Shot noise in mesoscopic systems

This is a review of shot noise, the time-dependent fluctuations in the electrical current due to the discreteness of the electron charge, in small conductors. The shot-noise power can be smaller than that of a Poisson process as a result of correlations in the electron transmission imposed by the Pauli principle. This suppression takes on simple universal values in a symmetric double-barrier junction (suppression factor 1/2), a disordered metal (factor 1/3), and a chaotic cavity (factor 1/4). Loss of phase coherence has no effect on this shot-noise suppression, while thermalization of the electrons due to electron-electron scattering increases the shot noise slightly. Sub-Poissonian shot noise has been observed experimentally. So far unobserved phenomena involve the interplay of shot noise with the Aharonov-Bohm effect, Andreev reflection, and the fractional quantum Hall effect.Comment: 37 pages, Latex, 10 figures (eps). To be published in "Mesoscopic Electron Transport," edited by L. P. Kouwenhoven, G. Schoen, and L. L. Sohn, NATO ASI Series E (Kluwer Academic Publishing, Dordrecht

Challenges and recent progress in drug discovery for tropical diseases

Infectious tropical diseases have a huge effect in terms of mortality and morbidity, and impose a heavy economic burden on affected countries. These diseases predominantly affect the world’s poorest people. Currently available drugs are inadequate for the majority of these diseases, and there is an urgent need for new treatments. This Review discusses some of the challenges involved in developing new drugs to treat these diseases and highlights recent progress. While there have been notable successes, there is still a long way to go.</p

Combined Tevatron upper limit on gg->H->W+W- and constraints on the Higgs boson mass in fourth-generation fermion models

Report number: FERMILAB-PUB-10-125-EWe combine results from searches by the CDF and D0 collaborations for a standard model Higgs boson (H) in the process gg->H->W+W- in p=pbar collisions at the Fermilab Tevatron Collider at sqrt{s}=1.96 TeV. With 4.8 fb-1 of integrated luminosity analyzed at CDF and 5.4 fb-1 at D0, the 95% Confidence Level upper limit on \sigma(gg->H) x B(H->W+W-) is 1.75 pb at m_H=120 GeV, 0.38 pb at m_H=165 GeV, and 0.83 pb at m_H=200 GeV. Assuming the presence of a fourth sequential generation of fermions with large masses, we exclude at the 95% Confidence Level a standard-model-like Higgs boson with a mass between 131 and 204 GeV.We combine results from searches by the CDF and D0 collaborations for a standard model Higgs boson (H) in the process gg→H→W+W- in pp̅ collisions at the Fermilab Tevatron Collider at √s=1.96  TeV. With 4.8  fb-1 of integrated luminosity analyzed at CDF and 5.4  fb-1 at D0, the 95% confidence level upper limit on σ(gg→H)×B(H→W+W-) is 1.75 pb at mH=120  GeV, 0.38 pb at mH=165  GeV, and 0.83 pb at mH=200  GeV. Assuming the presence of a fourth sequential generation of fermions with large masses, we exclude at the 95% confidence level a standard-model-like Higgs boson with a mass between 131 and 204 GeV.Peer reviewe

A Universal Behavior of Half BPS Probes in the Superstar Ensemble

In this paper we probe the typical states of the superstar ensemble of (hep-th/0508023) using half-BPS states of type-IIB string theory on AdS$_5 \times$ S$^5$. We find a very simple universal result that has the structure \log\, \lag\lag \y \; \y \rag\rag_\calo \approx \a\, h \, \log N, where $h$ is the conformal weight of the probe \y and \a is a constant that depends mainly of the shape of the probe \y. A complete understanding of some properties of this leading term from the dual effective superstar geometry point of view is still lacking.Comment: 34 pages + appendice

Invasive meningococcal disease epidemiology and control measures: a framework for evaluation

