ESTABLISHMENT OF NOVEL URINARY KIDNEY DISEASE NEW BIOMARKERS AND THERAPEUTIC EFFECT OF METHANOL FRACTION OF TERMINALIA ARJUNA ON ACETAMINOPHEN INDUCED KIDNEY DISEASE IN RATS

Objective: There were main two objectives, first was the identification of best biomarkers for early screening of kidney diseases whether plasma urea and creatinine or novel urinary low molecular weight protein biomarkers Interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), and cystatin-C. Second was the therapeutic efficacy of methanol fraction of Terminalia arjuna (MFTA) on urinary novel biomarkers. Methods: A total of 35 adult male rats were divided into three Groups (n=5), Group 1 was fed normal food, Group 2, normal food with administration of acetaminophen (APAP) for 5 days, 10 days, and 15 days, and Group 3, normal food with administration of APAP and coadministration of MFTA for 5 days, 10 days, and 15 days. All rats were sacrificed at 15th day of the experiment. Results: Results showed 5 days, 10 days, and 15 days administrations of APAP increased novel urinary biomarkers as IL-18, KIM-1 near two-folds and cystatin-C near six-folds increased than old biomarkers plasma urea and plasma creatinine. Administration of APAP with coadministration of MFTA represented the protective effect by decreasing old and new novel biomarkers with superoxide dismutase and catalase but malondialdehyde level increased. Sodium dodecyle sulphate-polyacrylamide gel electrophoresis showed new low molecular weight urinary protein bands in APAP administration rats, the protective effect of MFTA presents no band at this molecular level as normal rats. Conclusion: MFTA is the most potent nephroprotective agent, and urinary low molecular proteins are the best thing diagnostic tools for early detection of kidney disease over common plasma urea and creatinine

Improved performance of immobilized lipase from optimized biosupport material (polyvinyl alcohol/AlgNa) and its characterization

Enzymes play an imminent role as biocatalyst for various biotechnological applications as well as production of biodiesel. Here, we focused on the preparation of biosupport materials (polyvinyl alcohol/AlgNa) and their use in immobilization of lipase from Pseudomonas cepacia. Lipase was successfully immobilized onto polyvinyl alcohol/AlgNa in the form of biosupport materials by entrapment method. The mechanical strength, swelling ratio, thermal properties, optimum temperature and pH, lipase loading, leaching, immobilization yields and activity, characterization of the support materials were performed. The optimized pH and temperature for free lipase were 8.0 and 40°C, respectively, while the best pH and temperature for polyvinyl alcohol/AlgNa immobilized lipase were 8.0 and 50°C. 73.12% of the initial activity was retained for the immobilized biosupport catalyst in 6 cycles. The biosupport catalyst beads showed a fascinating degree of immobilized lipase activity along with high immobilization yield. The highest immobilized lipase activity and loading efficiency found to be 87.28 (U/g) and 55.2%, respectively. SEM analysis confirms the development of macro-porous structure from the combination of alginate. No sharp chemical interaction was observed in the behaviour of the functional groups of polyvinyl alcohol and AlgNa in the polyvinyl alcohol/sodium alginate blends, which were confirmed from Fourier transform infrared (FTIR) spectra. The immobilized biosupport catalysts are easily separable, recyclable and could be frequently used for transesterification

Improved performance of immobilized lipase from optimized biosupport material (polyvinyl alcohol/AlgNa) and its characterization

803-810Enzymes play an imminent role as biocatalyst for various biotechnological applications as well as production of biodiesel. Here, we focused on the preparation of biosupport materials (polyvinyl alcohol/AlgNa) and their use in immobilization of lipase from Pseudomonas cepacia. Lipase was successfully immobilized onto polyvinyl alcohol/AlgNa in the form of biosupport materials by entrapment method. The mechanical strength, swelling ratio, thermal properties, optimum temperature and pH, lipase loading, leaching, immobilization yields and activity, characterization of the support materials were performed. The optimized pH and temperature for free lipase were 8.0 and 40°C, respectively, while the best pH and temperature for polyvinyl alcohol/AlgNa immobilized lipase were 8.0 and 50°C. 73.12% of the initial activity was retained for the immobilized biosupport catalyst in 6 cycles. The biosupport catalyst beads showed a fascinating degree of immobilized lipase activity along with high immobilization yield. The highest immobilized lipase activity and loading efficiency found to be 87.28 (U/g) and 55.2%, respectively. SEM analysis confirms the development of macro-porous structure from the combination of alginate. No sharp chemical interaction was observed in the behaviour of the functional groups of polyvinyl alcohol and AlgNa in the polyvinyl alcohol/sodium alginate blends, which were confirmed from Fourier transform infrared (FTIR) spectra. The immobilized biosupport catalysts are easily separable, recyclable and could be frequently used for transesterification

