Self-organized nanostructuring in Zr0.69Al0.31N thin films studied by atom probe tomography

We have applied atom probe tomography (APT) to analyze self-organizing structures of wear-resistant Zr0.69Al0.31N thin films grown by magnetron sputtering. Transmission electron microscopy shows that these films grow as a three-dimensional nanocomposite, consisting of interleaved lamellae in a labyrinthine structure, with an in-plane size scale of ~ 5 nm. The structure was recovered in the Al APT signal, while the Zr and N data lacked structural information. The onset of the self-organized labyrinthine growth was observed to occur by surface nucleation, 5–8 nm above the MgO substrate, due to increasing Zr–Al compositional fluctuations during elemental segregation. At a final stage, the labyrinthine growth mode was observed to be interrupted by the formation of larger ZrN grains

Identification of a Novel Drug Lead That Inhibits HCV Infection and Cell-to-Cell Transmission by Targeting the HCV E2 Glycoprotein

Hepatitis C Virus (HCV) infects 200 million individuals worldwide. Although several FDA approved drugs targeting the HCV serine protease and polymerase have shown promising results, there is a need for better drugs that are effective in treating a broader range of HCV genotypes and subtypes without being used in combination with interferon and/or ribavirin. Recently, two crystal structures of the core of the HCV E2 protein (E2c) have been determined, providing structural information that can now be used to target the E2 protein and develop drugs that disrupt the early stages of HCV infection by blocking E2’s interaction with different host factors. Using the E2c structure as a template, we have created a structural model of the E2 protein core (residues 421–645) that contains the three amino acid segments that are not present in either structure. Computational docking of a diverse library of 1,715 small molecules to this model led to the identification of a set of 34 ligands predicted to bind near conserved amino acid residues involved in the HCV E2: CD81 interaction. Surface plasmon resonance detection was used to screen the ligand set for binding to recombinant E2 protein, and the best binders were subsequently tested to identify compounds that inhibit the infection of Huh-7 cells by HCV. One compound, 281816, blocked E2 binding to CD81 and inhibited HCV infection in a genotype-independent manner with IC50’s ranging from 2.2 µM to 4.6 µM. 281816 blocked the early and late steps of cell-free HCV entry and also abrogated the cell-to-cell transmission of HCV. Collectively the results obtained with this new structural model of E2c suggest the development of small molecule inhibitors such as 281816 that target E2 and disrupt its interaction with CD81 may provide a new paradigm for HCV treatment

Enabling Efficient Coexistence of DSRC and C-V2X in Vehicular Networks

Radio access technologies, such as Cellular vehicleto-everything (C-V2X) and dedicated short range communications (DSRC), have been used to support robust communication in connected vehicles’ scenarios. However, existing studies mostly dealt with homogenous vehicular networks, where coexistence of different radio access technologies in vehicles are not considered. More precisely, such multi radio interface environments burden communications among vehicles. In this paper, we first review DSRC and C-V2X radio access technologies and existing packet relaying mechanisms that are specifically designed for homogenous or heterogeneous vehicular environments. We then present quality of service aware relaying algorithm (QR) that incorporates multi metric to prioritize dual interface vehicles (DVs) and provide robust communications among vehicles that are equipped with different radio access technologies. The simulation results confirm the superiority of the proposed QR in terms of message reception and relaying count as compared to the standard protocols

Structural and biochemical characterization of the exopolysaccharide deacetylase Agd3 required for Aspergillus fumigatus biofilm formation

The exopolysaccharide galactosaminogalactan (GAG) is an important virulence factor of the fungal pathogen Aspergillus fumigatus. Deletion of a gene encoding a putative deacetylase, Agd3, leads to defects in GAG deacetylation, biofilm formation, and virulence. Here, we show that Agd3 deacetylates GAG in a metal-dependent manner, and is the founding member of carbohydrate esterase family CE18. The active site is formed by four catalytic motifs that are essential for activity. The structure of Agd3 includes an elongated substrate-binding cleft formed by a carbohydrate binding module (CBM) that is the founding member of CBM family 87. Agd3 homologues are encoded in previously unidentified putative bacterial exopolysaccharide biosynthetic operons and in other fungal genomes. The exopolysaccharide galactosaminogalactan (GAG) is an important virulence factor of the fungal pathogen Aspergillus fumigatus. Here, the authors study an A. fumigatus enzyme that deacetylates GAG in a metal-dependent manner and constitutes a founding member of a new carbohydrate esterase family.Bio-organic Synthesi

