_JSE76 * JSE76
+d_J9Z38/dt = + f_cyan_free_to_J9Z38 * k_cyan_free * cyan_free - k_J9Z38
+           * J9Z38
+d_JSE76/dt = + f_JCZ38_to_JSE76 * k_JCZ38 * JCZ38 - k_JSE76 * JSE76
+
+Data:
+433 observations of 4 variable(s) grouped in 5 datasets
+
+Model predictions using solution type deSolve 
+
+Fitted in 1723.343 s
+Using 300, 100 iterations and 10 chains
+
+Variance model: Two-component variance function 
+
+Starting values for degradation parameters:
+          cyan_free_0       log_k_cyan_free log_k_cyan_free_bound 
+              101.751                -2.837                -3.016 
+log_k_cyan_bound_free           log_k_JCZ38           log_k_J9Z38 
+               -3.660                -2.299                -5.313 
+          log_k_JSE76          f_cyan_ilr_1          f_cyan_ilr_2 
+               -3.699                 0.672                 5.873 
+       f_JCZ38_qlogis        f_JSE76_qlogis 
+               13.216                13.338 
+
+Fixed degradation parameter values:
+None
+
+Starting values for random effects (square root of initial entries in omega):
+                      cyan_free_0 log_k_cyan_free log_k_cyan_free_bound
+cyan_free_0                 5.629           0.000                 0.000
+log_k_cyan_free             0.000           0.446                 0.000
+log_k_cyan_free_bound       0.000           0.000                 1.449
+log_k_cyan_bound_free       0.000           0.000                 0.000
+log_k_JCZ38                 0.000           0.000                 0.000
+log_k_J9Z38                 0.000           0.000                 0.000
+log_k_JSE76                 0.000           0.000                 0.000
+f_cyan_ilr_1                0.000           0.000                 0.000
+f_cyan_ilr_2                0.000           0.000                 0.000
+f_JCZ38_qlogis              0.000           0.000                 0.000
+f_JSE76_qlogis              0.000           0.000                 0.000
+                      log_k_cyan_bound_free log_k_JCZ38 log_k_J9Z38 log_k_JSE76
+cyan_free_0                           0.000      0.0000       0.000      0.0000
+log_k_cyan_free                       0.000      0.0000       0.000      0.0000
+log_k_cyan_free_bound                 0.000      0.0000       0.000      0.0000
+log_k_cyan_bound_free                 1.213      0.0000       0.000      0.0000
+log_k_JCZ38                           0.000      0.7801       0.000      0.0000
+log_k_J9Z38                           0.000      0.0000       1.575      0.0000
+log_k_JSE76                           0.000      0.0000       0.000      0.8078
+f_cyan_ilr_1                          0.000      0.0000       0.000      0.0000
+f_cyan_ilr_2                          0.000      0.0000       0.000      0.0000
+f_JCZ38_qlogis                        0.000      0.0000       0.000      0.0000
+f_JSE76_qlogis                        0.000      0.0000       0.000      0.0000
+                      f_cyan_ilr_1 f_cyan_ilr_2 f_JCZ38_qlogis f_JSE76_qlogis
+cyan_free_0                 0.0000         0.00           0.00           0.00
+log_k_cyan_free             0.0000         0.00           0.00           0.00
+log_k_cyan_free_bound       0.0000         0.00           0.00           0.00
+log_k_cyan_bound_free       0.0000         0.00           0.00           0.00
+log_k_JCZ38                 0.0000         0.00           0.00           0.00
+log_k_J9Z38                 0.0000         0.00           0.00           0.00
+log_k_JSE76                 0.0000         0.00           0.00           0.00
+f_cyan_ilr_1                0.6519         0.00           0.00           0.00
+f_cyan_ilr_2                0.0000        10.78           0.00           0.00
+f_JCZ38_qlogis              0.0000         0.00          13.96           0.00
+f_JSE76_qlogis              0.0000         0.00           0.00          14.69
+
+Starting values for error model parameters:
+a.1 b.1 
+  1   1 
+
+Results:
+
+Likelihood computed by importance sampling
+   AIC  BIC logLik
+  2240 2232  -1098
+
+Optimised parameters:
+                              est.     lower    upper
+cyan_free_0              101.10205  98.99221 103.2119
+log_k_cyan_free           -3.16929  -3.61395  -2.7246
+log_k_cyan_free_bound     -3.38259  -3.63022  -3.1350
+log_k_cyan_bound_free     -3.81075  -4.13888  -3.4826
+log_k_JCZ38               -2.42057  -3.00756  -1.8336
