112 research outputs found
Influence of Calcium Sulfoaluminate Cement on the Pullout Performance of Reinforcing Fibers: An Evaluation of the Micro-Mechanical Behavior
The objective of this research was to determine the influence of calcium sulfoaluminate (CSA) cement on reinforcing fibers by evaluating the fiber pullout behavior, and bonding characteristics, of a single fiber embedded in a cementitious paste matrix. Four types of fibers commonly used in industry were evaluated: 1) Polyvinyl alcohol; 2) Polypropylene; 3) Coated Steel; and 4) Plain Steel.
Upward trends in energy costs and potential greenhouse gas regulations favor an increased use of construction materials that require lower energy and lower CO2 emissions to fabricate, such as CSA cement, as opposed to the production of ordinary portland cement (OPC), which is more energy intensive and produces more CO2 emissions. However, widespread use of CSA cement requires a more in-depth understanding of the engineering characteristics that govern its performance, including interaction with reinforcing fibers.
The overarching objective of this research was to provide the engineering base needed for the utilization of reinforcing fibers in CSA cement-based construction materials. The aims of the research were (1) to develop an ettringite-rich calcium sulfoaluminate cement, and (2) evaluate the pullout characteristics of reinforcing fibers embedded in a CSA-cement matrix. Key elements of the strategy included (1) Compare the performance of a laboratory-fabricated CSA cement to a commercial CSA cement and OPC, (2) Evaluate the peak load, and toughness of reinforcing fibers in CSA cement and OPC, (3) Evaluate the debonding-energy density and multiple-cracking behavior of fibers in CSA cement and OPC, and (4) Evaluate the shear bond strength of reinforcing fibers in CSA cement and OPC.
Based on the findings of this PhD dissertation, calcium sulfoaluminate cement has a significant influence on the characteristics and behavior of embedded reinforcing fibers. An important factor contributing to the bond strength between fiber and matrix was the ability to transfer interfacial stresses from fiber to matrix. The more rigid-dense morphology of the CSA cement paste related to the ettringite crystal structure yielded higher peak loads, toughness, debonding-energy densities and shear-bond strengths for both steel and synthetic fibers. In addition to cement phase morphology, the reduction of the fiber/matrix elastic modulus ratio was found to be a primary factor affecting the performance and behavior of fibers embedded in a cementitious matrix
Interfacial Bond between Reinforcing Fibers and Calcium Sulfoaluminate Cements: Fiber Pullout Characteristics
The results of an experimental investigation on the influence of the interfacial bond of reinforcing fibers embedded in a calcium sulfoaluminate matrix on the fiber-pullout peak load and energy consumption are presented. Bonding at the fiber-matrix interface plays an important role in controlling the mechanical performance of cementitious composites—in particular, composites formed from sulfate-based systems (calcium sulfoaluminate [CSA] cements), as opposed to the silicate systems found in portland cement. Various types of fibers were selected, including polyvinyl alcohol (PVA), polypropylene, and copper-coated steel. The fibers were embedded in three different matrixes: two sulfate-based cements including one commercially available CSA cement and a CSA fabricated from coal-combustion by-products. The third matrix was a silicatebased ordinary portland cement (OPC). In this study, the results of the single-fiber pullout test were coupled with scanning electron microscopy (SEM) to examine the interfacial bond between the fiber and CSA matrix for evidence of debonding and possible hydration reaction products
Alite calcium sulfoaluminate cement: chemistry and thermodynamics
Calcium sulfoaluminate (CA) cements can combine the favourable characteristics of Portland cement (PC) with those of CA clinkers. The first is a thermodynamic study demonstrating that the production of a-CA 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
p27Kip1 in Stage III Colon Cancer: Implications for Outcome following Adjuvant Chemotherapy in Cancer and Leukemia Group B Protocol 89803
In retrospective studies, loss of p27Kip1 (p27), a cyclin dependent kinase inhibitor, has been associated with poor prognosis following colorectal cancer treatment. In a prospective study, we validated this relationship in patients enrolled on a trial of adjuvant chemotherapy for Stage III colon cancer
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
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
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
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
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