The effect of queue size on the throughput, in group failure mode, for the loaded transport channel

The external data flow decreases the throughput of the transport connection. The indicator of this external load is the queue size in front of the protocol data. In this article, using a mathematical model in analytical and numerical forms, the relation between the throughput of the channel and the protocol parameters are presented including the queue size parameter. In this work the effect of the queue size on time-out duration has been shown, which is one of the important parameters and it's studied weakly in researches. Also, the relation between round-trip delay, the reliability of the transmission of the information segments with queue size are also shown

The Validity, Generalizability and Feasibility of Summative Evaluation Methods in Visual Analytics

Many evaluation methods have been used to assess the usefulness of Visual Analytics (VA) solutions. These methods stem from a variety of origins with different assumptions and goals, which cause confusion about their proofing capabilities. Moreover, the lack of discussion about the evaluation processes may limit our potential to develop new evaluation methods specialized for VA. In this paper, we present an analysis of evaluation methods that have been used to summatively evaluate VA solutions. We provide a survey and taxonomy of the evaluation methods that have appeared in the VAST literature in the past two years. We then analyze these methods in terms of validity and generalizability of their findings, as well as the feasibility of using them. We propose a new metric called summative quality to compare evaluation methods according to their ability to prove usefulness, and make recommendations for selecting evaluation methods based on their summative quality in the VA domain.Comment: IEEE VIS (VAST) 201

Chemically homogeneous boron carbide 10B/11B isotope modulated neutron interference mirrors

We introduce a novel type of neutron interference mirrors based on a chemically homogeneous BxC (x>4) matrix with internal high precision 10B/11B isotope modulation. Simulations predict that these mirrors exhibit very high neutron reflectivities for a small number of bilayer periods. This is experimentally confirmed by neutron reflectivity measurements of mirrors synthesized by ion-assisted magnetron sputter deposition. For example, a 120 nm thick multilayer consisting of just 20 bilayer periods of 10B5.7C/11B5.7C, with a periodicity of 61.5 {\AA}, exhibits a neutron reflectivity of 13 percent at an incidence angle of 4.7 deg for neutrons with a wavelength of 4.825 {\AA}. This is attributed to a high scattering length density contrast between the layers with an interface width <5 {\AA}. Structural analyses by X-ray diffraction, X-ray reflectivity, and transmission electron microscopy demonstrate that the 10B5.7C/11B5.7C multilayer mirrors are composed of amorphous, chemically homogenous B5.7C, without any internal chemical modulation. The data show that 10BxC/11BxC multilayer mirrors have the potential for higher neutron reflectivities at higher q-values using fewer and thinner layers, compared to todays state-of-the-art chemically modulated neutron multilayer mirrors

Assessment of pelvic organ prolapse with the Pelvic Inclination Correction System: defining the normal range and threshold to pathology

PURPOSE: To define the normal range and threshold values for pathologic prolapse on MRI using the PICS line and assess its correlation with the pubococcygeal line (PCL). METHODS: This prospective, IRB-approved study included 20 nulliparous volunteers and 18 prolapse patients (POP-Q Stage ≥ 2). Organ positions (bladder, cervix, anorectal junction) relative to PICS and PCL were measured on dynamic MRI. Differences in organ position were compared. Receiver-operating characteristic (ROC) analysis was performed to identify cutoff values for prolapse using the PICS line. The correlation between PICS and PCL measurements was tested with Spearman's rank correlation. RESULTS: In volunteers, median bladder and cervix positions measured to the PICS at rest were - 2.7 cm and - 5.3 cm compared to - 1.9 cm and - 2.7 cm in patients (p < 0.001). During straining, bladder and cervix were at - 0.9 cm and - 3.2 cm in volunteers versus + 2.5 cm and + 2.5 cm in patients (p < 0.001). Correlation was strong for PICS and PCL measurements for all three compartments (δ = 0.883-0.970, p ≤ 0.001). AUCs of PICS for the anterior and middle compartment were 0.98 (95% confidence interval [CI] 0.96-1.00, p < 0.001) and 0.96 (95% CI 0.89-1.00, p < 0.001) for differentiating patients from healthy volunteers. AUC for the posterior compartment was 0.76 (95% CI 0.57-0.96, p = 0.034). CONCLUSION: PICS measurements reliably differentiate patients from volunteers in the anterior and middle compartment. Future studies need to identify a reliable threshold for the posterior compartment. PICS and PCL measurements are strongly correlated

