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- Research article
- Open Access
Thermodynamic modeling of transcription: sensitivity analysis differentiates biological mechanism from mathematical model-induced effects
- Jacqueline M Dresch1,
- Xiaozhou Liu2,
- David N Arnosti2Email author and
- Ahmet Ay3, 4Email author
© Dresch et al; licensee BioMed Central Ltd. 2010
- Received: 6 May 2010
- Accepted: 24 October 2010
- Published: 24 October 2010
Quantitative models of gene expression generate parameter values that can shed light on biological features such as transcription factor activity, cooperativity, and local effects of repressors. An important element in such investigations is sensitivity analysis, which determines how strongly a model's output reacts to variations in parameter values. Parameters of low sensitivity may not be accurately estimated, leading to unwarranted conclusions. Low sensitivity may reflect the nature of the biological data, or it may be a result of the model structure. Here, we focus on the analysis of thermodynamic models, which have been used extensively to analyze gene transcription. Extracted parameter values have been interpreted biologically, but until now little attention has been given to parameter sensitivity in this context.
We apply local and global sensitivity analyses to two recent transcriptional models to determine the sensitivity of individual parameters. We show that in one case, values for repressor efficiencies are very sensitive, while values for protein cooperativities are not, and provide insights on why these differential sensitivities stem from both biological effects and the structure of the applied models. In a second case, we demonstrate that parameters that were thought to prove the system's dependence on activator-activator cooperativity are relatively insensitive. We show that there are numerous parameter sets that do not satisfy the relationships proferred as the optimal solutions, indicating that structural differences between the two types of transcriptional enhancers analyzed may not be as simple as altered activator cooperativity.
Our results emphasize the need for sensitivity analysis to examine model construction and forms of biological data used for modeling transcriptional processes, in order to determine the significance of estimated parameter values for thermodynamic models. Knowledge of parameter sensitivities can provide the necessary context to determine how modeling results should be interpreted in biological systems.
- Root Mean Square Error
- Thermodynamic Model
- Sensitivity Coefficient
- Global Sensitivity Analysis
- High Dimensional Model Representation
Mathematical modeling of gene transcription is becoming a common approach to gain insight into the physical and chemical properties that drive transcription and to characterize the nature of gene networks that form the basis of biological systems [1–9]. By formulating the transcriptional process quantitatively, one can derive parameter values that highlight important features of gene regulation, including protein-protein interactions, protein-DNA interactions, and their effects on gene expression. Major types of models in use include Boolean, ordinary differential equation (ODE), and thermodynamic; these models employ parameters such as synthesis, decay, and diffusion rates for proteins and mRNA, as well as binding affinity, repression efficiency, and cooperativity of transcription factors [1–9]. Below, we focus on analysis of thermodynamic models, which unlike other types of models, specifically consider the DNA sequence in transcriptional control regions. For all of these models, parameters are usually not known and the derivation of these parameters from biological data, such as images from confocal microscopy, is complicated by the noisy nature of biological data. Two major challenges then face the modeler who seeks a biological interpretation of the parameter values. First, large parameter ranges are often found, leading to uncertainty about where realistic parameter values lie. In many cases, relevant experimental measurements have not been conducted - mathematical models are often in fact the best method to determine such values. Second, parameter values can be strongly influenced by the form used to shape the problem, thus the problem then becomes whether these extracted values are realistic - are the values due to properties of the biological system or the mathematical model?
To address these questions, one must examine the mathematical model itself to determine the uncertainty in parameter values and ascertain the impact that perturbations in parameter values will have on the model output. This question of parameter uncertainty and sensitivity analysis has been addressed in many different applications, including biological, chemical and risk assessment [10–16]. Parameter uncertainties have been explored extensively for ODE models, which typically have a very large number of parameters, resulting in a great deal of model variation and parameter uncertainty [10–13]. The sensitivity of parameters derived from thermodynamic transcription models, however, has not yet been examined in such a context; studies have focused simply on extracting and interpreting parameter values or parameter ranges [1–4, 6].
Thermodynamic models, also termed fractional occupancy models, are based on formulations originating from statistical physics. For transcriptional analysis, these models consider all possible states of a DNA regulatory element, where a state refers to a specific configuration of regulatory proteins (transcription factors) bound to DNA [1–4, 6]. Each state is awarded a weight, which depends on properties such as the binding affinity and concentration of proteins. In many thermodynamic models, including those examined in this study, the mathematical formula used to calculate the expression level is a rational function in which parameters to be estimated can be found in both the numerator and denominator [1, 2].
Sensitivity analysis, whether local or global, has the primary goal of determining how a given model responds to variations in parameter values. Local sensitivity analysis (also known as differential analysis or nominal range sensitivity analysis) focuses on a particular point in parameter space, varying parameters one at a time to obtain a local response of the model to each parameter [13, 15, 20, 21]. Global sensitivity analysis, on the other hand, tries to capture the entire parameter space all at once, allowing multiple parameter values to be explored simultaneously. Parameters are individually analyzed by averaging the variation in model output over the entire space [20]. It is possible to explore multiparameter responses using local sensitivity analysis, employing techniques such as second-order partial derivatives, but this analysis can be computationally costly. For this reason, in this study we use global sensitivity analysis to investigate multiparameter effects.
Our approach initially used local sensitivity analysis to calculate the model's rate of change with respect to each variable at a given point in parameter space, quantifying at that point how small changes in each variable will affect the model output. Then, we turned to global analysis, employing three different methods. The first simply takes an average of results obtained from local sensitivity analyses on different points in parameter space. The other two global methods each rely on determining which parameters and parameter combinations contribute most to the variation in the model output that resulted from sampling a wide range of parameter values. The eFAST algorithm does this through Fourier analysis, while the HDMR algorithm does this through polynomial approximation. For more details on each individual method, see the following text and the model descriptions and formulas found in the Additional file 1.
Local Sensitivity Analysis
A major advantage of local sensitivity analysis is its ease of implementation [21]. The formula is straightforward and the results are simple to interpret, but must be viewed with caution, because the analysis is only valid in the small region around a particular point [11, 12, 14]. Also, this method does not account for parameter interactions, so in non-linear models, this often results in an underestimation of true model sensitivities [15, 21]. In many mathematical models of biological events, including differential equation models of the gap gene network in Drosophila, parameter ranges are fairly well constrained due to previous studies which have estimated values for parameters such as diffusion and decay rates [23–25]. This allows a great deal of information to be extracted from a local analysis. With the large uncertainty of parameter values and ranges in models such as those we focus on in this study, this method is not robust, so global sensitivity techniques are preferred.
