Direct acceleration of electrons by a CO2 laser in a curved plasma waveguide.

Laser plasma interaction with micro-engineered targets at relativistic intensities has been greatly promoted by recent progress in the high contrast lasers and the manufacture of advanced micro- and nano-structures. This opens new possibilities for the physics of laser-matter interaction. Here we propose a novel approach that leverages the advantages of high-pressure CO2 laser, laser-waveguide interaction, as well as micro-engineered plasma structure to accelerate electrons to peak energy greater than 1 GeV with narrow slice energy spread (~1%) and high overall efficiency.

Multiple Targeting Approaches on Histamine H3 Receptor Antagonists.

With the very recent market approval of pitolisant (Wakix®), the interest in clinical applications of novel multifunctional histamine H3 receptor antagonists has clearly increased. Since histamine H3 receptor antagonists in clinical development have been tested for a variety of different indications, the combination of pharmacological properties in one molecule for improved pharmacological effects and reduced unwanted side-effects is rationally based on the increasing knowledge on the complex neurotransmitter regulations. The polypharmacological approaches on histamine H3 receptor antagonists on different G-protein coupled receptors, transporters, enzymes as well as on NO-signaling mechanism are described, supported with some lead structures.

Discovery of potent adenosine A2a antagonists as potential anti-Parkinson disease agents. Non-linear QSAR analyses integrated with pharmacophore modeling.

Adenosine A2A receptor antagonists are of great interest in the treatment for Parkinson's disease. In this study, we combined extensive pharmacophore modeling and quantitative structure-activity relationship (QSAR) analysis to explore the structural requirements for potent Adenosine A2A antagonists. Genetic function algorithm (GFA) joined with k nearest neighbor (kNN) analyses were applied to build predictive QSAR models.

Accumulation of formamide in hydrothermal pores to form prebiotic nucleobases.

Formamide is one of the important compounds from which prebiotic molecules can be synthesized, provided that its concentration is sufficiently high. For nucleotides and short DNA strands, it has been shown that a high degree of accumulation in hydrothermal pores occurs, so that temperature gradients might play a role in the origin of life [Baaske P, et al. (2007)Proc Natl Acad Sci USA104(22):9346-9351].

A re-examination of the selection of the sensory organ precursor of the bristle sensilla of Drosophila melanogaster.

The bristle sensillum of the imago of Drosophila is made of four cells that arise from a sensory organ precursor cell (SOP). This SOP is selected within proneural clusters (PNC) through a mechanism that involves Notch signalling. PNCs are defined through the expression domains of the proneural genes, whose activities enables cells to become SOPs.

Experimental amine-epoxide sealer: a physicochemical study in comparison with AH Plus and EasySeal.

Aim: To compare selected physicochemical and biological properties of an experimental sealer with those of two commercially available sealers.

Methodology: AH Plus and EasySeal were used as model materials for commercially available amine-epoxide sealers. They were mixed as stated by the manufacturer.

Meroterpenes from endophytic fungus A1 of mangrove plant Scyphiphora hydrophyllacea.

Four new meroterpenes, guignardones F-I (1-4), together with two known compounds guignardones A (5) and B (6) were isolated from the endophytic fungus A1 of the mangrove plant Scyphiphora hydrophyllacea. Their structures and relative configurations were elucidated by spectroscopic data and single-crystal X-ray crystallography. A possible biogenetic pathway of compounds 1-6 was also proposed.

Bioactive compounds from marine bacteria and fungi.

Marine bacteria and fungi are of considerable importance as new promising sources of a huge number of biologically active products. Some of these marine species live in a stressful habitat, under cold, lightless and high pressure conditions. Surprisingly, a large number of species with high diversity survive under such conditions and produce fascinating and structurally complex natural products.

Interleukin-10 and -12 predict chemotherapy-associated toxicity in esophageal adenocarcinoma.

Introduction: Chemotherapy-associated mucositis often prevents completion of an entire chemotherapy cycle. The underlying pathophysiology of chemotherapy-associated mucositis has not been well established. The individual immunologic predisposition of patients seems to play an important role.

Improving self-report measures of medication non-adherence using a cheating detection extension of the randomised-response-technique.

Medication non-adherence is a serious problem for medical research and clinical practice. Self-reports are only moderately valid, and objective methods are cumbersome and expensive to administer. We sought to improve self-reports of medication non-adherence using a cheating detection extension of the randomised-response-technique (RRT).

Estimating the prevalence of negative attitudes towards people with disability: a comparison of direct questioning, projective questioning and randomised response.

