Enhancing life cycles of total pressure vacuum gauges in deposition applications (enhancing life cycles of vacuum gauges)

The application of hot cathode ionisation gauges in vacuum deposition processes (PVD, CVD) is critical regarding durability of the sensors, due to the inherent risk of contamination and discharges. Unstable calibration after relatively short periods of operation is an often reported problem, which arises from contamination with film forming substances contained in the residual gas. Furthermore, contamination often lead to early gauge drop outs and consequently to unsatisfyingly short life cycles of the gauges. Research was conducted to obtain improved solutions for prevention of gauge contamination on the one side, as well as optimised sensor designs for improved robustness and insensitivity against contaminants on the other side. This contribution discusses approaches for the desired improvements by evaluating the effectiveness of system-based methods to reduce the exposure of the sensor to contaminations, by indicating interactions between those system-based means and gauges, and by indicating options for improving gauge durability.     

Methods to detect objects in photon-limited images

We investigate the problem of detecting and localizing a known signal in a photon-limited image, where Poisson noise is the dominant source of image degradation. For this purpose we developed and evaluated three new algorithms. The first two are based on the impulse restoration (IR) principle and the third is based on the generalized likelihood ratio test (GLRT). In the IR approach, the problem is formulated as one of restoring a delta function at the location of the desired object. In the GLRT approach, which is a well-known variation on the optimal likelihood ratio test, the problem is formulated as a hypothesis testing problem, in which the unknown background intensity of the image and the intensity scale of the object are obtained by maximum-likelihood estimation. We used Monte Carlo simulations and localization receiver operating characteristic (LROC) curves to evaluate the proposed algorithms quantitatively. LROC curves demonstrate the ability of an algorithm to detect and locate objects in a scene correctly. Our simulations demonstrate that the GLRT approach is superior to all other tested algorithms.     

Genetic and environmental influences on ADHD symptom dimensions of inattention and hyperactivity: A meta-analysis.

Behavioral genetic investigations have consistently demonstrated large genetic influences for the core symptom dimensions of attention-deficit/hyperactivity disorder (ADHD), namely inattention (INATT) and hyperactivity (HYP). Yet little is known regarding potential similarities and differences in the type of genetic influence (i.e., additive vs. nonadditive) on INATT and HYP. As these symptom dimensions form the basis of the current Diagnostic and Statistical Manual of Mental Disorders subtype classification system, evidence of differential genetic influences would have important implications for research investigating causal mechanisms for ADHD. The current meta-analysis aimed to investigate the nature of etiological influences for INATT and HYP by comparing the type and magnitude of genetic and environmental influences each. A comprehensive literature search yielded 79 twin and adoption studies of INATT and/or HYP. Of these, 13 samples of INATT and 9 samples of HYP were retained for analysis. Results indicated that both dimensions were highly heritable (genetic factors accounted for 71% and 73% of the variance in INATT and HYP, respectively). However, the 2 dimensions were distinct as to the type of genetic influence. Dominant genetic effects were significantly larger for INATT than for HYP, whereas additive genetic effects were larger for HYP than for INATT. Estimates of unique environmental effects were small to moderate and shared environmental effects were negligible for both symptom dimensions. The pattern of results generally persisted across several moderating factors, including gender, age, informant, and measurement method. These findings highlight the need for future studies to disambiguate INATT and HYP when investigating the causal mechanisms, and particularly genetic influences, behind ADHD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dialysis desiderata*

Microarray immunoassay systems, proteomics, separation of polypeptides in plasma by electrophoresis, and detection by mass spectrometry have shown that low molecular weight proteins, cytokines, and chemokines are present in high concentration in chronic kidney disease (CKD) subjects receiving dialysis. That these substances are also found in high concentration in sepsis, postcardiac bypass, acute respiratory distress, burns, and in brain death suggest that these syndromes have a common pathogenesis via a systemic inflammatory response syndrome (SIRS). It is not yet clear whether the profiles of such substances differ among the SIRS states. Dialysis membranes are not capable of removing these substances because such moieties exceed the molecular weight cutoff of modern synthetic hemodialysis membranes. On the other hand, sorbents directly in contact with blood or indirectly with filtered plasma, may be designed with pore structures with the capability of removing these substances. Such sorbents could be exploited in the treatment of CKD. While few human studies have been performed, animal experiments suggest that human trials should be initiated. The potential advantages of sorbents for CKD will be described.     

