Reinforced Concrete Beams with Drop-in- Ends of Vertical and Inclined Reinforcement and having Pockets Loaded by In-Plane Static Forces

This research presents an experimental investigation on the behaviour of RC dapped end beams with loaded openings that have been strengthened initially with four different techniques including steel fibre concrete, inclined crossed bars, jacketing with steel plates and the composite section technique. Ten specimens with a rectangular opening at the midspan are tested under in-plane point load within opening. Such beams are categorized into two groups with five specimens per group. The dapped end zone of the first group is reinforced with standard vertical stirrups, while for the other groups inclined bar reinforcement has been used. Two main parameters have been considered which are the detailing of the reinforcement around the opening and the effect of inclusion of the dapped ends. The response has been discussed in terms the first cracking load, ultimate load, maximum deflection, failure modes, load-deflection curves, crack patterns, crack width, to recognize the optimum strengthening proposal of the opening. Results indicated that the modified reinforcement configurations of the dapped ends yielded better response and the ultimate load increased when adopting the composite section method in (21-23%) relative to the conventional beams.  Regarding strengthening by steel SFRC method, an improvement in load capacity by (8-10%) has been observed. Whereas, strengthening with crossed inclined bars yielded an enhancement of (8.5-11%). Furthermore, using steel plates increases the load capacity by about (11-13%)

Reinforced Concrete Beams with Drop-in- Ends of Vertical and Inclined Reinforcement and having Pockets Loaded by In-Plane Static Forces

This research presents an experimental investigation on the behaviour of RC dapped end beams with loaded openings that have been strengthened initially with four different techniques including steel fibre concrete, inclined crossed bars, jacketing with steel plates and the composite section technique. Ten specimens with a rectangular opening at the midspan are tested under in-plane point load within opening. Such beams are categorized into two groups with five specimens per group. The dapped end zone of the first group is reinforced with standard vertical stirrups, while for the other groups inclined bar reinforcement has been used. Two main parameters have been considered which are the detailing of the reinforcement around the opening and the effect of inclusion of the dapped ends. The response has been discussed in terms the first cracking load, ultimate load, maximum deflection, failure modes, load-deflection curves, crack patterns, crack width, to recognize the optimum strengthening proposal of the opening. Results indicated that the modified reinforcement configurations of the dapped ends yielded better response and the ultimate load increased when adopting the composite section method in (21-23%) relative to the conventional beams.  Regarding strengthening by steel SFRC method, an improvement in load capacity by (8-10%) has been observed. Whereas, strengthening with crossed inclined bars yielded an enhancement of (8.5-11%). Furthermore, using steel plates increases the load capacity by about (11-13%)

Review of the AMLAS Methodology for Application in Healthcare

In recent years, the number of machine learning (ML) technologies gaining regulatory approval for healthcare has increased significantly allowing them to be placed on the market. However, the regulatory frameworks applied to them were originally devised for traditional software, which has largely rule-based behaviour, compared to the data-driven and learnt behaviour of ML. As the frameworks are in the process of reformation, there is a need to proactively assure the safety of ML to prevent patient safety being compromised. The Assurance of Machine Learning for use in Autonomous Systems (AMLAS) methodology was developed by the Assuring Autonomy International Programme based on well-established concepts in system safety. This review has appraised the methodology by consulting ML manufacturers to understand if it converges or diverges from their current safety assurance practices, whether there are gaps and limitations in its structure and if it is fit for purpose when applied to the healthcare domain. Through this work we offer the view that there is clear utility for AMLAS as a safety assurance methodology when applied to healthcare machine learning technologies, although development of healthcare specific supplementary guidance would benefit those implementing the methodology

Adherence to Immunosuppressive Medications in Kidney Transplant Patients at Three Centers in Khartoum State, Sudan: A Cross-sectional Hospital Study

