New Tolerance Factor to Predict the Stability of Perovskite Oxides and Halides

Predicting the stability of the perovskite structure remains a longstanding challenge for the discovery of new functional materials for many applications including photovoltaics and electrocatalysts. We developed an accurate, physically interpretable, and one-dimensional tolerance factor, {\tau}, that correctly predicts 92% of compounds as perovskite or nonperovskite for an experimental dataset of 576 $ABX_3$ materials ($\textit{X} =$ $O^{2-}$, $F^-$, $Cl^-$, $Br^-$, $I^-$) using a novel data analytics approach based on SISSO (sure independence screening and sparsifying operator). {\tau} is shown to generalize outside the training set for 1,034 experimentally realized single and double perovskites (91% accuracy) and is applied to identify 23,314 new double perovskites ($A_2$$\textit{BB'}$$X_6$) ranked by their probability of being stable as perovskite. This work guides experimentalists and theorists towards which perovskites are most likely to be successfully synthesized and demonstrates an approach to descriptor identification that can be extended to arbitrary applications beyond perovskite stability predictions

A systematic review of the diagnostic and prognostic value of urinary protein biomarkers in urothelial bladder cancer

For over 80 years, cystoscopy has remained the gold-standard for detecting tumours of the urinary bladder. Since bladder tumours have a tendency to recur and progress, many patients are subjected to repeated cystoscopies during long-term surveillance, with the procedure being both unpleasant for the patient and expensive for healthcare providers. The identification and validation of bladder tumour specific molecular markers in urine could enable tumour detection and reduce reliance on cystoscopy, and numerous classes of biomarkers have been studied. Proteins represent the most intensively studied class of biomolecule in this setting. As an aid to researchers searching for better urinary biomarkers, we report a comprehensive systematic review of the literature and a searchable database of proteins that have been investigated to date. Our objective was to classify these proteins as: 1) those with robustly characterised sensitivity and specificity for bladder cancer detection; 2) those that show potential but further investigation is required; 3) those unlikely to warrant further investigation; and 4) those investigated as prognostic markers. This work should help to prioritise certain biomarkers for rigorous validation, whilst preventing wasted effort on proteins that have shown no association whatsoever with the disease, or only modest biomarker performance despite large-scale efforts at validation

Exploring the roles of urinary HAI-1, EpCAM and EGFR in bladder cancer prognosis and risk stratification

Objectives: To investigate whether elevated urinary HAI-1, EpCAM and EGFR are independent prognostic biomarkers within non-muscle-invasive bladder cancer (NMIBC) patients, and have utility for risk stratification to facilitate treatment decisions. Results: After accounting for EAU risk group in NMIBC patients, the risk of BC-specific death was 2.14 times higher (95% CI: 1.08 to 4.24) if HAI-1 was elevated and 2.04 times higher (95% CI: 1.02 to 4.07) if EpCAM was elevated. The majority of events occurred in the high-risk NMIBC group and this is where the biggest difference is seen in the survival curves when plotted for EAU risk groups separately. In MIBC patients, being elevated for any of the three biomarkers was significantly associated with BC-specific mortality after accounting for other risk factors, HR = 4.30 (95% CI: 1.85 to 10.03). Patients and Methods: Urinary levels of HAI-1, EpCAM and EGFR were measured by ELISA in 683 and 175 patients with newly-diagnosed NMIBC and MIBC, respectively, recruited to the Bladder Cancer Prognosis Programme. Associations between biomarkers and progression, BC-specific mortality and all-cause mortality were evaluated using univariable and multivariable Cox regression models, adjusted for European Association of Urology (EAU) NMIBC risk groups. The upper 25% of values for each biomarker within NMIBC patients were considered as elevated. Exploratory analyses in urine from MIBC patients were also undertaken. Conclusion: Urinary HAI-1 and EpCAM are prognostic biomarkers for NMIBC patients. These biomarkers have potential to guide treatment decisions for high-risk NMIBC patients. Further analyses are required to define the roles of HAI-1, EpCAM and EGFR in MIBC patients

Intestinal Epithelial Cell–Derived μ-Opioid Signaling Protects against Ischemia Reperfusion Injury through PI3K Signaling

