Complete gate control of supercurrent in graphene p-n junctions

In a conventional Josephson junction of graphene, the supercurrent is not turned off even at the charge neutrality point, impeding further development of superconducting quantum information devices based on graphene. Here we fabricate bipolar Josephson junctions of graphene, in which a p-n potential barrier is formed in graphene with two closely spaced superconducting contacts, and realize supercurrent ON/OFF states using electrostatic gating only. The bipolar Josephson junctions of graphene also show fully gate-driven macroscopic quantum tunnelling behaviour of Josephson phase particles in a potential well, where the confinement energy is gate tuneable. We suggest that the supercurrent OFF state is mainly caused by a supercurrent dephasing mechanism due to a random pseudomagnetic field generated by ripples in graphene, in sharp contrast to other nanohybrid Josephson junctions. Our study may pave the way for the development of new gate-tuneable superconducting quantum information devices.open114344sciescopu

T145 Comprehensive flow cytometry tracking of regulatory T cells and other lymphocyte subsets during HD IL-2 therapy for melanoma

High dose IL-2 (HD IL-2) has been extensively used as an immunotherapy against metastatic melanoma However, why HD IL-2 is effective only in a subset of patients and whether predictive biomarkers, before or early during the course of therapy, can be used to improve response rates remain unresolved. In addition, it has been found that IL-2 therapy potently expands CD4+CD25+Foxp3+ T-regulatory cells (Tregs) but how Treg cell levels, phenotype, and function change and whether specific subsets of Tregs are activated and expanded during HD IL-2 therapy is remain unclear. In this study, we performed comprehensive multi-parameter FACS analysis of patient blood before and two days after the last bolus of IL-2 infusion during cycle 1 of HD IL-2 therapy. Two lymphocyte subsets were found to expand the most during the first cycle of IL-2 therapy: CD4+CD25+Foxp3+ Tregs expressing an activation marker, inducible costimulator (ICOS), and CD3-CD56hiCD16loPerforin+ NK cells. ICOS+ Tregs expressed significantly higher levels of CD25, Foxp3 and had a more activated phenotype than ICOS− Tregs as indicated by lower levels of CD45RA and CD127 expression. Further phenotypic characterization revealed a more suppressive phenotype on ICOS+ Treg with higher expression levels of CD39, CD73, and TGF-β/LAP than ICOS− Treg. ICOS+ Tregs were also the predominant Treg cells that secreted IL-10 and have potent T-cell suppressor function. Majority of ICOS+ Tregs from HD IL-2-treated patients were Ki67+ and exhibited an enhanced proliferative response to IL-2 ex vivo relative to ICOS− Tregs. Functional analysis revealed that ICOS+ Tregs secreted little IFN- and IL-2 in comparison to CD4+Foxp3 – cells. Furthermore, analysis on 38 IL-2-treated patients at MD Anderson, we found that non-responders had a significantly higher degree of ICOS+ Treg expansion than responders during the first cycle of IL-2 therapy, while no significant changes in the ICOS− or bulk Treg population. In conclusion, our data suggests that tracking changes in ICOS+ Tregs early during the course of HD IL-2 therapy may be a new predictive biomarker of clinical outcome

A New Remote Guided Method for Supervised Web-Based Cognitive Testing to Ensure High Quality Data

Background. The global COVID-19 pandemic has triggered a fundamental reexamination of how human psychological research can be conducted both safely and robustly in a new era of digital working and physical distancing. Online web-based testing has risen to the fore as a promising solution for rapid mass collection of cognitive data without requiring human contact. However, a long-standing debate exists over the data quality and validity of web-based studies. Here, we examine the opportunities and challenges afforded by the societal shift toward web-based testing, highlight an urgent need to establish a standard data quality assurance framework for online studies, and develop and validate a new supervised online testing methodology, remote guided testing (RGT). Methods. A total of 85 healthy young adults were tested on 10 cognitive tasks assessing executive functioning (flexibility, memory and inhibition) and learning. Tasks were administered either face-to-face in the laboratory (N=41) or online using remote guided testing (N=44), delivered using identical web-based platforms (CANTAB, Inquisit and i-ABC). Data quality was assessed using detailed trial-level measures (missed trials, outlying and excluded responses, response times), as well as overall task performance measures. Results. The results indicated that, across all measures of data quality and performance, RGT data was statistically-equivalent to data collected in person in the lab. Moreover, RGT participants out-performed the lab group on measured verbal intelligence, which could reflect test environment differences, including possible effects of mask-wearing on communication. Conclusions. These data suggest that the RGT methodology could help to ameliorate concerns regarding online data quality and - particularly for studies involving high-risk or rare cohorts - offer an alternative for collecting high-quality human cognitive data without requiring in-person physical attendance.Biotechnology and Biological Sciences Research Council (H012508 and BB/P021255/1). Wellcome Trust (205067/Z/16/Z)

