Pair production in laser fields oscillating in space and time

The production of electron-positron pairs from vacuum by counterpropagating laser beams of linear polarization is calculated. In contrast to the usual approximate approach, the spatial dependence and magnetic component of the laser field are taken into account. We show that the latter strongly affects the creation process at high laser frequency: the production probability is reduced, the kinematics is fundamentally modified, the resonant Rabi-oscillation pattern is distorted and the resonance positions are shifted, multiplied and split.Comment: 5 pages, 5 figure

Critical sets of nonlinear Sturm-Liouville operators of Ambrosetti-Prodi type

The critical set C of the operator F:H^2_D([0,pi]) -> L^2([0,pi]) defined by F(u)=-u''+f(u) is studied. Here X:=H^2_D([0,pi]) stands for the set of functions that satisfy the Dirichlet boundary conditions and whose derivatives are in L^2([0,pi]). For generic nonlinearities f, C=\cup C_k decomposes into manifolds of codimension 1 in X. If f''0, the set C_j is shown to be non-empty if, and only if, -j^2 (the j-th eigenvalue of u -> u'') is in the range of f'. The critical components C_k are (topological) hyperplanes.Comment: 6 pages, no figure

The Structure and Mechanism of Cytochrome P450

The unusual hemoprotein called cytochrome P450 is now recognized as representing a variety of monooxygenases with entirely different substrate specificities. In comparison with hememercaptide models it can be concluded that the unusual spectral properties reside in a heme-mercaptide linkage to the protein. The sixth ligand in the ferric form could be a hydroxyl group which is absent in the enzyme-substrate complex. In the reaction cycle the enzyme-substrate complex is reduced and then reacts with dioxygen to form an oxy-complex. Further reduction is believed to yield an »oxenoid« complex of the structure [Fe0]3+, which transfers the oxygen atom to the substrate

Setting up an enhanced surveillance of newly acquired hepatitis C infection in men who have sex with men: a pilot in London and South East region of England.

Preliminary findings suggest ongoing HCV transmission among MSM infected with human immunodeficiency virus (HIV) and that enhanced surveillance for newly acquired HCV in MSM is feasible

Understanding the Basis for Down Syndrome Phenotypes

Down syndrome is a collection of features that are caused by trisomy for human Chromosome 21. While elevated transcript levels of the more than 350 genes on the chromosome are primarily responsible, it is likely that multiple genetic mechanisms underlie the numerous ways in which development and function diverge in individuals with trisomy 21 compared to euploid individuals. We consider genotype–phenotype interactions with the goal of producing working concepts that will be useful for approaches to ameliorate the effects of trisomy

Microbiological, histological, immunological, and toxin response to antibiotic treatment in the mouse model of Mycobacterium ulcerans disease.

Mycobacterium ulcerans infection causes a neglected tropical disease known as Buruli ulcer that is now found in poor rural areas of West Africa in numbers that sometimes exceed those reported for another significant mycobacterial disease, leprosy, caused by M. leprae. Unique among mycobacterial diseases, M. ulcerans produces a plasmid-encoded toxin called mycolactone (ML), which is the principal virulence factor and destroys fat cells in subcutaneous tissue. Disease is typically first manifested by the appearance of a nodule that eventually ulcerates and the lesions may continue to spread over limbs or occasionally the trunk. The current standard treatment is 8 weeks of daily rifampin and injections of streptomycin (RS). The treatment kills bacilli and wounds gradually heal. Whether RS treatment actually stops mycolactone production before killing bacilli has been suggested by histopathological analyses of patient lesions. Using a mouse footpad model of M. ulcerans infection where the time of infection and development of lesions can be followed in a controlled manner before and after antibiotic treatment, we have evaluated the progress of infection by assessing bacterial numbers, mycolactone production, the immune response, and lesion histopathology at regular intervals after infection and after antibiotic therapy. We found that RS treatment rapidly reduced gross lesions, bacterial numbers, and ML production as assessed by cytotoxicity assays and mass spectrometric analysis. Histopathological analysis revealed that RS treatment maintained the association of the bacilli with (or within) host cells where they were destroyed whereas lack of treatment resulted in extracellular infection, destruction of host cells, and ultimately lesion ulceration. We propose that RS treatment promotes healing in the host by blocking mycolactone production, which favors the survival of host cells, and by killing M. ulcerans bacilli

