Revealing Nanoscale Solid-Solid Interfacial Phenomena for Long-Life and High-Energy All-Solid-State Batteries.

Enabling long cyclability of high-voltage oxide cathodes is a persistent challenge for all-solid-state batteries, largely because of their poor interfacial stabilities against sulfide solid electrolytes. While protective oxide coating layers such as LiNbO3 (LNO) have been proposed, its precise working mechanisms are still not fully understood. Existing literature attributes reductions in interfacial impedance growth to the coating's ability to prevent interfacial reactions. However, its true nature is more complex, with cathode interfacial reactions and electrolyte electrochemical decomposition occurring simultaneously, making it difficult to decouple each effect. Herein, we utilized various advanced characterization tools and first-principles calculations to probe the interfacial phenomenon between solid electrolyte Li6PS5Cl (LPSCl) and high-voltage cathode LiNi0.85Co0.1Al0.05O2 (NCA). We segregated the effects of spontaneous reaction between LPSCl and NCA at the interface and quantified the intrinsic electrochemical decomposition of LPSCl during cell cycling. Both experimental and computational results demonstrated improved thermodynamic stability between NCA and LPSCl after incorporation of the LNO coating. Additionally, we revealed the in situ passivation effect of LPSCl electrochemical decomposition. When combined, both these phenomena occurring at the first charge cycle result in a stabilized interface, enabling long cyclability of all-solid-state batteries

Regulation of the fibrosis and angiogenesis promoter SPARC/osteonectin in human adipose tissue by weight change, leptin, insulin, and glucose

This is the final version of the article. Available from the publisher via the DOI in this record.OBJECTIVE: Matricellular Secreted Protein, Acidic and Rich in Cysteine (SPARC), originally discovered in bone as osteonectin, is a mediator of collagen deposition and promotes fibrosis. Adipose tissue collagen has recently been found to be linked with metabolic dysregulation. Therefore, we tested the hypothesis that SPARC in human adipose tissue is influenced by glucose metabolism and adipokines. RESEARCH DESIGN AND METHODS: Serum and adipose tissue biopsies were obtained from morbidly obese nondiabetic subjects undergoing bariatric surgery and lean control subjects for analysis of metabolic markers, SPARC, and various cytokines (RT-PCR). Additionally, 24 obese subjects underwent a very-low-calorie diet of 1,883 kJ (450 kcal)/day for 16 weeks and serial subcutaneous-abdominal-adipose tissue (SCAT) biopsies (weight loss: 28 +/- 3.7 kg). Another six lean subjects underwent fast-food-based hyperalimentation for 4 weeks (weight gain: 7.2 +/- 1.6 kg). Finally, visceral adipose tissue explants were cultured with recombinant leptin, insulin, and glucose, and SPARC mRNA and protein expression determined by Western blot analyses. RESULTS: SPARC expression in human adipose tissue correlated with fat mass and was higher in SCAT. Weight loss induced by very-low-calorie diet lowered SPARC expression by 33% and increased by 30% in adipose tissue of subjects gaining weight after a fast-food diet. SPARC expression was correlated with leptin independent of fat mass and correlated with homeostasis model assessment-insulin resistance. In vitro experiments showed that leptin and insulin potently increased SPARC production dose dependently in visceral adipose tissue explants, while glucose decreased SPARC protein. CONCLUSIONS: Our data suggest that SPARC expression is predominant in subcutaneous fat and its expression and secretion in adipose tissue are influenced by fat mass, leptin, insulin, and glucose. The profibrotic effects of SPARC may contribute to metabolic dysregulation in obesity.This work was supported by Diabetes UK, Swedish Research Council (11285), University Hospital of Linkoping Research Funds; Diabetes Research Centre of Linkoping University; and the Gamla Tjaenarinnor Foundation. No potential conflicts of interest relevant to this article were reported. Parts of this study were presented in abstract form at the 69th Scientific Sessions of the American Diabetes Association, New Orleans, Louisiana, 5–9 June 2009

Site-specific incorporation of phosphotyrosine using an expanded genetic code.

Access to phosphoproteins with stoichiometric and site-specific phosphorylation status is key to understanding the role of protein phosphorylation. Here we report an efficient method to generate pure, active phosphotyrosine-containing proteins by genetically encoding a stable phosphotyrosine analog that is convertible to native phosphotyrosine. We demonstrate its general compatibility with proteins of various sizes, phosphotyrosine sites and functions, and reveal a possible role of tyrosine phosphorylation in negative regulation of ubiquitination

New generalized nonspherical black hole solutions

We present numerical evidence for the existence of several types of static black hole solutions with a nonspherical event horizon topology in $d\geq 6$ spacetime dimensions. These asymptotically flat configurations are found for a specific metric ansatz and can be viewed as higher dimensional counterparts of the $d=5$ static black rings, dirings and black Saturn. Similar to that case, they are supported against collapse by conical singularities. The issue of rotating generalizations of these solutions is also considered.Comment: 47 pages, 11 figures, some comments adde