+log_k_J9Z38               -5.07501  -5.85138  -4.2986
+log_k_JSE76               -3.12442  -4.21277  -2.0361
+f_cyan_ilr_1               0.70577   0.35788   1.0537
+f_cyan_ilr_2               1.14824   0.15810   2.1384
+f_JCZ38_qlogis             3.52245   0.43257   6.6123
+f_JSE76_qlogis             5.65140 -21.22295  32.5257
+a.1                        2.07062   1.84329   2.2980
+b.1                        0.06227   0.05124   0.0733
+SD.log_k_cyan_free         0.49468   0.18566   0.8037
+SD.log_k_cyan_bound_free   0.28972   0.07188   0.5076
+SD.log_k_JCZ38             0.58852   0.16800   1.0090
+SD.log_k_J9Z38             0.82500   0.24730   1.4027
+SD.log_k_JSE76             1.19201   0.40313   1.9809
+SD.f_cyan_ilr_1            0.38534   0.13640   0.6343
+SD.f_cyan_ilr_2            0.72463   0.10076   1.3485
+SD.f_JCZ38_qlogis          1.38223  -0.20997   2.9744
+SD.f_JSE76_qlogis          2.07989 -72.53027  76.6901
+
+Correlation: 
+                      cyn_f_0 lg_k_c_ lg_k_cyn_f_ lg_k_cyn_b_ l__JCZ3 l__J9Z3
+log_k_cyan_free        0.1117                                                
+log_k_cyan_free_bound  0.1763  0.1828                                        
+log_k_cyan_bound_free  0.0120  0.0593  0.5030                                
+log_k_JCZ38           -0.0459 -0.0230 -0.0931     -0.0337                    
+log_k_J9Z38           -0.0381 -0.0123 -0.0139      0.0237      0.0063        
+log_k_JSE76           -0.0044 -0.0038 -0.0175     -0.0072      0.1120  0.0003
+f_cyan_ilr_1          -0.0199 -0.0087 -0.0407     -0.0233      0.0268 -0.0552
+f_cyan_ilr_2          -0.4806 -0.1015 -0.2291     -0.0269      0.1156  0.1113
+f_JCZ38_qlogis         0.1805  0.0825  0.3085      0.0963     -0.1674 -0.0314
+f_JSE76_qlogis        -0.1586 -0.0810 -0.3560     -0.1563      0.2025  0.0278
+                      l__JSE7 f_cy__1 f_cy__2 f_JCZ38
+log_k_cyan_free                                      
+log_k_cyan_free_bound                                
+log_k_cyan_bound_free                                
+log_k_JCZ38                                          
+log_k_J9Z38                                          
+log_k_JSE76                                          
+f_cyan_ilr_1           0.0024                        
+f_cyan_ilr_2           0.0087  0.0172                
+f_JCZ38_qlogis        -0.0016 -0.1047 -0.4656        
+f_JSE76_qlogis         0.0119  0.1034  0.4584 -0.8137
+
+Random effects:
+                           est.     lower   upper
+SD.log_k_cyan_free       0.4947   0.18566  0.8037
+SD.log_k_cyan_bound_free 0.2897   0.07188  0.5076
+SD.log_k_JCZ38           0.5885   0.16800  1.0090
+SD.log_k_J9Z38           0.8250   0.24730  1.4027
+SD.log_k_JSE76           1.1920   0.40313  1.9809
+SD.f_cyan_ilr_1          0.3853   0.13640  0.6343
+SD.f_cyan_ilr_2          0.7246   0.10076  1.3485
+SD.f_JCZ38_qlogis        1.3822  -0.20997  2.9744
+SD.f_JSE76_qlogis        2.0799 -72.53027 76.6901
+
+Variance model:
+       est.   lower  upper
+a.1 2.07062 1.84329 2.2980
+b.1 0.06227 0.05124 0.0733
+
+Backtransformed parameters:
+                          est.     lower     upper
+cyan_free_0          1.011e+02 9.899e+01 103.21190
+k_cyan_free          4.203e-02 2.695e-02   0.06557
+k_cyan_free_bound    3.396e-02 2.651e-02   0.04350
+k_cyan_bound_free    2.213e-02 1.594e-02   0.03073
+k_JCZ38              8.887e-02 4.941e-02   0.15984
+k_J9Z38              6.251e-03 2.876e-03   0.01359
+k_JSE76              4.396e-02 1.481e-02   0.13054
+f_cyan_free_to_JCZ38 6.590e-01 5.557e-01   0.95365
+f_cyan_free_to_J9Z38 2.429e-01 5.557e-01   0.95365
+f_JCZ38_to_JSE76     9.713e-01 6.065e-01   0.99866
+f_JSE76_to_JCZ38     9.965e-01 6.067e-10   1.00000
+
+Estimated Eigenvalues of SFORB model(s):
+cyan_b1 cyan_b2  cyan_g 
+0.08749 0.01063 0.40855 
+
+Resulting formation fractions:
+                     ff
+cyan_free_JCZ38 0.65905
+cyan_free_J9Z38 0.24291
+cyan_free_sink  0.09805
+cyan_free       1.00000
+JCZ38_JSE76     0.97132
+JCZ38_sink      0.02868
+JSE76_JCZ38     0.99650
+JSE76_sink      0.00350
+
+Estimated disappearance times:
+        DT50   DT90 DT50back DT50_cyan_b1 DT50_cyan_b2
+cyan   24.91 167.16    50.32        7.922        65.19
+JCZ38   7.80  25.91       NA           NA           NA
+J9Z38 110.89 368.36       NA           NA           NA
+JSE76  15.77  52.38       NA           NA           NA
+
+

