Damage estimation of low to medium rise reinforced concrete buildings considering vertical irregularity

In current study, Damage estimation is carried out using new methodology using parameters such as absorbed energy and degrading stiffness by pushover analysis. A new stiffness-based damage index is developed for each increasing step of pushover analysis, which takes into account the cumulative effects of increasing each lateral load and displacement. Non-cumulative absorbed energy-based damage index is calculated using the pushover curve's first maximal hysteretic cycle. These suggested methods can be utilised to quickly calculate the global damage index for low to medium rise vertical irregular buildings. The proposed two methods are evaluated using three regular and vertical irregular buildings considering various parameters such as varying heights, setback orientations, plastic hinges and monotonic loads. Furthermore, existing deformation and strength-based damage indices are used to calibrate the proposed damage indices. Both proposed damage indices may calculate damage index at any point on the pushover curve, however the damage indices are computed at different performance levels. The research based on damage index showed that two approaches for evaluating damage to irregular buildings are easy to use and accurate, Also, using the results of pushover analysis, structural designers may estimate the global damage index as a performance criterion in  short period of time

Damage estimation of low to medium rise reinforced concrete buildings considering vertical irregularity

In current study, Damage estimation is carried out using new methodology using parameters such as absorbed energy and degrading stiffness by pushover analysis. A new stiffness-based damage index is developed for each increasing step of pushover analysis, which takes into account the cumulative effects of increasing each lateral load and displacement. Non-cumulative absorbed energy-based damage index is calculated using the pushover curve's first maximal hysteretic cycle. These suggested methods can be utilised to quickly calculate the global damage index for low to medium rise vertical irregular buildings. The proposed two methods are evaluated using three regular and vertical irregular buildings considering various parameters such as varying heights, setback orientations, plastic hinges and monotonic loads. Furthermore, existing deformation and strength-based damage indices are used to calibrate the proposed damage indices. Both proposed damage indices may calculate damage index at any point on the pushover curve, however the damage indices are computed at different performance levels. The research based on damage index showed that two approaches for evaluating damage to irregular buildings are easy to use and accurate, Also, using the results of pushover analysis, structural designers may estimate the global damage index as a performance criterion in  short period of time

Comparison of Peptide Array Substrate Phosphorylation of c-Raf and Mitogen Activated Protein Kinase Kinase Kinase 8

Kinases are pivotal regulators of cellular physiology. The human genome contains more than 500 putative kinases, which exert their action via the phosphorylation of specific substrates. The determinants of this specificity are still only partly understood and as a consequence it is difficult to predict kinase substrate preferences from the primary structure, hampering the understanding of kinase function in physiology and prompting the development of technologies that allow easy assessment of kinase substrate consensus sequences. Hence, we decided to explore the usefulness of phosphorylation of peptide arrays comprising of 1176 different peptide substrates with recombinant kinases for determining kinase substrate preferences, based on the contribution of individual amino acids to total array phosphorylation. Employing this technology, we were able to determine the consensus peptide sequences for substrates of both c-Raf and Mitogen Activated Protein Kinase Kinase Kinase 8, two highly homologous kinases with distinct signalling roles in cellular physiology. The results show that although consensus sequences for these two kinases identified through our analysis share important chemical similarities, there is still some sequence specificity that could explain the different biological action of the two enzymes. Thus peptide arrays are a useful instrument for deducing substrate consensus sequences and highly homologous kinases can differ in their requirement for phosphorylation events

Vascular Remodeling in Health and Disease

The term vascular remodeling is commonly used to define the structural changes in blood vessel geometry that occur in response to long-term physiologic alterations in blood flow or in response to vessel wall injury brought about by trauma or underlying cardiovascular diseases.1, 2, 3, 4 The process of remodeling, which begins as an adaptive response to long-term hemodynamic alterations such as elevated shear stress or increased intravascular pressure, may eventually become maladaptive, leading to impaired vascular function. The vascular endothelium, owing to its location lining the lumen of blood vessels, plays a pivotal role in regulation of all aspects of vascular function and homeostasis.5 Thus, not surprisingly, endothelial dysfunction has been recognized as the harbinger of all major cardiovascular diseases such as hypertension, atherosclerosis, and diabetes.6, 7, 8 The endothelium elaborates a variety of substances that influence vascular tone and protect the vessel wall against inflammatory cell adhesion, thrombus formation, and vascular cell proliferation.8, 9, 10 Among the primary biologic mediators emanating from the endothelium is nitric oxide (NO) and the arachidonic acid metabolite prostacyclin [prostaglandin I2 (PGI2)], which exert powerful vasodilatory, antiadhesive, and antiproliferative effects in the vessel wall