<p>Abstract</p> <p>Background</p> <p>Meningococcal disease can have devastating consequences. As new vaccines emerge, it is necessary to assess their impact on public health. In the absence of long-term real world data, modeling the effects of different vaccination strategies is required. Discrete event simulation provides a flexible platform with which to conduct such evaluations.</p> <p>Methods</p> <p>A discrete event simulation of the epidemiology of invasive meningococcal disease was developed to quantify the potential impact of implementing routine vaccination of adolescents in the United States with a quadrivalent conjugate vaccine protecting against serogroups A, C, Y, and W-135. The impact of vaccination is assessed including both the direct effects on individuals vaccinated and the indirect effects resulting from herd immunity. The simulation integrates a variety of epidemiologic and demographic data, with core information on the incidence of invasive meningococcal disease and outbreak frequency derived from data available through the Centers for Disease Control and Prevention. Simulation of the potential indirect benefits of vaccination resulting from herd immunity draw on data from the United Kingdom, where routine vaccination with a conjugate vaccine has been in place for a number of years. Cases of disease are modeled along with their health consequences, as are the occurrence of disease outbreaks.</p> <p>Results</p> <p>When run without a strategy of routine immunization, the simulation accurately predicts the age-specific incidence of invasive meningococcal disease and the site-specific frequency of outbreaks in the Unite States. 2,807 cases are predicted annually, resulting in over 14,000 potential life years lost due to invasive disease. In base case analyses of routine vaccination, life years lost due to infection are reduced by over 45% (to 7,600) when routinely vaccinating adolescents 12 years of age at 70% coverage. Sensitivity analyses indicate that herd immunity plays an important role when this population is targeted for vaccination. While 1,100 cases are avoided annually when herd immunity effects are included, in the absence of any herd immunity, the number of cases avoided with routine vaccination falls to 380 annually. The duration of vaccine protection also strongly influences results.</p> <p>Conclusion</p> <p>In the absence of appropriate real world data on outcomes associated with large-scale vaccination programs, decisions on optimal immunization strategies can be aided by discrete events simulations such as the one described here. Given the importance of herd immunity on outcomes associated with routine vaccination, published estimates of the economic efficiency of routine vaccination with a quadrivalent conjugate vaccine in the United States may have considerably underestimated the benefits associated with a policy of routine immunization of adolescents.</p

DNA methylation levels in candidate genes associated with chronological age in mammals are not conserved in a long-lived seabird

© 2017 De Paoli-Iseppi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Most seabirds do not have any outward identifiers of their chronological age, so estimation of seabird population age structure generally requires expensive, long-term banding studies. We investigated the potential to use a molecular age biomarker to estimate age in short-tailed shearwaters (Ardenna tenuirostris). We quantified DNA methylation in several A. tenuirostris genes that have shown age-related methylation changes in mammals. In birds ranging from chicks to 21 years of age, bisulphite treated blood and feather DNA was sequenced and methylation levels analysed in 67 CpG sites in 13 target gene regions. From blood samples, five of the top relationships with age were identified in KCNC3 loci (CpG66: R2 = 0.325, p = 0.019). In feather samples ELOVL2 (CpG42: R2 = 0.285, p = 0.00048) and EDARADD (CpG46: R2 = 0.168, p = 0.0067) were also weakly correlated with age. However, the majority of markers had no clear association with age (of 131 comparisons only 12 had a p-value &lt; 0.05) and statistical analysis using a penalised lasso approach did not produce an accurate ageing model. Our data indicate that some age-related signatures identified in orthologous mammalian genes are not conserved in the long-lived short tailed shearwater. Alternative molecular approaches will be required to identify a reliable biomarker of chronological age in these seabirds

Oral abstracts of the 21st International AIDS Conference 18-22 July 2016, Durban, South Africa

The rate at which HIV-1 infected individuals progress to AIDS is highly variable and impacted by T cell immunity. CD8 T cell inhibitory molecules are up-regulated in HIV-1 infection and associate with immune dysfunction. We evaluated participants (n=122) recruited to the SPARTAC randomised clinical trial to determine whether CD8 T cell exhaustion markers PD-1, Lag-3 and Tim-3 were associated with immune activation and disease progression.Expression of PD-1, Tim-3, Lag-3 and CD38 on CD8 T cells from the closest pre-therapy time-point to seroconversion was measured by flow cytometry, and correlated with surrogate markers of HIV-1 disease (HIV-1 plasma viral load (pVL) and CD4 T cell count) and the trial endpoint (time to CD4 count <350 cells/μl or initiation of antiretroviral therapy). To explore the functional significance of these markers, co-expression of Eomes, T-bet and CD39 was assessed.Expression of PD-1 on CD8 and CD38 CD8 T cells correlated with pVL and CD4 count at baseline, and predicted time to the trial endpoint. Lag-3 expression was associated with pVL but not CD4 count. For all exhaustion markers, expression of CD38 on CD8 T cells increased the strength of associations. In Cox models, progression to the trial endpoint was most marked for PD-1/CD38 co-expressing cells, with evidence for a stronger effect within 12 weeks from confirmed diagnosis of PHI. The effect of PD-1 and Lag-3 expression on CD8 T cells retained statistical significance in Cox proportional hazards models including antiretroviral therapy and CD4 count, but not pVL as co-variants.Expression of ‘exhaustion’ or ‘immune checkpoint’ markers in early HIV-1 infection is associated with clinical progression and is impacted by immune activation and the duration of infection. New markers to identify exhausted T cells and novel interventions to reverse exhaustion may inform the development of novel immunotherapeutic approaches

How doctors generate diagnostic hypotheses: a study of radiological diagnosis with functional magnetic resonance imaging.

In medical practice, diagnostic hypotheses are often made by physicians in the first moments of contact with patients; sometimes even before they report their symptoms. We propose that generation of diagnostic hypotheses in this context is the result of cognitive processes subserved by brain mechanisms that are similar to those involved in naming objects or concepts in everyday life