Pathway 2, refined fits +

+ +Hierarchical FOMC path 2 fit with reduced random effects, two-component +error + +


+saemix version used for fitting:      3.2 
+mkin version used for pre-fitting:  1.2.2 
+R version used for fitting:         4.2.2 
+Date of fit:     Sat Jan 28 11:18:41 2023 
+Date of summary: Sat Jan 28 11:22:29 2023 
+
+Equations:
+d_cyan/dt = - (alpha/beta) * 1/((time/beta) + 1) * cyan
+d_JCZ38/dt = + f_cyan_to_JCZ38 * (alpha/beta) * 1/((time/beta) + 1) *
+           cyan - k_JCZ38 * JCZ38 + f_JSE76_to_JCZ38 * k_JSE76 * JSE76
+d_J9Z38/dt = + f_cyan_to_J9Z38 * (alpha/beta) * 1/((time/beta) + 1) *
+           cyan - k_J9Z38 * J9Z38
+d_JSE76/dt = + f_JCZ38_to_JSE76 * k_JCZ38 * JCZ38 - k_JSE76 * JSE76
+
+Data:
+433 observations of 4 variable(s) grouped in 5 datasets
+
+Model predictions using solution type deSolve 
+
+Fitted in 1957.271 s
+Using 300, 100 iterations and 10 chains
+
+Variance model: Two-component variance function 
+
+Starting values for degradation parameters:
+        cyan_0    log_k_JCZ38    log_k_J9Z38    log_k_JSE76   f_cyan_ilr_1 
+      101.9028        -1.9055        -5.0249        -2.5646         0.6807 
+  f_cyan_ilr_2 f_JCZ38_qlogis f_JSE76_qlogis      log_alpha       log_beta 
+        4.8883        16.0676         9.3923        -0.1346         3.0364 
+
+Fixed degradation parameter values:
+None
+
+Starting values for random effects (square root of initial entries in omega):
+               cyan_0 log_k_JCZ38 log_k_J9Z38 log_k_JSE76 f_cyan_ilr_1
+cyan_0          6.321       0.000       0.000       0.000       0.0000
+log_k_JCZ38     0.000       1.392       0.000       0.000       0.0000
+log_k_J9Z38     0.000       0.000       1.561       0.000       0.0000
+log_k_JSE76     0.000       0.000       0.000       3.614       0.0000
+f_cyan_ilr_1    0.000       0.000       0.000       0.000       0.6339
+f_cyan_ilr_2    0.000       0.000       0.000       0.000       0.0000
+f_JCZ38_qlogis  0.000       0.000       0.000       0.000       0.0000
+f_JSE76_qlogis  0.000       0.000       0.000       0.000       0.0000
+log_alpha       0.000       0.000       0.000       0.000       0.0000
+log_beta        0.000       0.000       0.000       0.000       0.0000
+               f_cyan_ilr_2 f_JCZ38_qlogis f_JSE76_qlogis log_alpha log_beta
+cyan_0                 0.00           0.00           0.00    0.0000   0.0000
+log_k_JCZ38            0.00           0.00           0.00    0.0000   0.0000
+log_k_J9Z38            0.00           0.00           0.00    0.0000   0.0000
+log_k_JSE76            0.00           0.00           0.00    0.0000   0.0000
+f_cyan_ilr_1           0.00           0.00           0.00    0.0000   0.0000
+f_cyan_ilr_2          10.41           0.00           0.00    0.0000   0.0000
+f_JCZ38_qlogis         0.00          12.24           0.00    0.0000   0.0000
+f_JSE76_qlogis         0.00           0.00          15.13    0.0000   0.0000
+log_alpha              0.00           0.00           0.00    0.3701   0.0000
+log_beta               0.00           0.00           0.00    0.0000   0.5662
+
+Starting values for error model parameters:
+a.1 b.1 
+  1   1 
+
+Results:
+
+Likelihood computed by importance sampling
+   AIC  BIC logLik
+  2251 2244  -1106
+
+Optimised parameters:
+                      est.   lower   upper
+cyan_0           101.05768      NA      NA
+log_k_JCZ38       -2.73252      NA      NA
+log_k_J9Z38       -5.07399      NA      NA
+log_k_JSE76       -3.52863      NA      NA
+f_cyan_ilr_1       0.72176      NA      NA
+f_cyan_ilr_2       1.34610      NA      NA
+f_JCZ38_qlogis     2.08337      NA      NA
+f_JSE76_qlogis  1590.31880      NA      NA
+log_alpha         -0.09336      NA      NA
+log_beta           3.10191      NA      NA
+a.1                2.08557 1.85439 2.31675
+b.1                0.06998 0.05800 0.08197
+SD.log_k_JCZ38     1.20053 0.43329 1.96777
+SD.log_k_J9Z38     0.85854 0.26708 1.45000
+SD.log_k_JSE76     0.62528 0.16061 1.08995
+SD.f_cyan_ilr_1    0.35190 0.12340 0.58039
+SD.f_cyan_ilr_2    0.85385 0.15391 1.55378
+SD.log_alpha       0.28971 0.08718 0.49225
+SD.log_beta        0.31614 0.05938 0.57290
+
+Correlation is not available
+
+Random effects:
+                  est.   lower  upper
+SD.log_k_JCZ38  1.2005 0.43329 1.9678
+SD.log_k_J9Z38  0.8585 0.26708 1.4500
+SD.log_k_JSE76  0.6253 0.16061 1.0900
+SD.f_cyan_ilr_1 0.3519 0.12340 0.5804
+SD.f_cyan_ilr_2 0.8538 0.15391 1.5538
+SD.log_alpha    0.2897 0.08718 0.4923
+SD.log_beta     0.3161 0.05938 0.5729
+
+Variance model:
+       est. lower   upper
+a.1 2.08557 1.854 2.31675
+b.1 0.06998 0.058 0.08197
+
+Backtransformed parameters:
+                      est. lower upper
+cyan_0           1.011e+02    NA    NA
+k_JCZ38          6.506e-02    NA    NA
+k_J9Z38          6.257e-03    NA    NA
+k_JSE76          2.935e-02    NA    NA
+f_cyan_to_JCZ38  6.776e-01    NA    NA
+f_cyan_to_J9Z38  2.442e-01    NA    NA
+f_JCZ38_to_JSE76 8.893e-01    NA    NA
+f_JSE76_to_JCZ38 1.000e+00    NA    NA
+alpha            9.109e-01    NA    NA
+beta             2.224e+01    NA    NA
+
+Resulting formation fractions:
+                 ff
+cyan_JCZ38  0.67761
+cyan_J9Z38  0.24417
+cyan_sink   0.07822
+JCZ38_JSE76 0.88928
+JCZ38_sink  0.11072
+JSE76_JCZ38 1.00000
+JSE76_sink  0.00000
+
+Estimated disappearance times:
+        DT50   DT90 DT50back
+cyan   25.36 256.37    77.18
+JCZ38  10.65  35.39       NA
+J9Z38 110.77 367.98       NA
+JSE76  23.62  78.47       NA
+
+

