Control of cationic amino acid transport and retroviral receptor functions in a membrane protein family

A partial cDNA sequence indicated that the T lymphocyte early-activation gene (Tea) encodes a protein related to the dual-function ecotropic retrovirus receptor/cationic amino acid transporter (ecoR/CAT1), and RNA blots suggested highest Tea expression in T lymphocytes and liver (MacLeod, C.L., Finley, K., Kakuda, D. Kozad, C.A., and Wilkinson, M.F. (1990) Mol. Cell. Biol. 7, 3663-3674). The sequence of full-length Tea cDNA from liver (3683 bases) predicts a 657-amino-acid protein (CAT2 alpha) with 12-14 transmembrane domains. A long (515 base) region with six initiation codons and termination codons precedes the translation start codon. The liver Tea cDNA is identical to Tea cDNA from T lymphocytes (encoding CAT2 beta) with the exception of an apparent alternatively spliced sequence encoding a hydrophilic loop of 43 amino acids. The liver-specific sequence contains unique consensus sites for phosphorylation by cyclic AMP-dependent protein kinase and by protein kinase C. Injection of Xenopus oocytes with CAT2 alpha or CAT2 beta messenger RNA resulted in expression of Na(+)-independent cationic amino acid transport that was detected by current measurements under voltage-clamp. Although the amino acid sequences of the isoforms differ in only 21 of 43 residues with the majority of substitutions being conservative, the apparent affinity of CAT2 beta for arginine uptake was 70-fold higher than the CAT2 alpha isoform (Km 38 microM versus 2.7 mM). Neither isoform functioned as a receptor for ecotropic or amphotropic murine retroviruses. However, CAT1-CAT2 chimeric proteins that contain the first three putative extracellular loops of ecoR/CAT1 functioned as ecotropic receptors despite a diminished capacity to bind the viral envelope glycoprotein. The chimeric proteins also functioned as basic amino acid transporters with substrate affinities corresponding to the CAT2 isoform constituting the carboxyl-terminal portion. These results demonstrate that domains of these transporters can function in chimeric combinations to control viral receptor and transport functions

Estimating groundwater recharge for Great Britain

Groundwater plays an important role in supporting public water supplies and sustaining river flows. For example, groundwater supplies up to 80% drinking water in southern England. Groundwater recharge determines how much water is available to groundwater system. It is necessary to develop a groundwater recharge model for Great Britain to support the national water resource management. A national groundwater model was constructed using a SLiM model in this study. SLiM, a distributed rainfall-runoff-recharge model, can objectively estimate groundwater recharge and surface runoff based on climate and catchment characteristics. The datasets of Digital Terrain Model (DTM), daily distributed rainfall, potential evapotranspiration, land-cover and hydrology of soil types were collected in this study. The model was then calibrated using river flow datasets from 102 gauging stations across Great Britain. Nash–Sutcliffe coefficient was used to measure the goodness-of-fit between modelled and observed river flow. After calibration, the Nash–Sutcliffe coefficient values for more than 70% of the gauging stations are larger than 0.5. This means that this model can be used to provide sensible groundwater recharge across Great Britain. The model can produce both long-term-average and daily time variant distributed groundwater recharge in Great Britain. Therefore, it can be used to feed recharge datasets to other groundwater models, such as groundwater flow, groundwater vulnerability assessment, and groundwater pollutant transport models. This can also be a basis to investigate the impacts of climate and land-cover changes on groundwater recharge and hence the groundwater system

Thermal-dephasing-tolerant generation of mesoscopic superposition states with Rydberg dressed blockade

Multipartite entangled states involving non-locality are one of the most fascinating characteristics of quantum mechanics. In this work, we propose a thermal-dephasing-tolerant generation of mesoscopic entangled states with Rydberg dressed atoms. We encode logical state on dressed states rather than Rydberg states. Such treatment can increase the lifetime of multipartite entanglement coherence to around 3 times compared to the Rydberg-state-coding one at the same system size, and therefore induce solid fidelities of mesoscopic superposition states generation. The current work theoretically verifies the advantages of using Rydberg dressed states in many-body quantum entan-glement, which is helpful for large-scale quantum computation and many-body Rydberg quantum simulation