High-Efficiency Photodetector Based On CVD-Grown WS2_2 Monolayer

Future generation technologies demand high efficiency photodetectors to enable sensing and switching devices for ultrafast communication and machine vision. This require direct-band gap materials with high photosensitivity, high detectivity and high quantum efficiency. Monolayered two- Dimensional (2D)-Semiconductors based photodetectors are the most promising materials for such applications, although experimental realization has been limited due to unavailability of high quality sample. In the current manuscript, we report about WS$_2$ based photodetector having sensitivity of 290 AW-1 upon 405 nm excitation and incident power density as low as 0.06 mW/cm$^2$. The fabricated device shows detectivity of 52*10^14 with external quantum efficiency of 89*10$^3$%. The observed superior photo-response parameters of CVD grown WS$_2$ based photodetector as compared to Si-detectors establishes it capability to replace the Si-photodetectors with monolayered ultrathin device having superior performance parameters.Comment: 26 Pages, 8 figure

Attitudes of Fruit and Vegetable Farmers towards Organic Farming in Kathmandu Valley, Nepal

Organic farming is increasingly popular among the farmers of Kathmandu valley. However, the organic growers have been facing issues in production, organic certification, and product marketing. To date, little is known about the challenges faced by the organic growers in Kathmandu valley. This study aimed to explore the status of organic farming, attitudes of farmers towards organic farming, their suggestions for improvement, and strengthening the value chain of organic products. Face-to-face interviews were conducted at Agriculture Knowledge Centre, Lalitpur, Nepal during December 2019 with 37 organic growers directly or indirectly involved in organic farming. The results showed that organic growers face challenges in marketing and institutional recognition. Challenges in product certification and marketing were reported by 45.95% of the total interviewed organic growers while following organic practices (transitional organic). Our study suggested that reducing the cost of production through easy access to organic inputs like organic seeds, fertilizers, and biopesticides are highly desired by the growers. Participatory Guarantee System (PGS) or group certification along with collective marketing could be the policy implications to address the issues. Organic farming in Kathmandu valley is limited to a niche market; however, due to increasing consumer demand for safe, fresh, and local food, the popularity of organic products is extending to other regions within the country

Flavor and CP violating Z exchange and the rate asymmetry in B --> phi K_S

Recent measurements of time dependent CP asymmetry in B --> phi K_S, if confirmed, would indicate a new source of CP violation. We examine flavor violating tree-level Z currents in models with extra down-type quark singlets that arise naturally in string compactified gauge groups like E_6. We evaluate the new operators at the scale mu = m_b in NLO, and using QCD improved factorization to describe B --> phi K_S, find the allowed range of parameters for rho and psi, the magnitude and phase of the flavor violating parameter U_{bs}. This allowed range does satisfy the constraint from flavor changing process b --> s l+ l- . However, further improvement in measurement of these rates could severely constrain the model.Comment: 15 pages, Latex, 2 postscript figures. Sections 2 and 3 are reordered. More references are added. Version to be published in PL

Obesity-Associated Alterations in Inflammation, Epigenetics, and Mammary Tumor Growth Persist in Formerly Obese Mice

Using a murine model of basal-like breast cancer, we tested the hypothesis that chronic obesity, an established breast cancer risk and progression factor in women, induces mammary gland epigenetic reprogramming and increases mammary tumor growth. Moreover, we assessed whether the obesity-induced epigenetic and protumor effects are reversed by weight normalization. Ovariectomized female C57BL/6 mice were fed a control diet or diet-induced obesity (DIO) regimen for 17 weeks, resulting in a normal weight or obese phenotype, respectively. Mice on the DIO regimen were then randomized to continue the DIO diet or were switched to the control diet, resulting in formerly obese (FOb) mice with weights comparable to control mice. At week 24, all mice were orthotopically injected with MMTV-Wnt-1 mouse mammary tumor cells. Mean tumor volume, serum IL-6 levels, expression of pro-inflammatory genes in the mammary fat pad, and mammary DNA methylation profiles were similar in DIO and FOb mice, and higher than in controls. Many of the genes found to have obesity-associated hypermethylation in mice were also found to be hypermethylated in the normal breast tissue of obese versus non-obese human subjects, and nearly all of these concordant genes remained hypermethylated after significant weight loss in the FOb mice. Our findings suggest that weight normalization may not be sufficient to reverse the effects of chronic obesity on epigenetic reprogramming and inflammatory signals in the microenvironment that are associated with breast cancer progression