Challenges and Rewards in Medicinal Chemistry Targeting Cardiovascular and Metabolic Diseases

Medicinal chemistry has been transformed by major technological and conceptual innovations over the last three decades: structural biology and bioinformatics, structure and property based molecular design, the concepts of multidimensional optimization (MDO), in silico and experimental high-throughput molecular property analysis. The novel technologies advanced gradually and in synergy with biology and Roche has been at the forefront. Applications in drug discovery programs towards new medicines in cardiovascular and metabolic diseases are highlighted to show impact and advancement: the early discovery of endothelin antagonists for endothelial dysfunction (Bosentan), 11-beta hydroxysteroid dehydrogenase (11?-HSD1) inhibitors for dysregulated cellular glucocorticoid tonus (type 2 diabetes and metabolic syndrome) and non-covalent hormone sensitive lipase (HSL) inhibitors to study the scope of direct inhibition of lipolysis in the conceptual frame of lipotoxicity and type 2 diabetes

Prevalence of carbohydrate metabolism disorders and association with cardiovascular diseases in a large Siberian region

Aim. To study the prevalence of carbohydrate metabolism disorders in a repre - sentative sample of the working-age population of the Krasnoyarsk Krai aged 25-64 years and to identify the association of these disorders with cardiovascular pathology.Material and methods. A random representative sample within the all-Russian epidemiological study ESSE-RF included 1603 residents of the Krasnoyarsk Krai aged 25 to 64 years. The gradation of carbohydrate metabolism disorders was carried out on the basis of fasting plasma glucose level in accordance with the criteria of the American Diabetes Association (ADA). Hypertension (HTN) was defined as office BP ≥140/90 mm Hg or an indication of previous use of antihypertensive drugs. The presence of myocardial infarction (MI), stroke, coronary artery disease (CAD) was detected by anamnesis collection. Statistical processing was carried out using IBM SPSS v 22 and Microsoft Excel 2021 programs. When comparing differences by sex, age, level of education, and type of residence, differences was assessed by chi-squared test and considered significant at p≤0,05.Results. In total representative sample of Krasnoyarsk Krai population, 3,6% of participants indicated prior diabetes, while its prevalence naturally increased with age. The detection rate of fasting glucose of 5,6-6,9 mmol/l among individuals without prior diabetes (impaired fasting glycemia (IFG), as one of the criteria for prediabetes, according to ADA guidelines) was 22,5% of the general population. Fasting hyperglycemia (HG) ≥7,0 mmol/l without prior diabetes was registered in 3,8%. This figure can be roughly considered as the proportion of people with newly diagnosed diabetes. IFG and HG were significantly more common among men, as well as among those with primary and secondary education compared with higher education. In rural residents, all types of carbohydrate metabolism disorders were more common than in urban ones. Compared with the normoglycemic group, the presence of prior diabetes, IFG and GH was associated with a significantly higher prevalence of hypertension, CAD and stroke.Conclusion. The prevalence of IFG, fasting HG ≥7,0 mmol/l and diagnosed diabetes in a representative sample of the Krasnoyarsk Krai aged 25-64 years exceeds the national average, although it is consistent with the data of a number of other Siberian regions. The prevalence of both carbohydrate metabolism disorders in general and the percentage of possible undiagnosed diabetes increases with age. At the same time, there are more such individuals among those with primary and secondary education, as well as among rural residents. The approximate proportion of undiagnosed diabetes in the study population reaches 50%. Timely detection of carbohydrate metabolism disorders can contribute to the earlier implementation of active preventive measures and reduce the risk of cardiovascular events

Effect of quantum confinement on exciton-phonon interactions

We investigate the homogeneous linewidth of localized type-I excitons in type-II GaAs/AlAs superlattices. These localizing centers represent the intermediate case between quasi-two-dimensional (Q2D) and quasi-zero-dimensional localizations. The temperature dependence of the homogeneous linewidth is obtained with high precision from micro-photoluminescence spectra. We confirm the reduced interaction of the excitons with their environment with decreasing dimensionality except for the coupling to LO-phonons. The low-temperature limit for the linewidth of these localized excitons is five times smaller than that of Q2D excitons. The coefficient of exciton-acoustic-phonon interaction is 5 ~ 6 times smaller than that of Q2D excitons. An enhancement of the average exciton-LO-phonon interaction by localization is found in our sample. But this interaction is very sensitive to the detailed structure of the localizing centers.Comment: 6 pages, 4 figure