Defect and Hodge numbers of hypersurfaces

We define defect for hypersurfaces with A-D-E singularities in complex projective normal Cohen-Macaulay fourfolds having some vanishing properties of Bott-type and prove formulae for Hodge numbers of big resolutions of such hypersurfaces. We compute Hodge numbers of Calabi-Yau manifolds obtained as small resolutions of cuspidal triple sextics and double octics with higher A_j singularities.Comment: 25 page

Decomposition of semigroup algebras

Let A \subseteq B be cancellative abelian semigroups, and let R be an integral domain. We show that the semigroup ring R[B] can be decomposed, as an R[A]-module, into a direct sum of R[A]-submodules of the quotient ring of R[A]. In the case of a finite extension of positive affine semigroup rings we obtain an algorithm computing the decomposition. When R[A] is a polynomial ring over a field we explain how to compute many ring-theoretic properties of R[B] in terms of this decomposition. In particular we obtain a fast algorithm to compute the Castelnuovo-Mumford regularity of homogeneous semigroup rings. As an application we confirm the Eisenbud-Goto conjecture in a range of new cases. Our algorithms are implemented in the Macaulay2 package MonomialAlgebras.Comment: 12 pages, 2 figures, minor revisions. Package may be downloaded at http://www.math.uni-sb.de/ag/schreyer/jb/Macaulay2/MonomialAlgebras/html

Head Position in Stroke Trial (HeadPoST)- sitting-up vs lying-flat positioning of patients with acute stroke: study protocol for a cluster randomised controlled trial

Background Positioning a patient lying-flat in the acute phase of ischaemic stroke may improve recovery and reduce disability, but such a possibility has not been formally tested in a randomised trial. We therefore initiated the Head Position in Stroke Trial (HeadPoST) to determine the effects of lying-flat (0°) compared with sitting-up (≥30°) head positioning in the first 24 hours of hospital admission for patients with acute stroke. Methods/Design We plan to conduct an international, cluster randomised, crossover, open, blinded outcome-assessed clinical trial involving 140 study hospitals (clusters) with established acute stroke care programs. Each hospital will be randomly assigned to sequential policies of lying-flat (0°) or sitting-up (≥30°) head position as a ‘business as usual’ stroke care policy during the first 24 hours of admittance. Each hospital is required to recruit 60 consecutive patients with acute ischaemic stroke (AIS), and all patients with acute intracerebral haemorrhage (ICH) (an estimated average of 10), in the first randomised head position policy before crossing over to the second head position policy with a similar recruitment target. After collection of in-hospital clinical and management data and 7-day outcomes, central trained blinded assessors will conduct a telephone disability assessment with the modified Rankin Scale at 90 days. The primary outcome for analysis is a shift (defined as improvement) in death or disability on this scale. For a cluster size of 60 patients with AIS per intervention and with various assumptions including an intracluster correlation coefficient of 0.03, a sample size of 16,800 patients at 140 centres will provide 90 % power (α 0.05) to detect at least a 16 % relative improvement (shift) in an ordinal logistic regression analysis of the primary outcome. The treatment effect will also be assessed in all patients with ICH who are recruited during each treatment study period. Discussion HeadPoST is a large international clinical trial in which we will rigorously evaluate the effects of different head positioning in patients with acute stroke. Trial registration ClinicalTrials.gov identifier: NCT02162017 (date of registration: 27 April 2014); ANZCTR identifier: ACTRN12614000483651 (date of registration: 9 May 2014). Protocol version and date: version 2.2, 19 June 2014

Income and education as predictors of return to working life among younger stroke patients

<p>Abstract</p> <p>Background</p> <p>Socioeconomic conditions are not only related to poor health outcomes, they also contribute to the chances of recovery from stroke. This study examines whether income and education were predictors of return to work after a first stroke among persons aged 40-59.</p> <p>Methods</p> <p>All first-stroke survivors aged 40-59 who were discharged from a hospital in 1996-2000 and who had received income from work during the year prior to the stroke were sampled from the Swedish national register of in-patient care (n = 7,081). Income and education variables were included in hazard regressions, modelling the probability of returning to work from one to four years after discharge. Adjustments for age, sex, stroke subtype, and length of in-patient care were included in the models.</p> <p>Results</p> <p>Both higher income and higher education were associated with higher probability of returning to work. While the association between education and return to work was attenuated by income, individuals with university education were 13 percent more likely to return than those who had completed only compulsory education, and individuals in the highest income quartile were about twice as likely to return as those in the lowest. The association between socioeconomic position and return to work was similar for different stroke subtypes. Income differences between men and women also accounted for women's lower probability of returning to work.</p> <p>Conclusions</p> <p>The study demonstrates that education and income were independent predictors of returning to work among stroke patients during the first post-stroke years. Taking the relative risk of return to work among those in the higher socioeconomic positions as the benchmark, there may be considerable room for improvement among patients in lower socioeconomic strata.</p

Modular protein-RNA interactions regulating mRNA metabolism: a role for NMR

Here we review the role played by transient interactions between multi-functional proteins and their RNA targets in the regulation of mRNA metabolism, and we describe the important function of NMR spectroscopy in the study of these systems. We place emphasis on a general approach for the study of different features of modular multi-domain recognition that uses well-established NMR techniques and that has provided important advances in the general understanding of post-transcriptional regulation

Disease-Associated Mutant Ubiquitin Causes Proteasomal Impairment and Enhances the Toxicity of Protein Aggregates