+ +Hierarchical DFOP path 2 fit with reduced random effects, constant +variance + +


+saemix version used for fitting:      3.2 
+mkin version used for pre-fitting:  1.2.2 
+R version used for fitting:         4.2.2 
+Date of fit:     Sat Jan 28 11:16:32 2023 
+Date of summary: Sat Jan 28 11:22:29 2023 
+
+Equations:
+d_cyan/dt = - ((k1 * g * exp(-k1 * time) + k2 * (1 - g) * exp(-k2 *
+           time)) / (g * exp(-k1 * time) + (1 - g) * exp(-k2 * time)))
+           * cyan
+d_JCZ38/dt = + f_cyan_to_JCZ38 * ((k1 * g * exp(-k1 * time) + k2 * (1 -
+           g) * exp(-k2 * time)) / (g * exp(-k1 * time) + (1 - g) *
+           exp(-k2 * time))) * cyan - k_JCZ38 * JCZ38 +
+           f_JSE76_to_JCZ38 * k_JSE76 * JSE76
+d_J9Z38/dt = + f_cyan_to_J9Z38 * ((k1 * g * exp(-k1 * time) + k2 * (1 -
+           g) * exp(-k2 * time)) / (g * exp(-k1 * time) + (1 - g) *
+           exp(-k2 * time))) * cyan - k_J9Z38 * J9Z38
+d_JSE76/dt = + f_JCZ38_to_JSE76 * k_JCZ38 * JCZ38 - k_JSE76 * JSE76
+
+Data:
+433 observations of 4 variable(s) grouped in 5 datasets
+
+Model predictions using solution type deSolve 
+
+Fitted in 1828.403 s
+Using 300, 100 iterations and 10 chains
+
+Variance model: Constant variance 
+
+Starting values for degradation parameters:
+        cyan_0    log_k_JCZ38    log_k_J9Z38    log_k_JSE76   f_cyan_ilr_1 
+      102.4358        -2.3107        -5.3123        -3.7120         0.6753 
+  f_cyan_ilr_2 f_JCZ38_qlogis f_JSE76_qlogis         log_k1         log_k2 
+        1.1462        12.4095        12.3630        -1.9317        -4.4557 
+      g_qlogis 
+       -0.5648 
+
+Fixed degradation parameter values:
+None
+
+Starting values for random effects (square root of initial entries in omega):
+               cyan_0 log_k_JCZ38 log_k_J9Z38 log_k_JSE76 f_cyan_ilr_1
+cyan_0          4.594      0.0000       0.000         0.0       0.0000
+log_k_JCZ38     0.000      0.7966       0.000         0.0       0.0000
+log_k_J9Z38     0.000      0.0000       1.561         0.0       0.0000
+log_k_JSE76     0.000      0.0000       0.000         0.8       0.0000
+f_cyan_ilr_1    0.000      0.0000       0.000         0.0       0.6349
+f_cyan_ilr_2    0.000      0.0000       0.000         0.0       0.0000
+f_JCZ38_qlogis  0.000      0.0000       0.000         0.0       0.0000
+f_JSE76_qlogis  0.000      0.0000       0.000         0.0       0.0000
+log_k1          0.000      0.0000       0.000         0.0       0.0000
+log_k2          0.000      0.0000       0.000         0.0       0.0000
+g_qlogis        0.000      0.0000       0.000         0.0       0.0000
+               f_cyan_ilr_2 f_JCZ38_qlogis f_JSE76_qlogis log_k1 log_k2
+cyan_0                0.000           0.00            0.0  0.000 0.0000
+log_k_JCZ38           0.000           0.00            0.0  0.000 0.0000
+log_k_J9Z38           0.000           0.00            0.0  0.000 0.0000
+log_k_JSE76           0.000           0.00            0.0  0.000 0.0000
+f_cyan_ilr_1          0.000           0.00            0.0  0.000 0.0000
+f_cyan_ilr_2          1.797           0.00            0.0  0.000 0.0000
+f_JCZ38_qlogis        0.000          13.85            0.0  0.000 0.0000
+f_JSE76_qlogis        0.000           0.00           14.1  0.000 0.0000
+log_k1                0.000           0.00            0.0  1.106 0.0000
+log_k2                0.000           0.00            0.0  0.000 0.6141
+g_qlogis              0.000           0.00            0.0  0.000 0.0000
+               g_qlogis
+cyan_0            0.000
+log_k_JCZ38       0.000
+log_k_J9Z38       0.000
+log_k_JSE76       0.000
+f_cyan_ilr_1      0.000
+f_cyan_ilr_2      0.000
+f_JCZ38_qlogis    0.000
+f_JSE76_qlogis    0.000
+log_k1            0.000
+log_k2            0.000
+g_qlogis          1.595
+
+Starting values for error model parameters:
+a.1 
+  1 
+
+Results:
+
+Likelihood computed by importance sampling
+   AIC  BIC logLik
+  2282 2274  -1121
+
+Optimised parameters:
+                     est.   lower  upper
+cyan_0           102.5254      NA     NA
+log_k_JCZ38       -2.9358      NA     NA
+log_k_J9Z38       -5.1424      NA     NA
+log_k_JSE76       -3.6458      NA     NA
+f_cyan_ilr_1       0.6957      NA     NA
+f_cyan_ilr_2       0.6635      NA     NA
+f_JCZ38_qlogis  4984.8163      NA     NA
+f_JSE76_qlogis     1.9415      NA     NA
+log_k1            -1.9456      NA     NA
+log_k2            -4.4705      NA     NA
+g_qlogis          -0.5117      NA     NA
+a.1                2.7455 2.55392 2.9370
+SD.log_k_JCZ38     1.3163 0.47635 2.1563
+SD.log_k_J9Z38     0.7162 0.16133 1.2711
+SD.log_k_JSE76     0.6457 0.15249 1.1390
+SD.f_cyan_ilr_1    0.3424 0.11714 0.5677
+SD.f_cyan_ilr_2    0.4524 0.09709 0.8077
+SD.log_k1          0.7353 0.25445 1.2161
+SD.log_k2          0.5137 0.18206 0.8453
+SD.g_qlogis        0.9857 0.35651 1.6148
+
+Correlation is not available
+
+Random effects:
+                  est.   lower  upper
+SD.log_k_JCZ38  1.3163 0.47635 2.1563
+SD.log_k_J9Z38  0.7162 0.16133 1.2711
+SD.log_k_JSE76  0.6457 0.15249 1.1390
+SD.f_cyan_ilr_1 0.3424 0.11714 0.5677
+SD.f_cyan_ilr_2 0.4524 0.09709 0.8077
+SD.log_k1       0.7353 0.25445 1.2161
+SD.log_k2       0.5137 0.18206 0.8453
+SD.g_qlogis     0.9857 0.35651 1.6148
+
+Variance model:
+     est. lower upper
+a.1 2.745 2.554 2.937
+
+Backtransformed parameters:
+                      est. lower upper
+cyan_0           1.025e+02    NA    NA
+k_JCZ38          5.309e-02    NA    NA
+k_J9Z38          5.844e-03    NA    NA
+k_JSE76          2.610e-02    NA    NA
+f_cyan_to_JCZ38  6.079e-01    NA    NA
+f_cyan_to_J9Z38  2.272e-01    NA    NA
+f_JCZ38_to_JSE76 1.000e+00    NA    NA
+f_JSE76_to_JCZ38 8.745e-01    NA    NA
+k1               1.429e-01    NA    NA
+k2               1.144e-02    NA    NA
+g                3.748e-01    NA    NA
+
+Resulting formation fractions:
+                ff
+cyan_JCZ38  0.6079
+cyan_J9Z38  0.2272
+cyan_sink   0.1649
+JCZ38_JSE76 1.0000
+JCZ38_sink  0.0000
+JSE76_JCZ38 0.8745
+JSE76_sink  0.1255
+
+Estimated disappearance times:
+        DT50   DT90 DT50back DT50_k1 DT50_k2
+cyan   22.29 160.20    48.22    4.85   60.58
+JCZ38  13.06  43.37       NA      NA      NA
+J9Z38 118.61 394.02       NA      NA      NA
+JSE76  26.56  88.22       NA      NA      NA
+
+

+ +Hierarchical DFOP path 2 fit with reduced random effects, two-component +error + +


