152 research outputs found
Development of a Semirigid Pavement Incorporating Ultrarapid Hardening Cement and Chemical Admixtures for Cement Grouts
Mechanical tests were carried out to evaluate the influence and effects of fluidity and compressive strength of cement grout on semirigid asphalt pavement. An open graded asphalt skeleton was designed in order to achieve target porosity in the range of 18~22%. In addition, four types of cement grout mixtures were produced with varying mix proportions with ultrarapid hardening cement and chemical admixtures, that is, accelerating and retarding agents. For the semirigid pavement specimens, mechanical experiments to measure properties such as porosity, flexural strength, Marshall stability, and wheel tracking resistance were carried out. The test results demonstrated that the flow time (fluidity) of cement grout is the most significant factor that determines the mechanical properties of semirigid asphalt specimens under constant condition of the open graded asphalt skeleton. For the semirigid pavement mixing proportion in the current study, it is recommended that the porosity of the open graded asphalt skeleton and flow time of cement grout should be 20% and within 12 seconds, respectively
Performance Analysis of CFRP Composite Strips Confined RC Columns under Axial Compression
In an attempt to mitigate the high cost of FRP composite strengthening, an experimental investigation was carried out that sought to achieve efficient and most favorable FRP strengthening using CFRP composite strips. 50 mm wide CFRP composite strips were used in two different spacings (20 mm and 40 mm) to confine columns. The test results of the column confined with smaller spacing (20 mm) showed significant restraint of axial deformation of the column and enhanced the strength capacity to a maximum of 99.20% compared to that of reference column. In contrast, the column confined by strips with larger spacing (40 mm) failed by crushing of concrete alone, which occurred even before the CFRP strips reached their ultimate strain. In addition, the embodied energy that exists in the CFRP strips could not be utilized effectively. The stress and strength enhancement ratio of this present study was compared with the previous research that has been conducted on columns confined with full wrapping. From the obtained results, it is recommended that CFRP strips with a spacing of 20 mm be used to improve the strength capacity of the RC column; in addition, this wrapping technique provides economic benefits compared to a column confined with full wrapping
Development of Ecoefficient Engineered Cementitious Composites Using Supplementary Cementitious Materials as a Binder and Bottom Ash Aggregate as Fine Aggregate
The purpose of this study is to develop ecoefficient engineered cementitious composites (ECC) using supplementary cementitious materials (SCMs), including fly ash (FA) and blast furnace slag (SL) as a binder material. The cement content of the ECC mixtures was replaced by FA and SL with a replacement rate of 25%. In addition, the fine aggregate of the ECC was replaced by bottom ash aggregate (BA) with a substitution rate of 10%, 20%, and 30%. The influences of ecofriendly aggregates on fresh concrete properties and on mechanical properties were experimentally investigated. The test results revealed that the substitution of SCMs has an advantageous effect on fresh concrete’s properties; however, the increased water absorption and the irregular shape of the BA can potentially affect the fresh concrete’s properties. The substitution of FA and SL in ECC led to an increase in frictional bond at the interface between PVA fibers and matrix, improved the fiber dispersion, and showed a tensile strain capacity ranging from 3.3% to 3.5%. It is suggested that the combination of SCMs (12.5% FA and 12.5% SL) and the BA aggregate with the substitution rate of 10% can be effectively used in ECC preparation
Effect of W/C Ratio on Durability and Porosity in Cement Mortar with Constant Cement Amount
