Conditioned stochastic particle systems and integrable quantum spin systems

We consider from a microscopic perspective large deviation properties of several stochastic interacting particle systems, using their mapping to integrable quantum spin systems. A brief review of recent work is given and several new results are presented: (i) For the general disordered symmectric exclusion process (SEP) on some finite lattice conditioned on no jumps into some absorbing sublattice and with initial Bernoulli product measure with density $\rho$ we prove that the probability $S_\rho(t)$ of no absorption event up to microscopic time $t$ can be expressed in terms of the generating function for the particle number of a SEP with particle injection and empty initial lattice. Specifically, for the symmetric simple exclusion process on $\mathbb Z$ conditioned on no jumps into the origin we obtain the explicit first and second order expansion in $\rho$ of $S_\rho(t)$ and also to first order in $\rho$ the optimal microscopic density profile under this conditioning. For the disordered ASEP on the finite torus conditioned on a very large current we show that the effective dynamics that optimally realizes this rare event does not depend on the disorder, except for the time scale. For annihilating and coalescing random walkers we obtain the generating function of the number of annihilated particles up to time $t$, which turns out to exhibit some universal features.Comment: 25 page

HPV infection and immunochemical detection of cell-cycle markers in verrucous carcinoma of the penis

Penile verrucous carcinoma is a rare disease and little is known of its aetiology or pathogenesis. In this study we examined cell-cycle proteins expression and correlation with human papillomavirus infection in a series of 15 pure penile verrucous carcinomas from a single centre. Of 148 penile tumours, 15 (10%) were diagnosed as pure verrucous carcinomas. The expression of the cell-cycle-associated proteins p53, p21, RB, p16INK4A and Ki67 were examined by immunohistochemistry. Human papillomavirus infection was determined by polymerase chain reaction to identify a wide range of virus types. The expression of p16INK4A and Ki67 was significantly lower in verrucous carcinoma than in usual type squamous cell carcinoma, whereas the expression of p53, p21 and RB was not significantly different. p53 showed basal expression in contrast to usual type squamous cell carcinoma. Human papillomavirus infection was present in only 3 out of 13 verrucous carcinomas. Unique low-risk, high-risk and mixed viral infections were observed in each of the three cases. In conclusion, lower levels of p16INK4A and Ki67 expressions differentiate penile verrucous carcinoma from usual type squamous cell carcinoma. The low Ki67 index reflects the slow-growing nature of verrucous tumours. The low level of p16INK4A expression and human papillomavirus detection suggests that penile verrucous carcinoma pathogenesis is unrelated to human papillomavirus infection and the oncogenes and tumour suppressor genes classically altered by virus infection.Peer reviewedFinal Accepted Versio

Investigating hyper-vigilance for social threat of lonely children

The hypothesis that lonely children show hypervigilance for social threat was examined in a series of three studies that employed different methods including advanced eye-tracking technology. Hypervigilance for social threat was operationalized as hostility to ambiguously motivated social exclusion in a variation of the hostile attribution paradigm (Study 1), scores on the Children’s Rejection-Sensitivity Questionnaire (Study 2), and visual attention to socially rejecting stimuli (Study 3). The participants were 185 children (11 years-7 months to 12 years-6 months), 248 children (9 years-4 months to 11 years-8 months) and 140 children (8 years-10 months to 12 years-10 months) in the three studies, respectively. Regression analyses showed that, with depressive symptoms covaried, there were quadratic relations between loneliness and these different measures of hypervigilance to social threat. As hypothesized, only children in the upper range of loneliness demonstrated elevated hostility to ambiguously motivated social exclusion, higher scores on the rejection sensitivity questionnaire, and disengagement difficulties when viewing socially rejecting stimuli. We found that very lonely children are hypersensitive to social threat

Potential climatic transitions with profound impact on Europe

We discuss potential transitions of six climatic subsystems with large-scale impact on Europe, sometimes denoted as tipping elements. These are the ice sheets on Greenland and West Antarctica, the Atlantic thermohaline circulation, Arctic sea ice, Alpine glaciers and northern hemisphere stratospheric ozone. Each system is represented by co-authors actively publishing in the corresponding field. For each subsystem we summarize the mechanism of a potential transition in a warmer climate along with its impact on Europe and assess the likelihood for such a transition based on published scientific literature. As a summary, the ‘tipping’ potential for each system is provided as a function of global mean temperature increase which required some subjective interpretation of scientific facts by the authors and should be considered as a snapshot of our current understanding. <br/

A primary care, multi-disciplinary disease management program for opioid-treated patients with chronic non-cancer pain and a high burden of psychiatric comorbidity

