Ballistic Josephson junctions in edge-contacted graphene

Hybrid graphene-superconductor devices have attracted much attention since the early days of graphene research. So far, these studies have been limited to the case of diffusive transport through graphene with poorly defined and modest quality graphene-superconductor interfaces, usually combined with small critical magnetic fields of the superconducting electrodes. Here we report graphene based Josephson junctions with one-dimensional edge contacts of Molybdenum Rhenium. The contacts exhibit a well defined, transparent interface to the graphene, have a critical magnetic field of 8 Tesla at 4 Kelvin and the graphene has a high quality due to its encapsulation in hexagonal boron nitride. This allows us to study and exploit graphene Josephson junctions in a new regime, characterized by ballistic transport. We find that the critical current oscillates with the carrier density due to phase coherent interference of the electrons and holes that carry the supercurrent caused by the formation of a Fabry-P\'{e}rot cavity. Furthermore, relatively large supercurrents are observed over unprecedented long distances of up to 1.5 $\mu$m. Finally, in the quantum Hall regime we observe broken symmetry states while the contacts remain superconducting. These achievements open up new avenues to exploit the Dirac nature of graphene in interaction with the superconducting state.Comment: Updated version after peer review. Includes supplementary material and ancillary file with source code for tight binding simulation

ACE inhibition attenuates uremia-induced aortic valve thickening in a novel mouse model

<p>Abstract</p> <p>Background</p> <p>We examined whether impaired renal function causes thickening of the aortic valve leaflets in hyperlipidemic apoE-knockout (apoE^-/-) mice, and whether the putative effect on the aortic valves could be prevented by inhibiting the angiotensin-converting enzyme (ACE) with enalapril.</p> <p>Methods</p> <p>Thickening of the aortic valve leaflets in apoE^-/-mice was induced by producing mild or moderate chronic renal failure resulting from unilateral nephrectomy (1/2 NX, n = 18) or subtotal nephrectomy (5/6 NX, n = 22), respectively. Additionally, the 5/6 NX mice were randomized to no treatment (n = 8) or enalapril treatment (n = 13). The maximal thickness of each leaflet was measured from histological sections of the aortic roots.</p> <p>Results</p> <p>Leaflet thickness was significantly greater in the 5/6 NX mice than in the 1/2 NX mice (P = 0.030) or the unoperated mice (P = 0.003). The 5/6 NX mice treated with enalapril had significantly thinner leaflets than did the untreated 5/6 NX mice (P = 0.014).</p> <p>Conclusion</p> <p>Moderate uremia causes thickening of the aortic valves in apoE^-/-mice, which can be attenuated by ACE inhibition. The nephrectomized apoE^-/-mouse constitutes a new model for investigating the mechanisms of uremia-induced aortic valve disease, and also provides an opportunity to study its pharmacologic prevention.</p

Risk factor studies of age-at-onset in a sample ascertained for Parkinson disease affected sibling pairs: a cautionary tale

An association between exposure to a risk factor and age-at-onset of disease may reflect an effect on the rate of disease occurrence or an acceleration of the disease process. The difference in age-at-onset arising from case-only studies, however, may also reflect secular trends in the prevalence of exposure to the risk factor. Comparisons of age-at-onset associated with risk factors are commonly performed in case series enrolled for genetic linkage analysis of late onset diseases. We describe how the results of age-at-onset studies of environmental risk factors reflect the underlying structure of the source population, rather than an association with age-at-onset, by contrasting the effects of coffee drinking and cigarette smoking on Parkinson disease age-at-onset with the effects on age-at-enrollment in a population based study sample. Despite earlier evidence to suggest a protective association of coffee drinking and cigarette smoking with Parkinson disease risk, the age-at-onset results are comparable to the patterns observed in the population sample, and thus a causal inference from the age-at-onset effect may not be justified. Protective effects of multivitamin use on PD age-at-onset are also shown to be subject to a bias from the relationship between age and multivitamin initiation. Case-only studies of age-at-onset must be performed with an appreciation for the association between risk factors and age and ageing in the source population

Multi-agent modeling of the South Korean avian influenza epidemic

<p>Abstract</p> <p>Background</p> <p>Several highly pathogenic avian influenza (AI) outbreaks have been reported over the past decade. South Korea recently faced AI outbreaks whose economic impact was estimated to be 6.3 billion dollars, equivalent to nearly 50% of the profit generated by the poultry-related industries in 2008. In addition, AI is threatening to cause a human pandemic of potentially devastating proportions. Several studies show that a stochastic simulation model can be used to plan an efficient containment strategy on an emerging influenza. Efficient control of AI outbreaks based on such simulation studies could be an important strategy in minimizing its adverse economic and public health impacts.</p> <p>Methods</p> <p>We constructed a spatio-temporal multi-agent model of chickens and ducks in poultry farms in South Korea. The spatial domain, comprised of 76 (37.5 km × 37.5 km) unit squares, approximated the size and scale of South Korea. In this spatial domain, we introduced 3,039 poultry flocks (corresponding to 2,231 flocks of chickens and 808 flocks of ducks) whose spatial distribution was proportional to the number of birds in each province. The model parameterizes the properties and dynamic behaviors of birds in poultry farms and quarantine plans and included infection probability, incubation period, interactions among birds, and quarantine region.</p> <p>Results</p> <p>We conducted sensitivity analysis for the different parameters in the model. Our study shows that the quarantine plan with well-chosen values of parameters is critical for minimize loss of poultry flocks in an AI outbreak. Specifically, the aggressive culling plan of infected poultry farms over 18.75 km radius range is unlikely to be effective, resulting in higher fractions of unnecessarily culled poultry flocks and the weak culling plan is also unlikely to be effective, resulting in higher fractions of infected poultry flocks.</p> <p>Conclusions</p> <p>Our results show that a prepared response with targeted quarantine protocols would have a high probability of containing the disease. The containment plan with an aggressive culling plan is not necessarily efficient, causing a higher fraction of unnecessarily culled poultry farms. Instead, it is necessary to balance culling with other important factors involved in AI spreading. Better estimations for the containment of AI spreading with this model offer the potential to reduce the loss of poultry and minimize economic impact on the poultry industry.</p

