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Background Germline mutations in BAP1 have been associated with BAP1 -Tumor Predisposition Syndrome ( BAP1 -TPDS), a predisposition to multiple tumors within a family that includes uveal melanoma (UM), cutaneous melanoma, malignant mesothelioma and renal cell carcinoma. Alternatively, somatic mutations in BAP1 in UM have been associated with high risk for metastasis. In this study, we compare the risk of metastasis in UM that carry germline versus somatic BAP1 mutations and mutation-negative tumors. Methods DNA extracted from 142 UM and matched blood samples was sequenced using Sanger or next generation sequencing to identify BAP1 gene mutations. Results Eleven of 142 UM (8%) carried germline BAP1 mutations, 43 (30%) had somatic mutations, and 88 (62%) were mutation-negative. All BAP1 mutations identified in blood samples were also present in the matched UM. There were 52 unique mutations in 54 tumors. All were pathogenic or likely pathogenic. A comparison of tumors carrying somatic vs. germline mutations, or no mutations, showed a higher frequency of metastasis in tumors carrying somatic mutations: 74% vs. 36%, P =0.03 and 74% vs. 26% P <0.001, respectively. Tumors with a somatic mutation compared to mutation-negative had an older age of diagnosis of (61.8 vs. 52.2 years, P =0.002), and shorter time to metastasis (16 vs. 26 months, P =0.04). Kaplan-Meier analysis further showed that tumors with somatic (vs. germline) mutations demonstrated a greater metastatic risk ( P =0.03). Cox multivariate analysis showed in addition to chromosome-3 monosomy and larger tumor diameter, the presence of BAP1 somatic, but not germline mutations, was significantly associated with risk of metastasis( P =0.02). Personal or family history of BAP1 -TPDS was available for 79 of the cases. All eight cases with germline mutations reported a history of BAP1 -TPDS, which was significantly greater than what was observed in cases with somatic mutations (10 of 23, P =0.009) or mutation-negative cases (11 of 48, P <0.001). Conclusions Defining germline vs. somatic nature of BAP1 mutations in UM can inform the individual about both the risk of metastasis, and the time to metastasis, which are critically important outcomes for the individual. This information can also change the cascade screening and surveillance of family members.

Background Mesenchymal stem/stromal cells (MSCs) have attracted interest as a potential therapy given their anti-inflammatory and immunomodulatory properties. However, clinical trials using MSCs for acute respiratory distress syndrome (ARDS) have produced mixed and inconclusive data. In previous work, we performed a “head-to-head” comparison between different sources of MSCs and showed that each source had a unique genomic and proteomic “signature”. Method This study investigated which sources of MSC: bone marrow derived-MSCs (BM-MSCs), adipose tissue derived-MSCs (AD-MSCs) and umbilical cord derived-MSCs (UC-MSCs)  would be the optimal candidate to be used as a therapy in an LPS-induced mouse model of ARDS. Immune cells assessment, tissue transcriptomics, animal survival, and endothelial-epithelial barrier assessment were used to evaluate their effects. Results When comparing the three most commonly used MSC sources, we found that UC-MSCs exhibited greater efficacy compared to other MSCs in improving animal survival, mitigating epithelial/endothelial damage, decreasing lung inflammation via reducing neutrophil infiltration, T cell proliferation, and M1 polarization. Bulk RNA sequencing of lung tissue also showed that UC-MSCs have the capability to downregulate extracellular trap formation, by the downregulation of key genes like Elane and Padi4 . Notably, treatment with UC-MSCs demonstrated a significant reduction in Fc-γ R mediated phagocytosis, which has been associated with monocyte pyroptosis and intense inflammation in the context of COVID-19. Conclusion Our findings suggest that UC-MSCs are an optimal source of MSC to treat acute inflammatory conditions in the lungs, such as ARDS.