Circulating miRNA Expression Profiles and Machine Learning Models in Association with Response to Irinotecan-Based Treatment in Metastatic Colorectal Cancer

Colorectal cancer represents a leading cause of cancer-related morbidity and mortality. Despite improvements, chemotherapy remains the backbone of colorectal cancer treatment. The aim of this study is to investigate the variation of circulating microRNA expression profiles and the response to irinotecan-based treatment in metastatic colorectal cancer and to identify relevant target genes and molecular functions. Serum samples from 95 metastatic colorectal cancer patients were analyzed. The microRNA expression was tested with a NucleoSpin miRNA kit (Machnery-Nagel, Germany), and a machine learning approach was subsequently applied for microRNA profiling. The top 10 upregulated microRNAs in the non-responders group were hsa-miR-181b-5p, hsa-miR-10b-5p, hsa-let-7f-5p, hsa-miR-181a-5p, hsa-miR-181d-5p, hsa-miR-301a-3p, hsa-miR-92a-3p, hsa-miR-155-5p, hsa-miR-30c-5p, and hsa-let-7i-5p. Similarly, the top 10 downregulated microRNAs were hsa-let-7d-5p, hsa-let-7c-5p, hsa-miR-215-5p, hsa-miR-143-3p, hsa-let-7a-5p, hsa-miR-10a-5p, hsa-miR-142-5p, hsa-miR-148a-3p, hsa-miR-122-5p, and hsa-miR-17-5p. The upregulation of microRNAs in the miR-181 family and the downregulation of those in the let-7 family appear to be mostly involved with non-responsiveness to irinotecan-based treatment.     

Investigation of thermochemical conversion of biomass in supercritical water using a batch reactor

This study focused on gasification of biomass and a biomass model compound. Data are presented that show the presence of supercritical water enhances gasification efficiency, as it participates as both a solvent and a reactant. It is established that biomass gasification efficiencies are in the same range for all types of biomass. The thermodynamic changes of state are functions of elemental composition, not biomass species. The oxidation state of carbon atom of biomass is a key variable in determining the changes in enthalpy during both conventional combustion and supercritical water gasification. The oxidation state of the feed (together with the reaction conditions that influence the degree to which water participates as a reactant) also determines the vapor product composition.Decomposition reactions to vapor products are rapid and complete at high temperature (?550 °C), catalytic mediation is not required. Temperature and residence time are important operating parameters for SCW gasification. Less important are the pressure of gasification (in the range of 40-67 MPa) and the presence of catalyst. The vapor yield, gas composition, the carbon and hydrogen balance of SCW gasification are functions of gasification temperature, residence time and biomass load (concentration).     

Synthesis and Structure-Activity Relationships of N-(4-Benzamidino)-Oxazolidinones: Potent and Selective Inhibitors of Kallikrein-Related Peptidase 6

Kallikrein-related peptidase 6 (KLK6) is a secreted serine protease that belongs to the family of tissue kallikreins. Aberrant expression of KLK6 has been found in different cancers and neurodegenerative diseases, and KLK6 is currently studied as a potential target in these pathologies. We report a novel series of KLK6 inhibitors discovered in a high-throughput screen within the European Lead Factory program. Structure-guided design based on docking studies enabled rapid progression of a hit cluster to inhibitors with improved potency, selectivity and pharmacokinetic properties. In particular, inhibitors 32 ((5R)-3-(4-carbamimidoylphenyl)-N-((S)-1-(naphthalen-1-yl)propyl)-2-oxooxazolidine-5-carboxamide) and 34 ((5R)-3-(6-carbamimidoylpyridin-3-yl)-N-((1S)-1-(naphthalen-1-yl)propyl)-2-oxooxazolidine-5-carboxamide) have single-digit nanomolar potency against KLK6, with over 25-fold and 100-fold selectivities against the closely related enzyme trypsin, respectively. The most potent compound, 32 , effectively reduces KLK6-dependent invasion of HCT116 cells. The high potency in combination with good solubility and low clearance of 32 make it a good chemical probe for KLK6 target validation in vitro and potentially in vivo.     

k-RNN: Extending NN-heuristics for the TSP

Mobile Networks and Applications - In this paper we present an extension of existing Nearest-Neighbor heuristics to an algorithm called k-Repetitive-Nearest-Neighbor. The idea is to start with a...     

Characterization of Critical Determinants of ACE2–SARS CoV-2 RBD Interaction

Despite sequence similarity to SARS-CoV-1, SARS-CoV-2 has demonstrated greater widespread virulence and unique challenges to researchers aiming to study its pathogenicity in humans. The interaction of the viral receptor binding domain (RBD) with its main host cell receptor, angiotensin-converting enzyme 2 (ACE2), has emerged as a critical focal point for the development of anti-viral therapeutics and vaccines. In this study, we selectively identify and characterize the impact of mutating certain amino acid residues in the RBD of SARS-CoV-2 and in ACE2, by utilizing our recently developed NanoBiT technology-based biosensor as well as pseudotyped-virus infectivity assays. Specifically, we examine the mutational effects on RBD-ACE2 binding ability, efficacy of competitive inhibitors, as well as neutralizing antibody activity. We also look at the implications the mutations may have on virus transmissibility, host susceptibility, and the virus transmission path to humans. These critical determinants of virus–host interactions may provide more effective targets for ongoing vaccines, drug development, and potentially pave the way for determining the genetic variation underlying disease severity.