Inferring hidden Markov models from noisy time sequences: a method to alleviate degeneracy in molecular dynamics

We present a new method for inferring hidden Markov models from noisy time sequences without the necessity of assuming a model architecture, thus allowing for the detection of degenerate states. This is based on the statistical prediction techniques developed by Crutchfield et al., and generates so called causal state models, equivalent to hidden Markov models. This method is applicable to any continuous data which clusters around discrete values and exhibits multiple transitions between these values such as tethered particle motion data or Fluorescence Resonance Energy Transfer (FRET) spectra. The algorithms developed have been shown to perform well on simulated data, demonstrating the ability to recover the model used to generate the data under high noise, sparse data conditions and the ability to infer the existence of degenerate states. They have also been applied to new experimental FRET data of Holliday Junction dynamics, extracting the expected two state model and providing values for the transition rates in good agreement with previous results and with results obtained using existing maximum likelihood based methods.Comment: 19 pages, 9 figure

Toward physical realizations of thermodynamic resource theories

Conventional statistical mechanics describes large systems and averages over many particles or over many trials. But work, heat, and entropy impact the small scales that experimentalists can increasingly control, e.g., in single-molecule experiments. The statistical mechanics of small scales has been quantified with two toolkits developed in quantum information theory: resource theories and one-shot information theory. The field has boomed recently, but the theorems amassed have hardly impacted experiments. Can thermodynamic resource theories be realized experimentally? Via what steps can we shift the theory toward physical realizations? Should we care? I present eleven opportunities in physically realizing thermodynamic resource theories.Comment: Publication information added. Cosmetic change

On Identifying the Optimal Number of Population Clusters via the Deviance Information Criterion

Inferring population structure using Bayesian clustering programs often requires a priori specification of the number of subpopulations, , from which the sample has been drawn. Here, we explore the utility of a common Bayesian model selection criterion, the Deviance Information Criterion (DIC), for estimating . We evaluate the accuracy of DIC, as well as other popular approaches, on datasets generated by coalescent simulations under various demographic scenarios. We find that DIC outperforms competing methods in many genetic contexts, validating its application in assessing population structure

Emergent global patterns of ecosystem structure and function from a mechanistic general ecosystem model

Anthropogenic activities are causing widespread degradation of ecosystems worldwide, threatening the ecosystem services upon which all human life depends. Improved understanding of this degradation is urgently needed to improve avoidance and mitigation measures. One tool to assist these efforts is predictive models of ecosystem structure and function that are mechanistic: based on fundamental ecological principles. Here we present the first mechanistic General Ecosystem Model (GEM) of ecosystem structure and function that is both global and applies in all terrestrial and marine environments. Functional forms and parameter values were derived from the theoretical and empirical literature where possible. Simulations of the fate of all organisms with body masses between 10 µg and 150,000 kg (a range of 14 orders of magnitude) across the globe led to emergent properties at individual (e.g., growth rate), community (e.g., biomass turnover rates), ecosystem (e.g., trophic pyramids), and macroecological scales (e.g., global patterns of trophic structure) that are in general agreement with current data and theory. These properties emerged from our encoding of the biology of, and interactions among, individual organisms without any direct constraints on the properties themselves. Our results indicate that ecologists have gathered sufficient information to begin to build realistic, global, and mechanistic models of ecosystems, capable of predicting a diverse range of ecosystem properties and their response to human pressures

Responses of marine benthic microalgae to elevated CO<inf>2</inf>

Increasing anthropogenic CO2 emissions to the atmosphere are causing a rise in pCO2 concentrations in the ocean surface and lowering pH. To predict the effects of these changes, we need to improve our understanding of the responses of marine primary producers since these drive biogeochemical cycles and profoundly affect the structure and function of benthic habitats. The effects of increasing CO2 levels on the colonisation of artificial substrata by microalgal assemblages (periphyton) were examined across a CO2 gradient off the volcanic island of Vulcano (NE Sicily). We show that periphyton communities altered significantly as CO2 concentrations increased. CO2 enrichment caused significant increases in chlorophyll a concentrations and in diatom abundance although we did not detect any changes in cyanobacteria. SEM analysis revealed major shifts in diatom assemblage composition as CO2 levels increased. The responses of benthic microalgae to rising anthropogenic CO2 emissions are likely to have significant ecological ramifications for coastal systems. © 2011 Springer-Verlag

The clinical features of the piriformis syndrome: a systematic review

Piriformis syndrome, sciatica caused by compression of the sciatic nerve by the piriformis muscle, has been described for over 70 years; yet, it remains controversial. The literature consists mainly of case series and narrative reviews. The objectives of the study were: first, to make the best use of existing evidence to estimate the frequencies of clinical features in patients reported to have PS; second, to identify future research questions. A systematic review was conducted of any study type that reported extractable data relevant to diagnosis. The search included all studies up to 1 March 2008 in four databases: AMED, CINAHL, Embase and Medline. Screening, data extraction and analysis were all performed independently by two reviewers. A total of 55 studies were included: 51 individual and 3 aggregated data studies, and 1 combined study. The most common features found were: buttock pain, external tenderness over the greater sciatic notch, aggravation of the pain through sitting and augmentation of the pain with manoeuvres that increase piriformis muscle tension. Future research could start with comparing the frequencies of these features in sciatica patients with and without disc herniation or spinal stenosis