Multilayer insulation (MLI) technique has provided a reliable thermal protection mechanism for cryostat’s cold wall boundary against the ambient heat load, in particular, the thermal radiation heat load. The aim of the current work is to attain an improved thermal performance from MLI technique by scrutinizing its insulation potential in terms of the heat load. The intervening medium in this investigation is made up of three suitable spacer and radiation shield materials: perforated Double Aluminized Mylar (DAM) with Dacron, perforated DAM with Glass−tissue, and unperforated DAM with Silk−net. The thermal performance of MLI system is evaluated by exploring the impact of associated physical parameters such as emissivity and residual gas pressure, geometry of the radiation shields (perforation styles of radiation shields), and analyzing the effect of the radiation shield’s arrangement on the heat load. We have observed that for perforated DAM with Dacron, the radiation heat load is the lowest. A medium vacuum level < 0.01 Torr, perforation style PS A in the radiation shield (in low−temperature region), and positioning radiation shields with decreasing spacing from the cold to hot wall boundary region facilitates a significant reduction in the heat load.

In this paper, a novel scheme of a solar powered vapour absorption refrigeration supported greenhouse with indirect evaporative cooler has been proposed. The main objective of this work is to create a favorable microclimatic condition for strawberry cultivation inside the greenhouse for a country with sub-tropical climatic conditions like India when the ambient temperature and humidity are high. The maximum yield of strawberry is achieved for a temperature ranging between 15-25 °C with a relative humidity varying from 55 to 65%. It is quite impossible to achieve a favorable temperature range for strawberry cultivation in the greenhouse under such condition by using the existing greenhouse cooling techniques. A double effect parallel flow LiBr-H 2 O absorption cooling system along with an IDEC powered through solar energy has been used. A thermal model for the greenhouse has been developed and analyzed for the climatic condition of Kolkata, India. The study reveals that the proposed system can very well maintain a conducive climate for the growth of target plantation for the given location.

In this paper, a novel scheme of biomass regenerated desiccant supported greenhouse cooling with distributed fan-pad evaporative system has been proposed. The system aims to provide suitable thermal condition inside the greenhouse for cultivation of high value flowers like varieties of Orchid which require a temperature between 21 °C to 26 °C and humidity from 50 to 70% for the sub-tropical climate prvailing in the plains of India. In the proposed system two stage desiccant based cooling is used to obtain a low humidity ratio. A biomass based heating system is coupled for regeneration of the desiccant. Thermal modeling of desiccant wheel and greenhouse are done to estimate air temperature inside the greenhouse. A comparative study has been made based on estimated greenhouse air temperature with the results of the reference model available in the literature. From the performance analysis of the proposed system, it is revealed that the maximum temperature of the greenhouse air can be restricted within 25 °C and 25.8 °C for a hot and humid day prevailing in the month of July and September respectively. However the system can maintain a lower temperature of 19 °C during the morning time which is more conducive for target plantation (Orchid) in the given region.

Cirrhinus reba (Hamilton, 1822) has gained high recognition in southern Asia for its nutritional and commercial benefits, although the carp is now facing productivity constraints. Probiotic-based captive breeding of the carp can be a promising technique to enhance the productivity and health status of the carp. The comprehensive study was performed on bacteria in the intestinal tract of C. reba . The total load of culturable bacteria in the gut of the carp was (8.34 ± 1.64) × 10 7 CFU/g comprising 19 different types of colonies. Most (73.7%) of the isolates were Gram-positive and rod-shaped bacteria. Among them, two intestinal isolates (PKS9 and PKS10) had shown significant antagonism against common fish pathogens namely, Staphylococcus aureus , Vibrio harveyi , and Vibrio parahaemolyticus . 16S rDNA sequencing identified the isolates PKS9 and PKS10 as Bacillus paramycoides (OM038513) and Bacillus cereus (OM033468), respectively. The isolates were determined to be biofilm formers, could persist in both acidic and alkaline environments, had high resistance to bile salts, possess surface hydrophobicity and auto-aggregation efficacy. The tests on pathogenicity and bio-safety confirmed the non-pathogenic nature of the isolates. Moreover, the strains had liberated extracellular enzymes and exhibited antioxidative properties. Hence, the isolates might be used as potential candidate probiotics for the cultivation of C. reba to enhance the nutritional and health status of the species. To the best of our knowledge, this is the first report analyzing the gut microbiota of Reba carp and establishing B. paramycoides as aquaculture probiotics.