Global Sensitivity Analysis
These approaches vary parameters over a larger parameter space and have the ability to quantify parameter interactions [12, 14, 15, 21]. Global sensitivity analysis covers a much wider range of methods than that of local sensitivity analysis. A common element is that global sensitivity methods explore the full parameter space, quantifying a model's sensitivity to perturbations in each parameter. Due to computational limitations, this exploration of parameter space requires a sampling method that randomly samples parameter space, while evenly covering individual parameter ranges [13]. Here, we focus on three global sensitivity methods: a basic, easily-implemented method of average local sensitivities, and two more complex methods that capture first-order sensitivities, as well as higher order sensitivities, those sensitivities derived from varying more than one parameter. Higher order sensitivities can capture possible parameter interactions. An example of higher order interactions would be the relationship between the intrinsic activity of a transcription factor and cooperative binding. Solutions to a model would include those that ascribed high cooperativity between weak neighboring transcription factors, as well as low cooperativity between inherently powerful transcription factors. Thus, the higher order sensitivity would quantify the impact this relationship has on the model output. For a particular system, varying cooperativity or transcription factor activity alone may have little effect on model output, thus these parameters would have small first-order sensitivity indices, because the two effects can "cancel each other out" or compensate. If cooperativity and activity are simultaneously varied, large effects might be observed, producing significant second-order sensitivities.
i) Method 1
To overcome the major disadvantage of the small region of sampling in local sensitivity analysis while retaining the ease of computational simplicity, some studies have used a global approach of averaging local sensitivities taken throughout the parameter space [13]. This method chooses sets of parameters randomly using realistic ranges of each parameter space, then local sensitivity analysis is applied to each set of parameters, and results are averaged over the entire space for each parameter to provide a global sensitivity coefficient. This method can be computationally expensive.
ii) Method 2
The search-curve used to sample the parameter space is defined by a collection of sinusoidal functions, one for each parameter. The assigned frequencies of these functions are then used to partition the variance amongst parameters and calculate the first-order sensitivity indices by Fourier analysis. For each parameter, the eFAST algorithm calculates the first order sensitivity of that parameter as well as the first order sensitivity of the entire set of remaining parameters. The total-order sensitivity coefficient for the parameter of interest is then approximated by the sum of that parameter's first-order sensitivity and the remaining variance after first-order partitioning. (See Additional file 1 for mathematical formulas.)
iii) Method 3
where f0 is the main effect (also designated the zeroth order term, or the overall mean) [14, 21]. Note that this method is distinct from the ANOVA commonly used in biological studies when comparing two or more groups of experimental data. We will refer to ANOVA in this study as the high dimensional model representation (HDMR) expansion [14]. The underlying assumption for an HDMR method is that the objective function is normally distributed [14, 15, 21]. Due to random sampling, this is typically not violated, but if a violation occurs, corrective measures can be taken [15]. Previous studies have shown that, when implemented, first and second-order effect terms are typically sufficient for a good approximation of the total sensitivity [27, 28]. In calculating the terms in the expansion, the Monte Carlo integration method is used [14]. The HDMR algorithm used in this study is computationally highly efficient due to the use of orthonormal polynomial approximations for first and second-order terms [14]. These terms are then normalized by the total variance to obtain first and second-order sensitivity indices corresponding to the main effect of each parameter, and the effects from pair-wise parameter interactions [14]. (See Additional file 1 for mathematical formulas.)
To determine parameter sensitivities, we analyzed two different thermodynamic models recently used to study transcriptional regulation in the early Drosophila embryo; neither publication included a thorough sensitivity analysis of the parameters. In the first work, Arnosti and colleagues extracted their model parameters using protein and mRNA concentration data from a set of simplified regulatory elements functionally tested in embryos [Figure 1; [1]]. This model was implemented using 9 different variations, with the total number of parameters ranging from 8 to 13. The parameters represent the overall repressor activity (R), distance-function for repression (Q), and homotypic repressor cooperativities (C). In the second model, Levine and colleagues extracted their model parameters using protein and mRNA concentration data representing the activity of two endogenous regulatory elements [2]. Their model analyzes the expected activity of 128 different hypothetical regulatory sequences, with 9 different parameters for each element representing protein binding affinities, and homotypic and heterotypic cooperativities. In this study, we focused on the 8 forms that produced the best correlation with the experimental data, published in Table S2 of Zinzen et al..
Local Sensitivity Analysis of the Fakhouri et al. Model
To initiate our study, we performed the local sensitivity analysis on the model of Fakhouri et al. In this study, Arnosti and colleagues pursued a unique "bottom up" approach to understand the mechanistic processing of regulatory elements by the transcriptional machinery, using a well defined and characterized set of repressors and activators in Drosophila blastoderm embryos. Their approach not only incorporated cooperativity between transcription factors and a quenching activity of repressor proteins, as other models have done [2–9], but included distance dependence and relative enhancer positioning of these activities with no a priori assumptions. In contrast to earlier enhancer based studies, which use many bioinformatically determined binding sites, they created and systematically analyzed a well-defined set of transcriptional regulatory elements in the Drosophila embryo with experimentally determined binding sites, focusing on repressor-activator spacing, stoichiometry and arrangement. Due to this well defined construct design, their data set also depends on a fewer number of features than previous studies. They used experimental data from 12 of these elements to extract parameter values representing repressor scaling factor, efficiencies, and cooperativities. Fakhouri et al. used the root mean square error (RMSE) to determine the quality of fit, thus, for the sensitivity analysis of this model, RMSE was used as the objective function [1]. Their study employed nine model schemes, which differ slightly in their treatment of distance effects and cooperativity. Each scheme uses the same general formula as the equations shown in Figure 1B, but the treatment of distance-dependent repression and cooperativity differs. In different schemes, repressor-activator distances were "binned" into different intervals, (e.g. 0-6 bp, 28-41 bp, 50-56 bp etc. vs. 0-6 bp, 28-31 bp, 41-50 bp etc.) and cooperativity was represented as a single term or two different terms for genes containing three repressor binding sites, resulting a in different number of parameters for each scheme. For a full description of all nine schemes, refer to [1].
The global/local approach avoids the problem of dependence on estimated parameter values, and is global in the sense that the whole parameter space is sampled, but it fails to capture higher-level interactions of parameters. Therefore, we applied global analyses to test this model using two well-established methods.
Global Sensitivity Analysis of the Fakhouri et al. Model
From a strictly mathematical viewpoint, the enhanced sensitivity of quenching parameters over cooperativity parameters is also not surprising. The form of this model itself suggests that small changes in quenching parameters will have the largest effects on the model output, because quenching parameters appear only in the numerator of the expression function, while the repressor scaling factor and cooperativity parameters of the same form appear in both the numerator and denominator [Figure 1]. Thus, small changes in the repressor scaling factor or cooperativity parameters will have much smaller effects on the overall change in expression. This representation of cooperativity parameters in the model is the standard method of describing interactions in thermodynamic models, thus a resulting low sensitivity may permit more non-physiological parameters to be accepted. Experimental evidence suggests that at least in some cases, however, there should be a high degree of sensitivity to reflect the important protein-protein cooperative interactions on enhancers [29–31].