+saemix version used for fitting:      3.2 
+mkin version used for pre-fitting:  1.2.2 
+R version used for fitting:         4.2.2 
+Date of fit:     Sat Jan 28 11:22:28 2023 
+Date of summary: Sat Jan 28 11:22:29 2023 
+
+Equations:
+d_cyan/dt = - ((k1 * g * exp(-k1 * time) + k2 * (1 - g) * exp(-k2 *
+           time)) / (g * exp(-k1 * time) + (1 - g) * exp(-k2 * time)))
+           * cyan
+d_JCZ38/dt = + f_cyan_to_JCZ38 * ((k1 * g * exp(-k1 * time) + k2 * (1 -
+           g) * exp(-k2 * time)) / (g * exp(-k1 * time) + (1 - g) *
+           exp(-k2 * time))) * cyan - k_JCZ38 * JCZ38 +
+           f_JSE76_to_JCZ38 * k_JSE76 * JSE76
+d_J9Z38/dt = + f_cyan_to_J9Z38 * ((k1 * g * exp(-k1 * time) + k2 * (1 -
+           g) * exp(-k2 * time)) / (g * exp(-k1 * time) + (1 - g) *
+           exp(-k2 * time))) * cyan - k_J9Z38 * J9Z38
+d_JSE76/dt = + f_JCZ38_to_JSE76 * k_JCZ38 * JCZ38 - k_JSE76 * JSE76
+
+Data:
+433 observations of 4 variable(s) grouped in 5 datasets
+
+Model predictions using solution type deSolve 
+
+Fitted in 2183.989 s
+Using 300, 100 iterations and 10 chains
+
+Variance model: Two-component variance function 
+
+Starting values for degradation parameters:
+        cyan_0    log_k_JCZ38    log_k_J9Z38    log_k_JSE76   f_cyan_ilr_1 
+      101.7523        -1.5948        -5.0119        -2.2723         0.6719 
+  f_cyan_ilr_2 f_JCZ38_qlogis f_JSE76_qlogis         log_k1         log_k2 
+        5.1681        12.8238        12.4130        -2.0057        -4.5526 
+      g_qlogis 
+       -0.5805 
+
+Fixed degradation parameter values:
+None
+
+Starting values for random effects (square root of initial entries in omega):
+               cyan_0 log_k_JCZ38 log_k_J9Z38 log_k_JSE76 f_cyan_ilr_1
+cyan_0          5.627       0.000       0.000       0.000       0.0000
+log_k_JCZ38     0.000       2.327       0.000       0.000       0.0000
+log_k_J9Z38     0.000       0.000       1.664       0.000       0.0000
+log_k_JSE76     0.000       0.000       0.000       4.566       0.0000
+f_cyan_ilr_1    0.000       0.000       0.000       0.000       0.6519
+f_cyan_ilr_2    0.000       0.000       0.000       0.000       0.0000
+f_JCZ38_qlogis  0.000       0.000       0.000       0.000       0.0000
+f_JSE76_qlogis  0.000       0.000       0.000       0.000       0.0000
+log_k1          0.000       0.000       0.000       0.000       0.0000
+log_k2          0.000       0.000       0.000       0.000       0.0000
+g_qlogis        0.000       0.000       0.000       0.000       0.0000
+               f_cyan_ilr_2 f_JCZ38_qlogis f_JSE76_qlogis log_k1 log_k2
+cyan_0                  0.0           0.00           0.00 0.0000 0.0000
+log_k_JCZ38             0.0           0.00           0.00 0.0000 0.0000
+log_k_J9Z38             0.0           0.00           0.00 0.0000 0.0000
+log_k_JSE76             0.0           0.00           0.00 0.0000 0.0000
+f_cyan_ilr_1            0.0           0.00           0.00 0.0000 0.0000
+f_cyan_ilr_2           10.1           0.00           0.00 0.0000 0.0000
+f_JCZ38_qlogis          0.0          13.99           0.00 0.0000 0.0000
+f_JSE76_qlogis          0.0           0.00          14.15 0.0000 0.0000
+log_k1                  0.0           0.00           0.00 0.8452 0.0000
+log_k2                  0.0           0.00           0.00 0.0000 0.5968
+g_qlogis                0.0           0.00           0.00 0.0000 0.0000
+               g_qlogis
+cyan_0            0.000
+log_k_JCZ38       0.000
+log_k_J9Z38       0.000
+log_k_JSE76       0.000
+f_cyan_ilr_1      0.000
+f_cyan_ilr_2      0.000
+f_JCZ38_qlogis    0.000
+f_JSE76_qlogis    0.000
+log_k1            0.000
+log_k2            0.000
+g_qlogis          1.691
+
+Starting values for error model parameters:
+a.1 b.1 
+  1   1 
+
+Results:
+
+Likelihood computed by importance sampling
+   AIC  BIC logLik
+  2232 2224  -1096
+
+Optimised parameters:
+                     est.   lower   upper
+cyan_0          101.20051      NA      NA
+log_k_JCZ38      -2.93542      NA      NA
+log_k_J9Z38      -5.03151      NA      NA
+log_k_JSE76      -3.67679      NA      NA
+f_cyan_ilr_1      0.67290      NA      NA
+f_cyan_ilr_2      0.99787      NA      NA
+f_JCZ38_qlogis  348.32484      NA      NA
+f_JSE76_qlogis    1.87846      NA      NA
+log_k1           -2.32738      NA      NA
+log_k2           -4.61295      NA      NA
+g_qlogis         -0.38342      NA      NA
+a.1               2.06184 1.83746 2.28622
+b.1               0.06329 0.05211 0.07447
+SD.log_k_JCZ38    1.29042 0.47468 2.10617
+SD.log_k_J9Z38    0.84235 0.25903 1.42566
+SD.log_k_JSE76    0.56930 0.13934 0.99926
+SD.f_cyan_ilr_1   0.35183 0.12298 0.58068
+SD.f_cyan_ilr_2   0.77269 0.17908 1.36631
+SD.log_k2         0.28549 0.09210 0.47888
+SD.g_qlogis       0.93830 0.34568 1.53093
+
+Correlation is not available
+
+Random effects:
+                  est.  lower  upper
+SD.log_k_JCZ38  1.2904 0.4747 2.1062
+SD.log_k_J9Z38  0.8423 0.2590 1.4257
+SD.log_k_JSE76  0.5693 0.1393 0.9993
+SD.f_cyan_ilr_1 0.3518 0.1230 0.5807
+SD.f_cyan_ilr_2 0.7727 0.1791 1.3663
+SD.log_k2       0.2855 0.0921 0.4789
+SD.g_qlogis     0.9383 0.3457 1.5309
+
+Variance model:
+       est.   lower   upper
+a.1 2.06184 1.83746 2.28622
+b.1 0.06329 0.05211 0.07447
+
+Backtransformed parameters:
+                      est. lower upper
+cyan_0           1.012e+02    NA    NA
+k_JCZ38          5.311e-02    NA    NA
+k_J9Z38          6.529e-03    NA    NA
+k_JSE76          2.530e-02    NA    NA
+f_cyan_to_JCZ38  6.373e-01    NA    NA
+f_cyan_to_J9Z38  2.461e-01    NA    NA
+f_JCZ38_to_JSE76 1.000e+00    NA    NA
+f_JSE76_to_JCZ38 8.674e-01    NA    NA
+k1               9.755e-02    NA    NA
+k2               9.922e-03    NA    NA
+g                4.053e-01    NA    NA
+
+Resulting formation fractions:
+                ff
+cyan_JCZ38  0.6373
+cyan_J9Z38  0.2461
+cyan_sink   0.1167
+JCZ38_JSE76 1.0000
+JCZ38_sink  0.0000
+JSE76_JCZ38 0.8674
+JSE76_sink  0.1326
+
+Estimated disappearance times:
+        DT50   DT90 DT50back DT50_k1 DT50_k2
+cyan   24.93 179.68    54.09   7.105   69.86
+JCZ38  13.05  43.36       NA      NA      NA
+J9Z38 106.16 352.67       NA      NA      NA
+JSE76  27.39  91.00       NA      NA      NA
+
+

+ +Hierarchical SFORB path 2 fit with reduced random effects, constant +variance + +


