3,677 research outputs found

    Unconventional quantum Hall effect and Berry’s phase 2pi in bilayer graphene.

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    There are known two distinct types of the integer quantum Hall effect. One is the conventional quantum Hall effect, characteristic of two-dimensional semiconductor systems, and the other is its relativistic counterpart recently observed in graphene, where charge carriers mimic Dirac fermions characterized by Berry’s phase pi, which results in a shifted positions of Hall plateaus. Here we report a third type of the integer quantum Hall effect. Charge carriers in bilayer graphene have a parabolic energy spectrum but are chiral and exhibit Berry’s phase 2pi affecting their quantum dynamics. The Landau quantization of these fermions results in plateaus in Hall conductivity at standard integer positions but the last (zero-level) plateau is missing. The zero-level anomaly is accompanied by metallic conductivity in the limit of low concentrations and high magnetic fields, in stark contrast to the conventional, insulating behavior in this regime. The revealed chiral fermions have no known analogues and present an intriguing case for quantum-mechanical studies

    Conditionally-live attenuated SIV upregulates global T effector memory cell frequency under replication permissive conditions.

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    Background: Live attenuated SIV induces potent protection against superinfection with virulent virus; however the mechanism of this vaccine effect is poorly understood. Such knowledge is important for the development of clinically acceptable vaccine modalities against HIV. Results: Using a novel, doxycycline dependent, replication-competent live-attenuated SIVmac239Δnef (SIVrtTAΔnef), we show that under replication-permissive conditions SIV-rtTAΔnef is fully viable. Twelve rhesus macaques were infected with a peak plasma vRNA on average two log10 lower than in 6 macaques infected with unconditionally replication-competent SIVΔnef. Consistent with the attenuated phenotype of the viruses the majority of animals displayed low or undetectable levels of viraemia by 42-84 days after infection. Next, comparison of circulating T cells before and after chronic infection with parental SIVΔnef revealed a profound global polarisation toward CD28-CCR7- T-effector memory 2 (TEM2) cells within CD95+CD4+ and CD95+CD8+ populations. Critically, a similar effect was seen in the CD95+ CD4+ population and to somewhat lesser extent in the CD95+ CD8+ population of SIV-rtTAΔnef chronically infected macaques that were maintained on doxycycline, but was not seen in animals from which doxycycline had been withdrawn. The proportions of gut-homing T-central memory (TCM) and TEM defined by the expression of α4β7 and CD95 and differential expression of CD28 were increased in CD4 and CD8 cells under replication competent conditions and gut-homing CD4 TCM were also significantly increased under non-permissive conditions. TEM2 polarisation was seen in the small intestines of animals under replication permissive conditions but the effect was less pronounced than in the circulation. Intracellular cytokine staining of circulating SIV-specific T cells for IL-2, IFN-γ, TNF-α and IL-17 showed that the extent of polyfunctionality in CD4 and CD8 T cells was associated with replication permissivity; however, signature patterns of cytokine combinations were not distinguishable between groups of macaques. Conclusion: Taken together our results show that the global T memory cell compartment is profoundly skewed towards a mature effector phenotype by attenuated SIV. Results with the replication-conditional mutant suggest that maintenance of this effect, that may be important in vaccine design, might require persistence of replicating virus

    Oesophageal Metastasis from Colorectal Cancer

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    Metastasis to the oesophagus is most frequently described in association with lung or breast cancer. Diagnosis is frequently complicated as often only normal tissue is present in endoscopic biopsy specimens. Although oesophagectomy for metastasis has been described, few patients are suitable for curative resection. We report the case of a 62-year-old man who developed an oesophageal metastasis from colorectal cancer and review the available literature

    Original Contributions Tobacco Industry Promotion of Cigarettes and Adolescent Smoking