Background: Graft survival post-kidney transplantation is of paramount importance to patients and nephrologists. Nonadherence to immunosuppressive therapy can be associated with deterioration of renal function and graft rejection. This study aimed to evaluate the adherence to immunosuppressive medications in kidney transplant patients at three centers in Khartoum, Sudan. Methods: In this descriptive cross-sectional hospital-based survey, 277 post-kidneytransplant patients were recruited. Data were collected using a questionnaire and analyzed using the SPSS v.23. Our scoring method was calculated based on Morisky Medication Adherence Scale (MMAS-8) related to immunosuppressive medications and was expressed as questions in the questionnaire; every correct answer was given one mark, then the marks were gathered and their summation was expressed. Results: Overall, 33% ,45%, and 22% of the studied participants reported high, medium, and low adherence, respectively. The major factor for nonadherence was forgetfulness affecting 36.1% of those who did not adhere. The cost of the immunosuppressive medications did not negatively affect any of the participants’ adherence (100%). However, a significant association was seen between adherence and occupational status, duration of transplantation, shortage of immunosuppressants, recognizing the name of immunosuppressant, side effect, and forgetfulness (P-values = 0.002, 0.01, 0.006 , 0.000, 0.022, and 0.000, respectively). Logistic regression analysis showed a significant association with occupational status, side effects, and forgetfulness Conclusion: Only one-third of the participants were classed as “highly adherent” to their immunosuppressant medications. Factors that can affect adherence to immunosuppressant medications were occupational status, side effects, and forgetfulness

Interaction of eukaryotic proliferating cell nuclear antigen (PCNA) with the replication-associated protein (Rep) of cotton leaf curl Multan virus and pedilanthus leaf curl virus.

peer reviewedThe replication-associated (Rep) proteins of pathogenic begomoviruses, including cotton leaf curl Multan virus (CLCuMuV) and pedilanthus leaf curl virus (PeLCV), interact with the DNA replication machinery of their eukaryotic hosts. The analysis of Rep protein sequences showed that there is 13-28% sequence variation among CLCuMuV and PeLCV isolates, with phylogenetic clusters that can separated at least in part based on the country of origin of the respective viruses. To identify specific host factors involved in the virus replication cycle, we conducted yeast two-hybrid assays to detect possible interactions between the CLCuMuV and PeLCV Rep proteins and 30 protein components of the Saccharomyces cerevisiae DNA replication machinery. This showed that the proliferating cell nuclear antigen (PCNA) protein of S. cerevisiae interacts with Rep proteins from both CLCuMuV and PeLCV. We used the yeast PCNA sequence in BLAST comparisons to identify two PCNA orthologs each in Gossypium hirsutum (cotton), Arabidopsis thaliana (Arabidopsis), and Nicotiana benthamiana (tobacco). Sequence comparisons showed 38-40% identity between the yeast and plant PCNA proteins, and > 91% identity among the plant PCNA proteins, which clustered together in one phylogenetic group. The expression of the six plant PCNA proteins in the yeast two-hybrid system confirmed interactions with the CLCuMuV and PeLCV Rep proteins. Our results demonstrate that the interaction of begomovirus Rep proteins with eukaryotic PCNA proteins is strongly conserved, despite significant evolutionary variation in the protein sequences of both of the interacting partners

Use and outcomes of antihypertensive medication treatment in the US hypertensive population: A gender comparison

Background: Although effective antihypertensive medications have existed for decades, only about half of the hypertensive individuals are considered to have controlled blood pressure. Limited research studies have investigated gender disparity in the utilization and effectiveness of antihypertensive medications treatment. To examine the gender difference in antihypertensive medications’ use and the effect of using antihypertensive medication treatment on blood pressure control among the U.S. adult with hypertension. Methods: Analysis of National Health and Nutrition Examination Survey (NHANES) data from (1999-2012) including individuals≥18 years old with hypertension. Study variables included gender, age, race/ethnicity, obesity, smoking, comorbidities, treatment medication type, and continuity of care. We used multivariate logistic regression in STATA V14. The data is presented as adjusted odds ratios (ORs) and 95% confidence interval (CI). Results: Of the 15719 participants, 52% were female. 49% of the antihypertensive medication users had their blood pressure under control (95% CI). In the adjusted logistic regression analysis, use of antihypertensive medications was found to be 12% greater in females as compared to males (OR=1.12; CI=1.02-1.22; P<0.05). No association between gender and blood pressure control was found. Blood pressure control was less likely achieved among 50 years or younger individuals, Blacks and Hispanics, obese, and those taking calcium channel blocker (CCB). Conclusion: Hypertensive females are more likely than males to use antihypertensive medications. The effectiveness of treatment to control blood pressure is equal across males and females. Our findings have implications for practitioners to account gender-specific approaches when discussing adherence to hypertension medication treatment with their patients

