EXPLOSIVE CYCLOGENESIS OVER THE SOUTH-EASTERN ROMANIA DECEMBER 2 – 3, 2012

Explosive cyclogenesis over the south-eastern Romania december 2-3, 2012 . This paper is devoted to the study of the synoptic- dynamical conditions that contributed to the development of an rare explosive cyclogenesis event occurred at the beginning of 2012-2013 winter in southwestern Romania, more precisely between 2nd and 3th of December, 2012. The minimum pressure observed was 980,2 hPa, the lowest ever observed record in the surface of Sulina observation station, and also over the western side of Black Sea during period 1961-2000 and 1965-2004. It was found that the cyclone was not a regular one, but a real „meteorological bomb” one where the central pressure at sea level has recorded an important decrease at about 32,3 hPa in 24 hours, equivalent with 1,7 Bergeron. Comparative by „XX century storms” Lothar and Martin (level 2 and 1 on hurricane scale) which desolated western and central Europe in December 1999, this case of explosive cyclogenesis can be considered one of the extreme for our area concerning both meteorological view as well as the effects

Training primary care physicians to offer their patients faecal occult blood testing and colonoscopy for colorectal cancer screening on an equal basis: a pilot intervention with before-after and parallel group surveys.

Primary care physicians (PCPs) should prescribe faecal immunochemical testing (FIT) or colonoscopy for colorectal cancer screening based on their patient's values and preferences. However, there are wide variations between PCPs in the screening method prescribed. The objective was to assess the impact of an educational intervention on PCPs' intent to offer FIT or colonoscopy on an equal basis. Survey before and after training seminars, with a parallel comparison through a mailed survey to PCPs not attending the training seminars. All PCPs in the canton of Vaud, Switzerland. Of 592 eligible PCPs, 133 (22%) attended a seminar and 106 (80%) filled both surveys. 109 (24%) PCPs who did not attend the seminars returned the mailed survey. A 2 h-long interactive seminar targeting PCP knowledge, skills and attitudes regarding offering a choice of colorectal cancer (CRC) screening options. The primary outcome was PCP intention of having their patients screened with FIT and colonoscopy in equal proportions (between 40% and 60% each). Secondary outcomes were the perceived role of PCPs in screening decisions (from paternalistic to informed decision-making) and correct answer to a clinical vignette. Before the seminars, 8% of PCPs reported that they had equal proportions of their patients screened for CRC by FIT and colonoscopy; after the seminar, 33% foresaw having their patients screened in equal proportions (p<0.001). Among those not attending, there was no change (13% vs 14%, p=0.8). Of those attending, there was no change in their perceived role in screening decisions, while the proportion responding correctly to a clinical vignette increased (88-99%, p<0.001). An interactive training seminar increased the proportion of physicians with the intention to prescribe FIT and colonoscopy in equal proportions

Recent Upgrades of the Gas Handling System for the Cryogenic Stopping Cell of the FRS Ion Catcher

In this paper, the major upgrades and technical improvements of the buffer gas handling system for the cryogenic stopping cell of the FRS Ion Catcher at GSI/FAIR (in Darmstadt, Germany) are described. The upgrades include implementation of new gas lines and gas purifiers to achieve a higher buffer gas cleanliness for a more efficient extraction of reactive ions as well as suppression of the molecular background ionized in the stopping cell. Furthermore, additional techniques have been implemented for improved monitoring and quantification of the purity of the helium buffer gas

Electromagnetic character of the competitive γγ/γ\gamma\gamma/\gamma-decay from 137m^{137\mathrm{m}}Ba

Second-order processes in physics is a research topic focusing attention from several fields worldwide including, for example, non-linear quantum electrodynamics with high-power lasers, neutrinoless double-$\beta$ decay, and stimulated atomic two-photon transitions. For the electromagnetic nuclear interaction, the observation of the competitive double-$\gamma$ decay from $^{137\mathrm{m}}$Ba has opened up the nuclear structure field for detailed investigation of second-order processes through the manifestation of off-diagonal nuclear polarizability. Here we confirm this observation with an $8.7\sigma$ significance, and an improved value on the double-photon versus single-photon branching ratio as $2.62\times10^{-6}(30)$. Our results, however, contradict the conclusions from the original experiment, where the decay was interpreted to be dominated by a quadrupole-quadrupole component. Here, we find a substantial enhancement in the energy distribution consistent with a dominating octupole-dipole character and a rather small quadrupole-quadrupole element in the decay, hindered due to an evolution of the internal nuclear structure. The implied strongly hindered double-photon branching in $^{137\mathrm{m}}$Ba opens up the possibility of the double-photon branching as a feasible tool for nuclear-structure studies on off-diagonal polarizability in nuclei where this hindrance is not present.Comment: 12 pages, 5 figures, 2 tabel

