Information transfer in signaling pathways : a study using coupled simulated and experimental data

Background: The topology of signaling cascades has been studied in quite some detail. However, how information is processed exactly is still relatively unknown. Since quite diverse information has to be transported by one and the same signaling cascade (e.g. in case of different agonists), it is clear that the underlying mechanism is more complex than a simple binary switch which relies on the mere presence or absence of a particular species. Therefore, finding means to analyze the information transferred will help in deciphering how information is processed exactly in the cell. Using the information-theoretic measure transfer entropy, we studied the properties of information transfer in an example case, namely calcium signaling under different cellular conditions. Transfer entropy is an asymmetric and dynamic measure of the dependence of two (nonlinear) stochastic processes. We used calcium signaling since it is a well-studied example of complex cellular signaling. It has been suggested that specific information is encoded in the amplitude, frequency and waveform of the oscillatory Ca2+-signal. Results: We set up a computational framework to study information transfer, e.g. for calcium signaling at different levels of activation and different particle numbers in the system. We stochastically coupled simulated and experimentally measured calcium signals to simulated target proteins and used kernel density methods to estimate the transfer entropy from these bivariate time series. We found that, most of the time, the transfer entropy increases with increasing particle numbers. In systems with only few particles, faithful information transfer is hampered by random fluctuations. The transfer entropy also seems to be slightly correlated to the complexity (spiking, bursting or irregular oscillations) of the signal. Finally, we discuss a number of peculiarities of our approach in detail. Conclusion: This study presents the first application of transfer entropy to biochemical signaling pathways. We could quantify the information transferred from simulated/experimentally measured calcium signals to a target enzyme under different cellular conditions. Our approach, comprising stochastic coupling and using the information-theoretic measure transfer entropy, could also be a valuable tool for the analysis of other signaling pathways

Information transfer in signaling pathways : a study using coupled simulated and experimental data

Background: The topology of signaling cascades has been studied in quite some detail. However, how information is processed exactly is still relatively unknown. Since quite diverse information has to be transported by one and the same signaling cascade (e.g. in case of different agonists), it is clear that the underlying mechanism is more complex than a simple binary switch which relies on the mere presence or absence of a particular species. Therefore, finding means to analyze the information transferred will help in deciphering how information is processed exactly in the cell. Using the information-theoretic measure transfer entropy, we studied the properties of information transfer in an example case, namely calcium signaling under different cellular conditions. Transfer entropy is an asymmetric and dynamic measure of the dependence of two (nonlinear) stochastic processes. We used calcium signaling since it is a well-studied example of complex cellular signaling. It has been suggested that specific information is encoded in the amplitude, frequency and waveform of the oscillatory Ca2+-signal. Results: We set up a computational framework to study information transfer, e.g. for calcium signaling at different levels of activation and different particle numbers in the system. We stochastically coupled simulated and experimentally measured calcium signals to simulated target proteins and used kernel density methods to estimate the transfer entropy from these bivariate time series. We found that, most of the time, the transfer entropy increases with increasing particle numbers. In systems with only few particles, faithful information transfer is hampered by random fluctuations. The transfer entropy also seems to be slightly correlated to the complexity (spiking, bursting or irregular oscillations) of the signal. Finally, we discuss a number of peculiarities of our approach in detail. Conclusion: This study presents the first application of transfer entropy to biochemical signaling pathways. We could quantify the information transferred from simulated/experimentally measured calcium signals to a target enzyme under different cellular conditions. Our approach, comprising stochastic coupling and using the information-theoretic measure transfer entropy, could also be a valuable tool for the analysis of other signaling pathways

Transition from stochastic to deterministic behavior in calcium oscillations

Simulation and modeling is becoming more and more important when studying complex biochemical systems. Most often, ordinary differential equations are employed for this purpose. However, these are only applicable when the numbers of participating molecules in the biochemical systems are large enough to be treated as concentrations. For smaller systems, stochastic simulations on discrete particle basis are more accurate. Unfortunately, there are no general rules for determining which method should be employed for exactly which problem to get the most realistic result. Therefore, we study the transition from stochastic to deterministic behavior in a widely studied system, namely the signal transduction via calcium, especially calcium oscillations. We observe that the transition occurs within a range of particle numbers, which roughly corresponds to the number of receptors and channels in the cell, and depends heavily on the attractive properties of the phase space of the respective systems dynamics. We conclude that the attractive properties of a system, expressed, e.g., by the divergence of the system, are a good measure for determining which simulation algorithm is appropriate in terms of speed and realism

