Enumeration of RNA structures by Matrix Models

We enumerate the number of RNA contact structures according to their genus, i.e. the topological character of their pseudoknots. By using a recently proposed matrix model formulation for the RNA folding problem, we obtain exact results for the simple case of an RNA molecule with an infinitely flexible backbone, in which any arbitrary pair of bases is allowed. We analyze the distribution of the genus of pseudoknots as a function of the total number of nucleotides along the phosphate-sugar backbone.Comment: RevTeX, 4 pages, 2 figure

Similarity-Detection and Localization

The detection of similarities between long DNA and protein sequences is studied using concepts of statistical physics. It is shown that mutual similarities can be detected by sequence alignment methods only if their amount exceeds a threshold value. The onset of detection is a continuous phase transition which can be viewed as a localization-delocalization transition. The ``fidelity'' of the alignment is the order parameter of that transition; it leads to criteria for the selection of optimal alignment parameters.Comment: 4 pages including 4 figures (308kb post-script file

Kidney Patients’ Intention to Receive a Deceased Donor Transplant: Development of Stage of Change, Decisional Balance and Self-efficacy Measures

In order to sustain life, patients whose kidneys fail must receive dialysis or obtain a transplant. This study reports on the development and validation of measures of Stage of Change, Decisional Balance and Self-efficacy based on the Transtheoretical Model (TTM) to assess patients’ readiness to receive a deceased donor transplant. We surveyed 293 transplant-eligible kidney patients about their deceased donation readiness. Exploratory and confirmatory analyses for all measures demonstrated factor structures similar to previous application of the TTM to other health behaviors, excellent model fit and good internal and external validity. These brief, reliable instruments with good psychometric properties can guide the development of improved, individually-tailored transplant education for patients

A New Mesenchymal Stem Cell (MSC) Paradigm: Polarization into a Pro-Inflammatory MSC1 or an Immunosuppressive MSC2 Phenotype

BACKGROUND: Our laboratory and others reported that the stimulation of specific Toll-like receptors (TLRs) affects the immune modulating responses of human multipotent mesenchymal stromal cells (hMSCs). Toll-like receptors recognize "danger" signals, and their activation leads to profound cellular and systemic responses that mobilize innate and adaptive host immune cells. The danger signals that trigger TLRs are released following most tissue pathologies. Since danger signals recruit immune cells to sites of injury, we reasoned that hMSCs might be recruited in a similar way. Indeed, we found that hMSCs express several TLRs (e.g., TLR3 and TLR4), and that their migration, invasion, and secretion of immune modulating factors is drastically affected by specific TLR-agonist engagement. In particular, we noted diverse consequences on the hMSCs following stimulation of TLR3 when compared to TLR4 by our low-level, short-term TLR-priming protocol. PRINCIPAL FINDINGS: Here we extend our studies on the effect on immune modulation by specific TLR-priming of hMSCs, and based on our findings, propose a new paradigm for hMSCs that takes its cue from the monocyte literature. Specifically, that hMSCs can be polarized by downstream TLR signaling into two homogenously acting phenotypes we classify here as MSC1 and MSC2. This concept came from our observations that TLR4-primed hMSCs, or MSC1, mostly elaborate pro-inflammatory mediators, while TLR3-primed hMSCs, or MSC2, express mostly immunosuppressive ones. Additionally, allogeneic co-cultures of TLR-primed MSCs with peripheral blood mononuclear cells (PBMCs) predictably lead to suppressed T-lymphocyte activation following MSC2 co-culture, and permissive T-lymphocyte activation in co-culture with MSC1. SIGNIFICANCE: Our study provides an explanation to some of the conflicting reports on the net effect of TLR stimulation and its downstream consequences on the immune modulating properties of stem cells. We further suggest that MSC polarization provides a convenient way to render these heterogeneous preparations of cells more uniform while introducing a new facet to study, as well as provides an important aspect to consider for the improvement of current stem cell-based therapies

Thermodynamics of protein folding: a random matrix formulation

The process of protein folding from an unfolded state to a biologically active, folded conformation is governed by many parameters e.g the sequence of amino acids, intermolecular interactions, the solvent, temperature and chaperon molecules. Our study, based on random matrix modeling of the interactions, shows however that the evolution of the statistical measures e.g Gibbs free energy, heat capacity, entropy is single parametric. The information can explain the selection of specific folding pathways from an infinite number of possible ways as well as other folding characteristics observed in computer simulation studies.Comment: 21 Pages, no figure

Global unions: chasing the dream or building the reality?