Purpose: Despite being susceptible to social desirability bias, attitudes towards people with disabilities are traditionally assessed via self-report. We investigated two methods presumably providing more valid prevalence estimates of sensitive attitudes than direct questioning (DQ). Most people projective questioning (MPPQ) attempts to reduce bias by asking interviewees to estimate the number of other people holding a sensitive attribute, rather than confirming or denying the attribute for themselves.

Amyloid formation: age-related mechanism in Creutzfeldt-Jakob disease?

Protein aggregation occurs in many age-related neurodegenerative diseases, where it can lead to deposits of naturally occurring proteins in the brain. In case of Creutzfeldt-Jakob disease (CJD), these deposits consist of prion protein (PrP). CJD has three etiologies: spontaneous, genetic, or caused by infection.

Impact of genetic polymorphisms of the renin-angiotensin system and of non-genetic factors on kidney transplant function--a single-center experience.

Renin-angiotensin-aldosterone system (RAAS) polymorphisms such as the angiotensinogen-gene-M235T-, the angiotensin-conversion enzyme (ACE)-gene I/D- and the angiotensin-II-type 1-receptor-(AT1R)-A1166C-polymorphism have been implicated in renal insufficiency and hypertension. We studied the association of these RAAS genotypes and non-genetic factors with transplant function and hypertension after renal graft transplantation (NTX). A total of 229 renal graft recipients, transplanted at a single center, were monitored up to 54 months and genotyped using polymerase chain reaction.

Prion infection: seeded fibrillization or more?

The prion infection is a conversion of host encoded prion protein (PrP) from its cellular isoform PrP(C) into the pathological and infectious isoform PrP(Sc); the conversion process was investigated by in vitro studies using recombinant and cellular PrP and natural PrP(Sc). We present a brief summary of the results determined with our in vitro conversion system and the derived mechanistic models. We describe well characterized intermediates and precursor states during the conversion process, kinetic studies of spontaneous and seeded fibrillogenesis and the impact of the membrane environment.

Spectral measurements of runaway electrons by a scanning probe in the TEXTOR tokamak.

Energy spectral measurements of runaway electrons were performed by a scanning probe with high spatial and temporal resolution in the TEXTOR tokamak. The probe consists of ten YSO (Y(2)SiO(5):Ce) crystals, which are shielded by tungsten filters. The probe can resolve electrons with different energies between 4 and 30 MeV.

Structural changes of membrane-anchored native PrP(C).

Misfolding and subsequent aggregation of endogenous proteins constitute essential steps in many human disorders, including Alzheimer and prion diseases. In most prion protein-folding studies, the posttranslational modifications, the lipid anchor in particular, were lacking. Here, we studied a fully posttranslationally modified cellular prion protein, carrying two N-glycosylations and the natural GPI anchor.

Spontaneous and BSE-prion-seeded amyloid formation of full length recombinant bovine prion protein.

The conversion of the cellular isoform of the prion protein into the pathogenic isoform PrP(Sc) is the key event in prion diseases. The disease can occur spontaneously genetically or by infection. In earlier studies we presented an in vitro conversion system which simulates the structural transition in recPrP by varying low concentrations of SDS at constant NaCl.

Mechanisms of prion protein assembly into amyloid.

The conversion of the alpha-helical, cellular isoform of the prion protein (PrP(C)) to the insoluble, beta-sheet-rich, infectious, disease-causing isoform (PrP(Sc)) is the key event in prion diseases. In an earlier study, several forms of PrP were converted into a fibrillar state by using an in vitro conversion system consisting of low concentrations of SDS and 250 mM NaCl. Here, we characterize the structure of the fibril precursor state, that is, the soluble state under fibrillization conditions.

Evidence for convergent nucleotide evolution and high allelic turnover rates at the complementary sex determiner gene of Western and Asian honeybees.

Our understanding of the impact of recombination, mutation, genetic drift, and selection on the evolution of a single gene is still limited. Here we investigate the impact of all these evolutionary forces at the complementary sex determiner (csd) gene that evolves under a balancing mode of selection. Females are heterozygous at the csd gene and males are hemizygous; diploid males are lethal and occur when csd is homozygous.

Quantifying the degree of disorder in micronized salbutamol sulfate using moisture sorption analysis.

Salbutamol sulfate is often micronized for use in dry powder inhalers. Therefore, it is of high interest to quantify the amorphous amount. It was investigated whether moisture sorption is able to measure the amorphous content of salbutamol sulfate.