Dielectric relaxation in NaNbO₃ single crystal

Dielectric permittivity studies of reduced samples of NaNbO₃ single crystal in the range of temperatures 30–500 °C and frequency 20 Hz-1 MHz are reported. In this temperature range a relaxation process is observed in the frequency range of about 100 kHz. This is an additional process to the earlier reported one [7]. The obtained data were fitted to Cole-Cole formula. The dispersion step ∆ǫ (the maximum value of ∆ǫ =1000) is temperature dependent. The mean relaxation time τ does not obey the Arrhenius law above TC. The occurrence of this relaxation process may be connected with oxygen vacancies.Досліджено діелектричну сприйнятливість зразків монокристалу NaNbO₃ в діапазонах температур 30–500 °C і частот 20 Гц–1 МГц. У цьому температурному проміжку в частотній області поблизу 100 кГц спостерігається релаксаційний процес, що є доповнювальним до виявленого раніше процесу [7]. Отримані дані апроксимуються за формулою Коул-Коула. Значення дисперсії ∆ε (максимальне значення ∆ε = 1000) залежить від температури. Закон Арреніуса не виконується для середнього часу релаксації τ вище TC. Поява цього релаксаційного процесу може пов’язуватися з кисневими вакансіями

Polyelectrolyte stars in planar confinement

We employ monomer-resolved Molecular Dynamics simulations and theoretical considerations to analyze the conformations of multiarm polyelectrolyte stars close to planar, uncharged walls. We identify three mechanisms that contribute to the emergence of a repulsive star-wall force, namely: the confinement of the counterions that are trapped in the star interior, the increase in electrostatic energy due to confinement as well as a novel mechanism arising from the compression of the stiff polyelectrolyte rods approaching the wall. The latter is not present in the case of interaction between two polyelectrolyte stars and is a direct consequence of the impenetrable character of the planar wall.Comment: 34 pages, 8 figures. Revised version of the manuscript. To appear in J. Chem. Phys. May, 200

Green Synthesis of Glycopolymers Using an Enzymatic Approach

beta-Glucosidase and horseradish peroxidase (HRP) are used as biocatalysts in aqueous solution for the enzymatic synthesis of glycomonomers and the respective enzymatic polymerization toward glycopolymers. The biocatalytically synthesized monomers contain (meth)acrylate functionalities that are able to be polymerized by an enzyme-initiated polymerization using an HRP/hydrogen peroxide/acetylacetone ternary system. The structure of the glycomonomers and the respective glycopolymers as well as the monomer conversion after the reaction are determined by H-1 NMR spectroscopy. The synthesized glycopolymers have a dispersity and a number-average molecular weight up to 5.8 and 297 kg mol(-1), respectively. Thermal and degradation properties of the glycopolymers are studied by differential scanning calorimetry and thermogravimetric analysis. In addition, preparation of glycopolymers via conventional free radical polymerization is performed and the properties of the obtained polymers are compared with the enzymatically synthesized glycopolymers

Analysis of clinical outcomes according to original treatment groups 16 years after the pivotal IFNB-1b trial

BACKGROUND: Evidence for efficacy of disease-modifying drugs in multiple sclerosis (MS) comes from trials of short duration. We report results from a 16 y, retrospective follow-up of the pivotal interferon beta-1b (IFNB-1b) study. METHODS: The 372 trial patients were randomly assigned to placebo (n=123), IFNB-1b 50 microg (n=125) or IFNB-1b 250 microg (n=124) subcutaneously every other day for at least 2 y. Some remained randomised for up to 5 y but, subsequently, patients received treatment according to physicians' discretion. Patients were re-contacted and asked to participate. Efficacy related measures included MRI parameters, relapse rate, the Expanded Disability Status Scale, the Multiple Sclerosis Functional Composite Measure and conversion to secondary progressive MS. RESULTS: Of the 88.2% (328/372) of patients who were identified, 69.9% (260/372) had available case report forms. No differences in outcome between original randomisation groups could be discerned using standard disability and MRI measures. However, mortality rates among patients originally treated with IFNB-1b were lower than in the original placebo group (18.3% (20/109) for placebo versus 8.3% (9/108) for IFNB-1b 50 microg and 5.4% (6/111) for IFNB-1b 250 microg). CONCLUSIONS: The original treatment assignment could not be shown to influence standard assessments of long-term efficacy. On-study behaviour of patients was influenced by factors that could not be controlled with the sacrifice of randomisation and blinding. Mortality was higher in patients originally assigned to placebo than those who had received IFNB-1b 50 microg or 250 microg. The dataset provides important resources to explore early predictors of long-term outcome