An expression signature of the angiogenic response in gastrointestinal neuroendocrine tumours: correlation with tumour phenotype and survival outcomes.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are heterogeneous with respect to biological behaviour and prognosis. As angiogenesis is a renowned pathogenic hallmark as well as a therapeutic target, we aimed to investigate the prognostic and clinico-pathological role of tissue markers of hypoxia and angiogenesis in GEP-NETs. METHODS: Tissue microarray (TMA) blocks were constructed with 86 tumours diagnosed from 1988 to 2010. Tissue microarray sections were immunostained for hypoxia inducible factor 1α (Hif-1α), vascular endothelial growth factor-A (VEGF-A), carbonic anhydrase IX (Ca-IX) and somatostatin receptors (SSTR) 1–5, Ki-67 and CD31. Biomarker expression was correlated with clinico-pathological variables and tested for survival prediction using Kaplan–Meier and Cox regression methods. RESULTS: Eighty-six consecutive cases were included: 51% male, median age 51 (range 16–82), 68% presenting with a pancreatic primary, 95% well differentiated, 51% metastatic. Higher grading (P=0.03), advanced stage (P<0.001), high Hif-1α and low SSTR-2 expression (P=0.03) predicted for shorter overall survival (OS) on univariate analyses. Stage, SSTR-2 and Hif-1α expression were confirmed as multivariate predictors of OS. Median OS for patients with SSTR-2+/Hif-1α-tumours was not reached after median follow up of 8.8 years, whereas SSTR-2-/Hif-1α+ GEP-NETs had a median survival of only 4.2 years (P=0.006). CONCLUSION: We have identified a coherent expression signature by immunohistochemistry that can be used for patient stratification and to optimise treatment decisions in GEP-NETs independently from stage and grading. Tumours with preserved SSTR-2 and low Hif-1α expression have an indolent phenotype and may be offered less aggressive management and less stringent follow up

Clinicopathological Profile and Surgical Treatment of Abdominal Tuberculosis: A Single Centre Experience in Northwestern Tanzania.

Abdominal tuberculosis continues to be a major public health problem worldwide and poses diagnostic and therapeutic challenges to general surgeons practicing in resource-limited countries. This study was conducted to describe the clinicopathological profile and outcome of surgical treatment of abdominal tuberculosis in our setting and compare with what is described in literature. A prospective descriptive study of patients who presented with abdominal tuberculosis was conducted at Bugando Medical Centre (BMC) in northwestern Tanzania from January 2006 to February 2012. Ethical approval to conduct the study was obtained from relevant authorities. Statistical data analysis was performed using SPSS version 17.0. Out of 256 patients enrolled in the study, males outnumbered females. The median age was 28 years (range = 16-68 years). The majority of patients (77.3%) had primary abdominal tuberculosis. A total of 127 (49.6%) patients presented with intestinal obstruction, 106 (41.4%) with peritonitis, 17 (6.6%) with abdominal masses and 6 (2.3%) patients with multiple fistulae in ano. Forty-eight (18.8%) patients were HIV positive. A total of 212 (82.8%) patients underwent surgical treatment for abdominal tuberculosis. Bands /adhesions (58.5%) were the most common operative findings. Ileo-caecal region was the most common bowel involved in 122 (57.5%) patients. Release of adhesions and bands was the most frequent surgical procedure performed in 58.5% of cases. Complication and mortality rates were 29.7% and 18.8% respectively. The overall median length of hospital stay was 32 days and was significantly longer in patients with complications (p < 0.001). Advanced age (age ≥ 65 years), co-morbid illness, late presentation, HIV positivity and CD4+ count < 200 cells/μl were statistically significantly associated with mortality (p < 0.0001). The follow up of patients were generally poor as only 37.5% of patients were available for follow up at twelve months after discharge. Abdominal tuberculosis constitutes a major public health problem in our environment and presents a diagnostic challenge requiring a high index of clinical suspicion. Early diagnosis, early anti-tuberculous therapy and surgical treatment of the associated complications are essential for survival

Polycation-π Interactions Are a Driving Force for Molecular Recognition by an Intrinsically Disordered Oncoprotein Family

Molecular recognition by intrinsically disordered proteins (IDPs) commonly involves specific localized contacts and target-induced disorder to order transitions. However, some IDPs remain disordered in the bound state, a phenomenon coined "fuzziness", often characterized by IDP polyvalency, sequence-insensitivity and a dynamic ensemble of disordered bound-state conformations. Besides the above general features, specific biophysical models for fuzzy interactions are mostly lacking. The transcriptional activation domain of the Ewing's Sarcoma oncoprotein family (EAD) is an IDP that exhibits many features of fuzziness, with multiple EAD aromatic side chains driving molecular recognition. Considering the prevalent role of cation-π interactions at various protein-protein interfaces, we hypothesized that EAD-target binding involves polycation- π contacts between a disordered EAD and basic residues on the target. Herein we evaluated the polycation-π hypothesis via functional and theoretical interrogation of EAD variants. The experimental effects of a range of EAD sequence variations, including aromatic number, aromatic density and charge perturbations, all support the cation-π model. Moreover, the activity trends observed are well captured by a coarse-grained EAD chain model and a corresponding analytical model based on interaction between EAD aromatics and surface cations of a generic globular target. EAD-target binding, in the context of pathological Ewing's Sarcoma oncoproteins, is thus seen to be driven by a balance between EAD conformational entropy and favorable EAD-target cation-π contacts. Such a highly versatile mode of molecular recognition offers a general conceptual framework for promiscuous target recognition by polyvalent IDPs. © 2013 Song et al

Transition probabilities for general birth-death processes with applications in ecology, genetics, and evolution

A birth-death process is a continuous-time Markov chain that counts the number of particles in a system over time. In the general process with $n$ current particles, a new particle is born with instantaneous rate $\lambda_n$ and a particle dies with instantaneous rate $\mu_n$. Currently no robust and efficient method exists to evaluate the finite-time transition probabilities in a general birth-death process with arbitrary birth and death rates. In this paper, we first revisit the theory of continued fractions to obtain expressions for the Laplace transforms of these transition probabilities and make explicit an important derivation connecting transition probabilities and continued fractions. We then develop an efficient algorithm for computing these probabilities that analyzes the error associated with approximations in the method. We demonstrate that this error-controlled method agrees with known solutions and outperforms previous approaches to computing these probabilities. Finally, we apply our novel method to several important problems in ecology, evolution, and genetics