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    Context.-Whether tobacco advertising and promotion increases the likelihood that youths will begin smoking has important public policy implications. Objective.-To evaluate the association between receptivity to tobacco advertising and promotional activities and progress in the smoking uptake process, defined sequentially as never smokers who would not consider experimenting with smoking, never smokers who would consider experimenting, experimenters (smoked at least once but fewer than 100 cigarettes), or established smokers (smoked at least 100 cigarettes). Design.-Prospective cohort study with a 3-year follow-up through November 1996. Setting and Participants.-A total of 1752 adolescent never smokers who were not susceptible to smoking when first interviewed in 1993 in a population-based random-digit dial telephone survey in California were reinterviewed in 1996. Main Outcome Measure.-Becoming susceptible to smoking or experimenting by 1996. Results.-More than half the sample (n=979) named a favorite cigarette advertisement in 1993 and Joe Camel advertisements were the most popular. Less than 5% (n=92) at baseline possessed a promotional item but a further 10% (n=172) were willing to use an item. While having a favorite advertisement in 1993 predicted which adolescents would progress by 1996 (odds ratio [OR] =1.82; 95% confidence interval [CI], 1.04-3.20), possession or willingness to use a promotional item was even more strongly associated with future progression (OR=2.89; 95% CI, 1. 47-5.68). From these data, we estimate that 34% of all experimentation in California between 1993 and 1996 can be attributed to tobacco promotional activities. Nationally, this would be over 700 000 adolescents each year. Conclusion.-These findings provide the first longitudinal evidence to our knowledge that tobacco promotional activities are causally related to the onset of smoking

    A systematic review of the effects of psychosocial interventions on social functioning for middle-aged and older-aged adults with severe mental illness

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    OBJECTIVES: The number of older adults with severe mental health problems such as schizophrenia is likely to double in the next 20 years. The needs of this patient group change across the life course, but difficulties with social functioning persist into older age. Poorer social functioning is associated with poorer outcomes and has been identified as a priority for intervention by patients themselves. This paper systematically reviews studies examining the effectiveness of psychosocial interventions on social functioning for people with severe mental health problems in later life. METHODS: A systematic review of peer-reviewed journal articles was conducted and databases were searched from inception to December 2017. The review was limited to psychosocial interventions, for mid to older aged adults (≥40 years of age) with severe mental illness that included a validated measure of social functioning. RESULTS: Fifteen studies (17 papers) met inclusion criteria. There was evidence to support skills training interventions that primarily focused on social skills training or integrated mental and physical health interventions. There was not sufficient evidence to recommend any other interventions. CONCLUSIONS: The results highlight the limited nature of interventions designed specifically for older people with severe mental health problems that target social functioning and the need for more robust, large-scale studies in the area. Current evidence suggests that cognitive behaviour therapy can be effective in targeting social functioning in younger age groups, but, as yet, there is insufficient evidence to recommend this intervention for an older population

    Thermal stress induces glycolytic beige fat formation via a myogenic state.

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    Environmental cues profoundly affect cellular plasticity in multicellular organisms. For instance, exercise promotes a glycolytic-to-oxidative fibre-type switch in skeletal muscle, and cold acclimation induces beige adipocyte biogenesis in adipose tissue. However, the molecular mechanisms by which physiological or pathological cues evoke developmental plasticity remain incompletely understood. Here we report a type of beige adipocyte that has a critical role in chronic cold adaptation in the absence of β-adrenergic receptor signalling. This beige fat is distinct from conventional beige fat with respect to developmental origin and regulation, and displays enhanced glucose oxidation. We therefore refer to it as glycolytic beige fat. Mechanistically, we identify GA-binding protein α as a regulator of glycolytic beige adipocyte differentiation through a myogenic intermediate. Our study reveals a non-canonical adaptive mechanism by which thermal stress induces progenitor cell plasticity and recruits a distinct form of thermogenic cell that is required for energy homeostasis and survival

    Gender-dependent differences in plasma matrix metalloproteinase-8 elevated in pulmonary tuberculosis.

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    Tuberculosis (TB) remains a global health pandemic and greater understanding of underlying pathogenesis is required to develop novel therapeutic and diagnostic approaches. Matrix metalloproteinases (MMPs) are emerging as key effectors of tissue destruction in TB but have not been comprehensively studied in plasma, nor have gender differences been investigated. We measured the plasma concentrations of MMPs in a carefully characterised, prospectively recruited clinical cohort of 380 individuals. The collagenases, MMP-1 and MMP-8, were elevated in plasma of patients with pulmonary TB relative to healthy controls, and MMP-7 (matrilysin) and MMP-9 (gelatinase B) were also increased. MMP-8 was TB-specific (p<0.001), not being elevated in symptomatic controls (symptoms suspicious of TB but active disease excluded). Plasma MMP-8 concentrations inversely correlated with body mass index. Plasma MMP-8 concentration was 1.51-fold higher in males than females with TB (p<0.05) and this difference was not due to greater disease severity in men. Gender-specific analysis of MMPs demonstrated consistent increase in MMP-1 and -8 in TB, but MMP-8 was a better discriminator for TB in men. Plasma collagenases are elevated in pulmonary TB and differ between men and women. Gender must be considered in investigation of TB immunopathology and development of novel diagnostic markers
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