814 research outputs found
Lumpability Abstractions of Rule-based Systems
The induction of a signaling pathway is characterized by transient complex
formation and mutual posttranslational modification of proteins. To faithfully
capture this combinatorial process in a mathematical model is an important
challenge in systems biology. Exploiting the limited context on which most
binding and modification events are conditioned, attempts have been made to
reduce the combinatorial complexity by quotienting the reachable set of
molecular species, into species aggregates while preserving the deterministic
semantics of the thermodynamic limit. Recently we proposed a quotienting that
also preserves the stochastic semantics and that is complete in the sense that
the semantics of individual species can be recovered from the aggregate
semantics. In this paper we prove that this quotienting yields a sufficient
condition for weak lumpability and that it gives rise to a backward Markov
bisimulation between the original and aggregated transition system. We
illustrate the framework on a case study of the EGF/insulin receptor crosstalk.Comment: In Proceedings MeCBIC 2010, arXiv:1011.005
Origin of symbol-using systems: speech, but not sign, without the semantic urge
Natural language—spoken and signed—is a multichannel phenomenon, involving facial and body expression, and voice and visual intonation that is often used in the service of a social urge to communicate meaning. Given that iconicity seems easier and less abstract than making arbitrary connections between sound and meaning, iconicity and gesture have often been invoked in the origin of language alongside the urge to convey meaning. To get a fresh perspective, we critically distinguish the origin of a system capable of evolution from the subsequent evolution that system becomes capable of. Human language arose on a substrate of a system already capable of Darwinian evolution; the genetically supported uniquely human ability to learn a language reflects a key contact point between Darwinian evolution and language. Though implemented in brains generated by DNA symbols coding for protein meaning, the second higher-level symbol-using system of language now operates in a world mostly decoupled from Darwinian evolutionary constraints. Examination of Darwinian evolution of vocal learning in other animals suggests that the initial fixation of a key prerequisite to language into the human genome may actually have required initially side-stepping not only iconicity, but the urge to mean itself. If sign languages came later, they would not have faced this constraint
Microbiota‐Dependent Metabolite Trimethylamine N‐Oxide and Coronary Artery Calcium in the Coronary Artery Risk Development in Young Adults Study (CARDIA)
BACKGROUND: Clinical studies implicate trimethylamine N-oxide (TMAO; a gut microbiota-dependent nutrient metabolite) in cardiovascular disease risk. There is a lack of population-based data on the role of TMAO in advancing early atherosclerotic disease. We tested the prospective associations between TMAO and coronary artery calcium (CAC) and carotid intima-media thickness (cIMT).
METHODS AND RESULTS: Data were from the Coronary Artery Risk Development in Young Adults Study (CARDIA), a biracial cohort of US adults recruited in 1985-1986 (n=5115). We randomly sampled 817 participants (aged 33-55 years) who attended examinations in 2000-2001, 2005-2006, and 2010-2011, at which CAC was measured by computed tomography and cIMT (2005-2006) by ultrasound. TMAO was quantified using liquid chromotography mass spectrometry on plasma collected in 2000-2001. Outcomes were incident CAC, defined as Agatston units=0 in 2000-2001 and >0 over 10-year follow-up, CAC progression (any increase over 10-year follow-up), and continuous cIMT. Over the study period, 25% (n=184) of those free of CAC in 2000-2001 (n=746) developed detectable CAC. In 2000-2001, median (interquartile range) TMAO was 2.6 (1.8-4.2) μmol/L. In multivariable-adjusted models, TMAO was not associated with 10-year CAC incidence (rate ratio=1.03; 95% CI: 0.71-1.52) or CAC progression (0.97; 0.68-1.38) in Poisson regression, or cIMT (beta coefficient: -0.009; -0.03 to 0.01) in linear regression, comparing the fourth to the first quartiles of TMAO.
CONCLUSIONS: In this population-based study, TMAO was not associated with measures of atherosclerosis: CAC incidence, CAC progression, or cIMT. These data indicate that TMAO may not contribute significantly to advancing early atherosclerotic disease risk among healthy early-middle-aged adults
The role of clathrin in post-golgi trafficking in toxoplasma gondii
Apicomplexan parasites are single eukaryotic cells with a highly polarised secretory system that contains unique secretory organelles (micronemes and rhoptries) that are required for host cell invasion. In contrast, the role of the endosomal system is poorly understood in these parasites. With many typical endocytic factors missing, we speculated that endocytosis depends exclusively on a clathrin-mediated mechanism. Intriguingly, in Toxoplasma gondii we were only able to observe the endogenous clathrin heavy chain 1 (CHC1) at the Golgi, but not at the parasite surface. For the functional characterisation of Toxoplasma gondii CHC1 we generated parasite mutants conditionally expressing the dominant negative clathrin Hub fragment and demonstrate that CHC1 is essential for vesicle formation at the trans-Golgi network. Consequently, the functional ablation of CHC1 results in Golgi aberrations, a block in the biogenesis of the unique secretory microneme and rhoptry organelles, and of the pellicle. However, we found no morphological evidence for clathrin mediating endocytosis in these parasites and speculate that they remodelled their vesicular trafficking system to adapt to an intracellular lifestyle
Short-term fate of dietary dieldrin in the digestive tract of Juvenile Lake Trout ( Salvelinus namaycush )
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47979/1/128_2005_Article_BF01685015.pd
Approximation Techniques for Stochastic Analysis of Biological Systems
There has been an increasing demand for formal methods in the design process
of safety-critical synthetic genetic circuits. Probabilistic model checking
techniques have demonstrated significant potential in analyzing the intrinsic
probabilistic behaviors of complex genetic circuit designs. However, its
inability to scale limits its applicability in practice. This chapter addresses
the scalability problem by presenting a state-space approximation method to
remove unlikely states resulting in a reduced, finite state representation of
the infinite-state continuous-time Markov chain that is amenable to
probabilistic model checking. The proposed method is evaluated on a design of a
genetic toggle switch. Comparisons with another state-of-art tool demonstrates
both accuracy and efficiency of the presented method
- …