Intestinal ischemia has a wide variety of causes, including, but not limited to, atherosclerosis, thrombosis, hypotension, and chronic inflammation. In severe cases, ischemic injury can result in death. μ-Opioid receptor (MOR) signaling has previously been shown to protect against chemically induced colitis, but the cellular origin of this effect remains unknown. Herein, we evaluated the role of intestinal epithelial cell (IEC)–derived MOR signaling in host responses to ischemia/reperfusion-induced injury. Ileal ischemia was accomplished through obstruction of the distal branches of the superior mesenteric artery (60 minutes) and reperfusion for 90 minutes (ischemia-reperfusion). Floxed-MOR mice were crossed to Villin-cre transgenic mice to selectively delete the MOR gene in IECs (MORIEC−/−). Radio-ligand binding assays demonstrated selective loss of MOR signaling in IECs of MORIEC−/− mice. The s.c. administration of the MOR agonist, [D-Arg2, Lys4] dermorphin (1–4) amide (DALDA), 10 minutes before surgery protected against both ischemic and reperfusion phases of intestinal injury, an effect abolished in MORIEC−/− mice. This cytoprotective effect was associated with enterocyte-mediated phosphoinositide 3-kinase (PI3K)/glycogen synthase kinase 3β signaling and decreased apoptosis, as determined by IHC and caspase-3 processing. PI3K blockade with Ly294002 resulted in loss of MOR-mediated cytoprotective function. Together, these data show that IEC-derived μ-opioid signaling uses the PI3K pathway to protect cells against the damaging effect of ischemia-reperfusion. Targeting MOR signaling may represent a novel mean to alleviate intestinal injury and promote the wound-healing response

Next Generation Very Large Array Memo No. 6, Science Working Group 1: The Cradle of Life

This paper discusses compelling science cases for a future long-baseline interferometer operating at millimeter and centimeter wavelengths, like the proposed Next Generation Vary Large Array (ngVLA). We report on the activities of the Cradle of Life science working group, which focused on the formation of low- and high-mass stars, the formation of planets and evolution of protoplanetary disks, the physical and compositional study of Solar System bodies, and the possible detection of radio signals from extraterrestrial civilizations. We propose 19 scientific projects based on the current specification of the ngVLA. Five of them are highlighted as possible Key Science Projects: (1) Resolving the density structure and dynamics of the youngest HII regions and high-mass protostellar jets, (2) Unveiling binary/multiple protostars at higher resolution, (3) Mapping planet formation regions in nearby disks on scales down to 1 AU, (4) Studying the formation of complex molecules, and (5) Deep atmospheric mapping of giant planets in the Solar System. For each of these projects, we discuss the scientific importance and feasibility. The results presented here should be considered as the beginning of a more in-depth analysis of the science enabled by such a facility, and are by no means complete or exhaustive.Comment: 51 pages, 12 figures, 1 table. For more information visit https://science.nrao.edu/futures/ngvl

The organisation and delivery of health improvement in general practice and primary care: a scoping study

Background This project examines the organisation and delivery of health improvement activities by and within general practice and the primary health-care team. The project was designed to examine who delivers these interventions, where they are located, what approaches are developed in practices, how individual practices and the primary health-care team organise such public health activities, and how these contribute to health improvement. Our focus was on health promotion and ill-health prevention activities. Aims The aim of this scoping exercise was to identify the current extent of knowledge about the health improvement activities in general practice and the wider primary health-care team. The key objectives were to provide an overview of the range and type of health improvement activities, identify gaps in knowledge and areas for further empirical research. Our specific research objectives were to map the range and type of health improvement activity undertaken by general practice staff and the primary health-care team based within general practice; to scope the literature on health improvement in general practice or undertaken by health-care staff based in general practice and identify gaps in the evidence base; to synthesise the literature and identify effective approaches to the delivery and organisation of health improvement interventions in a general practice setting; and to identify the priority areas for research as defined by those working in general practice. Methods We undertook a comprehensive search of the literature. We followed a staged selection process involving reviews of titles and abstracts. This resulted in the identification of 1140 papers for data extraction, with 658 of these papers selected for inclusion in the review, of which 347 were included in the evidence synthesis. We also undertook 45 individual and two group interviews with primary health-care staff. Findings Many of the research studies reviewed had some details about the type, process or location, or who provided the intervention. Generally, however, little attention is paid in the literature to examining the impact of the organisational context on the way services are delivered or how this affects the effectiveness of health improvement interventions in general practice. We found that the focus of attention is mainly on individual prevention approaches, with practices engaging in both primary and secondary prevention. The range of activities suggests that general practitioners do not take a population approach but focus on individual patients. However, it is clear that many general practitioners see health promotion as an integral part of practice, whether as individual approaches to primary or secondary health improvement or as a practice-based approach to improving the health of their patients. Our key conclusion is that there is currently insufficient good evidence to support many of the health improvement interventions undertaken in general practice and primary care more widely. Future Research Future research on health improvement in general practice and by the primary health-care team needs to move beyond clinical research to include delivery systems and be conducted in a primary care setting. More research needs to examine areas where there are chronic disease burdens – cancer, dementia and other disabilities of old age. Reviews should be commissioned that examine the whole prevention pathway for health problems that are managed within primary care drawing together research from general practice, pharmacy, community engagement, etc