The mathematical representation of cooperativity in this model is based on the interactions at the transcription factor-DNA binding level, thus cooperativities are represented in the same form in both the numerator and denominator of the expression function [Figure 1]. However, cooperativity between two transcription factors can be represented as a post-binding event, by constructing the model in such a way that all states of the enhancer are considered, then weighted by a cooperativity parameter. In this second case, the model formula would be written exactly the same as Figure 1B except that C1 would not be present in the denominator of the expression. Thus the cooperativity parameters would be present only in the numerator of the expression function, increasing their sensitivity, possibly to levels comparable to quenching parameters.
We noted that quenching parameters' sensitivities varied, with Q6 showing the lowest sensitivity (Figure 3). In the construction of the model, Q6 represents the quenching directed by a lone repressor binding to the 3' end of the regulatory region. There is no biological evidence that suggests a correlation between the particular position and short-range repression effectiveness, but some other model parameter might compensate for changes in Q6. For this reason, and the fact that some quenching parameters are seen in the same number of constructs, but have different sensitivity indices, we turned to another global sensitivity analysis technique to test for possible effects of interactions between parameters.
HDMR second-order interactions also suggested interactions between quenching parameters. Most often, this was observed between quenching parameters that were present together in more than one construct, such as Q3 and Q5. This effect may be due to compensation in the RMSE from one construct to another. RMSE is calculated by summing up the square errors over all constructs, therefore parameter values that increase the error in one construct, but severely decrease the error in another construct, would leave the RMSE unchanged. Hence, a sensitivity index interpreted as an interaction between two parameters may not be as simple as the two values affecting one another. A high sensitivity index between two quenching parameters may be a result of those two quenching parameters being present together in most constructs. In this case, it would be difficult to remove the dependence of one parameter on another because the parameters appear together in most terms of the RMSE calculation. This effect should be taken into consideration when designing the experiments and developing a model. The best way to avoid this ambiguity would be to design the experiments and the model in unison, to minimize the bias to a certain parameter or group of parameters.
To address this question, we designed new sets of hypothetical genes, created synthetic data sets, and performed global sensitivity analyses (see Additional file 1). The results show that improving construct design by uniformly representing quenching parameters partially equalizes parameter sensitivities, however, quenching parameters still remain more sensitive than repressor-repressor cooperativity parameters (Figure S4, compare to Figure 4). The structure of the mathematical model guarantees this disparity regardless of the experimental design or data.
We also gained insight into the effects the biological data has on parameter sensitivities. Clearly, from a mathematical point of view, the data has some effect on the sensitivity analysis, since the objective function used here is a measure of error. For these new gene constructs, when the data suggests parameter values that lie near the edge of realistic parameter space, we find much higher variation in the sensitivity coefficients of quenching parameters (Figure S4A vs. S4B). This effect is due to random sampling techniques used in global sensitivity methods. When choosing random values in a finite range, there is a higher probability that they lie close to a mean value than a value on either side of the mean. For synthetic data sets created using parameters set at mean values, the error will be minimized, thus decreasing the sensitivity of the parameters. We observe this effect for both the original constructs and the redesigned constructs (Figures S4 and S5). The results validate our hypothesis that the sensitivity coefficients are dependent, at least in part, on the true parameter values, those represented in the experimental data (Figures 3B vs. S5B).
Optimizing the design of constructs to equalize the frequency of parameters does decrease the range of parameter sensitivities, but not completely (Figure S4). Further equalization is possible by ensuring that quenching parameters are represented uniformly in a combinatorial fashion (Figure S6). This analysis on synthetic data underscores the need for global sensitivity analyses on modeling studies with the objective of reducing the error between predictions and experimental data. The analysis should be done both before and after experimental data collection, first to test for uniform sensitivity on synthetic data constructed with mean values; then a second time, to provide a level of confidence in extracted parameter values and their biological implications.
Global Sensitivity Analysis of the Zinzen et al. Model
Strikingly, transcription factor scaling factors are far more sensitive than the cooperativity parameters for almost every enhancer structure tested (Figures 5 and S7). The overall low sensitivities in cooperativity parameters do not necessarily contradict the conclusions made by the authors that different cooperativity parameters distinguish the expression patterns of rho and vnd, but they do draw into question how robust these conclusions can be [2]. Low sensitivity values do not mean that the parameters are of low importance, but rather indicate that changes in these parameter values do not have large effects on the output. Therefore, other sets of parameter values, with different relative importance of cooperativity parameters, may also allow the model to distinguish the expression patterns of rho and vnd. The study claimed that rho-like elements require 5-10 fold-higher Dorsal-Twist cooperativity, higher Twist-Twist cooperativity and lower Sna-Sna cooperativity than do vnd-like elements [2]. We explored the correlation in other regions of parameter space to determine how strict these relationships are and how much changes in these relationships would affect the model's correlation with experimental data.
Parameter relationships resulting in correlations as good as those found in Zinzen et al. from 100,000 tested parameters
all correct
DT wrong
TT wrong
SS wrong
DT and TT wrong
DT and SS wrong
TT and SS wrong
all wrong
57 (39%)
6 (4%)
43 (29%)
20 (14%)
0 (0%)
2 (1%)
18 (12%)
0 (0%)
49 (28%)
32 (18%)
45 (26%)
16 (9%)
8 (5%)
9 (5%)
13 (7%)
2 (1%)
3 and 9
59 (38%)
10 (6%)
47 (31%)
13 (8%)
1 (1%)
5 (3%)
19 (12%)
0 (0%)
4 and 7
48 (39%)
1 (1%)
44 (36%)
17 (14%)
0 (0%)
0 (0%)
13 (11%)
0 (0%)
5, 6, and 8
37 (35%)
2 (2%)
34 (32%)
17 (16%)
0 (0%)
0 (0%)
15 (14%)
0 (0%)
13 (11%)
4 (3%)
17 (15%)
29 (25%)
8 (7%)
12 (10%)
21 (18%)
13 (11%)
36 (24%)
1 (1%)
30 (20%)
37 (25%)
0 (0%)
8 (5%)
36 (24%)
0 (0%)
36 (28%)
3 (2%)
16 (13%)
38 (30%)
0 (0%)
3 (2%)
32 (25%)
0 (0%)
Table 1 also indicates how sensitivity analysis can guide model selection. The insensitivity of cooperativity parameters led us to test a large set of different parameter values, which revealed that multiple parameter sets with different biological interpretations produced satisfactory correlations between the experimental data and the model output. This modeling weakness may reflect the reliance on only one experimental data set to fit parameter values. In addition, information about positions of binding sites in enhancers was not considered, and somewhat arbitrary assumptions about which proteins are required for activity were made. Any of these factors may have led to insensitivity in the cooperativity parameters, and should be addressed before trying to improve upon the model or its biological interpretations.