+saemix version used for fitting:      3.2 
+mkin version used for pre-fitting:  1.2.2 
+R version used for fitting:         4.2.2 
+Date of fit:     Sat Jan 28 11:17:37 2023 
+Date of summary: Sat Jan 28 11:22:29 2023 
+
+Equations:
+d_cyan_free/dt = - k_cyan_free * cyan_free - k_cyan_free_bound *
+           cyan_free + k_cyan_bound_free * cyan_bound
+d_cyan_bound/dt = + k_cyan_free_bound * cyan_free - k_cyan_bound_free *
+           cyan_bound
+d_JCZ38/dt = + f_cyan_free_to_JCZ38 * k_cyan_free * cyan_free - k_JCZ38
+           * JCZ38 + f_JSE76_to_JCZ38 * k_JSE76 * JSE76
+d_J9Z38/dt = + f_cyan_free_to_J9Z38 * k_cyan_free * cyan_free - k_J9Z38
+           * J9Z38
+d_JSE76/dt = + f_JCZ38_to_JSE76 * k_JCZ38 * JCZ38 - k_JSE76 * JSE76
+
+Data:
+433 observations of 4 variable(s) grouped in 5 datasets
+
+Model predictions using solution type deSolve 
+
+Fitted in 1893.29 s
+Using 300, 100 iterations and 10 chains
+
+Variance model: Constant variance 
+
+Starting values for degradation parameters:
+          cyan_free_0       log_k_cyan_free log_k_cyan_free_bound 
+             102.4394               -2.7673               -2.8942 
+log_k_cyan_bound_free           log_k_JCZ38           log_k_J9Z38 
+              -3.6201               -2.3107               -5.3123 
+          log_k_JSE76          f_cyan_ilr_1          f_cyan_ilr_2 
+              -3.7120                0.6754                1.1448 
+       f_JCZ38_qlogis        f_JSE76_qlogis 
+              13.2672               13.3538 
+
+Fixed degradation parameter values:
+None
+
+Starting values for random effects (square root of initial entries in omega):
+                      cyan_free_0 log_k_cyan_free log_k_cyan_free_bound
+cyan_free_0                 4.589          0.0000                  0.00
+log_k_cyan_free             0.000          0.4849                  0.00
+log_k_cyan_free_bound       0.000          0.0000                  1.62
+log_k_cyan_bound_free       0.000          0.0000                  0.00
+log_k_JCZ38                 0.000          0.0000                  0.00
+log_k_J9Z38                 0.000          0.0000                  0.00
+log_k_JSE76                 0.000          0.0000                  0.00
+f_cyan_ilr_1                0.000          0.0000                  0.00
+f_cyan_ilr_2                0.000          0.0000                  0.00
+f_JCZ38_qlogis              0.000          0.0000                  0.00
+f_JSE76_qlogis              0.000          0.0000                  0.00
+                      log_k_cyan_bound_free log_k_JCZ38 log_k_J9Z38 log_k_JSE76
+cyan_free_0                           0.000      0.0000       0.000         0.0
+log_k_cyan_free                       0.000      0.0000       0.000         0.0
+log_k_cyan_free_bound                 0.000      0.0000       0.000         0.0
+log_k_cyan_bound_free                 1.197      0.0000       0.000         0.0
+log_k_JCZ38                           0.000      0.7966       0.000         0.0
+log_k_J9Z38                           0.000      0.0000       1.561         0.0
+log_k_JSE76                           0.000      0.0000       0.000         0.8
+f_cyan_ilr_1                          0.000      0.0000       0.000         0.0
+f_cyan_ilr_2                          0.000      0.0000       0.000         0.0
+f_JCZ38_qlogis                        0.000      0.0000       0.000         0.0
+f_JSE76_qlogis                        0.000      0.0000       0.000         0.0
+                      f_cyan_ilr_1 f_cyan_ilr_2 f_JCZ38_qlogis f_JSE76_qlogis
+cyan_free_0                 0.0000        0.000           0.00           0.00
+log_k_cyan_free             0.0000        0.000           0.00           0.00
+log_k_cyan_free_bound       0.0000        0.000           0.00           0.00
+log_k_cyan_bound_free       0.0000        0.000           0.00           0.00
+log_k_JCZ38                 0.0000        0.000           0.00           0.00
+log_k_J9Z38                 0.0000        0.000           0.00           0.00
+log_k_JSE76                 0.0000        0.000           0.00           0.00
+f_cyan_ilr_1                0.6349        0.000           0.00           0.00
+f_cyan_ilr_2                0.0000        1.797           0.00           0.00
+f_JCZ38_qlogis              0.0000        0.000          13.84           0.00
+f_JSE76_qlogis              0.0000        0.000           0.00          14.66
+
+Starting values for error model parameters:
+a.1 
+  1 
+
+Results:
+
+Likelihood computed by importance sampling
+   AIC  BIC logLik
+  2279 2272  -1120
+
+Optimised parameters:
+                              est.   lower  upper
+cyan_free_0               102.5621      NA     NA
+log_k_cyan_free            -2.8531      NA     NA
+log_k_cyan_free_bound      -2.6916      NA     NA
+log_k_cyan_bound_free      -3.5032      NA     NA
+log_k_JCZ38                -2.9436      NA     NA
+log_k_J9Z38                -5.1140      NA     NA
+log_k_JSE76                -3.6472      NA     NA
+f_cyan_ilr_1                0.6887      NA     NA
+f_cyan_ilr_2                0.6874      NA     NA
+f_JCZ38_qlogis           4063.6389      NA     NA
+f_JSE76_qlogis              1.9556      NA     NA
+a.1                         2.7460 2.55451 2.9376
+SD.log_k_cyan_free          0.3131 0.09841 0.5277
+SD.log_k_cyan_free_bound    0.8850 0.29909 1.4710
+SD.log_k_cyan_bound_free    0.6167 0.20391 1.0295
+SD.log_k_JCZ38              1.3555 0.49101 2.2200
+SD.log_k_J9Z38              0.7200 0.16166 1.2783
+SD.log_k_JSE76              0.6252 0.14619 1.1042
+SD.f_cyan_ilr_1             0.3386 0.11447 0.5627
+SD.f_cyan_ilr_2             0.4699 0.09810 0.8417
+
+Correlation is not available
+
+Random effects:
+                           est.   lower  upper
+SD.log_k_cyan_free       0.3131 0.09841 0.5277
+SD.log_k_cyan_free_bound 0.8850 0.29909 1.4710
+SD.log_k_cyan_bound_free 0.6167 0.20391 1.0295
+SD.log_k_JCZ38           1.3555 0.49101 2.2200
+SD.log_k_J9Z38           0.7200 0.16166 1.2783
+SD.log_k_JSE76           0.6252 0.14619 1.1042
+SD.f_cyan_ilr_1          0.3386 0.11447 0.5627
+SD.f_cyan_ilr_2          0.4699 0.09810 0.8417
+
+Variance model:
+     est. lower upper
+a.1 2.746 2.555 2.938
+
+Backtransformed parameters:
+                          est. lower upper
+cyan_free_0          1.026e+02    NA    NA
+k_cyan_free          5.767e-02    NA    NA
+k_cyan_free_bound    6.777e-02    NA    NA
+k_cyan_bound_free    3.010e-02    NA    NA
+k_JCZ38              5.267e-02    NA    NA
+k_J9Z38              6.012e-03    NA    NA
+k_JSE76              2.606e-02    NA    NA
+f_cyan_free_to_JCZ38 6.089e-01    NA    NA
+f_cyan_free_to_J9Z38 2.299e-01    NA    NA
+f_JCZ38_to_JSE76     1.000e+00    NA    NA
+f_JSE76_to_JCZ38     8.761e-01    NA    NA
+
+Estimated Eigenvalues of SFORB model(s):
+cyan_b1 cyan_b2  cyan_g 
+ 0.1434  0.0121  0.3469 
+
+Resulting formation fractions:
+                    ff
+cyan_free_JCZ38 0.6089
+cyan_free_J9Z38 0.2299
+cyan_free_sink  0.1612
+cyan_free       1.0000
+JCZ38_JSE76     1.0000
+JCZ38_sink      0.0000
+JSE76_JCZ38     0.8761
+JSE76_sink      0.1239
+
+Estimated disappearance times:
+        DT50   DT90 DT50back DT50_cyan_b1 DT50_cyan_b2
+cyan   23.94 155.06    46.68        4.832        57.28
+JCZ38  13.16  43.71       NA           NA           NA
+J9Z38 115.30 383.02       NA           NA           NA
+JSE76  26.59  88.35       NA           NA           NA
+
+