Wind from the black-hole accretion disk driving a molecular outflow in an active galaxy

Powerful winds driven by active galactic nuclei (AGN) are often invoked to play a fundamental role in the evolution of both supermassive black holes (SMBHs) and their host galaxies, quenching star formation and explaining the tight SMBH-galaxy relations. Recent observations of large-scale molecular outflows in ultra-luminous infrared galaxies (ULIRGs) have provided the evidence to support these studies, as they directly trace the gas out of which stars form. Theoretical models suggest an origin of these outflows as energy-conserving flows driven by fast AGN accretion disk winds. Previous claims of a connection between large-scale molecular outflows and AGN activity in ULIRGs were incomplete because they were lacking the detection of the putative inner wind. Conversely, studies of powerful AGN accretion disk winds to date have focused only on X-ray observations of local Seyferts and a few higher redshift quasars. Here we show the clear detection of a powerful AGN accretion disk wind with a mildly relativistic velocity of 0.25c in the X-ray spectrum of IRAS F11119+3257, a nearby (z = 0.189) optically classified type 1 ULIRG hosting a powerful molecular outflow. The AGN is responsible for ~80% of the emission, with a quasar-like luminosity of L_AGN = 1.5x10^46 erg/s. The energetics of these winds are consistent with the energy-conserving mechanism, which is the basis of the quasar mode feedback in AGN lacking powerful radio jets.Comment: Revised file including the letter, methods and supplementary information. Published in the March 26th 2015 issue of Natur

Spatial heterogeneity and peptide availability determine CTL killing efficiency in vivo

The rate at which a cytotoxic T lymphocyte (CTL) can survey for infected cells is a key ingredient of models of vertebrate immune responses to intracellular pathogens. Estimates have been obtained using in vivo cytotoxicity assays in which peptide-pulsed splenocytes are killed by CTL in the spleens of immunised mice. However the spleen is a heterogeneous environment and splenocytes comprise multiple cell types. Are some cell types intrinsically more susceptible to lysis than others? Quantitatively, what impacts are made by the spatial distribution of targets and effectors, and the level of peptide-MHC on the target cell surface? To address these questions we revisited the splenocyte killing assay, using CTL specific for an epitope of influenza virus. We found that at the cell population level T cell targets were killed more rapidly than B cells. Using modeling, quantitative imaging and in vitro killing assays we conclude that this difference in vivo likely reflects different migratory patterns of targets within the spleen and a heterogeneous distribution of CTL, with no detectable difference in the intrinsic susceptibilities of the two populations to lysis. Modeling of the stages involved in the detection and killing of peptide-pulsed targets in vitro revealed that peptide dose influenced the ability of CTL to form conjugates with targets but had no detectable effect on the probability that conjugation resulted in lysis, and that T cell targets took longer to lyse than B cells. We also infer that incomplete killing in vivo of cells pulsed with low doses of peptide may be due to a combination of heterogeneity in peptide uptake and the dissociation, but not internalisation, of peptide-MHC complexes. Our analyses demonstrate how population-averaged parameters in models of immune responses can be dissected to account for both spatial and cellular heterogeneity

The representation of voluntourism in search engines: The case of South Africa

© 2015, © 2015 Government Technical Advisory Centre (GTAC). This paper responds to the paucity of research on the linkages between voluntourism and digital technology and seeks to understand the online representation of the phenomenon in a developing context. In particular, the researchers investigate the so-called ‘online domain’ of voluntourism in South Africa. The researchers collected a series of web results from search engines and analysed the presence of traditional and social media websites, the most relevant presented topics, and the type of argumentation found. Results identify the context and representation of voluntourism as it transpires virtually. This will contribute to the understanding of the interplay between voluntourism and digital technology, with specific emphasis on web presence. Ultimately, results will shed light on how digitally accessible voluntourism is in South Africa and will set the basis for future investigations

Incidence, mortality and survival patterns of prostate cancer among residents in Singapore from 1968 to 2002