Thermodynamic models represent the most powerful approach to quantitative understanding of gene transcription because of their use of DNA sequence information that can capture subtle differences in enhancer architecture. As with other models, this approach involves many unknown parameters and interactions, however, a rigorous sensitivity analysis has not been applied to recent studies in this area. We show here, through local and global sensitivity analyses, that there is a wide range in sensitivities for parameters in these models. In some cases, this is due to the biology of the system, or the experimental data used to calculate the error, while in other cases it may simply be an artifact of the mathematical formulation (Figure 1), and the underlying assumptions that have gone into this model.
Our analysis also uncovered previously undescribed interactions between parameters that may reflect true biological interactions, and at the same time found very low sensitivities in parameters that were previously thought to be most informative in explaining the overall architecture of distinct enhancers. We used the insights drawn from sensitivity analysis to redesign experiments, and discover new parameter values that are well correlated with experimental data. Clearly, standard parameter estimation techniques used alone, in the absence of sensitivity analysis, cannot fully show the importance of possible biologically-driven or model-driven effects.
To improve upon thermodynamic modeling attempts to unlock key aspects of cis-regulatory grammar, we should recognize a need for sensitivity analysis and a thorough exploration of parameter space. With this analysis, new iterative parameter estimation and model selection techniques can be designed and implemented [17, 32]. Analysis of the effects parameters have on the model output, within their realistic ranges, can also help biologists to design experiments. As we demonstrated with our synthetic data sets, a tight coordination between experimental design and model formulation is required to maximize the effectiveness of these modeling studies. A conscious effort can be made to collect data evenly and models can be redesigned to make sure that model sensitivity is similar for various parameters. Thermodynamic models, as other models, benefit by such sensitivity analysis, providing important context in which to place biological interpretations suggested by the model.
Mathematical models of transcription are becoming increasingly widely applied, but analysis of the sensitivity of fractional occupancy (thermodynamic) models has lagged. We have examined two recent thermodynamic modeling studies of transcriptional regulation and shown how parameter sensitivities vary widely. From this examination, we have identified both biological and mathematical bases to differential sensitivity.
In our sensitivity analysis of the Fakhouri et al. model, we first observed that quenching parameters were found to be more sensitive than other model parameters and cooperativity parameters to be least sensitive. Through careful inspection of the model formulation, we concluded that this differential sensitivity was heavily dependent on the mathematical form of the model. We also noted that parameters that were represented in a larger portion of the data set were more sensitive than others. This effect can neither be attributed solely to the mathematical form of the model nor solely to the biology of the system; it is a combination of the two, which emphasizes the importance of designing the model and the experiments in unison. We created synthetic data sets and conducted global sensitivity analyses using these sets as our experimental data, and show that not only an evenly designed data set is important, but the parameter values as represented in the biological data also have a large impact on parameter sensitivities. Thus, sensitivity analysis is not only useful in dissecting the mathematical model formulation, but also in investigating the real parameter space and the impact the data set will have on the model's sensitivity to certain parameters.
Our examination of the Zinzen et al. model produced similar results, in which cooperativity parameters were the least sensitive of all parameters in almost every formulation of their model. We investigated these cooperativity parameters and found that this low sensitivity allowed for a wide array of acceptable cooperativity values, all of which showed high correlation with experimental data. Importantly, these alternative cooperativity values lead to very different biological interpretations of the system under investigation. Without thorough sensitivity analysis and parameter space exploration, parameter values extracted using thermodynamic models may be easily misinterpreted.
Our study underscores the importance of carrying out sensitivity analysis to identify model- and data-driven influences on parameters, and to improve the construction and interpretation of transcriptional models based on thermodynamic approaches.
We thank members of the Arnosti laboratory for their comments and Tilo Ziehn, University of Leeds, for the GUI-HDMR. This study was supported by NIH GM56976 to DNA, and by support from the MSU Quantitative Biology Program to AA and JMD.
Authors' Affiliations
- Fakhouri WD, Ay A, Sayal R, Dresch J, Dayringer E, Arnosti DN: Deciphering a transcriptional regulatory code: modeling short-range repression in the Drosophila embryo. Mol Syst Biol. 2010, 6: 341- 10.1038/msb.2009.97PubMed CentralView ArticlePubMedGoogle Scholar
- Zinzen RP, Senger K, Levine M, Papatsenko D: Computational models for neurogenic gene expression in the Drosophila embryo. Curr Biol. 2006, 16: 1358-1365. 10.1016/j.cub.2006.05.044View ArticlePubMedGoogle Scholar
- Segal E, Raveh-Sadka T, Schroeder M, Unnerstall U, Gaul U: Predicting expression patterns from regulatory sequence in Drosophila segmentation. Nature. 2008, 451: 535-540. 10.1038/nature06496View ArticlePubMedGoogle Scholar
- Reinitz J, Hou S, Sharp DH: Transcriptional Control in Drosophila. ComPlexUs. 2003, 1: 54-64. 10.1159/000070462.View ArticleGoogle Scholar
- Jaeger J, Surkova S, Blagov M, Janssens H, Kosman D, Kozlov KN, Manu , Myasnikova E, Vanario-Alonso CE, Samsonova M, Sharp D, Reinitz J: Dynamic control of positional information in the early Drosophila embryo. Nature. 2004, 430: 368-371. 10.1038/nature02678View ArticlePubMedGoogle Scholar