Increased phosphorylation on residue S795 of the retinoblastoma protein in esophageal adenocarcinoma

Due to its increasing incidence and relatively poor prognosis, esophageal adenocarcinoma (EAC) is becoming a significant health problem. Elucidating the mechanisms underlying EAC development is of great importance to improve upon current conventional treatment strategies. Insight into phosphorylation has proven to be useful for the development of diagnostic and molecular treatment strategies in cancer. A pathway largely dependent on phosphorylation and frequently deregulated in cancer is the cell cycle regulating p16-retinoblastoma (Rb) pathway. We investigated kinase activity, specifically phosphorylation within the p16-Rb pathway, in EAC. A high-throughput peptide tyrosine kinase array containing short peptides representing 100 proteins with known phosphorylation sites, was used to assess phosphorylation activity in EAC. Also, specific phosphorylation changes of the cell cycle protein Rb and its upstream regulator P16 were validated through immunoblotting in EAC and normal esophageal cells and tissues. Phosphorylation activity was higher in EAC tissues as compared to normal squamous esophageal tissues. A majority of the proteins significantly higher phosphorylated in EAC were found to be involved in cell structure maintenance and immunity. Validation of Rb phosphorylation in EAC biopsy specimens and cell lines showed hyper phosphorylation of Rb associated with aberrant P16 expression in the cancer tissues. The specific Rb (S795) residue was significantly higher phosphorylated in EAC compared to normal esophageal tissue (Wilcoxon paired rank test, p=0.004). Investigation of Rb (S795) phosphorylation may indicate targets for intervention and give more molecular insight in EA

Socio-demographic, Epidemiological and Environmental Determinants of Acute Gastroenteritis in Western India

Introduction: An outbreak of acute gastroenteritis had occurred in Rajpara village of Bhavnagar district. The objective of this study was to find out the socio-demographic, epidemiological and environmental determinants of this outbreak. Methods: A case-control study was conducted in Rajpara village among 238 cases of acute gastroenteritis and an equal number of controls in January 2015. Multiple logistic regression was used for identifying the variables independently predicting acute gastroenteritis. Results: Upper socio-economic status, occupation requiring travel outside village, source of drinking water from well of ‘new’ Rajpara village, change in taste of water, use of chlorine tablets, travel outside village in last week, another family member affected with acute gastroenteritis, using common utensil for hand washing, hand washing before eating, ate food from outside in last week, having sanitary latrine at house, waste disposal in a common dump (instead of at house), waste accumulation around house and flies inside house were significantly associated with occurrence of acute gastroenteritis. On multiple logistic regression, change in taste of water (P<0.001), waste disposal in a common dump (P=0.012), another family member been affected (P<0.001), waste accumulation around house (P<0.001), higher socio-economic status (P=0.002) and eating outside food (P=0.011) made a significant contribution to prediction. Conclusions: Socio-demographic factors (higher socio-economic status), epidemiological correlates (change in taste of water, another family member been affected with acute gastroenteritis and eating outside food) and environmental determinants (waste disposal in a common dump and waste accumulation around house) significantly determines the occurrence of cases of acute gastroenteritis. Keywords: case-control studies;diarrhea; epidemiologic determinants; gastroenteritis; social determinants of health. | PubMe

Practical consensus recommendations on management of HR + ve early breast cancer with specific reference to genomic profiling

Breast cancer is a heterogeneous disease and patients are managed clinically based on ER, PR, HER2 expression, and key risk factors. The use of gene expression assays for early stage disease is already common practice. These tests have found a place in risk stratifying the heterogeneous group of stage I–II breast cancers for recurrence, for predicting chemotherapy response, and for predicting breast cancer-related mortality. Most guidelines for hormone receptor (HR)–positive early breast cancer recommend addition of adjuvant chemotherapy for most women, leading to overtreatment, which causes considerable morbidity and cost. Expert oncologist discussed about strategies of gene expression assays and aid in chemotherapy recommendations for treatment of HR + ve EBC and the expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at this practical consensus recommendations for the benefit of community oncologists