Effective optical identification of type "0-IIb" early gastric cancer with narrow band imaging magnification endoscopy, successfully treated by endoscopic submucosal dissection

Background Endoscopic submucosal dissection (ESD) is currently considered the minimal invasive endoscopic treatment for early gastric cancer. Most superficial gastric neoplastic lesions are depressed type ”0-IIc” (70-80%), while totally flat, classified as type ”0-IIb” early gastric cancer, is rarely reported (0.4%). The aim of the present study was to assess the efficacy of narrow band imaging (NBI) magnification endoscopy in identifying type “0-IIb” early gastric cancer and ESD treatment with curative intention.Methods Twelve of 615 (2%) patients (10 males, median 72 years), treated by ESD at our center, were diagnosed as type “0-IIb” gastric cancer. Ten had exclusively type “0-IIb”, while two had combined types “0-IIb+IIc” and “0-IIa+IIb” gastric cancer. Initial diagnosis was made during screening gastroscopy, while NBI magnification endoscopy combined with indigo-carmine chromoendoscopy were also used.Results White light endoscopy showed only superficial redness. One patient with signet-ring carcinoma showed whitish appearance. Indigo-carmine chromoendoscopy showed better visualization, while NBI magnification endoscopy revealed abnormal mucosal microsurface and microvascular findings which enabled border marking. ESD with curative intention was completed without complications. Histological examination showed complete (R0) resection, in 10 patients (83%). One patient with positive margins received additional surgery (8%). Mean procedure time was 149 (range 60-190) min. One to six years post-ESD all patients remain alive.Conclusions ESD is considered a safe and effective curative treatment for type “0-IIb” gastric cancer, resulting in long-term disease-free survival. NBI magnification endoscopy is effective for accurate optical identification and border marking of type “0-IIb” early gastric cancer

Triamcinolone acetonide for rare ocular manifestations of pemphigus vulgaris: a case report

We present an interesting case of pemphigus vulgaris with severe and rare eye manifestations. An old lady with systemic and ocular manifestations of pemphigus vulgaris was treated with systemic corticosteroids and immunosuppressants, with no effect. Subconjunctival injection of triamcinolone acetate reduced the ocular signs and led to gradual reduction of the systemic medications

Common Bile-Duct Mucosa in Choledochoduodenostomy Patients — Histological and Histochemical Study

We describe the histological and histochemical changes of the common bile-duct mucosa in specimens obtained by means of peroral cholangioscopy, 1–12 years after choledochoduodenal anastomosis. Our findings — hyperplasia of the superficial epithelium, metaplastic goblet cells containing predominantly acid sialomucins, and pyloric-like gland formation containing neutral mucins — express a morphological and functional differentiation of the common bile-duct mucosa that probably facilitates its survival in a different environment. We consider that these adaptive changes may explain the uneventful long-term postoperative period of choledochoduodenostomized patients

Ground-based aerosol optical depth trends at three high-altitude sites in Switzerland and Southern Germany from 1995–2010

Ground-based aerosol optical depth (AOD) climatologies at three high-altitude sites in Switzerland (Jungfraujoch and Davos) and Southern Germany (Hohenpeissenberg) are updated and re-calibrated for the period 1995 – 2010. In addition, AOD time-series are augmented with previously unreported data, and are homogenized for the first time. Trend analysis revealed weak AOD trends (λ = 500 nm) at Jungfraujoch (JFJ; +0.007 decade-1), Davos (DAV; +0.002 decade-1) and Hohenpeissenberg (HPB; -0.011 decade-1) where the JFJ and HPB trends were statistically significant at the 95% and 90% confidence levels. However, a linear trend for the JFJ 1995 – 2005 period was found to be more appropriate than for 1995 – 2010 due to the influence of stratospheric AOD which gave a trend -0.003 decade-1 (significant at 95% level). When correcting for a recently available stratospheric AOD time-series, accounting for Pinatubo (1991) and more recent volcanic eruptions, the 1995 – 2010 AOD trends decreased slightly at DAV and HPB but remained weak at +0.000 decade-1 and -0.013 decade-1 (significant at 95% level). The JFJ 1995 – 2005 AOD time-series similarly decreased to -0.003 decade-1 (significant at 95% level). We conclude that despite a more detailed re40 analysis of these three time-series, which have been extended by five years to the end of 2010, a significant decrease in AOD at these three high-altitude sites has still not been observed

On the impact of competing intra- and intermolecular triplet-state quenching on photobleaching and photoswitching kinetics of organic fluorophores

While buffer cocktails remain the most commonly used method for photostabilization and photoswitching of fluorescent markers, intramolecular triplet-state quenchers emerge as an alternative strategy to impart fluorophores with 'self-healing' or even functional properties such as photoswitching. In this contribution, we evaluated combinations of both approaches and show that inter- and intramolecular triplet-state quenching processes compete with each other. We find that although the rate of triplet-state quenching is additive, the photostability is limited by the faster pathway. Often intramolecular processes dominate the photophysical situation for combinations of covalently-linked and solution-based photostabilizers and photoswitching agents. Furthermore we show that intramolecular photostabilizers can protect fluorophores from reversible off-switching events caused by solution-additives, which was previously misinterpreted as photobleaching. Our studies also provide practical guidance for usage of photostabilizer-dye conjugates for STORM-type super-resolution microscopy permitting the exploitation of their improved photophysics for increased spatio-temporal resolution. Finally, we provide evidence that the biochemical environment, e.g., proximity of aromatic amino-acids such as tryptophan, reduces the photostabilization efficiency of commonly used buffer cocktails. Not only have our results important implications for a deeper mechanistic understanding of self-healing dyes, but they will provide a general framework to select label positions for optimal and reproducible photostability or photoswitching kinetics in different biochemical environments