High‑Throughput Electron Diffraction Reveals a Hidden Novel Metal–Organic Framework for Electrocatalysis

AbstractMetal‐organic frameworks (MOFs) are known for their versatile combination of inorganic building units and organic linkers, which offers immense opportunities in a wide range of applications. However, many MOFs are typically synthesized as multiphasic polycrystalline powders, which are challenging for studies by X‐ray diffraction. Therefore, developing new structural characterization techniques is highly desired in order to accelerate discoveries of new materials. Here, we report a high‐throughput approach for structural analysis of MOF nano‐ and sub‐microcrystals by three‐dimensional electron diffraction (3DED). A new zeolitic‐imidazolate framework (ZIF), denoted ZIF‐EC1, was first discovered in a trace amount during the study of a known ZIF‐CO3‐1 material by 3DED. The structures of both ZIFs were solved and refined using 3DED data. ZIF‐EC1 has a dense 3D framework structure, which is built by linking mono‐ and bi‐nuclear Zn clusters and 2‐methylimidazolates (mIm−). With a composition of Zn3(mIm)5(OH), ZIF‐EC1 exhibits high N and Zn densities. We show that the N‐doped carbon material derived from ZIF‐EC1 is a promising electrocatalyst for oxygen reduction reaction (ORR). The discovery of this new MOF and its conversion to an efficient electrocatalyst highlights the power of 3DED in developing new materials and their applications

Promoting routine syphilis screening among men who have sex with men in China: study protocol for a randomised controlled trial of syphilis self-testing and lottery incentive.

BACKGROUND: Men who have sex with men (MSM) bear a high burden of syphilis infection. Expanding syphilis testing to improve timely diagnosis and treatment is critical to improve syphilis control. However, syphilis testing rates remain low among MSM, particularly in low- and middle-income countries. We describe the protocol for a randomised controlled trial (RCT) to assess whether provision of syphilis self-testing services can increase the uptake of syphilis testing among MSM in China. METHODS: Four hundred forty-four high-risk MSM will be recruited online and randomized in a 1:1:1 ratio to (1) standard syphilis self-testing arm; (2) a self-testing arm program enhanced with crowdsourcing and a lottery-based incentive, and (3) a standard of care (control). Self-testing services include a free syphilis self-test kit through the mail at monthly intervals. Participants in the lottery incentive arm will additionally receive health promotion materials generated from an open crowdsourcing contest and be given a lottery draw with a 10% chance to win 100 RMB (approximately 15 US Dollars) upon confirmed completion of syphilis testing. Syphilis self-test kits have step-by-step instructions and an instructional video. This is a non-blinded, open-label, parallel RCT. Participants in each arm will be followed-up at three and 6 months through WeChat (a social media app like Facebook messenger). Confirmation of syphilis self-test use will be determined by requiring participants to submit a photo of the used test kit to study staff via secure data messaging. Both self-testing and facility-based testing will be ascertained by sending a secure photographic image of the completed kit through an existing digital platform. The primary outcome is the proportion of participants who tested for syphilis in the past 3 months. DISCUSSION: Findings from this study will provide much needed insight on the impact of syphilis self-testing on promoting routine syphilis screening among MSM. The findings will also contribute to our understanding of the safety, effectiveness and acceptability of syphilis self-testing. These findings will have important implications for self-testing policy, both in China and internationally. TRIAL REGISTRATION: ChiCTR1900022409 (10 April, 2019)

Encapsulating lithium and sodium inside amorphous carbon nanotubes through gold-seeded growth

