Initial Filling of Tehri Reservoir — Analysis of Seepage Data

Initial Filling of reservoirs in dams, particularly the embankment type, is a very important phase as unusual behaviour / accidents of many dams have been reported during this period. A regular observation / analysis of quantum of seepage vis-à-vis the reservoir level is a significant activity so that any serious development inside the body of dam and foundation / abutments rocks are revealed in advance and remedial measures are taken up timely to prevent catastrophic failures. At Tehri, a 260.5m high earth & rockfill dam has been constructed across river Bhagirathi, a tributary of mighty river Ganga in India. Seepage discharge data of first two years of Initial Filling of Tehri reservoir has been analysed, which has led to a few important conclusions. The Analysis of Seepage data for the Initial Filling of Tehri reservoir is presented in the paper

Initial Filling of Tehri Reservoir — Analysis of Seepage Data

Initial Filling of reservoirs in dams, particularly the embankment type, is a very important phase as unusual behaviour / accidents of many dams have been reported during this period. A regular observation / analysis of quantum of seepage vis-à-vis the reservoir level is a significant activity so that any serious development inside the body of dam and foundation / abutments rocks are revealed in advance and remedial measures are taken up timely to prevent catastrophic failures. At Tehri, a 260.5m high earth & rockfill dam has been constructed across river Bhagirathi, a tributary of mighty river Ganga in India. Seepage discharge data of first two years of Initial Filling of Tehri reservoir has been analysed, which has led to a few important conclusions. The Analysis of Seepage data for the Initial Filling of Tehri reservoir is presented in the paper

Racial Differences in the Association Between Luminal Master Regulator Gene Expression Levels and Breast Cancer Survival

Compared with their European American (EA) counterparts, African American (AA) women are more likely to die from breast cancer in the United States. This disparity is greatest in hormone receptor-positive subtypes. Here we uncover biological factors underlying this disparity by comparing functional expression and prognostic significance of master transcriptional regulators of luminal differentiation.Fil: Byun, Jung S.. National Institutes of Health; Estados UnidosFil: Singhal, Sandeep K.. Columbia University; Estados UnidosFil: Park, Samson. National Institutes of Health; Estados UnidosFil: Yi, Dae Ik. National Institutes of Health; Estados UnidosFil: Yan, Tingfen. National Institutes of Health; Estados UnidosFil: Caban, Ambar. Columbia University Medical Center; Estados UnidosFil: Jones, Alana. National Institutes of Health; Estados UnidosFil: Mukhopadhyay, Partha. Columbia University Medical Center; Estados UnidosFil: Gille, Sarah. National Institutes of Health; Estados UnidosFil: Hewitt, Stephen M.. No especifíca;Fil: Newman, Lisa. No especifíca;Fil: Davis, Melissa B.. Henry Ford Health System; Estados UnidosFil: Jenkins, Brittany D.. Henry Ford Health System; Estados UnidosFil: Sepulveda, Jorge L.. Columbia University Medical Center; Estados UnidosFil: 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 Institute On Minority Health And Health Disparities; Estados UnidosFil: Vohra, Nasreen A.. East Carolina University; Estados UnidosFil: Gardner, Kevin. Columbia University Medical Center; Estados Unido

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

Daksha: On Alert for High Energy Transients

We present Daksha, a proposed high energy transients mission for the study of electromagnetic counterparts of gravitational wave sources, and gamma ray bursts. Daksha will comprise of two satellites in low earth equatorial orbits, on opposite sides of earth. Each satellite will carry three types of detectors to cover the entire sky in an energy range from 1 keV to >1 MeV. Any transients detected on-board will be announced publicly within minutes of discovery. All photon data will be downloaded in ground station passes to obtain source positions, spectra, and light curves. In addition, Daksha will address a wide range of science cases including monitoring X-ray pulsars, studies of magnetars, solar flares, searches for fast radio burst counterparts, routine monitoring of bright persistent high energy sources, terrestrial gamma-ray flashes, and probing primordial black hole abundances through lensing. In this paper, we discuss the technical capabilities of Daksha, while the detailed science case is discussed in a separate paper.Comment: 9 pages, 3 figures, 1 table. Additional information about the mission is available at https://www.dakshasat.in

Science with the Daksha High Energy Transients Mission

We present the science case for the proposed Daksha high energy transients mission. Daksha will comprise of two satellites covering the entire sky from 1~keV to $>1$~MeV. The primary objectives of the mission are to discover and characterize electromagnetic counterparts to gravitational wave source; and to study Gamma Ray Bursts (GRBs). Daksha is a versatile all-sky monitor that can address a wide variety of science cases. With its broadband spectral response, high sensitivity, and continuous all-sky coverage, it will discover fainter and rarer sources than any other existing or proposed mission. Daksha can make key strides in GRB research with polarization studies, prompt soft spectroscopy, and fine time-resolved spectral studies. Daksha will provide continuous monitoring of X-ray pulsars. It will detect magnetar outbursts and high energy counterparts to Fast Radio Bursts. Using Earth occultation to measure source fluxes, the two satellites together will obtain daily flux measurements of bright hard X-ray sources including active galactic nuclei, X-ray binaries, and slow transients like Novae. Correlation studies between the two satellites can be used to probe primordial black holes through lensing. Daksha will have a set of detectors continuously pointing towards the Sun, providing excellent hard X-ray monitoring data. Closer to home, the high sensitivity and time resolution of Daksha can be leveraged for the characterization of Terrestrial Gamma-ray Flashes.Comment: 19 pages, 7 figures. Submitted to ApJ. More details about the mission at https://www.dakshasat.in

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe

Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Purification and characterization of poly-ε-lysine from <i>Streptomyces noursei </i>NRRL 5126

33-40The present article reports on the development of an effective downstream technique for the recovery of poly-ε-lysine (ε-PL), an unusual cationic homo-polyamide of L-lysine produced by fermentation using Streptomyces noursei NRRL 5126. Purification of ε-PL using cation exchange chromatography, ultrafiltration, solvent precipitation, and gel permeation chromatography was investigated. Loading of fermentation broth on Amberlite IRC 50 chromatographic column could purify the ε-PL with 95.84 % recovery. Subsequent fractionation with ultrafiltration (20kDa, and 5kDa) was found to be effective at minimal transmembrane pressure and optimal flux which resulted in 91.66 % product purity. Further, solvent precipitation and gel permeation chromatography which gave the highest possible purity (97.58%) and ε-PL yield (90.42%). Exclusion of ultrafiltration step negotiated the yield (88.62%) and purity (95.15) of ε-PL, if final application doesn’t demand highly pure sample. Characterization with respect to molecular weight, thin layer chromatography, IR and NMR confirmed the identity of ε-PL in purified sample