357 research outputs found
Shear enhancement in RC beams loaded on the tension face
Shear strength of reinforced concrete beams significantly enhances when loads are applied closer to the support due to the arching action. This enhancement is widely investigated and has been included in the design codes. However, scarce resources are available in the literature regarding this enhancement for the case of multiple point loads applied within the enhancement zone; in addition, the available literature focuses on loads applied to the flexural compression face. Situations where multiple point loads are applied on the tension face are found in practice in structures like balanced-cantilever crosshead girders of bridges and transfer girders near the supports. Nevertheless, research considering this configuration has not been found in the available literature. The aim of this research is to study the effect of the loading arrangements on the shear strength enhancement of deep beams loaded on the compression or tension face with multiple point loads. This research was motivated by differences in the principal compressive stress trajectories obtained with nonlinear finite element analysis for the two different configurations.
The author conducted an experimental program to investigate the influence of loading face, the effect of varying the ratio between loads applied within the enhancement zone and the influence on shear enhancement of partly loading the beam outside the enhancement zone. Detailed measurements of the crack kinematics and global deformation were obtained during the tests using the digital images correlation system. These measurements were used to provide descriptive models of the deformed beams and to evaluate the shear transfer actions of the tested beams.
Strength of the tested beams was estimated using design codes (BS8110, EC2 2004 and MC2010) and non-linear finite element analysis. A novel practical strut-and-tie model was developed for the case of multiple point load applied to the tension face of the beams. This model correctly predicted the failure plane, fairly represented the stress field, and it is suitable for multiple loads applied entirely inside or partly outside the shear enhancement zone.Open Acces
Abrogating the Interaction Between p53 and Mortalin (Grp75/HSPA9/mtHsp70) for Cancer Therapy: The Story so far
Lysine degradation by ruminal Fusobacterium necrophorum
Three experiments were conducted to characterize lysine fermentation by Fusobacterium necrophorum, a ruminal bacterium that is known to degrade amino acids. In Experiment 1, 7 strains of Fusobacterium necrophorum were inoculated into media containing lysine (50 mM), lactate (50 mM), or lysine plus lactate (50 mM each) as the major energy substrate to evaluate growth and ammonia production. All strains grew with lysine, lactate, or lactate plus lysine as the primary substrate. When grown with lysine, all strains produced ammonia as an end product, even if lactate was also present. Smaller concentrations of ammonia for medium containing lactate plus lysine when compared with lysine alone indicate that the Fusobacterium strains used lactate as a growth substrate that stimulated utilization of ammonia. In Experiment 2, the 2 strains tested were able to degrade extensively both lysine and glutamic acid. Some evidence was detected for partial utilization for growth of histidine, methionine, and tryptophan by strain A21. In Experiment 3, the minimum inhibitory concentration (MIC) of the antibiotic tylosin was 25 μg/mL when Fusobacterium necrophorum strains A21 and B35 were grown in either lysine or lactate-enriched medium. The MIC of monensin was 6.25 and 3.9 μg/mL for strains A21 and B35, respectively, when grown in lysine-enriched medium, but \u3e 50 and 10.9 μg/mL when the strains were grown in lactate-enriched medium. These findings may lead to ways that ruminal lysine degradation may be controlled.; Dairy Day, 2010, Kansas State University, Manhattan, KS, 2010; Dairy Research, 2010 is known as Dairy Day, 201
Bioavailability of lysine from hydroxymethyl lysine
Twelve mature sheep were used as a ruminant model to estimate the bioavailability of lysine in hydroxymethyl lysine (HML) compared with a commercial product of rumen-protected lysine (RPL; LysiPEARL, Kemin Industries, Inc.) with known availability. The sheep were fed a diet with a forage to concentrate ratio similar to that of dairy diets. Following a control period in which plasma lysine was measured when sheep received no supplemental lysine, the sheep were provided 2 of 4 treatments during periods 2 and 3; treatments included RPL to provide 3 or 6 g/day of available lysine (actual amounts of product provided were based on the manufacturer\u27s data related to ruminal escape and intestinal availability) and 3 or 6 g/day of lysine provided as HML. Blood samples were collected at the end of each feeding period at 3 hours after feeding. Both HML and RPL significantly increased plasma lysine concentrations. By comparison with plasma lysine concentrations when known amounts of bioavailable lysine were provided as RPL, the bioavailability of lysine in HML was estimated to be 94%. Results indicate that HML may be an effective means of supplementing lysine to dairy cattle.; Dairy Day, 2010, Kansas State University, Manhattan, KS, 2010; Dairy Research, 2010 is known as Dairy Day, 201
Unlocking Dendritic Cell-Based Vaccine Efficacy through Genetic Modulation:How Soon Is Now?