- Janssens H, Hou S, Jaeger J, Kim A, Myasnikova E, Sharp D, Reinitz J: Quantitative and predictive model of transcriptional control of the Drosophila melanogaster even skipped gene. Nat Genet. 2006, 38: 1159-1165. 10.1038/ng1886View ArticlePubMedGoogle Scholar
- von Dassow G, Meir E, Munro EM, Odell GM: The segment polarity network is a robust developmental module. Nature. 2000, 406: 188-192. 10.1038/35018085View ArticlePubMedGoogle Scholar
- Sánchez L, Thieffry D: A logical analysis of the Drosophila gap-gene system. J Theor Biol. 2001, 211: 115-141. 10.1006/jtbi.2001.2335View ArticlePubMedGoogle Scholar
- Yuh CH, Bolouri H, Davidson EH: Cis-regulatory logic in the endo16 gene: switching from a specification to a differentiation mode of control. Development. 2001, 128: 617-629.PubMedGoogle Scholar
- Gutenkunst RN, Waterfall JJ, Casey FP, Brown KS, Myers CR, Sethna JP: Universally sloppy parameter sensitivities in systems biology models. PLoS Comput Biol. 2007, 3: e189-10.1371/journal.pcbi.0030189.PubMed CentralView ArticleGoogle Scholar
- Erb RS, Michaels GS: Sensitivity of biological models to errors in parameter estimates. Pac Symp Biocomput. 1999, 4: 53-64.Google Scholar
- Marino S, Hogue IB, Ray CJ, Kirschner DE: A methodology for performing global uncertainty and sensitivity analysis in systems biology. J Theor Biol. 2008, 254: 178-196. 10.1016/j.jtbi.2008.04.011PubMed CentralView ArticlePubMedGoogle Scholar
- van Riel NAW: Dynamic modeling and analysis of biochemical networks: mechanism-based models and model-based experiments. Briefings Bioinf. 2006, 7: 364-374. 10.1093/bib/bbl040.View ArticleGoogle Scholar
- Ziehn T, Tomlin AS: A global sensitivity study of sulfur chemistry in a premixed methane flame model using HDMR. Int J Chem Kinet. 2008, 40: 742-753. 10.1002/kin.20367.View ArticleGoogle Scholar
- Frey HC, Patil SR: Identification and review of sensitivity analysis methods. Risk Anal. 2002, 22: 553-578. 10.1111/0272-4332.00039View ArticlePubMedGoogle Scholar
- Bortz DM, Nelson PW: Sensitivity analysis of a nonlinear lumped parameter model of HIV infection dynamics. Bull Math Biol. 2004, 66: 1009-1026. 10.1016/j.bulm.2003.10.011View ArticlePubMedGoogle Scholar
- Pannell DJ: Sensitivity analysis of normative economic models: theoretical framework and practical strategies. Agr Econ. 1997, 16: 139-152. 10.1016/S0169-5150(96)01217-0.View ArticleGoogle Scholar
- Fernando EG, Luhr DR: Sensitivity analysis of predicted pavement performance. Transport Res Rec. 1988, 1200: 32-41.Google Scholar
- Ingalls B: Sensitivity analysis: from model parameters to system behaviour. Essays Biochem. 2008, 45: 177-193. 10.1042/BSE0450177View ArticlePubMedGoogle Scholar
- Saltelli A, Tarantola S, Chan KPS: A quantitative model-independent method for global sensitivity analysis of model output. Technometrics. 1999, 41: 39-56. 10.2307/1270993.View ArticleGoogle Scholar
- Tang Y, Reed P, Wagener T, van Werkhoven K: Comparing sensitivity analysis methods to advance lumped watershed model identification and evaluation. Hyrdol Earth Syst Sci Discuss. 2006, 3: 3333-3395. 10.5194/hessd-3-3333-2006.View ArticleGoogle Scholar
- Reeves GT, Fraser SE: Biological systems from an engineer's point of view. PLoS Biol. 2009, 7: 32-35. 10.1371/journal.pbio.1000021.View ArticleGoogle Scholar
- Ashyraliyev M, Jaeger J, Blom JG: Parameter estimation and determinability analysis applied to Drosophila gap gene circuits. BMC Syst Biol. 2008, 2: 83- 10.1186/1752-0509-2-83PubMed CentralView ArticlePubMedGoogle Scholar
- Ashyraliyev M, Siggens K, Janssens H, Blom JG, Akam M, Jaeger J: Gene circuit analysis of the terminal gap gene huckebein. PLoS Comput Biol. 2009, 5 (10): e1000696-10.1371/journal.pcbi.1000548.View ArticleGoogle Scholar
- Fomekong-Nanfack Y, Postma M, Kaandorp JA: Inferring Drosophila gap gene regulatory network: a parameter sensitivity and perturbation analysis. BMC Syst Biol. 2009, 3: 94- 10.1186/1752-0509-3-94PubMed CentralView ArticlePubMedGoogle Scholar
- Cukier RI, Fortuin CM, Shuler KE, Petschek AG, Schaibly JH: Study of the sensitivity of coupled reaction systems to uncertainties in rate coefficients. J Chem Phys. 1973, 59: 3873-3878. 10.1063/1.1680571.View ArticleGoogle Scholar
- Li G, Rosenthal C, Rabitz H: High Dimensional Model Representations. J Phys Chem A. 2001, 105: 7765-7777. 10.1021/jp010450t.View ArticleGoogle Scholar
- Liang X, Guo J: Intercomparison of land-surface parameterization schemes: Sensitivity of surface evergy and water fluxes to model parameters. J Hydrol. 2003, 279: 182-209. 10.1016/S0022-1694(03)00168-9.View ArticleGoogle Scholar
- Jiang J, Levine M: Binding affinities and cooperative interactions with bHLH activators delimit threshold responses to the dorsal gradient morphogen. Cell. 1993, 72: 741-752. 10.1016/0092-8674(93)90402-CView ArticlePubMedGoogle Scholar
- Szymanski P, Levine M: Multiple modes of dorsal-bHLB transcriptional synergy in the Drosophila embryo. EMBO J. 1995, 14: 2229-2238.PubMed CentralPubMedGoogle Scholar
- Crocker J, Tamori Y, Erives A: Evolution acts on enhancer organization to fine-tune gradient threshold readouts. PLoS Biol. 2008, 6: e263- 10.1371/journal.pbio.0060263PubMed CentralView ArticlePubMedGoogle Scholar
- Lillacci G, Khammash M: Parameter estimation and model selection in computational biology. PLoS Comput Biol. 2010, 6: e1000696- 10.1371/journal.pcbi.1000696PubMed CentralView ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


text: Here is our full Classic USA packing list. You'll notice there are a few asterisks (*) alongside some of the items. This is because these things are mandatory. We have a list of mandatory items because, for safety reasons, it's vital you have your own gear. But, mandatory equipment may be shared with your fellow trekkers if you're trekking in a group.


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Haa! That's funny.
heh, Amy's face is just...priceless: she's not frantic or terrified, just a little bit grumpy at being stolen by the Silent.
LOL, little Amy's face is adorable! And the Silent made me laugh like a demented seal xD
Note: only a member of this blog may post a comment.