+ +Hierarchical SFORB path 2 fit with reduced random effects, two-component +error + +


+saemix version used for fitting:      3.2 
+mkin version used for pre-fitting:  1.2.2 
+R version used for fitting:         4.2.2 
+Date of fit:     Sat Jan 28 11:21:01 2023 
+Date of summary: Sat Jan 28 11:22:29 2023 
+
+Equations:
+d_cyan_free/dt = - k_cyan_free * cyan_free - k_cyan_free_bound *
+           cyan_free + k_cyan_bound_free * cyan_bound
+d_cyan_bound/dt = + k_cyan_free_bound * cyan_free - k_cyan_bound_free *
+           cyan_bound
+d_JCZ38/dt = + f_cyan_free_to_JCZ38 * k_cyan_free * cyan_free - k_JCZ38
+           * JCZ38 + f_JSE76_to_JCZ38 * k_JSE76 * JSE76
+d_J9Z38/dt = + f_cyan_free_to_J9Z38 * k_cyan_free * cyan_free - k_J9Z38
+           * J9Z38
+d_JSE76/dt = + f_JCZ38_to_JSE76 * k_JCZ38 * JCZ38 - k_JSE76 * JSE76
+
+Data:
+433 observations of 4 variable(s) grouped in 5 datasets
+
+Model predictions using solution type deSolve 
+
+Fitted in 2097.842 s
+Using 300, 100 iterations and 10 chains
+
+Variance model: Two-component variance function 
+
+Starting values for degradation parameters:
+          cyan_free_0       log_k_cyan_free log_k_cyan_free_bound 
+              101.751                -2.837                -3.016 
+log_k_cyan_bound_free           log_k_JCZ38           log_k_J9Z38 
+               -3.660                -2.299                -5.313 
+          log_k_JSE76          f_cyan_ilr_1          f_cyan_ilr_2 
+               -3.699                 0.672                 5.873 
+       f_JCZ38_qlogis        f_JSE76_qlogis 
+               13.216                13.338 
+
+Fixed degradation parameter values:
+None
+
+Starting values for random effects (square root of initial entries in omega):
+                      cyan_free_0 log_k_cyan_free log_k_cyan_free_bound
+cyan_free_0                 5.629           0.000                 0.000
+log_k_cyan_free             0.000           0.446                 0.000
+log_k_cyan_free_bound       0.000           0.000                 1.449
+log_k_cyan_bound_free       0.000           0.000                 0.000
+log_k_JCZ38                 0.000           0.000                 0.000
+log_k_J9Z38                 0.000           0.000                 0.000
+log_k_JSE76                 0.000           0.000                 0.000
+f_cyan_ilr_1                0.000           0.000                 0.000
+f_cyan_ilr_2                0.000           0.000                 0.000
+f_JCZ38_qlogis              0.000           0.000                 0.000
+f_JSE76_qlogis              0.000           0.000                 0.000
+                      log_k_cyan_bound_free log_k_JCZ38 log_k_J9Z38 log_k_JSE76
+cyan_free_0                           0.000      0.0000       0.000      0.0000
+log_k_cyan_free                       0.000      0.0000       0.000      0.0000
+log_k_cyan_free_bound                 0.000      0.0000       0.000      0.0000
+log_k_cyan_bound_free                 1.213      0.0000       0.000      0.0000
+log_k_JCZ38                           0.000      0.7801       0.000      0.0000
+log_k_J9Z38                           0.000      0.0000       1.575      0.0000
+log_k_JSE76                           0.000      0.0000       0.000      0.8078
+f_cyan_ilr_1                          0.000      0.0000       0.000      0.0000
+f_cyan_ilr_2                          0.000      0.0000       0.000      0.0000
+f_JCZ38_qlogis                        0.000      0.0000       0.000      0.0000
+f_JSE76_qlogis                        0.000      0.0000       0.000      0.0000
+                      f_cyan_ilr_1 f_cyan_ilr_2 f_JCZ38_qlogis f_JSE76_qlogis
+cyan_free_0                 0.0000         0.00           0.00           0.00
+log_k_cyan_free             0.0000         0.00           0.00           0.00
+log_k_cyan_free_bound       0.0000         0.00           0.00           0.00
+log_k_cyan_bound_free       0.0000         0.00           0.00           0.00
+log_k_JCZ38                 0.0000         0.00           0.00           0.00
+log_k_J9Z38                 0.0000         0.00           0.00           0.00
+log_k_JSE76                 0.0000         0.00           0.00           0.00
+f_cyan_ilr_1                0.6519         0.00           0.00           0.00
+f_cyan_ilr_2                0.0000        10.78           0.00           0.00
+f_JCZ38_qlogis              0.0000         0.00          13.96           0.00
+f_JSE76_qlogis              0.0000         0.00           0.00          14.69
+
+Starting values for error model parameters:
+a.1 b.1 
+  1   1 
+
+Results:
+
+Likelihood computed by importance sampling
+   AIC  BIC logLik
+  2236 2228  -1098
+
+Optimised parameters:
+                              est.   lower   upper
+cyan_free_0              100.72760      NA      NA
+log_k_cyan_free           -3.18281      NA      NA
+log_k_cyan_free_bound     -3.37924      NA      NA
+log_k_cyan_bound_free     -3.77107      NA      NA
+log_k_JCZ38               -2.92811      NA      NA
+log_k_J9Z38               -5.02759      NA      NA
+log_k_JSE76               -3.65835      NA      NA
+f_cyan_ilr_1               0.67390      NA      NA
+f_cyan_ilr_2               1.15106      NA      NA
+f_JCZ38_qlogis           827.82299      NA      NA
+f_JSE76_qlogis             1.83064      NA      NA
+a.1                        2.06921 1.84443 2.29399
+b.1                        0.06391 0.05267 0.07515
+SD.log_k_cyan_free         0.50518 0.18962 0.82075
+SD.log_k_cyan_bound_free   0.30991 0.08170 0.53813
+SD.log_k_JCZ38             1.26661 0.46578 2.06744
+SD.log_k_J9Z38             0.88272 0.27813 1.48730
+SD.log_k_JSE76             0.53050 0.12561 0.93538
+SD.f_cyan_ilr_1            0.35547 0.12461 0.58633
+SD.f_cyan_ilr_2            0.91446 0.20131 1.62761
+
+Correlation is not available
+
+Random effects:
+                           est.  lower  upper
+SD.log_k_cyan_free       0.5052 0.1896 0.8207
+SD.log_k_cyan_bound_free 0.3099 0.0817 0.5381
+SD.log_k_JCZ38           1.2666 0.4658 2.0674
+SD.log_k_J9Z38           0.8827 0.2781 1.4873
+SD.log_k_JSE76           0.5305 0.1256 0.9354
+SD.f_cyan_ilr_1          0.3555 0.1246 0.5863
+SD.f_cyan_ilr_2          0.9145 0.2013 1.6276
+
+Variance model:
+       est.   lower   upper
+a.1 2.06921 1.84443 2.29399
+b.1 0.06391 0.05267 0.07515
+
+Backtransformed parameters:
+                          est. lower upper
+cyan_free_0          1.007e+02    NA    NA
+k_cyan_free          4.147e-02    NA    NA
+k_cyan_free_bound    3.407e-02    NA    NA
+k_cyan_bound_free    2.303e-02    NA    NA
+k_JCZ38              5.350e-02    NA    NA
+k_J9Z38              6.555e-03    NA    NA
+k_JSE76              2.578e-02    NA    NA
+f_cyan_free_to_JCZ38 6.505e-01    NA    NA
+f_cyan_free_to_J9Z38 2.508e-01    NA    NA
+f_JCZ38_to_JSE76     1.000e+00    NA    NA
+f_JSE76_to_JCZ38     8.618e-01    NA    NA
+
+Estimated Eigenvalues of SFORB model(s):
+cyan_b1 cyan_b2  cyan_g 
+0.08768 0.01089 0.39821 
+
+Resulting formation fractions:
+                     ff
+cyan_free_JCZ38 0.65053
+cyan_free_J9Z38 0.25082
+cyan_free_sink  0.09864
+cyan_free       1.00000
+JCZ38_JSE76     1.00000
+JCZ38_sink      0.00000
+JSE76_JCZ38     0.86184
+JSE76_sink      0.13816
+
+Estimated disappearance times:
+        DT50   DT90 DT50back DT50_cyan_b1 DT50_cyan_b2
+cyan   25.32 164.79    49.61        7.906        63.64
+JCZ38  12.96  43.04       NA           NA           NA
+J9Z38 105.75 351.29       NA           NA           NA
+JSE76  26.89  89.33       NA           NA           NA
+
+