Heat stress proteins assist cellular proteins in the acquisition of native structure. The present research was conducted to study how thermo-tolerance is modulated by HSP90 and HSP70 gene polymorphism and its association with hemato-physio-biochemical parameters, supported by their expression profiles in Chokla, Magra, Marwari, and Madras Red sheep breeds. Least square analysis revealed significant effect (P < 0.05) of season and breed on all the physiological parameters, i.e., temperature, respiratory rate, and pulse rate (a.m. and p.m.), as well as hematological parameters like Hb, packed cell volume, total erythrocyte count (TEC), neutrophil/lymphocyte (N/L) ratio, and total leukocyte count (TLC). There was a significant influence (P < 0.05) of breed on biochemical parameters such as glucose, SGOT, phosphorous, triglyceride, and cholesterol. Eight fragments were amplified and sequenced in HSP90, and 70 genes and 13 single-nucleotide polymorphisms (SNPs) were identified. Tetra-primer amplification refractory mutation system PCR, PCR-RFLP, and allele-specific PCR genotyping protocols were developed for large-scale genotyping of five SNPs. A significant difference (P < 0.05) of rectal temperature (a.m.), respiratory rate (p.m.), triglyceride, and total protein was observed at SNP01; albumin at SNP2; pulse rate (p.m.) at SNP3; and rectal temperature (p.m.), pulse rate (p.m.), Hb (g/dL), and N/L ratio at SNP4 and TLC at SNP5. Gene expression analysis revealed lower expression in less adapted animals with Madras Red < Magra < Chokla < Marwari expression pattern. Predominant allele was found to be superior in most of the SNPs (SNP1—4) indicating the selection acting in directional manner (positive selection). Finally, it is concluded that TACCA haplotype combination of SNP1-SNP2-SNP3-SNP4-SNP5 might be of some selection advantage for the identification of animals more adaptable to heat stress.

Background HHT is an autosomal dominant disease with an estimated prevalence of at least 1/5000 which can frequently be complicated by the presence of clinically significant arteriovenous malformations in the brain, lung, gastrointestinal tract and liver. HHT is under-diagnosed and families may be unaware of the available screening and treatment, leading to unnecessary stroke and life-threatening hemorrhage in children and adults. Objective The goal of this international HHT guidelines process was to develop evidence-informed consensus guidelines regarding the diagnosis of HHT and the prevention of HHT-related complications and treatment of symptomatic disease. Methods The overall guidelines process was developed using the AGREE framework, using a systematic search strategy and literature retrieval with incorporation of expert evidence in a structured consensus process where published literature was lacking. The Guidelines Working Group included experts (clinical and genetic) from eleven countries, in all aspects of HHT, guidelines methodologists, health care workers, health care administrators, HHT clinic staff, medical trainees, patient advocacy representatives and patients with HHT. The Working Group determined clinically relevant questions during the pre-conference process. The literature search was conducted using the OVID MEDLINE database, from 1966 to October 2006. The Working Group subsequently convened at the Guidelines Conference to partake in a structured consensus process using the evidence tables generated from the systematic searches. Results The outcome of the conference was the generation of 33 recommendations for the diagnosis and management of HHT, with at least 80% agreement amongst the expert panel for 30 of the 33 recommendations.

A novel symmetric structure of bipolar charge-plasma transistor (BCPT) is presented. It consists of symmetrical gates with platinum on top of a thin intrinsic silicon film, which forms hole plasma in emitter and collector regions. The base contact is formed with hafnium metal to induce electron plasma; hence, a p–n–p charge-plasma transistor is formed without any doping. The collector area that is chosen is the same as an emitter to make the device symmetrical. 2D simulation results revealed that the proposed BCPT possesses higher collector current and higher current gain than conventional p–n–p bipolar junction transistor (BJT) and almost the same characteristics such as asymmetrical p–n–p BCPT for different geometries. The major challenge of poor cut-off frequency (fT) of BCPT is also addressed by optimising the silicon film thickness and intrinsic gaps.