Water is often added to concrete placing for easy workability and finishability in construction site. The additional mixing water can help easy mixing and workability but causes increased porosity, which yields degradation of durability and structural performances. In this paper, cement mortar samples with 0.45 of W/C (water to cement) ratio are prepared for control case and durability performances are evaluated with additional water from 0.45 to 0.60 of W/C. Several durability tests including strength, chloride diffusion, air permeability, saturation, and moisture diffusion are performed, and they are analyzed with changed porosity. The changing ratios and patterns of durability performance are evaluated considering pore size distribution, total porosity, and additional water content
Adjuvant Chemotherapy in Microsatellite Instability-High Gastric Cancer
Purpose Microsatellite instability (MSI) status may affect the efficacy of adjuvant chemotherapy in gastric cancer. In this study, the clinical characteristics of MSI-high (MSI-H) gastric cancer and the predictive value of MSI-H for adjuvant chemotherapy in large cohorts of gastric cancer patients were evaluated. Materials and Methods This study consisted of two cohorts. Cohort 1 included gastric cancer patients who received curative resection with pathologic stage IB-IIIC. Cohort 2 included patients with MSI-H gastric cancer who received curative resection with pathologic stage II/III. MSI was examined using two mononucleotide markers and three dinucleotide markers. Results Of 359 patients (cohort 1), 41 patients (11.4%) had MSI-H. MSI-H tumors were more frequently identified in older patients (p < 0.001), other histology than poorly cohesive, signet ring cell type (p=0.005), intestinal type (p=0.028), lower third tumor location (p=0.005), and absent perineural invasion (p=0.027). MSI-H status has a tendency of better disease-free survival (DFS) and overall survival (OS) in multivariable analyses (hazard ratio [HR], 0.4; p=0.059 and HR, 0.4; p=0.063, respectively). In the analysis of 162 MSI-H patients (cohort 2), adjuvant chemotherapy showed a significant benefit with respect to longer DFS and OS (p=0.047 and p=0.043, respectively). In multivariable analysis, adjuvant chemotherapy improved DFS (HR, 0.4; p=0.040). Conclusion MSI-H gastric cancer had distinct clinicopathologic findings. Even in MSI-H gastric cancer of retrospective cohort, adjuvant chemotherapy could show a survival benefit, which was in contrast to previous prospective studies and should be investigated in a further prospective trial.
TDP1 and TOP1 Modulation in Olaparib-Resistant Cancer Determines the Efficacy of Subsequent Chemotherapy
The aim of this study was to elucidate the carryover effect of olaparib to subsequent chemotherapy and its underlying mechanisms. We generated olaparib-resistant SNU-484, SNU-601, SNU-668, and KATO-III gastric cancer cell lines and confirmed their resistance by cell viability and colony forming assays. Notably, olaparib-resistant cell lines displayed cross-resistance to cisplatin except for KATO-III. Inversely, olaparib-resistant SNU-484, SNU-668, and KATO-III were more sensitive to irinotecan than their parental cells. However, sensitivity to paclitaxel remained unaltered. There were compensatory changes in the ATM/ATR axis and p-Chk1/2 protein expression. ERCC1 was also induced in olaparib-resistant SNU-484, SNU-601, and SNU-668, which showed cross-resistance to cisplatin. Olaparib-resistant cells showed tyrosyl-DNA phosphodiesterase 1 (TDP1) downregulation with higher topoisomerase 1 (TOP1) activity, which is a target of irinotecan. These changes of TOP1 and TDP1 in olaparib-resistant cells was confirmed as the underlying mechanism for increased irinotecan sensitivity through manipulated gene expression of TOP1 and TDP1 by specific plasmid transfection and siRNA. The patient-derived xenograft model established from the patient who acquired resistance to olaparib with BRCA2 mutation showed increased sensitivity in irinotecan. In conclusion, the carryover effects of olaparib to improve antitumor effect of subsequent irinotecan were demonstrated. These effects should be considered when determining the subsequent therapy with olaparib.
