Photo-assisted Andreev reflection as a probe of quantum noise

Andreev reflection, which corresponds to the tunneling of two electrons from a metallic lead to a superconductor lead as a Cooper pair (or vice versa), can be exploited to measure high frequency noise. A detector is proposed, which consists of a normal lead--superconductor circuit, which is capacitively coupled to a mesoscopic circuit where noise is to be measured. We discuss two detector circuits: a single normal metal -- superconductor tunnel junction and a normal metal separated from a superconductor by a quantum dot operating in the Coulomb blockade regime. A substantial DC current flows in the detector circuit when an appropriate photon is provided or absorbed by the mesoscopic circuit, which plays the role of an environment for the junction to which it couples. Results for the current can be cast in all cases in the form of a frequency integral of the excess noise of the environment weighted by a kernel which is specific to the transport process (quasiparticle tunneling, Andreev reflection,...) which is considered. We apply these ideas to the measurement of the excess noise of a quantum point contact and we provide numerical estimates of the detector current.Comment: 19 pages, 11 figure

Well-posed results for nonlocal biparabolic equation with linear and nonlinear source terms

In this paper, we consider the biparabolic problem under nonlocal conditions with both linear and nonlinear source terms. We derive the regularity property of the mild solution for the linear source term while we apply the Banach fixed-point theorem to study the existence and uniqueness of the mild solution for the nonlinear source term. In both cases, we show that the mild solution of our problem converges to the solution of an initial value problem as the parameter epsilon tends to zero. The novelty in our study can be considered as one of the first results on biparabolic equations with nonlocal conditions.This research was funded by the National Research Foundation of Korea under grant number NRF-2020K1A3A1A05101625 and the support from Institute of Construction and Environmental Engineering at Seoul National University

Evaluation of CSF and plasma biomarkers of brain melanocortin activity in response to caloric restriction in humans

The melanocortin neuronal system, which consists of hypothalamic proopiomelanocortin (POMC) and agouti-related protein (AgRP) neurons, is a leptin target that regulates energy balance and metabolism, but studies in humans are limited by a lack of reliable biomarkers to assess brain melanocortin activity. The objective of this study was to measure the POMC prohormone and its processed peptide, β-endorphin (β-EP), in cerebrospinal fluid (CSF) and AgRP in CSF and plasma after calorie restriction to validate their utility as biomarkers of brain melanocortin activity. CSF and plasma were obtained from 10 lean and obese subjects after fasting (40 h) and refeeding (24 h), and from 8 obese subjects before and after 6 wk of dieting (800 kcal/day) to assess changes in neuropeptide and hormone levels. After fasting, plasma leptin decreased to 35%, and AgRP increased to 153% of baseline. During refeeding, AgRP declined as leptin increased; CSF β-EP increased, but POMC did not change. Relative changes in plasma and CSF leptin were blunted in obese subjects. After dieting, plasma and CSF leptin decreased to 46% and 70% of baseline, CSF POMC and β-EP decreased, and plasma AgRP increased. At baseline, AgRP correlated negatively with insulin and homeostasis model assessment (HOMA-IR), and positively with the Matsuda index. Thus, following chronic calorie restriction, POMC and β-EP declined in CSF, whereas acutely, only β-EP changed. Plasma AgRP, however, increased after both acute and chronic calorie restriction. These results support the use of CSF POMC and plasma AgRP as biomarkers of hypothalamic melanocortin activity and provide evidence linking AgRP to insulin sensitivity

GPX8 regulates clear cell renal cell carcinoma tumorigenesis through promoting lipogenesis by NNMT

Background Clear cell renal cell carcinoma (ccRCC), with its hallmark phenotype of high cytosolic lipid content, is considered a metabolic cancer. Despite the implication of this lipid-rich phenotype in ccRCC tumorigenesis, the roles and regulators of de novo lipid synthesis (DNL) in ccRCC remain largely unexplained. Methods Our bioinformatic screening focused on ccRCC-lipid phenotypes identified glutathione peroxidase 8 (GPX8), as a clinically relevant upstream regulator of DNL. GPX8 genetic silencing was performed with CRISPR-Cas9 or shRNA in ccRCC cell lines to dissect its roles. Untargeted metabolomics, RNA-seq analyses, and other biochemical assays (e.g., lipid droplets staining, fatty acid uptake, cell proliferation, xenograft, etc.) were carried out to investigate the GPX8s involvement in lipid metabolism and tumorigenesis in ccRCC. The lipid metabolic function of GPX8 and its downstream were also measured by isotope-tracing-based DNL flux measurement. Results GPX8 knockout or downregulation substantially reduced lipid droplet levels (independent of lipid uptake), fatty acid de novo synthesis, triglyceride esterification in vitro, and tumor growth in vivo. The downstream regulator was identified as nicotinamide N-methyltransferase (NNMT): its knockdown phenocopied, and its expression rescued, GPX8 silencing both in vitro and in vivo. Mechanically, GPX8 regulated NNMT via IL6-STAT3 signaling, and blocking this axis suppressed ccRCC survival by activating AMPK. Notably, neither the GPX8-NNMT axis nor the DNL flux was affected by the von Hippel Lindau (VHL) status, the conventional regulator of ccRCC high lipid content. Conclusions Taken together, our findings unravel the roles of the VHL-independent GPX8-NNMT axis in ccRCC lipid metabolism as related to the phenotypes and growth of ccRCC, which may be targeted for therapeutic purposes. Graphical abstractThe research was supported by the Basic Science Research Program (grant NRF-2018R1A3B1052328 to S.P.) funded by the Ministry of Science, Information and Communication Technology, by Future Planning through the National Research Foundation, and by the Basic Science Research Program through the National Research Foundation (NRF-2020R1I1A1A01073124 to J-M.K.) funded by the Ministry of Education of Korea

Expanding HIV Testing Efforts in Concentrated Epidemic Settings: A Population-Based Survey from Rural Vietnam

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The evolution of HIV policy in Vietnam: from punitive control measures to a more rights-based approach

Aim: Policymaking in Vietnam has traditionally been the preserve of the political elite, not open to the scrutiny of those outside the Communist Party. This paper aims to analyse Vietnam's HIV policy development in order to describe and understand the policy content, policy-making processes, actors and obstacles to policy implementation. Methods: Nine policy documents on HIV were analysed and 17 key informant interviews were conducted in Hanoi and Quang Ninh Province, based on a predesigned interview guide. Framework analysis, a type of qualitative content analysis, was applied for data analysis. Results: Our main finding was that during the last two decades, developments in HIV policy in Vietnam were driven in a top-down way by the state organs, with support and resources coming from international agencies. Four major themes were identified: HIV policy content, the policy-making processes, the actors involved and human resources for policy implementation. Vietnam's HIV policy has evolved from one focused on punitive control measures to a more rights-based approach, encompassing harm reduction and payment of health insurance for medical costs of patients with HIV-related illness. Low salaries and staff reluctance to work with patients, many of whom are drug users and female sex workers, were described as the main barriers to low health staff motivation. Conclusion: Health policy analysis approaches can be applied in a traditional one party state and can demonstrate how similar policy changes take place, as those found in pluralistic societies, but through more top-down and somewhat hidden processes. Enhanced participation of other actors, like civil society in the policy process, is likely to contribute to policy formulation and implementation that meets the diverse needs and concerns of its population