22,306 research outputs found

    Monotonicity and stability of periodic polling models

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    Polling Systems;Stability;operations research

    Bubble statistics and positioning in superhelically stressed DNA

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    We present a general framework to study the thermodynamic denaturation of double-stranded DNA under superhelical stress. We report calculations of position- and size-dependent opening probabilities for bubbles along the sequence. Our results are obtained from transfer-matrix solutions of the Zimm-Bragg model for unconstrained DNA and of a self-consistent linearization of the Benham model for superhelical DNA. The numerical efficiency of our method allows for the analysis of entire genomes and of random sequences of corresponding length (106−10910^6-10^9 base pairs). We show that, at physiological conditions, opening in superhelical DNA is strongly cooperative with average bubble sizes of 102−10310^2-10^3 base pairs (bp), and orders of magnitude higher than in unconstrained DNA. In heterogeneous sequences, the average degree of base-pair opening is self-averaging, while bubble localization and statistics are dominated by sequence disorder. Compared to random sequences with identical GC-content, genomic DNA has a significantly increased probability to open large bubbles under superhelical stress. These bubbles are frequently located directly upstream of transcription start sites.Comment: to be appeared in Physical Review

    Trust, Reciprocity, and Guanxi in China: An Experimental Investigation

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    We examine the influence of social distance on levels of trust and reciprocity in China. Social distance, reflected in the indigenous concept of guanxi, is of central importance to Chinese culture. In Study 1, some participants participated in two financially salient trust games to measure behavior, one with an anonymous classmate and the other with an anonymous, demographically identical nonclassmate. Other participants, drawn from the same population, completed hypothetical surveys to gauge both hypothetical behavior and expectations of others. Social distance effects on actual and hypothetical behavior were statistically consistent. The results together corroborated the hypothesized negative relationship between trust and social distance. However, reciprocity was not responsive to social distance. Study 2 found that affect-based trust, but not cognition-based trust, played a mediating role in the relationship between social distance and interpersonal trust in a hypothetical scenario. We conclude that close guanxi ties in China engender affect-based trust, which is extended to shouren classmates. This is true despite the fact that no more cognition-based trust is placed nor reciprocity received or expected from classmates compared to demographically identical shengren nonclassmates.Experiment; Affect-based Trust; China; Guanxi; Reciprocity; Trust; Social Distance

    Synergistic actions between angiotensin-converting enzyme inhibitors and statins in atherosclerosis

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    Aims: Hypertension and hypercholesterolemia are independent risk factors for atherosclerotic cardiovascular disease (ASCVD) by acting directly on the endothelium and activating the renin-angiotensin aldosterone system (RAAS) and mevalonate pathways. This review examines how the severity and duration of these risk factors may influence the cardiovascular risk through a reciprocal interplay leading to oxidative stress and pro-inflammatory response. Data synthesis: The review highlights the clinical evidence supporting the benefits of statins and angiotensin-converting enzyme (ACE) inhibitors for hypertension, lipid disorders and ASCVD management, both individually and combined, at all stages of the cardiovascular continuum. Conclusion: Drug strategies incorporating an ACE-inhibitor and a statin, and in particular perindopril and atorvastatin, have consistently demonstrated reductions in the rate of ASCVD events in patients with hypertension and lipid disorders, cementing their position as first-line therapies for the management of atherosclerosis complications

    Isoform-level gene signature improves prognostic stratification and accurately classifies glioblastoma subtypes.

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    Molecular stratification of tumors is essential for developing personalized therapies. Although patient stratification strategies have been successful; computational methods to accurately translate the gene-signature from high-throughput platform to a clinically adaptable low-dimensional platform are currently lacking. Here, we describe PIGExClass (platform-independent isoform-level gene-expression based classification-system), a novel computational approach to derive and then transfer gene-signatures from one analytical platform to another. We applied PIGExClass to design a reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) based molecular-subtyping assay for glioblastoma multiforme (GBM), the most aggressive primary brain tumors. Unsupervised clustering of TCGA (the Cancer Genome Altas Consortium) GBM samples, based on isoform-level gene-expression profiles, recaptured the four known molecular subgroups but switched the subtype for 19% of the samples, resulting in significant (P = 0.0103) survival differences among the refined subgroups. PIGExClass derived four-class classifier, which requires only 121 transcript-variants, assigns GBM patients' molecular subtype with 92% accuracy. This classifier was translated to an RT-qPCR assay and validated in an independent cohort of 206 GBM samples. Our results demonstrate the efficacy of PIGExClass in the design of clinically adaptable molecular subtyping assay and have implications for developing robust diagnostic assays for cancer patient stratification

    Large-Scale Structure Shocks at Low and High Redshifts

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    Cosmological simulations show that, at the present time, a substantial fraction of the gas in the intergalactic medium (IGM) has been shock-heated to T>10^5 K. Here we develop an analytic model to describe the fraction of shocked, moderately overdense gas in the IGM. The model is an extension of the Press & Schechter (1974) description for the mass function of halos: we assume that large-scale structure shocks occur at a fixed overdensity during nonlinear collapse. This in turn allows us to compute the fraction of gas at a given redshift that has been shock-heated to a specified temperature. We show that, if strong shocks occur at turnaround, our model provides a reasonable description of the temperature distribution seen in cosmological simulations at z~0, although it does overestimate the importance of weak shocks. We then apply our model to shocks at high redshifts. We show that, before reionization, the thermal energy of the IGM is dominated by large-scale structure shocks (rather than virialized objects). These shocks can have a variety of effects, including stripping ~10% of the gas from dark matter minihalos, accelerating cosmic rays, and creating a diffuse radiation background from inverse Compton and cooling radiation. This radiation background develops before the first stars form and could have measurable effects on molecular hydrogen formation and the spin temperature of the 21 cm transition of neutral hydrogen. Finally, we show that shock-heating will also be directly detectable by redshifted 21 cm measurements of the neutral IGM in the young universe.Comment: 12 pages, 8 figures, submitted to Ap
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