Abstract(#br)Metallic lithium promises the ultimate anode material for building next-generation Li batteries, though some fundamental hurdles remain unsolved. Li growth induced by hetero particles/atoms has recently emerged as a highly efficient route enabling spatial-control and dendrite-free Li deposition on anode hosts. However, the detailed mechanism of Li nucleation and its interaction with heterogeneous seeds are largely unknown. Herein, we investigate this issue by visualizing Au-seeded Li nucleation processes that guide Li deposition inside the one-dimensional hollow space of individual amorphous carbon nanotubes by in-situ transmission electron microscopy. A reversible two-step conversion process during Au–Li alloying/dealloying reactions is revealed, suggesting that the formation of Li 3 Au plays the actual role in inducing Li nucleation. We propose a front-growth scenario to explain the spatially confined Li growth and stripping kinetic behaviors, which involves the mass addition and removal at the deposition front through ion diffusion along the tubular carbon shell. As a comparison, nanotubes without gold seeds inside exhibit uncontrolled dendrite-like Li growth outside the carbon shell. We further demonstrate that Au-seed growth can be successful in encapsulating sodium metal for the first time. These findings provide mechanistic insights into heterogeneous seeded Li/Na nucleation and space-confined deposition for design of high-performance battery anodes

Robust Rydberg gate via Landau-Zener control of Förster resonance

In this paper, we propose a scheme to implement the two-qubit controlled-Z gate via the Stark-tuned Förster interaction of Rydberg atoms, where the Förster defect is driven by a time-dependent electric field of a simple sinusoidal function while the matrix elements of the dipole-dipole interaction are time independent. It is shown that when the system is initially in a specific state, it makes a cyclic evolution after a preset interaction time, returning to the initial state, but picks up a phase, which can be used for realizing a two-atom controlled-Z gate. Due to the interference of sequential Landau-Zener transitions, the population and phase of the state is quasideterministic after the cyclic evolution and therefore the gate fidelity is insensitive to fluctuations of the interaction time and the dipole-dipole matrix elements. Feasibility of the scheme realized with Cs atoms is discussed in detail, which shows that the two-qubit gate via Landau-Zener control can be realized with the state-of-the-art experimental setup

Assessing the predictive value of smoking history for immunotherapy outcomes in bladder cancer patients

BackgroundThe therapeutic effectiveness of immune checkpoint inhibitors (ICIs) in bladder cancer varies among individuals. Identifying reliable predictors of response to these therapies is crucial for optimizing patient outcomes.MethodsThis retrospective study analyzed 348 bladder cancer patients treated with ICIs, with additional validation using data from 248 patients at our institution who underwent PD-L1 immunohistochemical staining. We examined patient smoking history, clinicopathological characteristics, and immune phenotypes. The main focus was the correlation between smoking history and immunotherapy outcomes. Multivariate logistic and Cox proportional hazard regressions were used to adjust for confounders.ResultsThe study cohort comprised 348 bladder cancer patients receiving ICIs. Among them, 116 (33.3%) were never smokers, 197 (56.6%) were former smokers (median pack-years = 28), and 35 (10.1%) were current smokers (median pack-years = 40). Analysis revealed no statistically significant difference in overall survival across different smoking statuses (objective response rates were 11.4% for current smokers, 17.2% for never smokers, and 22.3% for former smokers; P = 0.142, 0.410, and 0.281, respectively). However, a notable trend indicated a potentially better response to immunotherapy in former smokers compared to current and never smokers. In the validation cohort of 248 patients from our institution, immunohistochemical analysis showed that PD-L1 expression was significantly higher in former smokers (55%) compared to current smokers (37%) and never smokers (47%). This observation underscores the potential influence of smoking history on the tumor microenvironment and its responsiveness to ICIs.ConclusionIn conclusion, our study demonstrates the importance of incorporating smoking history in predicting the response to immunotherapy in bladder cancer patients, highlighting its role in personalized cancer treatment approaches. Further research is suggested to explore the comprehensive impact of lifestyle factors on treatment outcomes