State of the Art in the Studies on Crotamine, a Cell Penetrating Peptide from South American Rattlesnake

Animal venoms comprise a naturally selected cocktail of bioactive peptides/proteins and other molecules, each of which playing a defined role thanks to the highly specific interactions with diverse molecular targets found in the prey. Research focused on isolation, structural, and functional characterizations of novel natural biologics (bioactive peptides/proteins from natural sources) has a long way to go through from the basic science to clinical applications. Herein, we overview the structural and functional characteristics of the myoneurotoxin crotamine, firstly isolated from the South American rattlesnake venom. Crotamine is the first venom peptide classified as a natural cell penetrating and antimicrobial peptide (CPP and AMP) with a more pronounced antifungal activity. in contrast to other known natural CPPs and AMPs, crotamine demonstrates a wide spectrum of biological activities with potential biotechnological and therapeutic values. More recent studies have demonstrated the selective in vitro anticancer activity of crotamine. in vivo, using a murine melanoma model, it was shown that crotamine delays tumor implantation, inhibits tumor cells proliferation, and also increases the survival of mice engrafted with subcutaneous melanoma. the structural and functional properties and also the possible biotechnological applications of minimized molecules derived from crotamine are also discussed.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Inst Butantan, Genet Lab, BR-05503900 São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Farmacol, São Paulo, BrazilUniv Fed Ceara, Labomar Inst Ciencias Mar, Fortaleza, CE, BrazilUniv Estado Amazonas, Manaus, AM, BrazilCBA, Lab Bioquim & Biol Mol, Manaus, AM, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Farmacol, São Paulo, BrazilWeb of Scienc

Switching Multiple Sclerosis Patients with Breakthrough Disease to Second-Line Therapy

BACKGROUND: Multiple sclerosis (MS) patients with breakthrough disease on immunomodulatory drugs are frequently offered to switch to natalizumab or immunosuppressants. The effect of natalizumab monotherapy in patients with breakthrough disease is unknown. METHODS: This is an open-label retrospective cohort study of 993 patients seen at least four times at the University of California San Francisco MS Center, 95 had breakthrough disease on first-line therapy (60 patients switched to natalizumab, 22 to immunosuppressants and 13 declined the switch [non-switchers]). We used Poisson regression adjusted for potential confounders to compare the relapse rate within and across groups before and after the switch. RESULTS: In the within-group analyses, the relapse rate decreased by 70% (95% CI 50,82%; p<0.001) in switchers to natalizumab and by 77% (95% CI 59,87%; p<0.001) in switchers to immunosuppressants; relapse rate in non-switchers did not decrease (6%, p =  0.87). Relative to the reduction among non-switchers, the relapse rate was reduced by 68% among natalizumab switchers (95% CI 19,87%; p = 0.017) and by 76% among the immunosuppressant switchers (95% CI 36,91%; p = 0.004). CONCLUSIONS: Switching to natalizumab or immunosuppressants in patients with breakthrough disease is effective in reducing clinical activity of relapsing MS. The magnitude of the effect and the risk-benefit ratio should be evaluated in randomized clinical trials and prospective cohort studies

Buku pintar terlengkap sistem-sistem pemerintahan sedunia : Ragam bentuk dan sistem pemerintahan negara-negara di dunia

Setiap negara, tentu mempunyai sistem pemerintaan tersendiri. Namun, tak jarang ada kemiripan antara satu dengan yang lain. Hal ini dapat dipengarui oleh sejarah terbentuknya suatu negara. Afrika Selatan misalnya. Negara itu menganut sistem pemerintahan parlementer kareana wilayahnya pernah dikuasai Inggris yang menganut sistem pemerintahan tersebut. Lalu, bagaimana dengan negara lainnya?Setiap negara, tentu mempunyai sistem pemerintahan tersendiri. Namun, tak jarang ada kemiripan antara satu dengan yang lain. Hal ini dapat dipengaruhi oleh sejarah terbentuknya suatu negara.Nah, buku di hadapan Anda ini menjelaskan mengenai pengertian dan macam-macam sistem pemerintahan, bentuk-bentuk pemerintahan, serta pelaksanaan pemerintahan dalam suatu negara. Setidaknya, lebih dari 20 negara yang dibahas secara tuntas di sini. Negara mana sajakah?300 hlm.; illus. 15,5 x 24 c

Using task-modular technologies for physics teaching at petroleum engineering high school

This paper presents the results of educational research conducted by the Department ofPhysics of Almetyevsk State Petroleum Institute (ASPI) for the organization and effectiveuse of task-modular technology in teaching physics to students of technical universities. The research was aimed at improving the training of qualified bachelors. As a result there is created a system of goals and tasks of different levels developing both physical and mathematical and professional knowledge and skills of students in technical colleges

THE METHODS OF TEACHING PHYSICS FOR UNDERGRADUATE STUDENTS AT OIL AND GAS INSTITUTE

The article addresses various forms and methods of teaching physics for undergraduate students at technical faculties of O&G Institutes. These methods allows lectures to provide an optimal way for students to study physics in conditions of cutting down the time for learning this discipline. The authors discuss the modern teaching methods and technologies used in the educational process at the Physics Department of Almetyevsk State Oil Institute. The importance of interdisciplinary communication is noted. An efficiency of score-rating system in the current and final assessment of students' knowledge is shown

In situ measurement and modelling of austenite grain growth in a Ti/Nb microalloyed steel

Using a novel laser ultrasonics technique in situ measurements of austenite grain growth were conducted during continuous heating (10 \ub0C s 121) and subsequent isothermal holding at various temperatures in the range 950\u20131250 \ub0C in a microalloyed linepipe steel. Based on the experimental results, a grain growth model was developed, which includes the pinning effect of precipitates present in the steel. Analyzing the grain growth behaviour and using the advanced thermo-kinetic software MatCalc, an approach was developed to estimate the initial distribution of precipitates in the as-received material and their dissolution kinetics. The evolution of the volume fractions and mean particle sizes of NbC and TiN leads to a time-dependent pinning pressure that is coupled with the proposed grain growth model to successfully describe the observed kinetics of austenite grain growth. The predictive capabilities of the model are illustrated by its application to independent grain growth data for rapid heat treatment cycles that are typical of the weld heat affected zone.Peer reviewed: YesNRC publication: Ye