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Resending attached mail closing issue 257 [1]. The previous subject line was misleading, and the issue # was missing. Thanks Nilo -----Original Message----- From: Nilo Mitra (EUS) Sent: Friday, September 06, 2002 10:48 AM To: 'email@example.com' Cc: email@example.com; 'Martin Duerst' Subject: RE: Your editorial comments on the SOAP Primer have been incorporated Your editorial comment on the SOAP Part0: Primer, marked as Last Call Issue# [1] has been accepted and handled in the latest editor's copy of the document, available at [2]. The passenger's name as well as fault texts have been "internationalized". Thank you, Nilo Mitra Editor, SOAP Primer [1] http://www.w3.org/2000/xp/Group/xmlp-lc-issues.html#x257 [2] http://www.w3.org/2000/xp/Group/2/06/LC/soap12-part0.htmlReceived on Friday, 6 September 2002 13:53:16 UTC
This archive was generated by hypermail 2.3.1 : Tuesday, 6 January 2015 20:16:59 UTC


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Federal prosecutors have dismissed a misdemeanor citation filed against a man who leaped off a cliff to save his wife, whose parachute had failed to open during the newlyweds' adventure in southern Utah.
Amber Marie Bellows, 28, died after she fell Saturday performing what's known as a BASE jump. BASE is an acronym for building, antenna, span, and earth, the fixed objects from which participants jump. A Zion National Park officer cited Clayton Hoyt Butler, 29, for flying a parachute through a national park without a permit. The charge could have led to six months in prison.
But the U.S. attorney's office for Utah said late Wednesday that the "interests of justice do not warrant prosecution" of Butler.
"To be sure, BASE jumping in Zion National Park is unlawful, and this tragic BASE jumping accident underscores some of the reasoning behind the regulations which prohibit such conduct," spokeswoman Melodie Rydalch said in a statement.
Many other parachuters have faced federal charges because they jumped off cliffs in national parks in what has been a decades-long battle between parks officials and thrill-sports enthusiasts.
Rydalch said sentences have reached as much as three months in prison for one defendant and a $5,000 fine for a company involved in a jump. She said the U.S. attorney's office could not determine exactly how many people have faced charges related to such jumps.
Butler and Bellows were married Jan. 24, according to an obituary published in the Salt Lake Tribune. The couple had completed several successful jumps, according to videos posted on Butler's YouTube profile. And he had posted a picture on Facebook just before the couple began hiking up the 3,000-foot mountain, which Bellows was the first to jump from.
"Her family wishes to express their heartfelt gratitude to the Zion National Park rescue team who risked their lives to help bring Amber home," the obituary read.
More than $8,000 had been raised for Butler in an online campaign. Bellows' funeral is scheduled for Friday.
Parks officials said this was the 29th case of a fatal fall at Zion, but the first involving a BASE jump. Because jumpers remain so close to the building or cliff from which they jumped, the sport is considered more dangerous than skydiving from a plane.
Pilot says laser pointers make 'mayhem ensue' in cockpit
Storm clutches Northeast in a snowy, icy grip; D.C. shut down
N.C. struggles with snow; 'Respect Mother Nature,' governor says


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Last week, Ryanair warned investors that there'd been a "perceptible dip" in bookings for September and the rest of the autumn, a fall that could show we're moving on from pursuing the cheapest prices in favour of getting the fairest treatment and not having to pay £1.50 for a Twix.
The company's earnings data shows how critical its additional "hidden" costs and extra fees are to the business. Last year, the average flier spent €48.20 on the cost of a ticket, although the average cost to the airline to fly everyone everywhere was €52.56 per passenger. It loses money on the actual flying and being an airline part of the deal.
However, the average "ancillary" fee paid by passengers for forgotten boarding cards, baggage checking, cups of tea and so on came to €13.43 per passenger, helping it to make a profit. If more people read the small print and brought drinks with them, it'd be in trouble.
As well as the threat of customers becoming tired of its business practises, Ryanair may also suffer from the austerity that's sweeping Europe. An "industry insider" quoted by the Telegraph explained how the airline is also reliant on local subsidies, saying: "A lot of local authorities subsidise Ryanair to fly to their tiny airstrips, because of all the tourists they bring. As austerity bites across Europe, will these areas be able to continue to fund Ryanair?" [Telegraph]


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Stanno Uni Sock Childs Size
Stanno Uni Sock Childs Size
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All things considered if you want a plain football sock to complete your kit, the Stanno Uni sock offers great value, a wide range of colours and a host of practical benefits.


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The following post comes from Debra L. Karplus at partner site The Dollar Stretcher.
The best-seller The Seven Habits of Highly Effective People by Dr. Stephen Covey was first published in 1989 and has sold more than 15 millions books since then – in 38 languages. Covey has since co-authored similar books targeted to highly effective teens, families, and marriages. His writing is positive and inspiring.
In one of his most recent books, Covey writes…
If you want to make minor, incremental changes and improvements, work on practices, behavior or attitude. But if you want to make significant, quantum improvement, work on paradigms.
Perhaps Covey would like to write about habits of highly frugal people. Here are some suggestions, Dr. Covey…
1. They save dollars by saving pennies
Frugal people know that frugality applies to both big and small issues. Frugal people are able to enjoy a $10 restaurant lunch occasionally but are fully aware that a daily routine of that same lunch amounts to nearly $4,000 a year.
So they organize potlucks instead of meals out. They do simple, small things – like use a tea bag more than once, empty and reuse a vacuum cleaner bag, and clip coupons to save a buck on a jar of peanut butter. However, they also save in much larger ways – like trading in their minivan or SUV (sport utility vehicle) for a more economical vehicle.
2. They're deliberate about making decisions
Frugal people have a good sense of perspective and are able to see the big picture. They don't always choose the cheaper option simply because it appears less expensive. They take their time and explore many options before making a decision. They plan and are generally well organized. Frugal people typically don't seek immediate gratification. And they try to go green whenever possible.
3. They're good managers of both time and money
Frugal people organize their errands for optimal efficiency. They place value on their time – they know how to recognize when saving money just isn't worth the time. They know better than to drive across town to save a quarter on a gallon of milk. They're disciplined and work before play. Frugal people know that how wealthy you are isn't about your income but rather about how you use your financial and intangible resources.
4. Frugal people embrace a do-it-yourself lifestyle
Fugal people anticipate and perform maintenance and repairs without procrastination. Before hiring a professional for doing household repairs, a frugal person researches on the Internet and confers with an expert at their local home-improvement center to determine if a repair person even needs to be called. Frugal people have made an investment in owning high-quality tools to tackle most simple repairs at home. They also barter with friends and neighbors to get the job done.
5. Frugal people see opportunities where others don't
Frugal people are intuitive and trust their gut feeling when an opportunity presents itself. School supplies at an April rummage sale or a pile of free firewood on a nearby parkway are true finds for the frugal person, requiring little speculation.
Frugal people are contrarians who don't go along with the crowd for the purpose of conformity – they're not mainstream shoppers. They don't own the newest and fastest electronic gadgets that everyone else is purchasing. Instead, they have adopted the Rule of One: owning no more than one of anything non-essential, including televisions, cell phones, computers, electronics, and cars.
