Regulation of NF-κB signaling and cell cycle progression by microRNA-30c-2-3p in breast cancer

NF-κB signaling is frequently deregulated in a variety of cancers and is constitutively active in estrogen receptor negative breast cancer subtypes. These molecular subtypes of breast cancer are associated with poor overall survival. During my PhD work, I focused on mechanisms of NF-κB regulation in breast cancer by miRNAs, key regulators of eukaryotic gene expression, which bind their target mRNAs via seed sequences and inhibit gene expression at the post transcriptional level. In a previous study, miR-30c-2-3p was found to be one of the strongest negative regulators of NF-κB signaling in a genome-wide miRNA screen. I uncovered the underlying molecular mechanisms by which miR-30c-2-3p regulates NF-κB signaling and cell cycle progression in breast cancer by combining in vitro data with publically available breast cancer patient datasets. I could show that miR-30c-2-3p directly targets TRADD, an adaptor protein of the TNFR/NF-κB signaling pathway as well as the cell cycle protein, CCNE1. Ectopic expression of miR-30c-2-3p downregulated essential cytokines IL8, IL6 and CXCL1, reduced cell proliferation, and invasion in MDA-MB-231 breast cancer cells. RNAi-induced silencing of TRADD phenocopied the effects on invasion and cytokine expression also observed with miR-30c-2-3p, while inhibition of CCNE1 phenocopied the effects of the miRNA on cell proliferation. The tumor suppressive role of miR-30c-2-3p was confirmed in a cohort of 781 breast tumors with matched mRNA and miRNA expression data where higher expression of miR-30c-2-3p was associated with better survival. Furthermore an anticorrelation with expression of target genes and miR-30c-2-3p was seen in these breast cancer patients. These findings are important in the context of breast cancer where NF-κB signaling has been implicated to play a role in tumor initiation, progression, metastasis and resistance to chemotherapy. During my thesis work I could establish that miR-30c-2-3p negatively regulates both NF-κB signaling and cell cycle progression, that are two important signaling pathways frequently deregulated in breast cancer. As a result, miR-30c-2-3p directly effects several hallmarks of cancer cells, i.e., proliferation, expression of inflammatory cytokines as well as invasion, and can be potentially used for therapeutic intervention in miRNA based cancer therapy

Design of Microstrip Antenna for Wireless Applications

In this thesis, the focus is not in designing any antenna for a particular wireless application but a study on the existing antennas has been made and the methods by which their performance can be improved. The antennas chosen are the standard designs, ones which are most rampantly used in the wireless applications like the Bluetooth, Wi-Fi & Wireless LAN applications in the frequency range of 2.45GHz. An antenna was also designed taking into consideration the GSM band. The bandwidth of the antenna has been given special attention since data rate criterion have to be met apart from the resonant frequency. A circularly polarised antenna was also designed that could be optimised for GPS applications. Further in the thesis a Patch antenna calculator has been designed in MATLAB to reduce the repetitive task of finding the antenna dimension for a rectangular microstrip patch. A GUI has been developed using MATLAB GUIDE tool to provide a user-friendly interface. The calculations are done in the background for several antenna parameters using the cavity model for microstrip patch antenna. This GUI would be helpful in getting the basic idea about a few basic antenna parameters before the design, simulation and parametric analysis in software like CST Microwave Studio, HFSS and IE3D. To miniaturize the antennae further a metamaterial based approach has been incorporated. A comparative analysis of different conventional and metamaterial based microstrip patch antenna. A study of SRR based microstrip antenna and their equivalent circuits have been carried out. A unit cell of SRR has also been designed for the frequency of 10.25 GHz. Using such metamaterial unit cell a miniaturized microstrip patch antenna can be realised as per our requirements

Awareness, Practice and Level of Anxiety using Coronavirus Anxiety Scale among the Indian Population regarding COVID -19 Pandemic