Australia's policy towards the aged: 1890-1972

Sections of the Australian aged community have received cash allowances on a non-contributory and selective basis since 1900. This makes Australia one of the first countries to establish an age pension scheme. It is also one of the very few that has not followed the world trend by adopting some form of compulsory social insurance. This thesis has three aims. Firstly, to explain why Australia decided to provide non-contributory and selective cash age pensions around the turn of the century. Secondly, to examine the various abortive attempts that were subsequently made to establish a comprehensive social insurance scheme. Thirdly, to examine the various changes that were made to the Australian age pension scheme between 1909 and 1972. The study has been divided into four sections

Alyawarr children's variable present temporal reference expression in two, closely-related languages of Central Australia

In a small, remote central Australian community, young children go about their daily lives mainly speaking Alyawarr English (AlyE), a new Central Australian contact language. At school they are acquiring Standard Australian English (SAE) as a second language. Much of what they encounter in SAE will seem familiar and much will be obviously different. In between, there will be many subtle differences that are possibly harder to detect, parse and maintain. This study investigates this remarkable bi-varietal language use, considering whether separate ‘codes’ are indeed evidenced, how they can be quantitatively modelled, and what they tell us about the impact of formal similarity between languages and emerging bilingualism. The use in childhood of multiple closely-related languages is somewhat of a final frontier for several strands of research: child language development, second language acquisition, and creole studies. However, the methodologies common in these fields don’t easily import to the present scenario: for while the assumption of existing, separate codes may be operationally practical (even if theoretically contestable), the presence of overlapping structures (i.e. morphemes that are used in both AlyE and SAE) in the present data set makes code separation on structural grounds problematic. The solution tested here takes a corpus of 50+ hours of naturalistic video recordings of six focus children, and first creates two maximally contrastive, contextually defined data sets: HOME (home, Alyawarr interlocutor) and SCHOOL (school, non-Alyawarr interlocutor). Each data set is then analysed using the Comparative Variationist method. Three variables of present temporal references clauses were selected: aspect morphology with variants V (e.g. ‘look’), Ving (e.g. ‘looking’), and Vbat (e.g. ‘lookbat’), 1sg subject pronouns (‘I’ and ‘AM’) and verb transitivity marking (-im and unmarked). In both HOME and SCHOOL data, variants, their distributions, respective envelopes of variation and variable grammar (modelled using logistic multiple regression conducted in Goldvarb X) are examined. The results show that code-separation is evidenced for all three variables, but that the locus of change is not the same in each case. For transitive marking and 1sg subject pronouns, the same variable grammar is deployed in both HOME and SCHOOL data, while non-SAE-like variants are increasingly avoided in the SCHOOL (i.e. -im and ‘AM’) and thus the envelope of variation for the SAE-compatible variant (i.e. -Ø and ‘I’) expands its range of use on the way to becoming the categorical variant in the children’s SAE. For aspectual morphology, the locus of change is located within the variable grammar where complex patterns of reorganisation are evidenced (e.g. HOME V is strongly associated with ‘stative’ clauses; SCHOOL V with ‘stative’ and ‘habitual’). Additionally, fundamental changes in the envelope of variation (e.g. Ving is not used on transitive verbs in the HOME but is in the SCHOOL) and the range of variants (e.g. Vbat is not used in the SCHOOL) indicate that these remain central considerations in the use of all three variables. This study therefore breaks new ground in both methodological terms, with the application of variationist modelling to child bi-varietal language use, and in advancing our understanding of the vectors of code-separation in the complex ecologies of the region

Acculturation and wellness of native american adolescents in the United States of North America

Cultural conflicts and the process of acculturation contribute to feelings of boredom, anxiety, depression, isolation, stress, self-doubt, alienation, and rejection among Native American high school students. Further, acculturation may have a negative impact on the identity development and wellness of these students. The purpose of this pilot study was to: (a) assess and compare the levels of acculturation of Native American and non-Native American 9th, 10th, 11th, and 12th grade students; and (b) examine the relationship between level of acculturation and wellness for the Native American students. Results indicated significant differences between Native American and non-Native American students’ levels of acculturation; and significant differences between the Native students’ three levels of acculturation on some of the 17 scales of wellness. Resumen: Conflictos culturales y el proceso de aculturación contribuyen a sentimientos de aburrimiento, ansiedad, depresión, aislamiento, presión, desconfianza, alienación, y del rechazo entre estudiantes de escuela superior que son indios americanos. Aún más, la aculturación puede tener un impacto negativo en el desarrollo de identidad y bienestar de estos estudiantes. El propósito de este estudio piloto fue: (a) evaluar y comparar los niveles de aculturación de estudiantes que eran indios americanos y no-indio americano en los grados académicos del noveno, décimo, décimo primero y de duodécimos; y (B) examinar la relación entre nivel de aculturación y bienestar de los estudiantes indio americanos. Los resultados indicaron diferencias significativas entre estudiantes indio americanos y estudiantes no-indio americano en los niveles de aculturación; y diferencias significativas entre los estudiantes indio americanos en tres niveles de aculturación en la parte de las 17 escalas del bienestar