Heterogenized Pyridine-Substituted Cobalt(II) Phthalocyanine Yields Reduction of CO2 by Tuning the Electron Affinity of the Co Center

Conversion of CO2 to reduced products is a promising route to alleviate irreversible climate change. Here we report the synthesis of a Co-based phthalocyanine with pyridine moieties (CoPc-Pyr), which is supported on a carbon electrode and shows Faradaic efficiency ∼90% for CO at 490 mV of overpotential (-0.6 V vs reversible hydrogen electrode (RHE)). In addition, its catalytic activity at -0.7 V versus RHE surpasses other Co-based molecular and metal-organic framework catalysts for CO2 reduction at this bias. Density functional theory calculations show that pyridine moieties enhance CO2 adsorption and electron affinity of the Co center by an inductive effect, thus lowering the overpotential necessary for CO2 conversion. Our study shows that CoPc-Pyr reduces CO2 at lower overpotential and with higher activity than noble metal electrodes, such as silver

Mathematical models for immunology:current state of the art and future research directions

The advances in genetics and biochemistry that have taken place over the last 10 years led to significant advances in experimental and clinical immunology. In turn, this has led to the development of new mathematical models to investigate qualitatively and quantitatively various open questions in immunology. In this study we present a review of some research areas in mathematical immunology that evolved over the last 10 years. To this end, we take a step-by-step approach in discussing a range of models derived to study the dynamics of both the innate and immune responses at the molecular, cellular and tissue scales. To emphasise the use of mathematics in modelling in this area, we also review some of the mathematical tools used to investigate these models. Finally, we discuss some future trends in both experimental immunology and mathematical immunology for the upcoming years

Comparing Effects of Nutrients on Algal Biomass in Streams in Two Regions with Different Disturbance Regimes and with Applications for Developing Nutrient Criteria

Responses of stream algal biomass to nutrient enrichment were studied in two regions where differences in hydrologic variability cause great differences in herbivory. Around northwestern Kentucky (KY) hydrologic variability constrains invertebrate biomass and their effects on algae, but hydrologic stability in Michigan (MI) streams permits accrual of high herbivore densities and herbivory of benthic algae. Multiple indicators of algal biomass and nutrient availability were measured in 104 streams with repeated sampling at each site over a 2−month period. Many measures of algal biomass and nutrient availability were positively correlated in both regions, however the amount of variation explained varied with measures of biomass and nutrient concentration and with region. Indicators of diatom biomass were higher in KY than MI, but were not related to nutrient concentrations in either region. Chl   a and % area of substratum covered by Cladophora were positively correlated to nutrient concentrations in both regions. Cladophora responded significantly more to nutrients in MI than KY. Total phosphorus (TP) and total nitrogen (TN) explained similar amounts of variation in algal biomass, and not significantly more variation in biomass than dissolved nutrient concentrations. Low N:P ratios in the benthic algae indicated N as well as P may be limiting their accrual. Most observed responses in benthic algal biomass occurred in nutrient concentrations between 10 and 30 μg TP  l −1 and between 400 and 1000 μg TN l −1 .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42905/1/10750_2005_Article_1611.pd

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

The condomlessness of bareback sex: Responses to the unrepresentability of HIV in Treasure Island Media’s Plantin’ Seed

This article focuses on the pornography produced by Treasure Island Media, specifically the two films Plantin’ Seed (2004) and Slammed (2012), in order to explore and analyze the ways in which they alternately seek to represent HIV and to skirt its unrepresentability with metaphorical substitutes. The article posits a link between the function of the representation of the condom and that of condomlessness; it accordingly proposes a problematization of the representation of condomlessness within bareback pornography and argues that to represent condomlessness is fundamentally antithetical to what bareback pornography postulates and indeed believes about itself.</p

Recruited Metastasis Suppressor NM23-H2 Attenuates Expression and Activity of Peroxisome Proliferator-Activated Receptor δ (PPARδ) in Human Cholangiocarcinoma