Protein homeostasis is critical for cellular survival and its dysregulation has been implicated in Alzheimer's disease (AD) and other neurodegenerative disorders. Despite the growing appreciation of the pathogenic mechanisms involved in familial forms of AD, much less is known about the sporadic cases. Aggregates found in both familial and sporadic AD often include proteins other than those typically associated with the disease. One such protein is a mutant form of ubiquitin, UBB+1, a frameshift product generated by molecular misreading of a wild-type ubiquitin gene. UBB+1 has been associated with multiple disorders. UBB+1 cannot function as a ubiquitin molecule, and it is itself a substrate for degradation by the ubiquitin/proteasome system (UPS). Accumulation of UBB+1 impairs the proteasome system and enhances toxic protein aggregation, ultimately resulting in cell death. Here, we describe a novel model system to investigate how UBB+1 impairs UPS function and whether it plays a causal role in protein aggregation. We expressed a protein analogous to UBB+1 in yeast (Ubext) and demonstrated that it caused UPS impairment. Blocking ubiquitination of Ubext or weakening its interactions with other ubiquitin-processing proteins reduced the UPS impairment. Expression of Ubext altered the conjugation of wild-type ubiquitin to a UPS substrate. The expression of Ubext markedly enhanced cellular susceptibility to toxic protein aggregates but, surprisingly, did not induce or alter nontoxic protein aggregates in yeast. Taken together, these results suggest that Ubext interacts with more than one protein to elicit impairment of the UPS and affect protein aggregate toxicity. Furthermore, we suggest a model whereby chronic UPS impairment could inflict deleterious consequences on proper protein aggregate sequestration

Pleiotropic Effects of Deubiquitinating Enzyme Ubp5 on Growth and Pathogenesis of Cryptococcus neoformans

Ubiquitination is a reversible protein modification that influences various cellular processes in eukaryotic cells. Deubiquitinating enzymes remove ubiquitin, maintain ubiquitin homeostasis and regulate protein degradation via the ubiquitination pathway. Cryptococcus neoformans is an important basidiomycete pathogen that causes life-threatening meningoencephalitis primarily in the immunocompromised population. In order to understand the possible influence deubiquitinases have on growth and virulence of the model pathogenic yeast Cryptococcus neoformans, we generated deletion mutants of seven putative deubiquitinase genes. Compared to other deubiquitinating enzyme mutants, a ubp5Δ mutant exhibited severely attenuated virulence and many distinct phenotypes, including decreased capsule formation, hypomelanization, defective sporulation, and elevated sensitivity to several external stressors (such as high temperature, oxidative and nitrosative stresses, high salts, and antifungal agents). Ubp5 is likely the major deubiquitinating enzyme for stress responses in C. neoformans, which further delineates the evolutionary divergence of Cryptococcus from the model yeast S. cerevisiae, and provides an important paradigm for understanding the potential role of deubiquitination in virulence by other pathogenic fungi. Other putative deubiquitinase mutants (doa4Δ and ubp13Δ) share some phenotypes with the ubp5Δ mutant, illustrating functional overlap among deubiquitinating enzymes in C. neoformans. Therefore, deubiquitinating enzymes (especially Ubp5) are essential for the virulence composite of C. neoformans and provide an additional yeast survival and propagation advantage in the host

КИНЕТИКА ПРОЦЕССА ОКИСЛИТЕЛЬНОГО ХЛОРИРОВАНИЯ МЕТАНА

Heterogeneous oxidative chlorination of methane was investigated. The target product is methyl chloride. The investigated terms and conditions of oxychlorination of methane: process temperature 400°C, pressure 0.1-0.9 MPa, catalyst (% weight.): copper chloride (II) 1-8%; potassium chloride 2.5%; lanthanum chloride 1%; carrier - aluminosilicate. Powder X-ray diffractometry and electron microscopy showed that the active catalyst components (CuCl2, KCl, LaCl3) are unevenly distributed on the support surface (α-Al2O3·SiO2) and form agglomerates with a high salt content, including binary chlorides such as KCuCl3, K2CuCl3 or K2CuCl4, hydrates K2CuCl4·2H2O and CuCl2·2H2O and hydroxychlorides Cu3Cl4(OH)2 and Cu2Cl(OH)3. The kinetics of methane oxychlorination was studied in a gradientless reactor at 400°C and pressure 0.1 - 0.9 MPa by varying the partial pressures of the reactants. Analysis of the products was carried out by GC. An equation of the reaction rate including partial pressures of methane, hydrogen chloride and water to the 0.77, 0.01 and 0.64 power, respectively, but of zero order by oxygen and chlorine provides an adequate description of methyl chloride formation rate. Significant influence of water partial pressure is proved for the reaction under consideration.Гетерогенно-каталитическая реакция окислительного хлорирования метана, целевым продуктом которой является хлористый метил, изучена при температуре 400°С и варьировании давления в диапазоне 0.1-0.9 МПа. Методами дифрактометрии и электронной микроскопии показано, что активные компоненты катализатора (CuCl2, KCl, LaCl3) распределяются неравномерно на поверхности носителя (α-Al2O3·SiO2), образуя агломераты с повышенным содержанием солей, в том числе двойных хлоридов, таких как KCuCl3, K2CuCl3 или K2CuCl4, гидрата K2CuCl4·2H2O и гидроксихлоридов состава Cu3Cl4(OH)2 и Cu2Cl(OH)3. Кинетические закономерности изучены в проточном безградиентном по парциальным давлениям реакторе при 400°С методом однофакторного эксперимента при варьировании парциальных давлений реагентов. Анализ продуктов проводили методом газовой хроматографии. Обработкой кинетических данных степенными уравнениями показано, что адекватное описание скорости образования хлористого метила обеспечивает уравнение, в которое входят парциальные давления метана, хлористого водорода и воды в степенях 0.77, 0.01 и 0.64, соответственно, при нулевых порядках по кислороду и хлору