REPercussions: how geminiviruses recruit host factors for replication

Circular single-stranded DNA viruses of the family Geminiviridae encode replication-associated protein (Rep), which is a multifunctional protein involved in virus DNA replication, transcription of virus genes, and suppression of host defense responses. Geminivirus genomes are replicated through the interaction between virus Rep and several host proteins. The Rep also interacts with itself and the virus replication enhancer protein (REn), which is another essential component of the geminivirus replicase complex that interacts with host DNA polymerases α and δ. Recent studies revealed the structural and functional complexities of geminivirus Rep, which is believed to have evolved from plasmids containing a signature domain (HUH) for single-stranded DNA binding with nuclease activity. The Rep coding sequence encompasses the entire coding sequence for AC4, which is intricately embedded within it, and performs several overlapping functions like Rep, supporting virus infection. This review investigated the structural and functional diversity of the geminivirus Rep

Kaiso (ZBTB33) subcellular partitioning functionally links LC3A/B, the tumor microenvironment, and breast cancer survival

The use of digital pathology for the histomorphologic profiling of pathological specimens is expanding the precision and specificity of quantitative tissue analysis at an unprecedented scale; thus, enabling the discovery of new and functionally relevant histological features of both predictive and prognostic significance. In this study, we apply quantitative automated image processing and computational methods to profile the subcellular distribution of the multi-functional transcriptional regulator, Kaiso (ZBTB33), in the tumors of a large racially diverse breast cancer cohort from a designated health disparities region in the United States. Multiplex multivariate analysis of the association of Kaiso’s subcellular distribution with other breast cancer biomarkers reveals novel functional and predictive linkages between Kaiso and the autophagy-related proteins, LC3A/B, that are associated with features of the tumor immune microenvironment, survival, and race. These findings identify effective modalities of Kaiso biomarker assessment and uncover unanticipated insights into Kaiso’s role in breast cancer progression.Fil: Singhal, Sandeep K.. North Dakota State University; Estados UnidosFil: Byun, Jung S.. National Institutes of Health; Estados UnidosFil: Park, Samson. National Institutes of Health; Estados UnidosFil: Yan, Tingfen. National Institutes of Health; Estados UnidosFil: Yancey, Ryan. Columbia University; Estados UnidosFil: Caban, Ambar. Columbia University; Estados UnidosFil: Hernandez, Sara Gil. National Institutes of Health; Estados UnidosFil: Hewitt, Stephen M.. U.S. Department of Health & Human Services. National Institute of Health. National Cancer Institute; Estados UnidosFil: Boisvert, Heike. Ultivue, Inc; Reino UnidoFil: Hennek, Stephanie. Ultivue Inc.; Reino UnidoFil: Bobrow, Mark. Ultivue Inc.; Reino UnidoFil: Ahmed, Md Shakir Uddin. Tuskegee University; Estados UnidosFil: White, Jason. Tuskegee University; Estados UnidosFil: Yates, Clayton. Tuskegee University; Estados UnidosFil: Aukerman, Andrew. Columbia University; Estados UnidosFil: Vanguri, Rami. Columbia University; Estados UnidosFil: Bareja, Rohan. Columbia University; Estados UnidosFil: Lenci, Romina. Columbia University; Estados UnidosFil: Farré, Paula Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: de Siervi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Nápoles, Anna María. National Institutes of Health; Estados UnidosFil: Vohra, Nasreen. East Carolina University; Estados UnidosFil: Gardner, Kevin. Columbia University; Estados Unido

Acylsugars protect Nicotiana benthamiana against insect herbivory and desiccation.

