The Influence of Temperature on the Manufactory of Optical Surfaces

Tato diplomová práce je zaměřená na zkoumání vlivu teploty při výrobě optických ploch. V této práci je popsána technologie výroby čoček, jsou uvedeny principy měření optických povrchů. Je proveden experiment zaměřený na experimentální určení teplotního namáhaní při tmelení čočky. Je zkoumán vliv různých typů tmelek na změnu tvaru povrchu čočky při tepelném namáhání. Měření zkoumaných optických povrchů je provedeno na Fizeau interferometru. Pro porovnání výsledků z experimentů je provedena numerická simulace v softwaru MSC.Marc/Mentat.This thesis is based on the research of temperature influence on the optical surfaces manufacture. The technology of manufacturing lenses is described, and the measurement principles of optical surfaces are also presented in this work. The experiment is aimed at the experimental determination of the thermal stress during lens cementing. The influence of different types of holders on the change in the shape of the lens surface under thermal stress is investigated. Measurement of the optical surfaces is performed on a Fizeau interferometer. To compare the results of experiments numerical simulation software MSC.Marc/Mentat was used

Calcium-permeable channels activated via guanine nucleotide-dependent mechanism in human carcinoma cells

AbstractPatch clamp experiments on human carcinoma A431 cells have revealed two types of Ca2+-permeable channels, the activity of which can be increased by the application of non-hydrolyzable analogues of GTP to the intracellular side of the membrane. With 105 mM Ca2+ in recording pipette at 30–33°C their unitary conductances (in pS) are 1.3 (SG-channels) and 2.4 (G-channels). G- and, possibly, SG-channels are activated from the extracellular side of the membrane with epidermal growth factor (EGF). The data are consistent with the hypothesis that both channels are activated via guanine nucleotide binding (G) proteins

Предвузовская подготовка по информатике и офисное программирование

Some features of the teaching of ICT in terms of building plans and learning objectives, to be the forefront in preparing students for the preparatory phase (in secondary and higher schools) which brings mass teaching of computer science at an early stage to a qualitatively new level in accordance with modern requirements both in terms of national and international aspects are discussed in the article. The materials of the article are the basis for further development of modern EMC in accordance with the trends and the spirit of the time.В статье рассматриваются некоторые наиболее важные особенности преподавания информационно-коммуникационных технологий (ИКТ) при подготовке студентов на подготовительном этапе (в школе и в вузе) с точки зрения формирования планов обучения и достижения целей, выводящих массовое преподавание информатики на начальной стадии на качественно новый уровень в соответствии с современными требованиями как в плане национальном, так и в международном. Материалы статьи являются основой для дальнейшей разработки современного учебно-методического комплекса (УМК)

Orbital effects of non-isotropic mass depletion of the atmospheres of evaporating hot Jupiters in extrasolar systems

We analytically and numerically investigate the long-term, i.e. averaged over one full revolution, orbital effects of the non-isotropic percent mass loss \dot m/m experienced by several transiting hot Jupiters whose atmospheres are hit by severe radiations flows coming from their close parent stars. The semi-major axis a, the argument of pericenter \omega and the mean anomaly M experience net variations, while the eccentricity e, the inclination I and the longitude of the ascending node remain unchanged, on average. In particular, a increases independently of e and of the speed Vesc of the ejected mass. By assuming |\dot m| <= 10^17 kg yr-1, corresponding to |\dot m/m| <= 10^-10 yr-1 for a Jupiter-like planet, it turns out \dot a = 2.5 m yr^-1 for orbits with a = 0.05 au. Such an effect may play a role in the dynamical history of the hot Jupiters, especially in connection with the still unresolved issue of the arrest of the planetary inward migrations after a distance a >= 0.01 au is reached. The retrograde pericenter variation depends, instead, on e and V_esc. It may, in principle, act as a source of systematic uncertainty in some proposed measurements of the general relativistic pericenter precession; however, it turns out to be smaller than it by several orders of magnitude.Comment: LaTex2e, 16 pages, no tables, 6 figures. To appear in New Astronomy (NA

Efficacy and Safety of Netakimab, A Novel Anti-IL-17 Monoclonal Antibody, in Patients with Moderate to Severe Plaque Psoriasis. Results of A 54-Week Randomized Double-Blind Placebo-Controlled PLANETA Clinical Trial

Altres ajuts: Sponsorship for this study and the Rapid Service Fee were funded by JSC BIOCAD, Ul. Italianskaya 17, St Petersburg, Russia, 191186Introduction: Netakimab (NTK), an original humanized anti-interleukin-17 monoclonal antibody, showed therapeutic efficacy in moderate-to-severe plaque psoriasis in a phase 2 clinical study. Herein we report the results of 54 weeks of a phase 3 PLANETA trial aimed to evaluate the efficacy and safety of two NTK regimens vs. placebo. Methods: Two hundred thirteen patients with moderate-to-severe plaque psoriasis were randomly assigned to receive NTK 120 mg once every 2 weeks (NTK Q2W), NTK 120 mg once every 4 weeks (NTK Q4W) or placebo. During the first 3 weeks, patients received subcutaneous injections of NTK or placebo (according to the allocation) once a week. Patients in the NTK Q2W group then received NTK at weeks 4, 6, 8 and 10. Subjects in the NTK Q4W group received NTK at weeks 6 and 10 and placebo at weeks 4 and 8. Patients in the placebo group received placebo injections at weeks 4, 6, 8 and 10. Treatment was unblinded at week 12. During the open-label phase, patients in both NTK groups continued to receive NTK Q4W. The primary efficacy endpoint was the proportion of patients in each group who achieved a ≥ 75% reduction from baseline in psoriasis area and severity index (PASI 75) at week 12. Results: A total of 77.7%, 83.3% and 0% of patients had a PASI 75 response at week 12 in the NTK Q2W, NTK Q4W and placebo groups, respectively (P < 0.0001, Fisher's exact test, ITT). The effect was maintained throughout the 1-year treatment. NTK showed a good safety profile and low immunogenicity. Conclusion: Treatment with NTK results in high rates of sustained clinical response in patients with moderate-to-severe plaque psoriasis. The study is ongoing; thus, long-term use efficacy and safety data are forthcoming. Clinical Trial Registration: The trial is registered at the US National Institutes of Health (ClinicalTrials.gov; NCT03390101)