The dendritic cell (DC) vaccine anti-cancer strategy involves tumour-associated antigen loading and maturation of autologous ex vivo cultured DCs, followed by infusion into the cancer patient. This strategy stemmed from the idea that to induce a robust anti-tumour immune response, it was necessary to bypass the fundamental immunosuppressive mechanisms of the tumour microenvironment that dampen down endogenous innate immune cell activation and enable tumours to evade immune attack. Even though the feasibility and safety of DC vaccines have long been confirmed, clinical response rates remain disappointing. Hence, the full potential of DC vaccines has yet to be reached. Whether this cellular-based vaccination approach will fully realise its position in the immunotherapy arsenal is yet to be determined. Attempts to increase DC vaccine immunogenicity will depend on increasing our understanding of DC biology and the signalling pathways involved in antigen uptake, maturation, migration, and T lymphocyte priming to identify amenable molecular targets to improve DC vaccine performance. This review evaluates various genetic engineering strategies that have been employed to optimise and boost the efficacy of DC vaccines
Utilising SMES-FCL to improve the transient behaviour of a doubly fed induction generator DC wind system
Wind energy is seen as one of the main pillars of renewable energy. However, the intermittent nature of these sources still poses as a major challenge. Moreover, sensitivity to grid faults and response to load changes are also main concerns. Superconducting devices have been introduced to solve grid faults and energy storage problems associated with renewable energy sources. Nevertheless, the cost of superconducting materials was still a major drawback for their application in power grids. In this paper, a novel power electronics circuit is used to connect the superconducting magnetic energy storage (SMES) to a DC system based on a doubly fed induction generator wind turbine. The proposed system merges energy storage function and the fault current limiting function into one device which is referred to as SMES-FCL in this paper. The role played by the SMES-FCL is studied under various scenarios that may affect the whole system. The study of the system is carried in MATLAB/SIMULINK where the system is simulated in standalone and grid-connected modes. In the end, the proposed SMES-FCL control circuit is tested in a small-scale DC system experimentally
Investigation of the Immunomodulatory effect of Berberis vulgaris on core-pulsed dendritic cell vaccine
Identification and Characterization of MortaparibPlus—A Novel Triazole Derivative That Targets Mortalin-p53 Interaction and Inhibits Cancer-Cell Proliferation by Wild-Type p53-Dependent and -Independent Mechanisms
p53 has an essential role in suppressing the carcinogenesis process by inducing cell cycle arrest/apoptosis/senescence. Mortalin/GRP75 is a member of the Hsp70 protein family that binds to p53 causing its sequestration in the cell cytoplasm. Hence, p53 cannot translocate to the nucleus to execute its canonical tumour suppression function as a transcription factor. Abrogation of mortalin-p53 interaction and subsequent reactivation of p53’s tumour suppression function has been anticipated as a possible approach in developing a novel cancer therapeutic drug candidate. A chemical library was screened in a high-content screening system to identify potential mortalin-p53 interaction disruptors. By four rounds of visual assays for mortalin and p53, we identified a novel synthetic small-molecule triazole derivative (4-[(1E)-2-(2-phenylindol-3-yl)-1-azavinyl]-1,2,4-triazole, henceforth named MortaparibPlus). Its activities were validated using multiple bioinformatics and experimental approaches in colorectal cancer cells possessing either wild-type (HCT116) or mutant (DLD-1) p53. Bioinformatics and computational analyses predicted the ability of MortaparibPlus to competitively prevent the interaction of mortalin with p53 as it interacted with the p53 binding site of mortalin. Immunoprecipitation analyses demonstrated the abrogation of mortalin-p53 complex formation in MortaparibPlus-treated cells that showed growth arrest and apoptosis mediated by activation of p21WAF1, or BAX and PUMA signalling, respectively. Furthermore, we demonstrate that MortaparibPlus-induced cytotoxicity to cancer cells is mediated by multiple mechanisms that included the inhibition of PARP1, up-regulation of p73, and also the down-regulation of mortalin and CARF proteins that play critical roles in carcinogenesis. MortaparibPlus is a novel multimodal candidate anticancer drug that warrants further experimental and clinical attention
Contribution of coagulation factor VII R353Q polymorphism to the risk of thrombotic disorders development (venous and arterial): A case-control study
Background: Elevated factor VII (FVII) level is a risk factor for thromboembolic disorders. It was reported that the FVII R353Q polymorphism is associated with variation in plasma FVII levels, where Q allele carriers were more associated with lower levels of FVII than R allele carriers. However, the association between coagulation FVII R353 Q polymorphisms and the risk of thrombosis is uncertain.Aim of the study: Is to investigate the contribution of factor VII R353Q gene polymorphism to the risk of thrombotic disorders development (venous and arterial) in a group of Egyptian patients.Subjects and methods: This study was conducted on 310 subjects: 110 acute myocardial infarction (AMI) patients, 108 deep venous thrombosis (DVT) patients and 92 healthy controls. FVII R353Q genotypes were assessed using restriction fragment length polymorphism analysis.Results: There were no statistically significant differences in the frequency of FVII R353Q polymorphism between each of the AMI and DVT patients and the control group (P = 0.9, 0.1). However the Q allele showed a significantly higher frequency in the AMI group (15.4%) vs. controls (8.7%) (OR: 1.92; 95% CI: 0.98–3.7). Bivariate analysis demonstrated no significant association between FVII R353Q genotypes and different studied risk factors, neither in arterial nor venous thrombosis.Conclusion: FVII R353Q polymorphism did not contribute to an increased risk of thrombosis (arterial and venous); also carrying the Q allele (of R353Q) did not confer protection against acute thrombotic events
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