Lobular Carcinomas In Situ Display Intralesion Genetic Heterogeneity and Clonal Evolution in the Progression to Invasive Lobular Carcinoma

Purpose:; Lobular carcinoma; in situ; (LCIS) is a preinvasive lesion of the breast. We sought to define its genomic landscape, whether intralesion genetic heterogeneity is present in LCIS, and the clonal relatedness between LCIS and invasive breast cancers.; Experimental Design:; We reanalyzed whole-exome sequencing (WES) data and performed a targeted amplicon sequencing validation of mutations identified in 43 LCIS and 27 synchronous more clinically advanced lesions from 24 patients [9 ductal carcinomas; in situ; (DCIS), 13 invasive lobular carcinomas (ILC), and 5 invasive ductal carcinomas (IDC)]. Somatic genetic alterations, mutational signatures, clonal composition, and phylogenetic trees were defined using validated computational methods.; Results:; WES of 43 LCIS lesions revealed a genomic profile similar to that previously reported for ILCs, with; CDH1; mutations present in 81% of the lesions. Forty-two percent (18/43) of LCIS were found to be clonally related to synchronous DCIS and/or ILCs, with clonal evolutionary patterns indicative of clonal selection and/or parallel/branched progression. Intralesion genetic heterogeneity was higher among LCIS clonally related to DCIS/ILC than in those nonclonally related to DCIS/ILC. A shift from aging to APOBEC-related mutational processes was observed in the progression from LCIS to DCIS and/or ILC in a subset of cases.; Conclusions:; Our findings support the contention that LCIS has a repertoire of somatic genetic alterations similar to that of ILCs, and likely constitutes a nonobligate precursor of breast cancer. Intralesion genetic heterogeneity is observed in LCIS and should be considered in studies aiming to develop biomarkers of progression from LCIS to more advanced lesions

Phase II Trial of Bicalutamide in Patients with Androgen Receptor-Positive, Estrogen Receptor-Negative Metastatic Breast Cancer

Patients with hormone receptor–negative breast cancer generally do not benefit from endocrine-targeted therapies. However, a subset with androgen receptor (AR) expression is predicted to respond to antiandrogen therapies. This phase II study explored bicalutamide in AR-positive, estrogen receptor (ER), and progesterone receptor (PgR)-negative metastatic breast cancer

Activation Status of Wnt/ß-Catenin Signaling in Normal and Neoplastic Breast Tissues: Relationship to HER2/neu Expression in Human and Mouse

Wnt/ß-catenin signaling is strongly implicated in neoplasia, but the role of this pathway in human breast cancer has been controversial. Here, we examined Wnt/ß-catenin pathway activation as a function of breast cancer progression, and tested for a relationship with HER2/neu expression, using a human tissue microarray comprising benign breast tissues, ductal carcinoma in situ (DCIS), and invasive carcinomas. Cores were scored for membranous ß-catenin, a key functional component of adherens junctions, and for nucleocytoplasmic ß-catenin, a hallmark of Wnt/ß-catenin pathway activation. Only 82% of benign samples exhibited membrane-associated ß-catenin, indicating a finite frequency of false-negative staining. The frequency of membrane positivity was similar in DCIS samples, but was significantly reduced in carcinomas (45%, P<0.001), consistent with loss of adherens junctions during acquisition of invasiveness. Negative membrane status in cancers correlated with higher grade (P = 0.04) and estrogen receptor-negative status (P = 0.03), both indices of poor prognosis. Unexpectedly, a substantial frequency of nucleocytoplasmic ß-catenin was observed in benign breast tissues (36%), similar to that in carcinomas (35%). Positive-staining basal nuclei observed in benign breast may identify putative stem cells. An increased frequency of nucleocytoplasmic ß-catenin was observed in DCIS tumors (56%), suggesting that pathway activation may be an early event in human breast neoplasia. A correlation was observed between HER2/neu expression and nucleocytoplasmic ß-catenin in node-positive carcinomas (P = 0.02). Furthermore, cytoplasmic ß-catenin was detected in HER2/neu-induced mouse mammary tumors. The Axin2NLSlacZ mouse strain, a previously validated reporter of mammary Wnt/ß-catenin signaling, was utilized to define in vivo transcriptional consequences of HER2/neu-induced ß-catenin accumulation. Discrete hyperplastic foci observed in mammary glands from bigenic MMTV/neu, Axin2NLSlacZ mice, highlighted by robust ß-catenin/TCF signaling, likely represent the earliest stage of mammary intraepithelial neoplasia in MMTV/neu mice. Our study thus provides provocative evidence for Wnt/ß-catenin signaling as an early, HER2/neu-inducible event in breast neoplasia