Background: Peroxisome proliferator-activated receptor δ (PPARδ) is a versatile regulator of distinct biological processes and overexpression of PPARδ in cancer may be partially related to its suppression of its own co-regulators. Aims: To determine whether recruited suppressor proteins bind to and regulate PPARδ expression, activity and PPARδ-dependent cholangiocarcinoma proliferation. Methods: Yeast two-hybrid assays were done using murine PPARδ as bait. PPARδ mRNA expression was determined by qPCR. Protein expression was measured by western blot. Immunohistochemistry and fluorescence microscopy were used to determine PPARδ expression and co-localization with NDP Kinase alpha (NM23-H2). Cell proliferation assays were performed to determine cell numbers. Results: Yeast two-hybrid screening identified NM23-H2 as a PPARδ binding protein and their interaction was confirmed. Overexpressed PPARδ or treatment with the agonist GW501516 resulted in increased cell proliferation. NM23-H2 siRNA activated PPARδ luciferase promoter activity, upregulated PPARδ RNA and protein expression and increased GW501516-stimulated CCA growth. Overexpression of NM23-H2 inhibited PPARδ luciferase promoter activity, downregulated PPARδ expression and AKT phosphorylation and reduced GW501516-stimulated CCA growth. Conclusions: We report the novel association of NM23-H2 with PPARδ and the negative regulation of PPARδ expression by NM23-H2 binding to the C-terminal region of PPARδ. These findings provide evidence that the metastasis suppressor NM23-H2 is involved in the regulation of PPARδ-mediated proliferation

Adaptive digital twins for energy-intensive industries and their local communities

Digital Twins (DTs) are high-fidelity virtual models that behave-like, look-like and connect-to a physical system. In this work, the physical systems are operations and processes from energy-intensive industrial plants and their local communities. The creation of DTs demands expertise not just in engineering, but also in computer science, data science, and artificial intelligence. Here, we introduce the Adaptive Digital Twins (ADT) concept, anchored in five attributes inspired by the self-adaptive systems field from software engineering. These attributes are self-learning, self-optimizing, self-evolving, self-monitoring, and self-protection. This new approach merges cutting-edge computing with pragmatic engineering needs. ADTs can enhance decision-making in both the design phase and real-time operation of industrial facilities and allow for versatile 'what-if' scenario simulations. Seven applications within the energy-intensive industries are described where ADTs could be transformative

Safety of Patients with Hepatitis C Virus Treated with Glecaprevir/Pibrentasvir from Clinical Trials and Real-World Cohorts

INTRODUCTION: More than 70 million people are estimated to be infected with hepatitis C virus (HCV) globally. If left untreated, HCV infection can lead to complications such as extensive liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Evolution of treatments has resulted in highly effective and well-tolerated all-oral direct-acting antivirals. The pangenotypic regimen of glecaprevir/pibrentasvir is approved for treating HCV for patients without cirrhosis or with compensated cirrhosis (CC). Guidelines have evolved to simplify treatment to enable non-specialists to manage and treat HCV-infected patients. Simultaneously, such treatment algorithms provide guidance on the pretreatment identification of small subsets of patients who may require specialist treatment and long-term follow-up for advanced liver disease, including those at risk of developing HCC. This study describes the safety profile of glecaprevir/pibrentasvir in patients identified using previously described noninvasive laboratory measures who may be eligible for treatment by non-liver specialists. METHODS: This post hoc analysis of glecaprevir/pibrentasvir in patients, identified by noninvasive laboratory measures, intended to exclude patients with advanced liver disease and severe renal impairment, who can be managed within non-liver specialist settings. Patients were included from clinical trials and real-world studies of glecaprevir/pibrentasvir for HCV treatment. Baseline demographics, clinical characteristics, and safety assessments, including adverse events and laboratory abnormalities, were summarized. RESULTS: Data across these large-scale studies confirm that glecaprevir/pibrentasvir is well tolerated across different patient populations, with fewer than 0.1% of patients experiencing a serious adverse event related to treatment drugs, and few patients developing HCC during or after treatment. CONCLUSION: The safety profile of glecaprevir/pibrentasvir enhances the confidence of non-liver specialists to treat the majority of HCV-infected patients, and provides an opportunity to expand the treater pool, potentially increasing diagnosis and treatment rates for HCV, contributing to elimination of HCV