Alite calcium sulfoaluminate cement: chemistry and thermodynamics

Calcium sulfoaluminate (C$A) cement is a binder of increasing interest to the cement industry and is undergoing rapid development. Current formulations do not contain alite; however, alite calcium sulfoaluminate (a-C$A) cements can combine the favourable characteristics of Portland cement (PC) with those of C$A cement while also having a lower carbon dioxide footprint than the current generation of PC clinkers. This paper presents two results on the formation of a-C$A clinkers. The first is a thermodynamic study demonstrating that the production of a-C$A clinker is possible without the use of mineralisers, doping with foreign elements, or using multiple stages of heating. It is established that a-C$A clinker can be readily produced in a standard process by controlling the oxygen and sulfur dioxide fugacity in the atmosphere. This allows for the stabilisation of ye’elimite to the higher temperatures required for alite stability. The second result establishes that when using fluorine to mineralise a-C$A clinker production, the iron content in the clinker is also an important variable. Although the exact mechanism of alite stabilisation is not known, it is shown that alite formation increases with the combination of calcium fluoride and iron (III) oxide in the mix

Disruption of TLR3 Signaling Due to Cleavage of TRIF by the Hepatitis A Virus Protease-Polymerase Processing Intermediate, 3CD

Toll-like receptor 3 (TLR3) and cytosolic RIG-I-like helicases (RIG-I and MDA5) sense viral RNAs and activate innate immune signaling pathways that induce expression of interferon (IFN) through specific adaptor proteins, TIR domain-containing adaptor inducing interferon-β (TRIF), and mitochondrial antiviral signaling protein (MAVS), respectively. Previously, we demonstrated that hepatitis A virus (HAV), a unique hepatotropic human picornavirus, disrupts RIG-I/MDA5 signaling by targeting MAVS for cleavage by 3ABC, a precursor of the sole HAV protease, 3Cpro, that is derived by auto-processing of the P3 (3ABCD) segment of the viral polyprotein. Here, we show that HAV also disrupts TLR3 signaling, inhibiting poly(I:C)-stimulated dimerization of IFN regulatory factor 3 (IRF-3), IRF-3 translocation to the nucleus, and IFN-β promoter activation, by targeting TRIF for degradation by a distinct 3ABCD processing intermediate, the 3CD protease-polymerase precursor. TRIF is proteolytically cleaved by 3CD, but not by the mature 3Cpro protease or the 3ABC precursor that degrades MAVS. 3CD-mediated degradation of TRIF depends on both the cysteine protease activity of 3Cpro and downstream 3Dpol sequence, but not 3Dpol polymerase activity. Cleavage occurs at two non-canonical 3Cpro recognition sequences in TRIF, and involves a hierarchical process in which primary cleavage at Gln-554 is a prerequisite for scission at Gln-190. The results of mutational studies indicate that 3Dpol sequence modulates the substrate specificity of the upstream 3Cpro protease when fused to it in cis in 3CD, allowing 3CD to target cleavage sites not normally recognized by 3Cpro. HAV thus disrupts both RIG-I/MDA5 and TLR3 signaling pathways through cleavage of essential adaptor proteins by two distinct protease precursors derived from the common 3ABCD polyprotein processing intermediate

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas

Bostonia: The Boston University Alumni Magazine. Volume 13

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs

Global Spatial Risk Assessment of Sharks Under the Footprint of Fisheries

Effective ocean management and conservation of highly migratory species depends on resolving overlap between animal movements and distributions and fishing effort. Yet, this information is lacking at a global scale. Here we show, using a big-data approach combining satellite-tracked movements of pelagic sharks and global fishing fleets, that 24% of the mean monthly space used by sharks falls under the footprint of pelagic longline fisheries. Space use hotspots of commercially valuable sharks and of internationally protected species had the highest overlap with longlines (up to 76% and 64%, respectively) and were also associated with significant increases in fishing effort. We conclude that pelagic sharks have limited spatial refuge from current levels of high-seas fishing effort. Results demonstrate an urgent need for conservation and management measures at high-seas shark hotspots and highlight the potential of simultaneous satellite surveillance of megafauna and fishers as a tool for near-real time, dynamic management

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study

BACKGROUND: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC. METHODS: Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. RESULTS: High-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss. CONCLUSION: This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC

Determinants of Collaborative Leadership: Civic Engagement, Gender or Organizational Norms?

This analysis attempts to unravel competing explanations of collaborative leadership styles of state legislative committee chairs. Specifically, the paper considers the influence of community or volunteer experience, gender, and institutional variables. The data show that women chairs are more likely than their male peers to cite as valuable the leadership skills and experiences that they gain through community and volunteer experience. Compared to their male colleagues, women committee chairs on average also report a greater reliance on collaborative strategies in the management of their committees. Prior community or volunteer experience has little or no direct effect on collaborative styles. In contrast, institutional factors have a much stronger and countervailing influence. Legislative professionalization produces a strong negative effect on collaborative style. Results suggest that conformity to institutional norms may be a more compelling influence than prior community experience. The analysis also points to the gendered nature of organizational leadership with men's and women's styles showing different associations to style depending on the number and power of women in a legislature.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Influences of Domestication and Island Evolution on Dental Growth in Sheep

Funder: Department of Zoology, University of CambridgeFunder: Leverhulme Trust; doi: http://dx.doi.org/10.13039/501100000275Abstract: Domestication and island evolution can lead to changes of life history along the slow-fast gradient. Shifts of life history patterns, in turn, are potentially related to alterations of patterns and timing of tooth eruption. Schultz’s rule predicts an earlier eruption of molars relative to premolars as fecundity increases during the domestication process. On the other hand, evolution on a predator-free, resource limited island might lead to a generally slow life history and delayed tooth eruption, as in the Plio-Pleistocene Balearic caprine Myotragus. In this study, we investigate tooth eruption and its relation to life history in a unique sheep population that is an example of both domestication and island evolution: the ancient and feral Soay sheep (Ovis aries) of the St. Kilda archipelago, Scotland. Tooth eruption timing and sequence is investigated in a comparative framework featuring new data on other domestic sheep (O. aries), including European mouflon (O. a. musimon), as well as wild sheep (O. vignei, O. cycloceros, O. arkal, O. orientalis, O. ammon). These data indicate that the order of eruption is similar in wild and domestic sheep, despite the fundamental life history changes that came about with domestication. However, in contrast to other domestic sheep breeds, Soay sheep erupt their teeth at an absolute older age and also tend to grow more slowly, which resembles the evolutionary trend in island-adapted Myotragus. Despite these similarities, Soay sheep do not share the slow life history pattern inferred for Myotragus, highlighting the distinctive nature of tooth eruption in Soay sheep

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease