Dynamic Response Control of a Building Model using Bracings

AbstractConstruction of tall and flexible structures has become easier now-a-days because of advances in analytical techniques and availability of more efficient materials. However, these structures are more sensitive towards dynamic loadings. Dynamic response of such structures under various excitations can be quantified by displacement and acceleration response time history. Excessive dynamic response of structure leads to substantial damage to the structural components and hence it need to be controlled. Passively, this is achieved by adding either mass or stiffness or both of them. This paper covers experimental study on controlling dynamic response of a building model using two types of bracings, namely, Concentric- and Eccentric bracing. A building model is fabricated using aluminum flats and plates and bracings are fabricated using linear springs of moderate stiffness. A model represented as Single Degree of Freedom (SDOF) system is subjected to sinusoidal excitations of various frequencies through small scale shake table. Acceleration response of a uncontrolled building model (model without bracings) is obtained using accelerometers and Data Acquisition System (DAQ) – LabVIEW 8.0. Displacement response is derived through numerical integration from acceleration response using LabVIEW. Acceleration and displacement response of controlled building model (model with bracings) are extracted and compared with uncontrolled system. Dynamic properties like Natural Time Period and Damping Ratio for both types of bracing systems are obtained and comparisons are made among them. It is found that natural time period and damping ratio of controlled building model is increased as compared to uncontrolled system due to stiffness addition. Displacement and Acceleration response are reduced appropriately for controlled system as compared to uncontrolled system

Regulation of wound strength by Ocimum sanctum: in silico and in vivo evidences

Background: The present work has been an attempt to facilitate the scientific understanding of the wound strength by Ocimum sanctum (OS, holy basil) a traditional knowledge practiced since ancient times in India.Methods: The in vivo Incision (wound strength) and Dead space wound models (biochemical estimation of components of ECM) in rats and  In silico method, where one of the target proteins from each class of MMPs involved in wound strength was selected for molecular docking with eugenol (one of the flavonoid present in OS).Results: Molecular docking showed that eugenol was able to inhibit all selected MMPs, i.e. collagenase (-6.37 Kcal/mol), gelatinase (-5.99 Kcal/mol), elastase (-6.31 Kcal/mol) and stromelysin (-5.79 Kcal/mol). Ethanolic extract of Ocimum sanctum (OSE, 200-800 mg/kg) when administered as suspension showed dose-dependent increase in wound breaking strength in in vivo Incision wound rat model. OSE 400 mg/kg produced a significant increase in protein and collagen constituents like hydroxyproline, hexuronic acid and hexosamine in the connective tissue content of extracellular matrix when studied in Dead space wound model in rat.Conclusions: The present study is an attempt to correlate the in vivo findings on wound strength promoting activity by Ocimum sanctum with in silico tools

Type 1 Diabetes: Current Advances in High-Throughput Technologies and Computational Biology for Biomarker Studies

Biomarkers are essential for the identification of high-risk populations as well as the monitoring of preventive and therapeutic outcomes for type 1 diabetes (T1D). In this chapter, we will discuss the progress made in T1D biomarker discovery using high throughput genomic, transcriptomic, and proteomic technologies collectively called as omic technologies. We also discuss the potential of artificial intelligence and omics data in the early prediction of T1D. Readers will gain an overview of the status of T1D biomarkers based on omic technologies. High throughput omic technologies combined with computational biology offer great opportunities for biomarker discovery. As we move forward, the utilization of a biomarker panel for the prediction and prevention of T1D is needed

Lack of correlation between the levels of soluble cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and the CT-60 genotypes

BACKGROUND: Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) plays a critical role in downregulation of antigen-activated immune response and polymorphisms at the CTLA-4 gene have been shown to be associated with several autoimmune diseases including type-1 diabetes (T1D). The etiological mutation was mapped to the CT60-A/G single nucleotide polymorphism (SNP) that is believed to control the processing and production of soluble CTLA-4 (sCTLA-4). METHODS: We therefore determined sCTLA-4 protein levels in the sera from 82 T1D patients and 19 autoantibody positive (AbP) subjects and 117 autoantibody negative (AbN) controls using ELISA. The CT-60 SNP was genotyped for these samples by using PCR and restriction enzyme digestion of a 268 bp DNA segment containing the SNP. Genotyping of CT-60 SNP was confirmed by dye terminating sequencing reaction. RESULTS: Higher levels of sCTLA-4 were observed in T1D (2.24 ng/ml) and AbP (mean = 2.17 ng/ml) subjects compared to AbN controls (mean = 1.69 ng/ml) with the differences between these subjects becoming significant with age (p = 0.02). However, we found no correlation between sCTLA-4 levels and the CTLA-4 CT-60 SNP genotypes. CONCLUSION: Consistent with the higher serum sCTLA-4 levels observed in other autoimmune diseases, our results suggest that sCTLA-4 may be a risk factor for T1D. However, our results do not support the conclusion that the CT-60 SNP controls the expression of sCTLA-4

Molecular cloning and characterization of the mouse Acdp gene family

BACKGROUND: We have recently cloned and characterized a novel gene family named ancient conserved domain protein (ACDP) in humans. To facilitate the functional study of this novel gene family, we have cloned and characterized Acdp, the mouse homologue of the human ACDP gene family. RESULTS: The four Acdp genes (Acdp1, Acdp2, Acdp3 and Acdp4) contain 3,631 bp, 3,244 bp, 2,684 bp and 2,743 bp of cDNA sequences, and encode deduced proteins of 951, 874, 713 and 771 amino acids, respectively. The mouse Acdp genes showed very strong homologies (>90%) in both nucleotide and amino acid sequences to their human counterparts. In addition, both nucleotide and amino acid sequences within the Ancient Conserved Domain (ACD) are highly conserved in many different taxonomic species. Particularly, Acdp proteins showed very strong AA homologies to the bacteria CorC protein (35% AA identity with 55% homology), which is involved in magnesium and cobalt efflux. The Acdp genes are widely expressed in all tissues tested except for Acdp1, which is only highly expressed in the brain with low levels of expression in kidney and testis. Immunostaining of Acdp1 in hippocampus neurons revealed a predominant localization on the plasma membrane. CONCLUSION: The Acdp genes are evolutionarily conserved in diverse species and ubiquitously expressed throughout development and adult tissues suggesting that Acdp may be an essential gene. Acdp showed strong homology to bacteria CorC protein and predominantly localized on the plasma membrane. These results suggest that Acdp is probably a family of proteins involved in ion transport in mammalian cell

Multiplex glycan bead array for high throughput and high content analyses of glycan binding proteins

Glycan-binding proteins (GBPs) play critical roles in diverse cellular functions such as cell adhesion, signal transduction and immune response. Studies of the interaction between GBPs and glycans have been hampered by the availability of high throughput and high-content technologies. Here we report multiplex glycan bead array (MGBA) that allows simultaneous analyses of 384 samples and up to 500 glycans in a single assay. The specificity, sensitivity and reproducibility of MGBA are evaluated using 39 plant lectins, 13 recombinant anti-glycan antibodies, and mammalian GBPs. We demonstrate the utility of this platform by the analyses of natural anti-glycan IgM and IgG antibodies in 961 human serum samples and the discovery of anti-glycan antibody biomarkers for ovarian cancer. Our data indicate that the MGBA platform is particularly suited for large population-based studies that require the analyses of large numbers of samples and glycans

Chemokine (C-C Motif) Ligand 2 (CCL2) in Sera of Patients with Type 1 Diabetes and Diabetic Complications

Chemokine (C-C motif) ligand 2 (CCL2), commonly known as monocyte chemoattractant protein-1 (MCP-1), has been implicated in the pathogenesis of many diseases characterized by monocytic infiltration. However, limited data have been reported on MCP-1 in type 1 diabetes (T1D) and the findings are inconclusive and inconsistent.In this study, MCP-1 was measured in the sera from 2,472 T1D patients and 2,654 healthy controls using a Luminex assay. The rs1024611 SNP in the promoter region of MCP-1 was genotyped for a subset of subjects (1764 T1D patients and 1323 controls) using the TaqMan-assay.Subject age, sex or genotypes of MCP-1 rs1024611SNP did not have a major impact on serum MCP-1 levels in either healthy controls or patients. While hemoglobin A1c levels did not have a major influence on serum MCP-1 levels, the mean serum MCP-1 levels are significantly higher in patients with multiple complications (mean = 242 ng/ml) compared to patients without any complications (mean = 201 ng/ml) (p = 3.5×10(-6)). Furthermore, mean serum MCP-1 is higher in controls (mean = 261 ng/ml) than T1D patients (mean = 208 ng/ml) (p<10(-23)). More importantly, the frequency of subjects with extremely high levels (>99(th) percentile of patients or 955 ng/ml) of serum MCP-1 is significantly lower in the T1D group compared to the control group (odds ratio = 0.11, p<10(-33)).MCP-1 may have a dual role in T1D and its complications. While very high levels of serum MCP-1 may be protective against the development of T1D, complications are associated with higher serum MCP-1 levels within the T1D group

Senescence-Associated Secretory Phenotype Determines Survival and Therapeutic Response in Cervical Cancer

Molecular biomarkers that can predict survival and therapeutic outcome are still lacking for cervical cancer. Here we measured a panel of 19 serum proteins in sera from 565 patients with stage II or III cervical cancer and identified 10 proteins that have an impact on disease specific survival (DSS) (Hazzard&rsquo;s ratio; HR = 1.51&ndash;2.1). Surprisingly, all ten proteins are implicated in senescence-associated secreted phenotype (SASP), a hallmark of cellular senescence. Machine learning using Ridge regression of these SASP proteins can robustly stratify patients with high SASP, which is associated with poor survival, and patients with low SASP associated with good survival (HR = 3.09&ndash;4.52). Furthermore, brachytherapy, an effective therapy for cervical cancer, greatly improves survival in SASP-high patients (HR = 3.3, p &lt; 5 &times; 10&minus;5) but has little impact on survival of SASP-low patients (HR = 1.5, p = 0.31). These results demonstrate that cellular senescence is a major determining factor for survival and therapeutic response in cervical cancer and suggest that senescence reduction therapy may be an efficacious strategy to improve the therapeutic outcome of cervical cancer

Chronic Kidney Disease: Role of Diet for a Reduction in the Severity of the Disease

Chronic kidney disease affects ~37 million adults in the US, and it is often undiagnosed due to a lack of apparent symptoms in early stages. Chronic kidney disease (CKD) interferes with the body’s physiological and biological mechanisms, such as fluid electrolyte and pH balance, blood pressure regulation, excretion of toxins and waste, vitamin D metabolism, and hormonal regulation. Many CKD patients are at risk of hyperkalemia, hyperphosphatemia, chronic metabolic acidosis, bone deterioration, blood pressure abnormalities, and edema. These risks may be minimized, and the disease’s progression may be slowed through careful monitoring of protein, phosphorus, potassium, sodium, and calcium, relieving symptoms experienced by CKD patients. In this review, the current Kidney Disease Outcomes Quality Initiative (KDOQI) recommendations are highlighted, reflecting the 2020 update, including explanations for the pathophysiology behind the recommendations. The Dietary Approaches to Stop Hypertension, the Mediterranean diet, and the whole foods plant-based diet are currently being examined for their potential role in delaying CKD progression. Biological explanations for why the whole foods plant-based diet may benefit CKD patients compared to diets that include animal products are examined. Strong evidence continues to support the importance of diet meeting the daily requirement in the prevention and progression of kidney disease, and medical nutrition therapy with a registered dietitian is a critical aspect in medical intervention for CKD