BACKGROUND: Chronic non-cancer pain is a common problem that is often accompanied by psychiatric comorbidity and disability. The effectiveness of a multi-disciplinary pain management program was tested in a 3 month before and after trial. METHODS: Providers in an academic general medicine clinic referred patients with chronic non-cancer pain for participation in a program that combined the skills of internists, clinical pharmacists, and a psychiatrist. Patients were either receiving opioids or being considered for opioid therapy. The intervention consisted of structured clinical assessments, monthly follow-up, pain contracts, medication titration, and psychiatric consultation. Pain, mood, and function were assessed at baseline and 3 months using the Brief Pain Inventory (BPI), the Center for Epidemiological Studies-Depression Scale scale (CESD) and the Pain Disability Index (PDI). Patients were monitored for substance misuse. RESULTS: Eighty-five patients were enrolled. Mean age was 51 years, 60% were male, 78% were Caucasian, and 93% were receiving opioids. Baseline average pain was 6.5 on an 11 point scale. The average CESD score was 24.0, and the mean PDI score was 47.0. Sixty-three patients (73%) completed 3 month follow-up. Fifteen withdrew from the program after identification of substance misuse. Among those completing 3 month follow-up, the average pain score improved to 5.5 (p = 0.003). The mean PDI score improved to 39.3 (p < 0.001). Mean CESD score was reduced to 18.0 (p < 0.001), and the proportion of depressed patients fell from 79% to 54% (p = 0.003). Substance misuse was identified in 27 patients (32%). CONCLUSIONS: A primary care disease management program improved pain, depression, and disability scores over three months in a cohort of opioid-treated patients with chronic non-cancer pain. Substance misuse and depression were common, and many patients who had substance misuse identified left the program when they were no longer prescribed opioids. Effective care of patients with chronic pain should include rigorous assessment and treatment of these comorbid disorders and intensive efforts to insure follow up

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

Lung adenocarcinoma originates from retrovirus infection of proliferating type 2 pneumocytes during pulmonary post-natal development or tissue repair

Jaagsiekte sheep retrovirus (JSRV) is a unique oncogenic virus with distinctive biological properties. JSRV is the only virus causing a naturally occurring lung cancer (ovine pulmonary adenocarcinoma, OPA) and possessing a major structural protein that functions as a dominant oncoprotein. Lung cancer is the major cause of death among cancer patients. OPA can be an extremely useful animal model in order to identify the cells originating lung adenocarcinoma and to study the early events of pulmonary carcinogenesis. In this study, we demonstrated that lung adenocarcinoma in sheep originates from infection and transformation of proliferating type 2 pneumocytes (termed here lung alveolar proliferating cells, LAPCs). We excluded that OPA originates from a bronchioalveolar stem cell, or from mature post-mitotic type 2 pneumocytes or from either proliferating or non-proliferating Clara cells. We show that young animals possess abundant LAPCs and are highly susceptible to JSRV infection and transformation. On the contrary, healthy adult sheep, which are normally resistant to experimental OPA induction, exhibit a relatively low number of LAPCs and are resistant to JSRV infection of the respiratory epithelium. Importantly, induction of lung injury increased dramatically the number of LAPCs in adult sheep and rendered these animals fully susceptible to JSRV infection and transformation. Furthermore, we show that JSRV preferentially infects actively dividing cell in vitro. Overall, our study provides unique insights into pulmonary biology and carcinogenesis and suggests that JSRV and its host have reached an evolutionary equilibrium in which productive infection (and transformation) can occur only in cells that are scarce for most of the lifespan of the sheep. Our data also indicate that, at least in this model, inflammation can predispose to retroviral infection and cancer

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

Modular reorganization of the global network of gene regulatory interactions during perinatal human brain development.

BACKGROUND During early development of the nervous system, gene expression patterns are known to vary widely depending on the specific developmental trajectories of different structures. Observable changes in gene expression profiles throughout development are determined by an underlying network of precise regulatory interactions between individual genes. Elucidating the organizing principles that shape this gene regulatory network is one of the central goals of developmental biology. Whether the developmental programme is the result of a dynamic driven by a fixed architecture of regulatory interactions, or alternatively, the result of waves of regulatory reorganization is not known. RESULTS Here we contrast these two alternative models by examining existing expression data derived from the developing human brain in prenatal and postnatal stages. We reveal a sharp change in gene expression profiles at birth across brain areas. This sharp division between foetal and postnatal profiles is not the result of pronounced changes in level of expression of existing gene networks. Instead we demonstrate that the perinatal transition is marked by the widespread regulatory rearrangement within and across existing gene clusters, leading to the emergence of new functional groups. This rearrangement is itself organized into discrete blocks of genes, each targeted by a distinct set of transcriptional regulators and associated to specific biological functions. CONCLUSIONS Our results provide evidence of an acute modular reorganization of the regulatory architecture of the brain transcriptome occurring at birth, reflecting the reassembly of new functional associations required for the normal transition from prenatal to postnatal brain development