<p>Abstract</p> <p>Background</p> <p>From 1968 to 2002, Singapore experienced an almost four-fold increase in prostate cancer incidence. This paper examines the incidence, mortality and survival patterns for prostate cancer among all residents in Singapore from 1968 to 2002.</p> <p>Methods</p> <p>This is a retrospective population-based cohort study including all prostate cancer cases aged over 20 (n = 3613) reported to the Singapore Cancer Registry from 1968 to 2002. Age-standardized incidence, mortality rates and 5-year Relative Survival Ratios (RSRs) were obtained for each 5-year period. Follow-up was ascertained by matching with the National Death Register until 2002. A weighted linear regression was performed on the log-transformed age-standardized incidence and mortality rates over period.</p> <p>Results</p> <p>The percentage increase in the age-standardized incidence rate per year was 5.0%, 5.6%, 4.0% and 1.9% for all residents, Chinese, Malays and Indians respectively. The percentage increase in age-standardized mortality rate per year was 5.7%, 6.0%, 6.6% and 2.5% for all residents, Chinese, Malays and Indians respectively. When all Singapore residents were considered, the RSRs for prostate cancer were fairly constant across the study period with slight improvement from 1995 onwards among the Chinese.</p> <p>Conclusion</p> <p>Ethnic differences in prostate cancer incidence, mortality and survival patterns were observed. There has been a substantial improvement in RSRs since the 1990s for the Chinese.</p

Complete Killing of Caenorhabditis elegans by Burkholderia pseudomallei Is Dependent on Prolonged Direct Association with the Viable Pathogen

Background: Burkholderia pseudomallei is the causative agent of melioidosis, a disease of significant morbidity and mortality in both human and animals in endemic areas. Much remains to be known about the contributions of genotypic variations within the bacteria and the host, and environmental factors that lead to the manifestation of the clinical symptoms of melioidosis. Methodology/Principal Findings: In this study, we showed that different isolates of B. pseudomallei have divergent ability to kill the soil nematode Caenorhabditis elegans. The rate of nematode killing was also dependent on growth media: B. pseudomallei grown on peptone-glucose media killed C. elegans more rapidly than bacteria grown on the nematode growth media. Filter and bacteria cell-free culture filtrate assays demonstrated that the extent of killing observed is significantly less than that observed in the direct killing assay. Additionally, we showed that B. pseudomallei does not persistently accumulate within the C. elegans gut as brief exposure to B. pseudomallei is not sufficient for C. elegans infection. Conclusions/Significance: A combination of genetic and environmental factors affects virulence. In addition, we have also demonstrated that a Burkholderia-specific mechanism mediating the pathogenic effect in C. elegans requires proliferating B

Burkholderia pseudomallei Is Genetically Diverse in Agricultural Land in Northeast Thailand

Burkholderia pseudomallei is the cause of melioidosis, a serious human infection most commonly diagnosed in southeast Asia and northern Australia. The organism lives in the soil in a specific geographical distribution and infection results from bacterial inoculation, inhalation or ingestion. The purpose of this study was to define the distribution and genetic diversity of B. pseudomallei in agricultural land where most human infections probably occur. We performed soil sampling and culture for the presence of B. pseudomallei in 100 equally spaced points within a rice paddy in northeast Thailand, and undertook genotyping of primary culture plate colonies from 11 sampling points. We identified 7 different genotypes, with relatively limited overlap between different sampling points. Two samples contained more than one B. pseudomallei genotype, in which a numerically dominant genotype coexisted with one or more additional genotypes present as a minority population. We conclude that genetic diversity and structuring of B. pseudomallei exists despite the effects of flooding and the physical and chemical processes associated with farming. These findings inform future efforts to define B. pseudomallei in the environment, and should be considered during the design stage of studies comparing B. pseudomallei isolated from the environment and from patients with invasive disease

Cumulative survival in early-onset unilateral and bilateral breast cancer: an analysis of 1907 Taiwanese women

As the epidemiological pattern of breast cancer in modernising Asian countries differs greatly from that in Western countries, it is worthwhile to investigate the long-term prognoses of unilateral and bilateral breast cancer in these nations. A retrospective cohort study composed of 1907 Taiwanese women was conducted to follow 1863 unilateral and 44 bilateral cases of breast cancer. Time-dependent Cox regression was used to assess the risk of breast cancer death by considering the time course of unilateral and bilateral tumour development. The 15-year survival rates were 68.37, 62.63, and 26.42% for unilateral, synchronous bilateral, and metachronous bilateral breast cancer, respectively. Differences among types were most apparent after 5 years of follow-up. After adjusting for significant prognostic factors, the risk of death for overall bilateral breast cancer was 2.50-fold greater (95% CI, 1.43–4.37) compared to unilateral breast cancer. The corresponding figures were 1.12-fold (95% CI, 0.42–3.02) and 6.11-fold (95% CI, 3.14–11.89) for synchronous and metachronous bilateral breast cancer, respectively. Taiwanese women, who are frequently diagnosed with breast cancer before 50 years of age, showed poorer survival for metachronous bilateral than for synchronous bilateral or unilateral breast cancer. Survival was markedly poorer compared to recent data from Sweden