6. Frugal people find new uses for old items
A container of brown shoe polish doubles as a quick fix for blemishes on woodwork in the house or furniture. Steel wool plugs holes to keep away household pests. Frugal people find free pallets from local stores and use them creatively in the backyard, garage, and basement, such as for storage. Frugal people devise uses for duct tape that you'd never imagine. To be frugal means to be creative.
7. Frugal people are proud of their frugal lifestyle
Frugal people have transformed their home into a haven where they can have fun while saving money. They've devised creative ways for their family to reduce house, food, transportation, insurance, entertainment, utilities, and other costs. They have turned household tasks into fun family activities, such as gardening or bicycling as a mode of in-town travel.
Frugal people reuse, recycle, barter, and share, and use the library for books and other materials. They don't need to purchase items such as DVDs, clothes, tools, and yard equipment. Frugal people raise money-savvy kids who learn to respect money and material objects. And they are always open to the possibility of discovering new ways to be a more frugal person.
Can you rework your own paradigm, as Dr. Covey suggests, to become a more frugal person?
Follow The Dollar Stretcher on Twitter.


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Whatever you want, you'll find it on the side of the road for sale, in the great city of Hialeah.
Tags: Sweet Home Hialeah Blog, Hialeah Blogger, Blog About Hialeah, City of Hialeah, South Florida Blogger, Hialeah Lifestyle, What's Happening in Hialeah, Only in Hialeah, Top 10 Miami Based Blogs and Bloggers,
Love Sweet Home Hialeah? Keep us blogging by sending us your photos, news and events from around Hialeah!


text: Show my pics to as many people as you can. I want you to print my pics out and leave them in very public places like bars and clubs, bus and train stations, anywhere where I will get seen! Please send me pics of my pics in public! I want to be exposed to email@example.com


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|She loves animal print - or maybe I do.....
Thursday, February 21, 2013
Blogger get together
8 comments:
- Lisa said...
Looks like a blast!! Glad you went and had fun. I totally get you about the crazies out there! It makes things like this very nerve racking.
And I believe a little girl has to have some sort of animal print ;)
- February 21, 2013 at 7:59 AM
- Kelli @ The Turquoise Piano said...
Fun! I just started meeting other bloggers too. Your baby is adorable!
- February 21, 2013 at 8:08 AM
- Life By Lex said...
I'm so glad you won your bed with the Man. Your going to love your HR Monitor!!! I totally should have blogged about meeting up for today's post but non-scale victory got in the way! Gah!
- February 21, 2013 at 8:10 AM
- Elizabeth said...
HR Monitors are the best. It is a great way to really track your workouts. I was amazed at the motivation it gave me.
- February 21, 2013 at 12:41 PM
- Ashlee said...
I am loving the face lift!! I am glad you had a good time meeting the ladies, I totally get your fear, haha people are nuts!! I love the snuggle picture of your sweet little girl!!
- February 21, 2013 at 3:25 PM
- Nichole Gaertner said...
Oh how fun! I'm sad I live so far away from most of all the other women that tend to be meeting up in bloggy World. :)
- February 21, 2013 at 5:02 PM
- Katie J said...
I know meeting people from the internet nowadays you can create some crazy situations in your mind! That's why I think it is best to always schedule something in public. . . maybe a freezing parking lot in the snow isn't the ideal place lol, but I'm so glad we met! I really enjoyed my night with you and Lex and hope we can do it again soon!
P.S. your daughter is so adorable!!!
- February 21, 2013 at 10:15 PM
- Ariel McCollums said...
Yes! Another Pittsburgh blogger! I hope to meet up sometime and join in the fun!
- February 23, 2013 at 8:33 PM


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Fall has arrived in Ottawa, bringing a cool breeze and a rhapsody of vibrant colours along with it. Coming to Ottawa for a meeting or a conference this fall? That's great! If you're not sure what to do with your downtime in the evening, we can help. Discover five activities for a lovely fall evening in Ottawa:
1. Visit the new Copper Spirits & Sights Rooftop Lounge:
Want a spectacular view of Ottawa in the sunset light? You'll get it here! Located on the top floor of the Hyatt Andaz Ottawa ByWard Market Hotel at 325 Dalhousie St., this brand new chic but casual bar is THE place for an after work drink.
Offering floor to ceiling windows, this bar is a place to relax while enjoying panoramic views of the city below. If you enjoy a crisp fall breeze, opt to sit on the bar's outdoor patio. But don't worry, you won't get cold. The patio offers cozy, cabana-style seating, complete with a warm fire pit. Copper Spirits & Sights is open Monday to Friday from 4 PM to 2 AM and from 3 PM to 2AM on Saturday and Sunday.
2. See a show at the National Arts Centre (NAC):
Located in the middle of Ottawa's downtown core at 1 Elgin St., the National Arts Centre makes it easy to catch a show after a full day of meetings or sessions. From ballet, to music, to musical theatre and more, you can be sure that there will be an evening performance to suit your tastes. Here are a few events going on at the National Arts Centre this fall:
Rodgers + Hammerstein's Cinderella
Oct. 25-30, 2016
From the creators of The Sound of Music, this Broadway show puts a new twist on a classic tale.
Shanghai Ballet's Giselle
Nov. 10-12, 2016
First shown in Paris in 1841, this classical ballet depicts the story of a lovely peasant girl betrayed in love.
Tchaikovsky's Fifth
Nov. 16-17, 2016
The NAC Orchestra will perform Tchaikovsky's Symphony No. 5 with Conductor Diego Matheuz. This piece is considered to be one of the composer's most popular works. This presentation is a world premiere!
3. Catch a Sens game:
The arrival of the cooler fall weather means the arrival of hockey season in Ottawa. Head just west of the downtown core to Canadian Tire Centre to see Ottawa's NHL team – the Ottawa Senators – play. Wear red and get ready to cheer along with the crowd. And as most of the games take place in the evening, this is the perfect after meeting or after conference activity! The 'Sens' play from roughly October through to April. Go Sens go!
4. Visit one of Ottawa's National Museums:
As Canada's Capital, Ottawa has several national museums for you to choose from. From the National Gallery of Canada, to the Canadian Museum of Nature, to the Canadian War Museum, the Canadian Museum of History, the Canada Aviation and Space Museum and more, there is sure to be a museum that will peak your interest. Also, most museums are open until 8 PM on Thursday evening, with admission being free on Thursday from either 4 or 5 PM.
5. Go on a walking tour of the city:
Ottawa is a very walkable city with most attractions being within a 20-minute walk from most downtown-area hotels.