Variability in school closure decisions in response to 2009 H1N1: a qualitative systems improvement analysis

<p>Abstract</p> <p>Background</p> <p>School closure was employed as a non-pharmaceutical intervention against pandemic 2009 H1N1, particularly during the first wave. More than 700 schools in the United States were closed. However, closure decisions reflected significant variation in rationales, decision triggers, and authority for closure. This variability presents the opportunity for improved efficiency and decision-making.</p> <p>Methods</p> <p>We identified media reports relating to school closure as a response to 2009 H1N1 by monitoring high-profile sources and searching Lexis-Nexis and Google news alerts, and reviewed reports for key themes. News stories were supplemented by observing conference calls and meetings with health department and school officials, and by discussions with decision-makers and community members.</p> <p>Results</p> <p>There was significant variation in the stated goal of closure decision, including limiting community spread of the virus, protecting particularly vulnerable students, and responding to staff shortages or student absenteeism. Because the goal of closure is relevant to its timing, nature, and duration, unclear rationales for closure can challenge its effectiveness. There was also significant variation in the decision-making authority to close schools in different jurisdictions, which, in some instances, was reflected in open disagreement between school and public health officials. Finally, decision-makers did not appear to expect the level of scientific uncertainty encountered early in the pandemic, and they often expressed significant frustration over changing CDC guidance.</p> <p>Conclusions</p> <p>The use of school closure as a public health response to epidemic disease can be improved by ensuring that officials clarify the goals of closure and tailor closure decisions to those goals. Additionally, authority to close schools should be clarified in advance, and decision-makers should expect to encounter uncertainty disease emergencies unfold and plan accordingly.</p

Guinea Pig Model for Evaluating the Potential Public Health Risk of Swine and Avian Influenza Viruses

BACKGROUND: The influenza viruses circulating in animals sporadically transmit to humans and pose pandemic threats. Animal models to evaluate the potential public health risk potential of these viruses are needed. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the guinea pig as a mammalian model for the study of the replication and transmission characteristics of selected swine H1N1, H1N2, H3N2 and avian H9N2 influenza viruses, compared to those of pandemic (H1N1) 2009 and seasonal human H1N1, H3N2 influenza viruses. The swine and avian influenza viruses investigated were restricted to the respiratory system of guinea pigs and shed at high titers in nasal tracts without prior adaptation, similar to human strains. None of the swine and avian influenza viruses showed transmissibility among guinea pigs; in contrast, pandemic (H1N1) 2009 virus transmitted from infected guinea pigs to all animals and seasonal human influenza viruses could also horizontally transmit in guinea pigs. The analysis of the receptor distribution in the guinea pig respiratory tissues by lectin histochemistry indicated that both SAα2,3-Gal and SAα2,6-Gal receptors widely presented in the nasal tract and the trachea, while SAα2,3-Gal receptor was the main receptor in the lung. CONCLUSIONS/SIGNIFICANCE: We propose that the guinea pig could serve as a useful mammalian model to evaluate the potential public health threat of swine and avian influenza viruses

Engineering T cells for cancer therapy

It is generally accepted that the immune system plays an important role in controlling tumour development. However, the interplay between tumour and immune system is complex, as demonstrated by the fact that tumours can successfully establish and develop despite the presence of T cells in tumour. An improved understanding of how tumours evade T-cell surveillance, coupled with technical developments allowing the culture and manipulation of T cells, has driven the exploration of therapeutic strategies based on the adoptive transfer of tumour-specific T cells. The isolation, expansion and re-infusion of large numbers of tumour-specific T cells generated from tumour biopsies has been shown to be feasible. Indeed, impressive clinical responses have been documented in melanoma patients treated with these T cells. These studies and others demonstrate the potential of T cells for the adoptive therapy of cancer. However, the significant technical issues relating to the production of natural tumour-specific T cells suggest that the application of this approach is likely to be limited at the moment. With the advent of retroviral gene transfer technology, it has become possible to efficiently endow T cells with antigen-specific receptors. Using this strategy, it is potentially possible to generate large numbers of tumour reactive T cells rapidly. This review summarises the current gene therapy approaches in relation to the development of adoptive T-cell-based cancer treatments, as these methods now head towards testing in the clinical trial setting

De-Novo Transcriptome Sequencing of a Normalized cDNA Pool from Influenza Infected Ferrets

The ferret is commonly used as a model for studies of infectious diseases. The genomic sequence of this animal model is not yet characterized, and only a limited number of fully annotated cDNAs are currently available in GenBank. The majority of genes involved in innate or adaptive immune response are still lacking, restricting molecular genetic analysis of host response in the ferret model. To enable de novo identification of transcriptionally active ferret genes in response to infection, we performed de-novo transcriptome sequencing of animals infected with H1N1 A/California/07/2009. We also included splenocytes induced with bacterial lipopolysaccharide to allow for identification of transcripts specifically induced by Gram-negative bacteria. We pooled and normalized the cDNA library in order to delimit the risk of sequencing only highly expressed genes. While normalization of the cDNA library removes the possibility of assessing expression changes between individual animals, it has been shown to increase identification of low abundant transcripts. In this study, we identified more than 19000 partial ferret transcripts, including more than 1000 gene orthologs known to be involved in the innate and the adaptive immune response