Cobalt-katalysierte enantioselektive Hydrierung von dreifach substituierten carbocyclischen Olefinen:Zugang zu chiralen cyclischen Amiden

Die enantioselektive Hydrierung von cyclischen Enamiden wurde mit einem Cobalt-Bisphosphin-Katalysator erreicht. Die Reduktion verschiedenster dreifach substituierter carbocyclischen Enamide zu den entsprechenden gesättigten Amiden erfolgte mit hoher Aktivität und ausgezeichneter Enantioselektivität (bis zu 99 %) unter Verwendung des Systems CoCl2/(S,S)-Ph-BPE. Die Methode lässt sich auf die Synthese chiraler Amine durch eine basische Hydrolyse der Hydrierungsprodukte ausweiten. Erste mechanistische Untersuchungen deuten auf die Anwesenheit einer high-spin Cobalt(II)-Spezie im katalytischen Cyclus hin. Wir postulieren die Hydrierung der Kohlenstoff-Kohlenstoff-Doppelbindung über einen Sigma-Bindungs-Metathese-Weg

Identification and Characterization of AES-135, a Hydroxamic Acid-Based HDAC Inhibitor That Prolongs Survival in an Orthotopic Mouse Model of Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive, incurable cancer with a 20% 1 year survival rate. While standard-of-care therapy can prolong life in a small fraction of cases, PDAC is inherently resistant to current treatments, and novel therapies are urgently required. Histone deacetylase (HDAC) inhibitors are effective in killing pancreatic cancer cells in in vitro PDAC studies, and although there are a few clinical studies investigating combination therapy including HDAC inhibitors, no HDAC drug or combination therapy with an HDAC drug has been approved for the treatment of PDAC. We developed an inhibitor of HDACs, AES-135, that exhibits nanomolar inhibitory activity against HDAC3, HDAC6, and HDAC11 in biochemical assays. In a three-dimensional coculture model, AES-135 kills low-passage patient-derived tumor spheroids selectively over surrounding cancer-associated fibroblasts and has excellent pharmacokinetic properties in vivo. In an orthotopic murine model of pancreatic cancer, AES-135 prolongs survival significantly, therefore representing a candidate for further preclinical testing

Fuzzy oil drop model to interpret the structure of antifreeze proteins and their mutants

Mutations in proteins introduce structural changes and influence biological activity: the specific effects depend on the location of the mutation. The simple method proposed in the present paper is based on a two-step model of in silico protein folding. The structure of the first intermediate is assumed to be determined solely by backbone conformation. The structure of the second one is assumed to be determined by the presence of a hydrophobic center. The comparable structural analysis of the set of mutants is performed to identify the mutant-induced structural changes. The changes of the hydrophobic core organization measured by the divergence entropy allows quantitative comparison estimating the relative structural changes upon mutation. The set of antifreeze proteins, which appeared to represent the hydrophobic core structure accordant with “fuzzy oil drop” model was selected for analysis

Autophagy is essential for effector CD8⁺ T cell survival and memory formation

The importance of autophagy in the generation of memory CD8+ T cells in vivo is not well defined. We report here that autophagy was dynamically regulated in virus-specific CD8+ T cells during acute infection of mice with lymphocytic choriomeningitis virus. In contrast to the current paradigm, autophagy decreased in activated proliferating effector CD8+ T cells and was then upregulated when the cells stopped dividing just before the contraction phase. Consistent with those findings, deletion of the gene encoding either of the autophagy-related molecules Atg5 or Atg7 had little to no effect on the proliferation and function of effector cells, but these autophagy-deficient effector cells had survival defects that resulted in compromised formation of memory T cells. Our studies define when autophagy is needed during effector and memory differentiation and warrant reexamination of the relationship between T cell activation and autophagy