In Ottawa, you'll find several walking tour options from ghost tours, to an Aboriginal history tour, to culinary tours, brewery tours and more. If you want to learn about Ottawa's darker past, opt to go on a tour with Ottawa Haunted Walks. Or if you want to get a taste of Ottawa's expanding culinary scene, try Ottawa Tasting Tours, Culinary Adventure Co. or Experience Food. But again, these are only a few of the many tours that are available.
Whichever tour you choose, you'll be sure to enjoy a lovely evening walk through the city. Also, a guided walking tour is a great way to see the city if you happen to be attending a meeting or a conference on your own.
These activities however, are only a few ideas to get your fall trip planning started. For more information on activities and tours that are available in Ottawa, explore our See & Do page.


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EASRA is comprised of the Capital Markets Authority Kenya (CMA (K)), Capital Markets Authority Uganda (CMA (U)) and the Capital Markets and Securities Authority in Tanzania (CMSA). It was established on 5th March 1997 through the signing of a Memorandum of Understanding (MOU) formally establishing a framework for mutual cooperation in the area of capital markets development and with a mission to facilitate the harmonization of securities laws among the East African member states and to promote information sharing and cooperation among the members. EASRA intends to provide mutual assistance to its member states in; the development of capital markets institutions, exchanging information to facilitate the enforcement of their respective laws and regulations, cross border surveillance, public education awareness, co-ordination on technical assistance and promotion of regional consultancies. This is done through three standing committees which are each charged with the task spelt out under the committee name. These are:
The formation of EASRA was based on the premise;
CISNA forms part of the Trade, Industry, Finance and Investment Directorate with the Southern African Development Community (SADC) and reports to the SADC Committee of Ministers of Finance and Investment through the Committee for Senior Treasury Officials. CISNA was established in 1998. It consists of the non-banking financial institution authorities, namely, capital markets, collective investment schemes, insurance companies, retirement funds and providers of intermediary services in the SADC.CISNA's Vision and MissionCISNA's Vision is to facilitate the development and implementation of a harmonised, risk based regulatory framework for member states in SADC that enables market growth and development, reduces the potential for systemic risk, informs and protects consumers, mobilises capital flows and contributes to prosperity in the region.CISNA's Mission is to achieve its vision through a process of co-operation, exchange of information and engagement between regional regulators. This process will be directed towards;
A FATF-style regional body founded in August 1999.The purpose of the group is to combat money laundering and terrorism financing by implementing the FATF Recommendations.The group's efforts are aimed at cooperation with other international organizations concerned with combating money laundering and terrorist financing as well as studying and researching regional typologies and coordinating technical assistance.Organizational structure of the ESAAMLG
All of the group's major decisions are made at the meeting of the Ministerial Council, which meets at least once a year.Member states:Botswana;Kenya;Lesotho;Malawi;Mauritius;Mozambique;Namibia;Seychelles;South Africa;Swaziland;Tanzania;Uganda;Zambia;Zimbabwe.Observers:FATF;Asia-Pacific Group on Money Laundering;Caribbean Financial Action Task Force against Money Laundering (CFATF);Commonwealth Secretariat;Egmont Group of Financial Intelligence Units;Interpol;United States;UN Office on Drugs and Crime;World Bank.
The International Organization of Securities Commissions (IOSCO) has its headquarters in Madrid and has approximately 140 members. The three objectives upon which IOSCO's securities regulation is based are the protection of investors, ensuring that markets are fair, efficient and transparent and the reduction of systemic risk. The benefits of IOSCO membership include information exchange at an international level, mutual legal assistance through a multilateral MOU, setting regulatory standards and best practice, resource persons for training, lower registration fees to events and market recognition. Tanzania is a member of IOSCO. The member agencies in the International Organization of Securities Commissions have resolved, through its permanent structures:


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Lamenting the fifth time he has appeared at a mass shooting's memorial service as president, Barack Obama said that tears, words, and prayers were no longer enough.
"If we really want to honor these 12 men and women — if we really want to be a country where we can go to work, go to school and walk our streets free from senseless violence without so many lives being stolen with a bullet from a gun — then we're going to have to change," Obama said at a memorial service for the victims of Monday's shooting at the Washington Navy Yard.
Even more so than a similar speech he gave following the elementary-school massacre in Newtown, Conn., last December, Obama's speech Sunday served as a plea for new gun laws.
Obama said that he worried the country was becoming numb to this sort of mass violence. He said it "ought to lead to some sort of transformation" as it did in other countries, like the United Kingdom and Australia.
"What is different in America is that it's easy to get your hands on a gun," Obama said, "and a lot of us know this."
He also addressed the reality — that members in Congress are not inclined to take up new measures, or even ones that failed during the last gun-control push. He said that change on the issue won't come from Washington — it will come from the outside, from people demanding action.
Obama noted that he has grieved with five communities in the wake of mass shootings — including in Newtown last December and in Tucson, Ariz., after the shooting that critically wounded former Rep. Gabby Giffords. Again, he wished it would be the last.
"We cannot accept this. As Americans bound in grief and love, we must insist here today there is nothing normal about innocent men and women being gunned down where they work," he said.


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Phone 09 442 4531
8 Tawa Drive, Albany
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Whilst installing a new Kitchen in our home, we had been looking for a wooden flooring option to compliment our sarked ceilings. We'd had some quotes from a couple of flooring providers, when our kitchen company suggested Pavimenti. They had heard good reports from other people they had installed Kitchens for, so we called into their showroom in Albany.
From the first introductions I knew this team was it. They were helpful but not pushy, samples were not a problem, and plenty of knowledgeable sensible advice was available.
Their installer was a treasure too and helped us fix an unseen problem before the flooring was laid. The end result was fabulous, just what I had envisaged. We have since moved into a new house and again Pavimenti was called on to transform the ordinary into something with the WOW factor. The personal service is second to none thanks to Stephen, Natashya and the team. I cannot recommend them highly enough.
L. Allinson - Birkenhead
I built a home last year and spent considerable time looking at tile places all over the North Shore, but went back to the first place which was Pavimenti. I am very happy to endorse the service I received in particular from Natashya, nothing was too much trouble for her and I am very happy with tiles I selected from Pavimenti.
S. Whibley - Warkworth
We'd been looking around for suitable flooring for our living area for some time when we discovered Pavimenti. From the outset Stephen and Natashya provided us with great advice and excellent service. Once we had made up our minds the installation process was quick, efficient and beautifully finished. We recently extended our house, and once again Pavimenti were our first port of call to provide us with a fantastic covering for our stairs. As a result the house looks stunning.
R. Clarke – Albany
It gives me the greatest of pleasure to be able to recommend the services of Stephen and Natashya at Pavimenti.
Their priority is customer satisfaction, and they go to incredible lengths to provide it.
Their product knowledge, helpfulness and understanding, made the task of selecting a large quantity of tiles for a new home a stress free experience.
D. Harris - Howick