This article takes as its theme the global restructuring of capital and its impact on worker organization. It argues for a reassertion of class in any analysis of global solidarity, and assesses the opportunities and barriers to effective global unionization. Rooted in the UK experience, the article analyzes the impact of the European social dimension on trade unions, before taking the discussion into a global dimension. It concludes by suggesting that there are reasons for cautious optimism in terms of solidarity building, despite difficult historical legacies and the common replacement of action with rhetoric

Internal lee wave closures : parameter sensitivity and comparison to observations

Author Posting. © American Geophysical Union, 2015. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Oceans 120 (2015): 7997–8019, doi:10.1002/2015JC010892.This paper examines two internal lee wave closures that have been used together with ocean models to predict the time-averaged global energy conversion rate into lee waves and dissipation rate associated with lee waves and topographic blocking: the Garner (2005) scheme and the Bell (1975) theory. The closure predictions in two Southern Ocean regions where geostrophic flows dominate over tides are examined and compared to microstructure profiler observations of the turbulent kinetic energy dissipation rate, where the latter are assumed to reflect the dissipation associated with topographic blocking and generated lee wave energy. It is shown that when applied to these Southern Ocean regions, the two closures differ most in their treatment of topographic blocking. For several reasons, pointwise validation of the closures is not possible using existing observations, but horizontally averaged comparisons between closure predictions and observations are made. When anisotropy of the underlying topography is accounted for, the two horizontally averaged closure predictions near the seafloor are approximately equal. The dissipation associated with topographic blocking is predicted by the Garner (2005) scheme to account for the majority of the depth-integrated dissipation over the bottom 1000 m of the water column, where the horizontally averaged predictions lie well within the spatial variability of the horizontally averaged observations. Simplifications made by the Garner (2005) scheme that are inappropriate for the oceanic context, together with imperfect observational information, can partially account for the prediction-observation disagreement, particularly in the upper water column.National Science Foundation Grant Number: OCE-0960820; Office of Naval Research (ONR) Grant Number: N00014-11-1-0487; Australian Research Council Grant Number: (DE120102927 and CE110001028); National Science and Engineering Research Council of Canada Grant Number: (22R23085)2016-06-1

String Matching and 1d Lattice Gases

We calculate the probability distributions for the number of occurrences $n$ of a given $l$ letter word in a random string of $k$ letters. Analytical expressions for the distribution are known for the asymptotic regimes (i) $k \gg r^l \gg 1$ (Gaussian) and $k,l \to \infty$ such that $k/r^l$ is finite (Compound Poisson). However, it is known that these distributions do now work well in the intermediate regime $k \gtrsim r^l \gtrsim 1$. We show that the problem of calculating the string matching probability can be cast into a determining the configurational partition function of a 1d lattice gas with interacting particles so that the matching probability becomes the grand-partition sum of the lattice gas, with the number of particles corresponding to the number of matches. We perform a virial expansion of the effective equation of state and obtain the probability distribution. Our result reproduces the behavior of the distribution in all regimes. We are also able to show analytically how the limiting distributions arise. Our analysis builds on the fact that the effective interactions between the particles consist of a relatively strong core of size $l$, the word length, followed by a weak, exponentially decaying tail. We find that the asymptotic regimes correspond to the case where the tail of the interactions can be neglected, while in the intermediate regime they need to be kept in the analysis. Our results are readily generalized to the case where the random strings are generated by more complicated stochastic processes such as a non-uniform letter probability distribution or Markov chains. We show that in these cases the tails of the effective interactions can be made even more dominant rendering thus the asymptotic approximations less accurate in such a regime.Comment: 44 pages and 8 figures. Major revision of previous version. The lattice gas analogy has been worked out in full, including virial expansion and equation of state. This constitutes the main part of the paper now. Connections with existing work is made and references should be up to date now. To be submitted for publicatio

Traction stress in focal adhesions correlates biphasically with actin retrograde flow speed

How focal adhesions (FAs) convert retrograde filamentous actin (F-actin) flow into traction stress on the extracellular matrix to drive cell migration is unknown. Using combined traction force and fluorescent speckle microscopy, we observed a robust biphasic relationship between F-actin speed and traction force. F-actin speed is inversely related to traction stress near the cell edge where FAs are formed and F-actin motion is rapid. In contrast, larger FAs where the F-actin speed is low are marked by a direct relationship between F-actin speed and traction stress. We found that the biphasic switch is determined by a threshold F-actin speed of 8–10 nm/s, independent of changes in FA protein density, age, stress magnitude, assembly/disassembly status, or subcellular position induced by pleiotropic perturbations to Rho family guanosine triphosphatase signaling and myosin II activity. Thus, F-actin speed is a fundamental regulator of traction force at FAs during cell migration