Cholesterol is critical to the integrity of neuronal porosome/fusion pore

Secretion is one of the most fundamental cellular processes. Porosomes have been demonstrated as the universal secretory machinery in cells. Earlier studies determine the presence of a number of proteins in porosomes, among them the N- and P/Q-type calcium channels, actin, syntaxin-1, synaptotagmin-1, vimentin, the N-ethylmaleimide-sensitive factor (NSF), the chloride channel CLC-3, and the alpha subunit of the heterotrimeric GTP-binding protein G(o). Studies demonstrate that t-SNAREs localize at the base of porosomes, and directly interact with calcium channels. In the present study, we demonstrate that Syntaxin-1 co-localizes with cholesterol in solubilized synaptosomal membrane preparations. Depletion of cholesterol, results in the dissociation of both Syntaxin-1 and N-type calcium channel from neuronal porosomes. Thus, cholesterol participates as an integral component of the neuronal porosome complex, and is required for its stability.     

Complex and controversial issues in locally advanced non-small cell lung carcinoma

Locally advanced non-small cell lung carcinoma (NSCLC) presents enormous challenges to clinicians and researchers. Because of the absence of metastatic disease, it is a potentially curable condition, greatly differentiating it from stage IV NSCLC. The median and actuarial survival rates are poor, though clearly improved in the past decade, and clearly better than several other types of locally advanced malignancies (e.g., pancreatic cancer, glioblastoma). As demonstrated in Table I, the combination of chemotherapy and radiotherapy has earned the designation of "standard of care" for most good-performance-status patients with locally advanced NSCLC. It is likely that improvements in radiotherapy have also contributed to the enhanced survival and local control rates in this disease. With concurrent chemoradiotherapy, the majority of patients can receive a substantial local response (Fig. 1). Many achieve durable local control, only to succumb to eventual distant metastatic failure. There remains much room for improvement, and there are several avenues for clinical and translational research that offer promise. These include new systemic chemotherapy options (and newer ways of combining these drugs with radiotherapy), improvements in radiotherapy fractionation and dose intensity, methods of protection from chemoradiotherapy toxicity, specific therapies to prevent brain metastatic failure, and the integration of biologically targeted molecules into chemoradiation programs. This article summarizes the advances in the treatment of locally advanced NSCLC over the past several decades and explores some of the many remaining controversies and areas for future investigation.     

Landmine detection and localization using chemical sensor arrayprocessing

We develop methods for automatic detection and localization of landmines using chemical sensor arrays and statistical signal processing techniques. The transport of explosive vapors emanating from buried landmines is modeled as a diffusion process in a two-layered system consisting of ground and air. Measurement and statistical models are then obtained from the associated concentration distribution. We derive two detectors (the generalized likelihood ratio (GLR) test and the mean detector) and determine their performance in terms of the probabilities of false alarm and detection. To determine the unknown location of a landmine, we derive a maximum likelihood (ML) estimation algorithm and evaluate its performance by computing the Cramer-Rao bound (CRB). The results are applied to the design of chemical sensor arrays, satisfying criteria specified in terms of detection and estimation performance measures and for optimally selecting the number and positions of sensors and the number of time samples. To illustrate the potential of the proposed techniques in a realistic demining scenario, we derive a moving-sensor algorithm in which the stationary sensor array is replaced by a single moving sensor. Numerical examples are given to demonstrate the applicability of our results     

Concurrent radiochemotherapy for patients with stage III non-small-cell lung cancer (NSCLC): long-term results of a phase II study

The distribution of estrogen and progesterone receptors (ER, PR) was assessed in the primary tumour in 1335 of 2704 (49%) consecutive new breast carcinoma patients (HORMREC). In a subgroup of 757 radically treated patients without systemic adjuvant treatment (RADOP) the relation of the ER and PR content to relapse and survival was evaluated. Three levels were defined for ER: ER-: <10 fmol/mg protein, ER+: moderate ER content >/= 10-99 fmol/mg protein, and high ER content >/= 100 fmol/mg protein. In 1288 patients of the HORMREC group who were evaluable for ER, 1061 (82%) had ER+ tumours, 685 (65%) of moderate content and 376 (35%) of high content, respectively. Among 917 patients, evaluable for PR, 723 (79%) tumours were PR+ (>/= 20 fmol/mg protein), of them 352 (49%) with a moderate content (>/= 20-99 fmol/mg protein) and 371 (51%) with a high content ( >/= 100 fmol/mg protein). The median ER content was significantly increased among the post-menopausal women as compared to the premenopausal women, whereas the median PR content showed no such differences. For the RADOP patients, no correlation between ER status and the first site of relapse was seen, whereas PR+ tumours tended to relapse more often locally than PR- tumours. In the univariate analysis the five-and 10-year tumour-related survival rates for all patients were not correlated with ER or PR positivity. One subgroup of patients with favourable outcome was identified on the basis of hormone receptors: Premenopausal women with tumours of moderately elevated ER content. In the multivariate analysis tumour size and axillary node status were the only independent predictors of survival. Measurements of hormone receptor status give weak prognostic information in radically treated patients with breast cancer as long as no adjuvant systemic treatment is applied. As todays' adjuvant treatment is based on the knowledge of hormone receptor status of the primary tumour, this information should be obtained routinely.     