Multi-performance optimisation framework for the selection of structural alternatives based on sustainable qualities

In recent years, the increasing demand for innovative sustainable policies in building engineering has shifted the decision rationale from traditional performance-based systems towards systems augmented by life-cycle sustainability notions. This paper investigates a novel optimisation framework, which supports the selection of buildings’ structural alternatives at concept stage by applying multiple performance, sustainable requirements. The established model explores ways to effectively compute and process expert knowledge across different stakeholders groups into a consolidated decision-making platform supported by Lean Theory. A systematic procedure based on the Quality Function Deployment is utilised to successfully translate 16 sustainability requirements into 27 corresponding engineering design requirements. The theoretical and mathematical principles of Analytic Network Process are applied on a pilot study to build general decision clusters, identify feedback links amongst the various engineering criteria and determine their inner dependences

A nexus of intrinsic dynamics underlies translocase priming

The cytoplasmic ATPase SecA and the membrane-embedded SecYEG channel assemble to form the Sec translocase. How this interaction primes and catalytically activates the translocase remains unclear. We show that priming exploits a nexus of intrinsic dynamics in SecA. Using atomistic simulations, smFRET, and HDX-MS, we reveal multiple dynamic islands that cross-talk with domain and quaternary motions. These dynamic elements are functionally important and conserved. Central to the nexus is a slender stem through which rotation of the preprotein clamp of SecA is biased by ATPase domain motions between open and closed clamping states. An H-bonded framework covering most of SecA enables multi-tier dynamics and conformational alterations with minimal energy input. As a result, cognate ligands select preexisting conformations and alter local dynamics to regulate catalytic activity and clamp motions. These events prime the translocase for high-affinity reception of non-folded preprotein clients. Dynamics nexuses are likely universal and essential in multi-liganded proteins.</p

The X-ray Telescope of CAST

The Cern Axion Solar Telescope (CAST) is in operation and taking data since 2003. The main objective of the CAST experiment is to search for a hypothetical pseudoscalar boson, the axion, which might be produced in the core of the sun. The basic physics process CAST is based on is the time inverted Primakoff effect, by which an axion can be converted into a detectable photon in an external electromagnetic field. The resulting X-ray photons are expected to be thermally distributed between 1 and 7 keV. The most sensitive detector system of CAST is a pn-CCD detector combined with a Wolter I type X-ray mirror system. With the X-ray telescope of CAST a background reduction of more than 2 orders off magnitude is achieved, such that for the first time the axion photon coupling constant g_agg can be probed beyond the best astrophysical constraints g_agg < 1 x 10^-10 GeV^-1.Comment: 19 pages, 25 figures and images, replaced by the revised version accepted for publication in New Journal of Physic

Preproteins couple the intrinsic dynamics of SecA to its ATPase cycle to translocate via a catch and release mechanism

Protein machines undergo conformational motions to interact with and manipulate polymeric substrates. The Sec translocase promiscuously recognizes, becomes activated, and secretes >500 non-folded preprotein clients across bacterial cytoplasmic membranes. Here, we reveal that the intrinsic dynamics of the translocase ATPase, SecA, and of preproteins combine to achieve translocation. SecA possesses an intrinsically dynamic preprotein clamp attached to an equally dynamic ATPase motor. Alternating motor conformations are finely controlled by the γ-phosphate of ATP, while ADP causes motor stalling, independently of clamp motions. Functional preproteins physically bridge these independent dynamics. Their signal peptides promote clamp closing; their mature domain overcomes the rate-limiting ADP release. While repeated ATP cycles shift the motor between unique states, multiple conformationally frustrated prongs in the clamp repeatedly “catch and release” trapped preprotein segments until translocation completion. This universal mechanism allows any preprotein to promiscuously recognize the translocase, usurp its intrinsic dynamics, and become secreted

CAST constraints on the axion-electron coupling

In non-hadronic axion models, which have a tree-level axion-electron interaction, the Sun produces a strong axion flux by bremsstrahlung, Compton scattering, and axio-recombination, the "BCA processes." Based on a new calculation of this flux, including for the first time axio-recombination, we derive limits on the axion-electron Yukawa coupling g_ae and axion-photon interaction strength g_ag using the CAST phase-I data (vacuum phase). For m_a < 10 meV/c2 we find g_ag x g_ae< 8.1 x 10^-23 GeV^-1 at 95% CL. We stress that a next-generation axion helioscope such as the proposed IAXO could push this sensitivity into a range beyond stellar energy-loss limits and test the hypothesis that white-dwarf cooling is dominated by axion emission