peer reviewedKEY MESSAGE: Nicotiana benthamiana acylsugar acyltransferase (ASAT) is required for protection against desiccation and insect herbivory. Knockout mutations provide a new resource for investigation of plant-aphid and plant-whitefly interactions. Nicotiana benthamiana is used extensively as a transient expression platform for functional analysis of genes from other species. Acylsugars, which are produced in the trichomes, are a hypothesized cause of the relatively high insect resistance that is observed in N. benthamiana. We characterized the N. benthamiana acylsugar profile, bioinformatically identified two acylsugar acyltransferase genes, ASAT1 and ASAT2, and used CRISPR/Cas9 mutagenesis to produce acylsugar-deficient plants for investigation of insect resistance and foliar water loss. Whereas asat1 mutations reduced accumulation, asat2 mutations caused almost complete depletion of foliar acylsucroses. Three hemipteran and three lepidopteran herbivores survived, gained weight, and/or reproduced significantly better on asat2 mutants than on wildtype N. benthamiana. Both asat1 and asat2 mutations reduced the water content and increased leaf temperature. Our results demonstrate the specific function of two ASAT proteins in N. benthamiana acylsugar biosynthesis, insect resistance, and desiccation tolerance. The improved growth of aphids and whiteflies on asat2 mutants will facilitate the use of N. benthamiana as a transient expression platform for the functional analysis of insect effectors and resistance genes from other plant species. Similarly, the absence of acylsugars in asat2 mutants will enable analysis of acylsugar biosynthesis genes from other Solanaceae by transient expression

Profiling estrogen, progesterone, and androgen receptors in colorectal cancer in relation to gender, menopausal status, clinical stage, and tumour sidedness

BackgroundAlthough estrogen (ERα/ERβ), progesterone (PGR), and androgen (AR) receptors are pathologically altered in colorectal cancer (CRC), their simultaneous expression within the same cohort of patients was not previously measured.MethodsERα/ERβ/PGR/AR proteins were measured in archived paired normal and malignant colon specimens (n =120 patients) by immunohistochemistry, and results were analyzed by gender, age (≤50 vs. ≥60 years), clinical stages (early-stage I/II vs. late-stage III/IV), and anatomical location (right; RSCs vs. left; LSCs). Effects of 17β-estradiol (E2), progesterone (P4), and testosterone alone or combined with the specific blockers of ERα (MPP dihydrochloride), ERβ (PHTPP), PGR (mifepristone), and AR (bicalutamide) on cell cycle and apoptosis were also measured in the SW480 male and HT29 female CRC cell lines. ResultsERα and AR proteins increased, whilst ERβ and PGR declined markedly in malignant specimens. Moreover, male neoplastic tissues showed highest AR expression, whilst ERβ and PGR weakest alongside ERα strongest expression was seen in cancerous tissues from women aged ≥60 years. Late-stage neoplasms also revealed maximal alterations in the expression of sex steroid receptors. By tumor location, LSCs disclosed significant elevations in ERα with marked declines in PGR compared with RSCs, and ERα strongest alongside PGR weakest expression was detected in advanced LSCs from women aged ≥60 years. Late-stage LSCs from females aged ≥60 years also showed weakest ERβ and strongest AR expression. In contrast, male RSC and LSC tissues exhibited equal ERβ and AR expression in all clinical stages. ERα and AR proteins also correlated positively, whereas ERβ and PGR inversely, with tumor characteristics. Concomitantly, E2 and P4 monotherapies triggered cell cycle arrest and apoptosis in the SW480 and HT29 cells, and while pre-treatment with ERα-blocker enhanced the effects of E2, ERβ-blocker and PGR-blocker suppressed the E2 and P4 anti-cancer actions, respectively. In contrast, treatment with the AR-blocker induced apoptosis, whilst co-treatment with testosterone hindered the effects. ConclusionsThis study advocates that protein expression of sex steroid receptors in malignant tissues could represent prognostic markers, as well as hormonal therapy could provide an alternative strategy against CRC, and their efficacies could be dependent on gender, clinical stage, and tumor location