Comparative efficacy of a DA2/alpha2 agonist and a beta-blocker in reducing adrenergic drive and cardiac fibrosis in an experimental model of left ventricular dysfunction after coronary artery occlusion

In a prepilot study, eight adults with chronic PTSD underwent three 90-minute sessions of eye movement desensitization and reprocessing (EMDR) at one-week intervals in an open trial. None of the seven who completed treatment met criteria for current PTSD two months later. Significant decreases in measures of pathology and disturbance were recorded. A controlled trial of EMDR is under way.     

Adhesion interaction of one-component polyurethane in cross-laminating southern pine wood treated with micronized copper azole—type C (MCA-C)

European Journal of Wood and Wood Products - Compatibility between preservative and resin plays an important role in determining the adhesive performance of preservative-treated engineered wood...     

Tribological Behavior of Composites Based on ZA-27 Alloy Reinforced with Graphite Particles

The objective of this investigation is to assess the influence of graphite reinforcement on tribological behavior of ZA-27 alloy. The composite with 2 wt% of graphite particles was produced by the compocasting procedure. Tribological properties of unreinforced alloy and composite were studied, using block-on-disk tribometer, under dry and lubricated sliding conditions at different specific loads and sliding speeds. The worn surfaces of the samples were examined by the scanning electron microscopy (SEM). The obtained results revealed that ZA-27/graphite composite specimens exhibited significantly lower wear rate and coefficient of friction than the matrix alloy specimens in all the combinations of applied loads (F _n ) and sliding speeds (v) in dry and lubricated tests. The positive tribological effects of graphite reinforcement of ZA-27 in dry sliding tests were provided by the tribo-induced graphite film on the contact surface of composite. In test conditions, characterized by the small graphite content and modest sliding speeds and applied loads, nonuniform tribo-induced graphite films were formed leading to the increase of the friction coefficient and wear rate, with increase of the sliding speed and applied load. In conditions of lubricated sliding, the very fine graphite particles formed in the contact interface mix with the lubricating oil forming the emulsion with improved tribological characteristics. Smeared graphite decreased the negative influence of F _n on tribological response of composites, what is manifested by the mild regime of the boundary lubrication, as well as by realization of the mixed lubrication at lower values of the v/F _n ratio, with respect to the matrix alloy.     

Describing and quantifying the chemical composition distribution in unimodal and multimodal ZN‐polyethylene using CRYSTAF

A new approach in describing and quantifying the chemical composition distribution (CCD) in Ziegler–Natta‐polyethylene copolymers was developed by using crystallization analysis fractionation (Crystaf). Copolymers of ethylene and α‐olefins (1‐butene and 1‐hexene) polymerized with different ZN catalyst systems were analyzed. Distinct differences in the CCD between the different polymer types (catalyst‐cocatalyst system and comonomer type) were observed and could be quantified. Same approach was applied to 2‐dimensional fractionation technique, cross fractionation chromatography, to describe and quantify the CCD of multimodal polyethylene copolymers. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43089.     

Visualization of artificial lignin supramolecular structures

In this paper we are presenting the results of our environmental scanning electron microscopy (ESEM) investigation of the lignin model compound--enzymatically polymerized coniferyl alcohol, also known as dehydrogenate polymer (DHP). The goals of this study were to visualize the supramolecular organization of DHP polymer on various substrates, namely graphite, mica, and glass, and to explore the influence of substrate surface properties and associated collective phenomena on the lignin self-assembled supramolecular structure. Based on results obtained with ESEM, combined with previously published results based on scanning tunneling microscopy (STM) and electron spin resonance (ESR) technique, we looked at lignin structure ranging from a monomer on a fraction of nanometer scale to a large aggregate on a fraction of millimeter scale, therefore using six orders of magnitude range of size. Herein, we are presenting evidence that there are at least four different levels of the supramolecular structure of lignin, and that its supramolecular organization is well dependent on the substrate surface characteristics, such as hydrophobicity, delocalized orbitals, and surface-free energy.     

Expanding the library of secondary ions that distinguish lignin and polysaccharides in time-of-flight secondary ion mass spectrometry analysis of wood

Extracted pine (Pinus spp.) wood and the holocellulose and cellulose fractions of pine were analyzed by time-of-flight secondary ion mass spectrometry (ToF-SIMS). The main sources of variation among wood constituents were elucidated by principal component analysis (PCA). Peaks characteristic of lignin or polysaccharides were identified through the combination of high mass resolution analyses of pine fractions and high lateral resolution image analyses distinguishing the lignin-rich middle lamella from the secondary cell wall layers in solid wood cross-sections. A collection of peaks was compiled which (1) extends the library of characteristic lignin and polysaccharide secondary ions in wood, (2) can be applied to both high and nominal mass resolution spectra, and (3) is free from peaks that contraindicate between wood components. The removal of additional peaks to avoid mass interferences with common contaminants was also successful. Many of the characteristic peaks were high-intensity fingerprint ions below m/z 100, which provided for rapid analysis of the lignin and polysaccharide biopolymers in woody samples. The analysis also identified important mass interferences with previously reported wood ions.