Quality Control of Hypericum perforatum L. Analytical challenges and recent progress

Objectives The most widely applied qualitative and quantitative analytical methods in the quality control of Hypericum perforatum extracts will be reviewed, including routine analytical tools and most modern approaches. Key findings Biologically active components of H. perforatum are chemically diverse, therefore different chromatographic and detection methods are required for the comprehensive analysis of St. John’s wort extracts. Naphthodianthrones, phloroglucinols and flavonoids are the most widely analysed metabolites of this plant. For routine quality control, detection of major compounds belonging to these groups seem to be sufficient, however closer characterisation requires the detection of minor compounds as well. Conclusions TLC and HPTLC are basic methods in the routine analysis, whereas HPLC-DAD is the most widely applied method for quantitative analysis due to its versatility. LC-MS is gaining importance in pharmacokinetic studies due to its sensitivity. Modern approaches, such as DNA barcoding, NIRS and NMR metabolomics may offer new possibilities for the more detailed characterization of secondary metabolite profile of Hypericum perforatum extracts

Activation of ERAD Pathway by Human Hepatitis B Virus Modulates Viral and Subviral Particle Production

Hepatitis B virus (HBV) belongs to the Hepadnaviridae family of enveloped DNA viruses. It was previously shown that HBV can induce endoplasmic reticulum (ER) stress and activate the IRE1-XBP1 pathway of the unfolded protein response (UPR), through the expression of the viral regulatory protein X (HBx). However, it remained obscure whether or not this activation had any functional consequences on the target genes of the UPR pathway. Of these targets, the ER degradation-enhancing, mannosidase-like proteins (EDEMs) are thought to play an important role in relieving the ER stress during UPR, by recognizing terminally misfolded glycoproteins and delivering them to the ER-associated degradation (ERAD). In this study, we investigated the role of EDEMs in the HBV life-cycle. We found that synthesis of EDEMs (EDEM1 and its homologues, EDEM2 and EDEM3) is significantly up-regulated in cells with persistent or transient HBV replication. Co-expression of the wild-type HBV envelope proteins with EDEM1 resulted in their massive degradation, a process reversed by EDEM1 silencing. Surprisingly, the autophagy/lysosomes, rather than the proteasome were involved in disposal of the HBV envelope proteins. Importantly, inhibition of the endogenous EDEM1 expression in HBV replicating cells significantly increased secretion of both, enveloped virus and subviral particles. This is the first report showing that HBV activates the ERAD pathway, which, in turn, reduces the amount of envelope proteins, possibly as a mechanism to control the level of virus particles in infected cells and facilitate the establishment of chronic infections

C-Terminus Glycans with Critical Functional Role in the Maturation of Secretory Glycoproteins

The N-glycans of membrane glycoproteins are mainly exposed to the extracellular space. Human tyrosinase is a transmembrane glycoprotein with six or seven bulky N-glycans exposed towards the lumen of subcellular organelles. The central active site region of human tyrosinase is modeled here within less than 2.5 Å accuracy starting from Streptomyces castaneoglobisporus tyrosinase. The model accounts for the last five C-terminus glycosylation sites of which four are occupied and indicates that these cluster in two pairs - one in close vicinity to the active site and the other on the opposite side. We have analyzed and compared the roles of all tyrosinase N-glycans during tyrosinase processing with a special focus on the proximal to the active site N-glycans, s6:N337 and s7:N371, versus s3:N161 and s4:N230 which decorate the opposite side of the domain. To this end, we have constructed mutants of human tyrosinase in which its seven N-glycosylation sites were deleted. Ablation of the s6:N337 and s7:N371 sites arrests the post-translational productive folding process resulting in terminally misfolded mutants subjected to degradation through the mannosidase driven ERAD pathway. In contrast, single mutants of the other five N-glycans located either opposite to the active site or into the N-terminus Cys1 extension of tyrosinase are temperature-sensitive mutants and recover enzymatic activity at the permissive temperature of 31°C. Sites s3 and s4 display selective calreticulin binding properties. The C-terminus sites s7 and s6 are critical for the endoplasmic reticulum retention and intracellular disposal. Results herein suggest that individual N-glycan location is critical for the stability, regional folding control and secretion of human tyrosinase and explains some tyrosinase gene missense mutations associated with oculocutaneous albinism type I