A pooling-based genome-wide analysis identifies new potential candidate genes for atopy in the European Community Respiratory Health Survey (ECRHS)

<p>Abstract</p> <p>Background</p> <p>Asthma and atopy are complex phenotypes with shared genetic component. In this study we attempt to identify genes related to these traits performing a two-stage DNA pooling genome-wide analysis in order to reduce costs. First, we assessed all markers in a subset of subjects using DNA pooling, and in a second stage we evaluated the most promising markers at an individual level.</p> <p>Methods</p> <p>For the genome-wide analysis, we constructed DNA pools from 75 subjects with atopy and asthma, 75 subjects with atopy and without asthma and 75 control subjects without atopy or asthma. In a second stage, the most promising regions surrounding significant markers after correction for false discovery rate were replicated with individual genotyping of samples included in the pools and an additional set of 429 atopic subjects and 222 controls from the same study centres.</p> <p>Results</p> <p><it>Homo sapiens </it>protein kinase-like protein SgK493 (<it>SGK493</it>) was found to be associated with atopy. To lesser extent mitogen-activated protein kinase 5 (<it>MAP3K5</it>), collagen type XVIII alpha 1 (<it>COL18A1</it>) and collagen type XXIX alpha 1 (<it>COL29A1</it>) were also found to be associated with atopy. Functional evidences points out a role for <it>MAP3K5</it>, <it>COL18A1 </it>and <it>COL29A1 </it>but the function of <it>SGK493 </it>is unknown.</p> <p>Conclusion</p> <p>In this analysis we have identified new candidate regions related to atopy and suggest <it>SGK493 </it>as an atopy locus, although these results need further replication.</p

Magnetism, FeS colloids, and Origins of Life

A number of features of living systems: reversible interactions and weak bonds underlying motor-dynamics; gel-sol transitions; cellular connected fractal organization; asymmetry in interactions and organization; quantum coherent phenomena; to name some, can have a natural accounting via $physical$ interactions, which we therefore seek to incorporate by expanding the horizons of `chemistry-only' approaches to the origins of life. It is suggested that the magnetic 'face' of the minerals from the inorganic world, recognized to have played a pivotal role in initiating Life, may throw light on some of these issues. A magnetic environment in the form of rocks in the Hadean Ocean could have enabled the accretion and therefore an ordered confinement of super-paramagnetic colloids within a structured phase. A moderate H-field can help magnetic nano-particles to not only overcome thermal fluctuations but also harness them. Such controlled dynamics brings in the possibility of accessing quantum effects, which together with frustrations in magnetic ordering and hysteresis (a natural mechanism for a primitive memory) could throw light on the birth of biological information which, as Abel argues, requires a combination of order and complexity. This scenario gains strength from observations of scale-free framboidal forms of the greigite mineral, with a magnetic basis of assembly. And greigite's metabolic potential plays a key role in the mound scenario of Russell and coworkers-an expansion of which is suggested for including magnetism.Comment: 42 pages, 5 figures, to be published in A.R. Memorial volume, Ed Krishnaswami Alladi, Springer 201

Large-Scale Evidence for the Effect of the COLIA1 Sp1 Polymorphism on Osteoporosis Outcomes: The GENOMOS Study.

Background Osteoporosis and fracture risk are considered to be under genetic control. Extensive work is being performed to identify the exact genetic variants that determine this risk. Previous work has suggested that a G/T polymorphism affecting an Sp1 binding site in the COLIA1 gene is a genetic marker for low bone mineral density (BMD) and osteoporotic fracture, but there have been no very-large-scale studies of COLIA1 alleles in relation to these phenotypes. Methods and Findings Here we evaluated the role of COLIA1 Sp1 alleles as a predictor of BMD and fracture in a multicenter study involving 20,786 individuals from several European countries. At the femoral neck, the average (95% confidence interval [CI]) BMD values were 25 mg/cm2 (CI, 16 to 34 mg/cm2) lower in TT homozygotes than the other genotype groups ( p &lt; 0.001), and a similar difference was observed at the lumbar spine; 21 mg/cm2 (CI, 1 to 42 mg/cm2), ( p = 0.039). These associations were unaltered after adjustment for potential confounding factors. There was no association with fracture overall (odds ratio [OR] = 1.01 [CI, 0.95 to 1.08]) in either unadjusted or adjusted analyses, but there was a non-significant trend for association with vertebral fracture and a nominally significant association with incident vertebral fractures in females (OR = 1.33 [CI, 1.00 to 1.77]) that was independent of BMD, and unaltered in adjusted analyses. Conclusions Allowing for the inevitable heterogeneity between participating teams, this study—which to our knowledge is the largest ever performed in the field of osteoporosis genetics for a single gene—demonstrates that the COLIA1 Sp1 polymorphism is associated with reduced BMD and could predispose to incident vertebral fractures in women, independent of BMD. The associations we observed were modest however, demonstrating the importance of conducting studies that are adequately powered to detect and quantify the effects of common genetic variants on complex diseases