Session info +

R version 4.2.2 Patched (2022-11-10 r83330)
+Platform: x86_64-pc-linux-gnu (64-bit)
+Running under: Debian GNU/Linux bookworm/sid
+
+Matrix products: default
+BLAS:   /usr/lib/x86_64-linux-gnu/openblas-serial/libblas.so.3
+LAPACK: /usr/lib/x86_64-linux-gnu/openblas-serial/libopenblas-r0.3.21.so
+
+locale:
+ [1] LC_CTYPE=de_DE.UTF-8       LC_NUMERIC=C              
+ [3] LC_TIME=de_DE.UTF-8        LC_COLLATE=de_DE.UTF-8    
+ [5] LC_MONETARY=de_DE.UTF-8    LC_MESSAGES=de_DE.UTF-8   
+ [7] LC_PAPER=de_DE.UTF-8       LC_NAME=C                 
+ [9] LC_ADDRESS=C               LC_TELEPHONE=C            
+[11] LC_MEASUREMENT=de_DE.UTF-8 LC_IDENTIFICATION=C       
+
+attached base packages:
+[1] parallel  stats     graphics  grDevices utils     datasets  methods  
+[8] base     
+
+other attached packages:
+[1] saemix_3.2 npde_3.3   knitr_1.41 mkin_1.2.2
+
+loaded via a namespace (and not attached):
+ [1] mclust_6.0.0      lattice_0.20-45   prettyunits_1.1.1 ps_1.7.2         
+ [5] zoo_1.8-11        assertthat_0.2.1  rprojroot_2.0.3   digest_0.6.31    
+ [9] lmtest_0.9-40     utf8_1.2.2        R6_2.5.1          cellranger_1.1.0 
+[13] evaluate_0.19     ggplot2_3.4.0     highr_0.9         pillar_1.8.1     
+[17] rlang_1.0.6       readxl_1.4.1      callr_3.7.3       jquerylib_0.1.4  
+[21] rmarkdown_2.19    pkgdown_2.0.7     textshaping_0.3.6 desc_1.4.2       
+[25] stringr_1.5.0     munsell_0.5.0     compiler_4.2.2    xfun_0.35        
+[29] pkgconfig_2.0.3   systemfonts_1.0.4 pkgbuild_1.4.0    htmltools_0.5.4  
+[33] tidyselect_1.2.0  tibble_3.1.8      gridExtra_2.3     codetools_0.2-18 
+[37] fansi_1.0.3       crayon_1.5.2      dplyr_1.0.10      grid_4.2.2       
+[41] nlme_3.1-161      jsonlite_1.8.4    gtable_0.3.1      lifecycle_1.0.3  
+[45] DBI_1.1.3         magrittr_2.0.3    scales_1.2.1      cli_3.5.0        
+[49] stringi_1.7.8     cachem_1.0.6      fs_1.5.2          bslib_0.4.2      
+[53] ragg_1.2.4        generics_0.1.3    vctrs_0.5.1       deSolve_1.34     
+[57] tools_4.2.2       glue_1.6.2        purrr_1.0.0       processx_3.8.0   
+[61] fastmap_1.1.0     yaml_2.3.6        inline_0.3.19     colorspace_2.0-3 
+[65] memoise_2.0.1     sass_0.4.4

Hardware info +

CPU model: AMD Ryzen 9 7950X 16-Core Processor

MemTotal:       64940452 kB

+ + + +

Testing hierarchical pathway kinetics with +residue data on cyantraniliprole

Johannes +Ranke

Last change on 6 January +2023, last compiled on 28 Januar 2023

Introduction +

Test data +

Parent only evaluations +

Pathway fits +

Evaluations with pathway established previously +

Alternative pathway fits +

Refinement of alternative pathway fits +

Conclusion +

Acknowledgements +

Appendix +

Plots of fits that were not refined further +

Hierarchical fit listings +

Pathway 1 +

Pathway 2 +

Pathway 2, refined fits +

Session info +

Hardware info +