Nonclinical cardiovascular safety of pitolisant: comparing International Conference on Harmonization S7B and Comprehensive in vitro Pro-arrhythmia Assay initiative studies

Background and purpose: We evaluated the concordance of results from two sets of nonclinical cardiovascular safety studies on pitolisant. Experimental approach: Nonclinical studies envisaged both in the ICH S7B guideline and Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative were undertaken. CiPA-initiative studies included in vitro ion channels and stem cell-derived human ventricular myocyte studies as well as in silico modelling of results to simulate human ventricular electrophysiology. ICH S7B-recommended studies included in vitro hERG studies, in vivo dog study with follow-up investigations in rabbit Purkinje fibres and in vivo studies in the Carlsson rabbit proarrhythmia model. Key results: Both sets of nonclinical studies consistently excluded pitolisant from having clinically relevant QT-liability or proarrhythmic potential. CiPA studies revealed pitolisant to have modest calcium channel blocking and late I Na reducing activities at high concentrations, which resulted in reduction of dofetilide-induced early after-depolarisations (EADs) by pitolisantin ICH S7B studies. Studies in stem cell-derived human cardiomyocytes with dofetilide or E-4031 given alone and in combination with pitolisant confirmed these properties. In silico modelling confirmed that the measured ion channel effects are consistent with results from both the stem cell-derived cardiomyocyte and rabbit Purkinje fibre studies and categorised pitolisant as a drug with low torsadogenic potential. The results from the two sets of nonclinical studies correlated well with two clinical QT studies. Conclusions and implications: Our experience supports the CiPA initiative but suggests that sponsors should consider investigating drug effects on EADs and the use of proarrhythmia models when the results from CiPA studies are ambiguous

Antimony Toxicity

Antimony toxicity occurs either due to occupational exposure or during therapy. Occupational exposure may cause respiratory irritation, pneumoconiosis, antimony spots on the skin and gastrointestinal symptoms. In addition antimony trioxide is possibly carcinogenic to humans. Improvements in working conditions have remarkably decreased the incidence of antimony toxicity in the workplace. As a therapeutic, antimony has been mostly used for the treatment of leishmaniasis and schistosomiasis. The major toxic side-effects of antimonials as a result of therapy are cardiotoxicity (~9% of patients) and pancreatitis, which is seen commonly in HIV and visceral leishmaniasis co-infections. Quality control of each batch of drugs produced and regular monitoring for toxicity is required when antimonials are used therapeutically

Glucocorticoids Inhibit CRH/AVP-Evoked Bursting Activity of Male Murine Anterior Pituitary Corticotrophs

This is the final version of the article. Available from the publisher via the DOI in this record.Corticotroph cells from the anterior pituitary are an integral component of the hypothalamic-pituitary-adrenal (HPA) axis, which governs the neuroendocrine response to stress. Corticotrophs are electrically excitable and fire spontaneous single-spike action potentials and also display secretagogue-induced bursting behavior. The HPA axis function is dependent on effective negative feedback in which elevated plasma glucocorticoids result in inhibition at the level of both the pituitary and the hypothalamus. In this study, we have used an electrophysiological approach coupled with mathematical modeling to investigate the regulation of spontaneous and CRH/arginine vasopressin-induced activity of corticotrophs by glucocorticoids. We reveal that pretreatment of corticotrophs with 100 nM corticosterone (CORT; 90 and 150 min) reduces spontaneous activity and prevents a transition from spiking to bursting after CRH/arginine vasopressin stimulation. In addition, previous studies have identified a role for large-conductance calcium- and voltage-activated potassium (BK) channels in the generation of secretagogue-induced bursting in corticotrophs. Using the dynamic clamp technique, we demonstrated that CRH-induced bursting can be switched to spiking by subtracting a fast BK current, whereas the addition of a fast BK current can induce bursting in CORT-treated cells. In addition, recordings from BK knockout mice (BK(-/-)) revealed that CORT can also inhibit excitability through BK-independent mechanisms to control spike frequency. Thus, we have established that glucocorticoids can modulate multiple properties of corticotroph electrical excitability through both BK-dependent and BK-independent mechanisms.This work was supported by Grant 082407 from the Wellcome Trust (to M.J.S. and P.R.), Grant J008893 from the Medical Research Council (to M.J.S.), and Grant DK43200 from the National Institutes of Health (to R.B.). P.J.D. was supported by a Medical Reseach Council PhD studentship in the College of Medicine and Veterinary Medicine, University of Edinburgh