Assessment of pelvic organ prolapse with the Pelvic Inclination Correction System: defining the normal range and threshold to pathology.

PURPOSE To define the normal range and threshold values for pathologic prolapse on MRI using the PICS line and assess its correlation with the pubococcygeal line (PCL). METHODS This prospective, IRB-approved study included 20 nulliparous volunteers and 18 prolapse patients (POP-Q Stage ≥ 2). Organ positions (bladder, cervix, anorectal junction) relative to PICS and PCL were measured on dynamic MRI. Differences in organ position were compared. Receiver-operating characteristic (ROC) analysis was performed to identify cutoff values for prolapse using the PICS line. The correlation between PICS and PCL measurements was tested with Spearman's rank correlation. RESULTS In volunteers, median bladder and cervix positions measured to the PICS at rest were - 2.7 cm and - 5.3 cm compared to - 1.9 cm and - 2.7 cm in patients (p < 0.001). During straining, bladder and cervix were at - 0.9 cm and - 3.2 cm in volunteers versus + 2.5 cm and + 2.5 cm in patients (p < 0.001). Correlation was strong for PICS and PCL measurements for all three compartments (δ = 0.883-0.970, p ≤ 0.001). AUCs of PICS for the anterior and middle compartment were 0.98 (95% confidence interval [CI] 0.96-1.00, p < 0.001) and 0.96 (95% CI 0.89-1.00, p < 0.001) for differentiating patients from healthy volunteers. AUC for the posterior compartment was 0.76 (95% CI 0.57-0.96, p = 0.034). CONCLUSION PICS measurements reliably differentiate patients from volunteers in the anterior and middle compartment. Future studies need to identify a reliable threshold for the posterior compartment. PICS and PCL measurements are strongly correlated

Pelvic organ movements in asymptomatic nulliparous and symptomatic premenopausal women with pelvic organ prolapse in dynamic MRI: a feasibility study comparing midsagittal single-slice with multi-slice sequences

PURPOSE To compare multi-slice (MS) MRI sequences of the pelvis acquired at rest and straining to dynamic midsagittal single-slice (SS) sequences for the assessment of pelvic organ prolapse (POP). METHODS This IRB-approved prospective single-center feasibility study included 23 premenopausal symptomatic patients with POP and 22 asymptomatic nulliparous volunteers. MRI of the pelvis at rest and straining was performed with midsagittal SS and MS sequences. Straining effort, visibility of organs and POP grade were scored on both. Organ points (bladder, cervix, anorectum) were measured. Differences between SS and MS sequences were compared with Wilcoxon test. RESULTS Straining effort was good in 84.4% on SS and in 64.4% on MS sequences (p = 0.003). Organ points were always visible on MS sequences, whereas the cervix was not fully visible in 31.1-33.3% on SS sequences. At rest, there were no statistically significant differences of organ point measurements between SS and MS sequences in symptomatic patients. At straining, positions of bladder, cervix, and anorectum were + 1.1 cm (± 1.8 cm), - 0.7 cm (± 2.9 cm), and + 0.7 cm (± 1.3 cm) on SS and + 0.4 mm (± 1.7 cm), - 1.4 cm (± 2.6 cm), and + 0.4 cm (± 1.3 cm) on MS sequences (p < 0.05). Only 2 cases of higher-grade POP were missed on MS sequences (both with poor straining effort). CONCLUSION MS sequences increase the visibility of organ points compared to SS sequences. Dynamic MS sequences can depict POP if images are acquired with sufficient straining effort. Further work is needed to optimize the depiction of the maximum straining effort with MS sequences