Abstract: The most important aspect of Public Health Emergency Preparedness (PHEP) involves the circulation of trustworthy and accurate information in the public health interest domain. Strict stringency measures such as nationwide lockdown impacted people's mental health. Hence, this study was planned to assess the knowledge, practice, and anxiety among the Indian population about the ongoing pandemic in the initial phase. Methods: A web-based cross-sectional study was conducted between August 1, 2020, to October 5, 2020. Coronavirus Anxiety Scale was used to determine dysfunctional anxiety. Results: Among 553 participants, 73.6% had overall good knowledge of COVID-19 with mean correct score of 6.9±1.1. Majority of participants (97%) wore mask regularly, and 93% of respondents regularly washed their hands with soap and water. Only 14 participants scored ?9 on CAS, suggesting probable cases of dysfunctional anxiety associated with the COVID-19 crisis. Conclusion: The knowledge and practices of citizens in a nation reflect their preparedness and ability to deal with a pandemic of such proportion. Good knowledge translates to good practices and therefore reduces anxiety among the population. It is deemed necessary that people's knowledge and habits, including the mental impact, be accessed at periodic intervals to track their adaptation to pandemics over time

Global gene expression profiling data analysis reveals key gene families and biological processes inhibited by Mithramycin in sarcoma cell lines

AbstractThe role of Mithramycin as an anticancer drug has been well studied. Sarcoma is a type of cancer arising from cells of mesenchymal origin. Though incidence of sarcoma is not of significant percentage, it becomes vital to understand the role of Mithramycin in controlling tumor progression of sarcoma. In this article, we have analyzed the global gene expression profile changes induced by Mithramycin in two different sarcoma lines from whole genome gene expression profiling microarray data. We have found that the primary mode of action of Mithramycin is by global repression of key cellular processes and gene families like phosphoproteins, kinases, alternative splicing, regulation of transcription, DNA binding, regulation of histone acetylation, negative regulation of gene expression, chromosome organization or chromatin assembly and cytoskeleton

Co-Infection of HSV in Gonococcal Urethritis Patients

Co-infection with two different pathogens may alter the classical clinical course that manifests infection as single pathogen. In STIs, such co-infection may trigger the reactivation of a latent infection, and syndromic approach may not be insufficient to free the host of the entire gamut of infectivity agents. Present study analyzed appropriate samples for Neisseria gonorrheae and HSV from 200 patients presented to STI clinic. Gonorrhea was detected in 4% and HSV in 5% of patients. 25% of gonorrhea patients had HSV-2 co-infection with an overall 4.5% yield of subclinical HSV cases which would have been missed leading to inappropriate treatment, risk of recurrence and transmission to contacts. Awareness regarding encounter with multiple infections is necessary for effective management

Alcohol, Stem Cells and Cancer.

Dosage, gender, and genetic susceptibility to the effects of alcohol remained only partially elucidated. In this review, we summarize the current knowledge of the mechanisms underlying the role of alcohol in liver and gastrointestinal cancers. In addition, two recent pathways- DNA repair and TGF-β signaling which provide new insights into alcohol in the regulation of cancers and stem cells are also discussed here

Ectopic expression of DnaJ type-I protein homolog of Vigna aconitifolia (VaDJI) confers ABA insensitivity and multiple stress tolerance in transgenic tobacco plants

Reduced crop productivity results from altered plant physiological processes caused by dysfunctional proteins due to environmental stressors. In this study, a novel DnaJ Type-I encoding gene, VaDJI having a zinc finger motif in its C-terminal domain was found to be induced early upon treatment with heat stress (within 5 min) in a heat tolerant genotype of Vigna aconitifolia RMO-40. VaDJI is induced by multiple stresses. In tobacco, ectopic expression of VaDJI reduced ABA sensitivity during seed germination and the early stages of seedling growth of transgenic tobacco plants. Concomitantly, it also improved the ability of transgenic tobacco plants to withstand drought stress by modulating the photosynthetic efficiency, with the transgenic plants having higher Fv/Fm ratios and reduced growth inhibition. Additionally, transgenic plants showed a reduced build-up of H2O2 and lower MDA levels and higher chlorophyll content during drought stress, which attenuated cell damage and reduced oxidative damage. An analysis using the qRT-PCR study demonstrated that VaDJI overexpression is associated with the expression of some ROS-detoxification-related genes and stress-marker genes that are often induced during drought stress responses. These findings suggest a hypothesis whereby VaDJI positively influences drought stress tolerance and ABA signalling in transgenic tobacco, and suggests that it is a potential gene for genetic improvement of drought and heat stress tolerance in crop plants

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good