Search results for " Basic"

A Molecular Dynamics-Shared Pharmacophore Approach to Boost Early-Enrichment Virtual Screening: A Case Study on Peroxisome Proliferator-Activated Rec…

2016

Molecular dynamics (MD) simulations can be used, prior to virtual screening, to add flexibility to proteins and study them in a dynamic way. Furthermore, the use of multiple crystal structures of the same protein containing different co-crystallized ligands can help elucidate the role of the ligand on a protein's active conformation, and then explore the most common interactions between small molecules and the receptor. In this work, we evaluated the contribution of the combined use of MD on crystal structures containing the same protein but different ligands to examine the crucial ligand-protein interactions within the complexes. The study was carried out on peroxisome proliferator-activat…

VBA-ohjelmoinnin mahdollisuudet raportoinnin ja etähuollon kehityksessä

2005

Supporting Impact Analysis by Program Dependence Graph Based Forward Slicing

2007

Since software must evolve to meet the typically changing requirements, source code modifications can not be avoided. Impact analysis is one of the central and relatively demanding tasks of software maintenance. It is constantly needed while aiming at ensuring the correctness of the made modifications. Due to its importance and challenging nature automated support techniques are required. Theoretically, forward slicing is a very suitable technique for that purpose. Therefore, we have implemented a program dependence graph (PDG) based tool, called GRACE, for it. For example, due to the typical rewritings of Visual Basic programs there is a great need to support their impact analysis. However…

Hypoxia Positively Regulates the Expression of pH-Sensing G-Protein–Coupled Receptor OGR1 (GPR68)

2016

Background & Aims: A novel family of proton-sensing G-proteinâcoupled receptors, including ovarian cancer G-proteinâcoupled receptor 1 (OGR1) (GPR68) has been identified to play a role in pH homeostasis. Hypoxia is known to change tissue pH as a result of anaerobic glucose metabolism through the stabilization of hypoxia-inducible factor-1α. We investigated how hypoxia regulates the expression of OGR1 in the intestinal mucosa and associated cells. Methods: OGR1 expression in murine tumors, human colonic tissue, and myeloid cells was determined by quantitative reverse-transcription polymerase chain reaction. The influence of hypoxia on OGR1 expression was studied in monocytes/macrophages and…

Wee1 inhibition potentiates Wip1-dependent p53-negative tumor cell death during chemotherapy

2016

AbstractInactivation of p53 found in more than half of human cancers is often associated with increased tumor resistance to anti-cancer therapy. We have previously shown that overexpression of the phosphatase Wip1 in p53-negative tumors sensitizes them to chemotherapeutic agents, while protecting normal tissues from the side effects of anti-cancer treatment. In this study, we decided to search for kinases that prevent Wip1-mediated sensitization of cancer cells, thereby interfering with efficacy of genotoxic anti-cancer drugs. To this end, we performed a flow cytometry-based screening in order to identify kinases that regulated the levels of γH2AX, which were used as readout. Another criter…

Disentangling canid howls across multiple species and subspecies: Structure in a complex communication channel

2016

Wolves, coyotes, and other canids are members of a diverse genus of top predators of considerable conservation and management interest. Canid howls are long-range communication signals, used both for territorial defence and group cohesion. Previous studies have shown that howls can encode individual and group identity. However, no comprehensive study has investigated the nature of variation in canid howls across the wide range of species. We analysed a database of over 2000 howls recorded from 13 different canid species and subspecies. We applied a quantitative similarity measure to compare the modulation pattern in howls from different populations, and then applied an unsupervised clusteri…

Continuous Theta-Burst Stimulation Intensity Dependently Facilitates Motor-Evoked Potentials Following Focal Electrical Stimulation of the Rat Motor …

2020

Although theta-burst stimulation (TBS) is known to differentially modify motor cortical excitability according to stimulus conditions in humans, whether similar effects can be seen in animals, in particular rats, remains to be defined. Given the importance of experimental rat models for humans, this study explored this stimulation paradigm in rats. Specifically, this study aimed to explore corticospinal excitability after TBS in anesthetized animals to confirm its comparability with human results. Both inhibition-facilitation configurations using paired electrical stimulation protocols and the effects of the TBS paradigm on motor-evoked potentials (MEPs) in rat descending motor pathways wer…

Targeting NUPR1 with the Small Compound ZZW-115 Is an Efficient Strategy to Treat Hepatocellular Carcinoma

2020

International audience; HCC is a highly lethal malignancy with Sorafenib as the only molecularly targeted drug. The multifunctional stress-associated protein, NUPR1, plays an essential role in controlling cell growth, migration, invasion and Sorafenib resistance in HCC. We report here that NUPR1 expression is absent in healthy liver and it is progressively upregulated in HCC premalignant lesions such as hepatitis and cirrhosis with a maximum expression in HCC samples, highlighting that NUPR1 is a potential drug target for HCC. We therefore assessed in this work, ZZW-115, a strong inhibitor of NUPR1, as a promising candidate for the treatment of HCC. We validated its extraordinary antitumor …

Building Anosov flows on $3$–manifolds

2014

We prove a result allowing to build (transitive or non-transitive) Anosov flows on 3-manifolds by gluing together filtrating neighborhoods of hyperbolic sets. We give several applications; for example: 1. we build a 3-manifold supporting both of a transitive Anosov vector field and a non-transitive Anosov vector field; 2. for any n, we build a 3-manifold M supporting at least n pairwise different Anosov vector fields; 3. we build transitive attractors with prescribed entrance foliation; in particular, we construct some incoherent transitive attractors; 4. we build a transitive Anosov vector field admitting infinitely many pairwise non-isotopic trans- verse tori.

Le vécu des sujets atteints de sclérose en plaques : modalités intersubjectives et conjugalité, stratégies adaptatives

2016

Supplément consacré aux Journées de Neurologie de langue française 2016; International audience; Introduction : Notre recherche porte sur l’illness, maladie du point de vue du malade, évènement corporel et psychique qui réorganise la vie psychique du sujet, influence son rapport à autrui.Objectifs : Nos objectifs consistent en l’évaluation et l’analyse de la perception des sujets quant à leur vécu émotionnel, leurs modalités intersubjectives, leurs stratégies adaptatives et leurs liens éventuels.Patients et méthodes : L’échantillon se compose de 79 sujets porteurs de SEP rémittente-récurrente (suivis EDMUS ; EDSS : m = 2,75[2,06] ; durée SEP : m = 10,47[6,08]). Sept auto-évaluations ont été…