PhiSiGns: an online tool to identify signature genes in phages and design PCR primers for examining phage diversity

<p>Abstract</p> <p>Background</p> <p>Phages (viruses that infect bacteria) have gained significant attention because of their abundance, diversity and important ecological roles. However, the lack of a universal gene shared by all phages presents a challenge for phage identification and characterization, especially in environmental samples where it is difficult to culture phage-host systems. Homologous conserved genes (or "signature genes") present in groups of closely-related phages can be used to explore phage diversity and define evolutionary relationships amongst these phages. Bioinformatic approaches are needed to identify candidate signature genes and design PCR primers to amplify those genes from environmental samples; however, there is currently no existing computational tool that biologists can use for this purpose.</p> <p>Results</p> <p>Here we present PhiSiGns, a web-based and standalone application that performs a pairwise comparison of each gene present in user-selected phage genomes, identifies signature genes, generates alignments of these genes, and designs potential PCR primer pairs. PhiSiGns is available at (<url>http://www.phantome.org/phisigns/</url>; <url>http://phisigns.sourceforge.net/</url>) with a link to the source code. Here we describe the specifications of PhiSiGns and demonstrate its application with a case study.</p> <p>Conclusions</p> <p>PhiSiGns provides phage biologists with a user-friendly tool to identify signature genes and design PCR primers to amplify related genes from uncultured phages in environmental samples. This bioinformatics tool will facilitate the development of novel signature genes for use as molecular markers in studies of phage diversity, phylogeny, and evolution.</p

Nef Decreases HIV-1 Sensitivity to Neutralizing Antibodies that Target the Membrane-proximal External Region of TMgp41

Primate lentivirus nef is required for sustained virus replication in vivo and accelerated progression to AIDS. While exploring the mechanism by which Nef increases the infectivity of cell-free virions, we investigated a functional link between Nef and Env. Since we failed to detect an effect of Nef on the quantity of virion-associated Env, we searched for qualitative changes by examining whether Nef alters HIV-1 sensitivity to agents that target distinct features of Env. Nef conferred as much as 50-fold resistance to 2F5 and 4E10, two potent neutralizing monoclonal antibodies (nAbs) that target the membrane proximal external region (MPER) of TMgp41. In contrast, Nef had no effect on HIV-1 neutralization by MPER-specific nAb Z13e1, by the peptide inhibitor T20, nor by a panel of nAbs and other reagents targeting gp120. Resistance to neutralization by 2F5 and 4E10 was observed with Nef from a diverse range of HIV-1 and SIV isolates, as well as with HIV-1 virions bearing Env from CCR5- and CXCR4-tropic viruses, clade B and C viruses, or primary isolates. Functional analysis of a panel of Nef mutants revealed that this activity requires Nef myristoylation but that it is genetically separable from other Nef functions such as the ability to enhance virus infectivity and to downregulate CD4. Glycosylated-Gag from MoMLV substituted for Nef in conferring resistance to 2F5 and 4E10, indicating that this activity is conserved in a retrovirus that does not encode Nef. Given the reported membrane-dependence of MPER-recognition by 2F5 and 4E10, in contrast to the membrane-independence of Z13e1, the data here is consistent with a model in which Nef alters MPER recognition in the context of the virion membrane. Indeed, Nef and Glycosylated-Gag decreased the efficiency of virion capture by 2F5 and 4E10, but not by other nAbs. These studies demonstrate that Nef protects lentiviruses from one of the most broadly-acting classes of neutralizing antibodies. This newly discovered activity for Nef has important implications for anti-HIV-1 immunity and AIDS pathogenesis

Сетевая система контроля технологического процесса выращивания полупроводниковых кристаллов и тонких пленок

Экспериментальное моделирование аппаратно-программного обеспечения показало достаточную надежность работы системы и значительное уменьшение трудоемкости контроля и управления параметрами технологического процесса

Properties and customization of sensor materials for biomedical applications.

Low-power chemo- and biosensing devices capable of monitoring clinically important parameters in real time represent a great challenge in the analytical field as the issue of sensor calibration pertaining to keeping the response within an accurate calibration domain is particularly significant (1–4). Diagnostics, personal health, and related costs will also benefit from the introduction of sensors technology (5–7). In addition, with the introduction of Registration, Evaluation, Authorization, and Restriction of Chemical Substances (REACH) regulation, unraveling the cause–effect relationships in epidemiology studies will be of outmost importance to help establish reliable environmental policies aimed at protecting the health of individuals and communities (8–10). For instance, the effect of low concentration of toxic elements is seldom investigated as physicians do not have means to access the data (11)