MDGA1 negatively regulates amyloid precursor protein-mediated synapse inhibition in the hippocampus
Abstract Balanced synaptic inhibition, controlled by multiple synaptic adhesion proteins, is critical for proper brain function. MDGA1 (meprin, A-5 protein, and receptor protein-tyrosine phosphatase mu [MAM] domain-containing glycosylphosphatidylinositol anchor protein 1) suppresses synaptic inhibition in mammalian neurons, yet the molecular mechanisms underlying MDGA1-mediated negative regulation of GABAergic synapses remain unresolved. Here, we show that the MDGA1 MAM domain directly interacts with the extension domain of amyloid precursor protein (APP). Strikingly, MDGA1-mediated synaptic disinhibition requires the MDGA1 MAM domain and is prominent at distal dendrites of hippocampal CA1 pyramidal neurons. Down-regulation of APP in presynaptic GABAergic interneurons specifically suppressed GABAergic, but not glutamatergic, synaptic transmission strength and inputs onto both the somatic and dendritic compartments of hippocampal CA1 pyramidal neurons. Moreover, APP deletion manifested differential effects in somatostatin- and parvalbumin-positive interneurons in the hippocampal CA1, resulting in distinct alterations in inhibitory synapse numbers, transmission, and excitability. The infusion of MDGA1 MAM protein mimicked postsynaptic MDGA1 gain-of-function phenotypes that involve the presence of presynaptic APP. The overexpression of MDGA1 wild type or MAM, but not MAM-deleted MDGA1, in the hippocampal CA1 impaired novel object-recognition memory in mice. Thus, our results establish unique roles of APP-MDGA1 complexes in hippocampal neural circuits, providing unprecedented insight into trans-synaptic mechanisms underlying differential tuning of neuronal compartment-specific synaptic inhibition.Peer reviewe
Sequenced BAC anchored reference genetic map that reconciles the ten individual chromosomes of Brassica rapa
<p>Abstract</p> <p>Background</p> <p>In view of the immense value of <it>Brassica rapa </it>in the fields of agriculture and molecular biology, the multinational <it>Brassica rapa </it>Genome Sequencing Project (BrGSP) was launched in 2003 by five countries. The developing BrGSP has valuable resources for the community, including a reference genetic map and seed BAC sequences. Although the initial <it>B. rapa </it>linkage map served as a reference for the BrGSP, there was ambiguity in reconciling the linkage groups with the ten chromosomes of <it>B. rapa</it>. Consequently, the BrGSP assigned each of the linkage groups to the project members as chromosome substitutes for sequencing.</p> <p>Results</p> <p>We identified simple sequence repeat (SSR) motifs in the <it>B. rapa </it>genome with the sequences of seed BACs used for the BrGSP. By testing 749 amplicons containing SSR motifs, we identified polymorphisms that enabled the anchoring of 188 BACs onto the <it>B. rapa </it>reference linkage map consisting of 719 loci in the 10 linkage groups with an average distance of 1.6 cM between adjacent loci. The anchored BAC sequences enabled the identification of 30 blocks of conserved synteny, totaling 534.9 cM in length, between the genomes of <it>B. rapa </it>and <it>Arabidopsis thaliana</it>. Most of these were consistent with previously reported duplication and rearrangement events that differentiate these genomes. However, we were able to identify the collinear regions for seven additional previously uncharacterized sections of the A genome. Integration of the linkage map with the <it>B. rapa </it>cytogenetic map was accomplished by FISH with probes representing 20 BAC clones, along with probes for rDNA and centromeric repeat sequences. This integration enabled unambiguous alignment and orientation of the maps representing the 10 <it>B. rapa </it>chromosomes.</p> <p>Conclusion</p> <p>We developed a second generation reference linkage map for <it>B. rapa</it>, which was aligned unambiguously to the <it>B. rapa </it>cytogenetic map. Furthermore, using our data, we confirmed and extended the comparative genome analysis between <it>B. rapa </it>and <it>A. thaliana</it>. This work will serve as a basis for integrating the genetic, physical, and chromosome maps of the BrGSP, as well as for studies on polyploidization, speciation, and genome duplication in the genus <it>Brassica</it>.</p
Ischemic Stroke and Cancer: Stroke Severely Impacts Cancer Patients, While Cancer Increases the Number of Strokes
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