bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐term cancer control outcomes in patients with biochemical recurrence and the impact of time from radical prostatectomy to biochemical recurrence
Authors: Pompe Raisa S. , Gild Philipp , Karakiewicz Pierre I. , Bock Lea‐Philine , Schlomm Thorsten , Steuber Thomas , Graefen Markus , Huland Hartwig , Tian Zhe , Tilki Derya 
Published: March 2018

BackgroundRates of metastatic progression (MP) and prostate cancer mortality (PCSM) are variable after biochemical recurrence (BCR) in patients who underwent radical prostatectomy (RP). To describe long‐term oncological outcomes of BCR patients and to analyze risk factors for further outcomes in these men with a special focus on RP‐BCR time.MethodsWe retrospectively analyzed the data of 5509 RP patients treated between 1992 and 2006. Of those, we included 1321 patients who experienced BCR (PSA level ≥0.2 ng/mL) and did not receive any neoadjuvant or adjuvant therapy. Kaplan‐Meier and time dependent Cox regression models were used.ResultsMedian follow‐up was 121 months. MP was recorded in 177 (13.4%), PCSM in 126 (9.5%), and overall mortality (OM) in 264 (20.0%) patients. Patients with MP had worse tumor characteristics such as higher Gleason Scores (GS), rapid PSA doubling‐time (DT), and shorter RP‐BCR time intervals. MP‐free, PCSM‐free, and overall survival rates were significantly worse in patients with RP‐BCR time of <12 months versus patients with 12‐35.9 or ≥36 months (P ≤ 0.001). Besides higher GS and rapid PSA‐DT, RP‐BCR time independently predicted MP, PCSM, and OM in multivariable regression analyses. Relative to the intermediate and longest RP‐BCR time interval, the shortest interval (<12) carried the highest risk for all three endpoints.ConclusionsOnly a small proportion of BCR patients proceed to MP or PCSM. Besides higher GS and rapid PSA‐DT a shorter RP‐BCR interval (<12 months) heralds the most aggressive phenotype for progression to all three examined endpoints: MP, PCSM, and OM.
Comprehensive mapping of cystic fibrosis mutations to CFTR protein identifies mutation clusters and molecular docking predicts corrector binding site
Authors: Molinski Steven V. , Shahani Vijay M. , Subramanian Adithya S. , MacKinnon Stephen S. , Woollard Geoffrey , Laforet Marcon , Laselva Onofrio , Morayniss Leonard D. , Bear Christine E. , Windemuth Andreas 
Published: March 2018

AbstractCystic Fibrosis (CF) is caused by mutations in the CFTR gene, of which over 2000 have been reported to date. Mutations have yet to be analyzed in aggregate to assess their distribution across the tertiary structure of the CFTR protein, an approach that could provide valuable insights into the structure‐function relationship of CFTR. In addition, the binding site of Class I correctors (VX‐809, VX‐661, and C18) is not well understood. In this study, exonic CFTR mutations and mutant allele frequencies described in 3 curated databases (ABCMdb, CFTR1, and CFTR2, comprising >130 000 data points) were mapped to 2 different structural models: a homology model of full‐length CFTR protein in the open‐channel state, and a cryo‐electron microscopy core‐structure of CFTR in the closed‐channel state. Accordingly, residue positions of 6 high‐frequency mutant CFTR alleles were found to spatially co‐localize in CFTR protein, and a significant cluster was identified at the NBD1:ICL4 interdomain interface. In addition, immunoblotting confirmed the approximate binding site of Class I correctors, demonstrating that these small molecules act via a similar mechanism in vitro, and in silico molecular docking generated binding poses for their complex with the cryo‐electron microscopy structure to suggest the putative corrector binding site is a multi‐domain pocket near residues F374‐L375. These results confirm the significance of interdomain interfaces as susceptible to disruptive mutation, and identify a putative corrector binding site. The structural pharmacogenomics approach of mapping mutation databases to protein models shows promise for facilitating drug discovery and personalized medicine for monogenetic diseases.
The dimerization of PSGL‐1 is driven by the transmembrane domain via a leucine zipper motif
Authors: Chai Mengya , Liu Bo , Sun Fude , Zhu Zhentai , Xu Lida , Luo Shi‐Zhong 
Published: March 2018

AbstractP‐selectin glycoprotein ligand‐1 (PSGL‐1) is a homodimeric mucin ligand that is important to mediate the earliest adhesive event during an inflammatory response by rapidly forming and dissociating the selectin‐ligand adhesive bonds. Recent research indicates that the noncovalent associations between the PSGL‐1 transmembrane domains (TMDs) can substitute for the C320‐dependent covalent bond to mediate the dimerization of PSGL‐1. In this article, we combined TOXCAT assays and molecular dynamics (MD) simulations to probe the mechanism of PSGL‐1 dimerization. The results of TOXCAT assays and Martini coarse‐grained molecular dynamics (CG MD) simulations demonstrated that PSGL‐1 TMDs strongly dimerized in a natural membrane and a leucine zipper motif was responsible for the noncovalent dimerization of PSGL‐1 TMD since mutations of the residues that occupied a or d positions in an (abcdefg)n leucine heptad repeat motif significantly reduced the dimer activity. Furthermore, we studied the effects of the disulfide bond on the PSGL‐1 dimer using MD simulations. The disulfide bond was critical to form the leucine zipper structure, by which the disulfide bond further improved the stability of the PSGL‐1 dimer. These findings provide insights to understand the transmembrane association of PSGL‐1 that is an important structural basis for PSGL‐1 preferentially binding to P‐selectin to achieve its biochemical and biophysical functions.
Structural effects of point mutations in proteins
Authors: Shanthirabalan Suvethigaa , Chomilier Jacques , Carpentier Mathilde 
Published: March 2018

AbstractA structural database of 11 families of chains differing by a single amino acid substitution has been built. Another structural dataset of 5 families with identical sequences has been used for comparison. The RMSD computed after a global superimposition of the mutated protein on each native one is smaller than the RMSD calculated among proteins of identical sequences. The effect of the perturbation is very local, and not necessarily the highest at the position of the mutation. A RMSD between mutated and native proteins is computed over a 3‐residue or a 7‐residue window at each position. To separate the effects of structural fluctuations due to point mutations from other sources, pair RMSD have been translated into P values which themselves are included in a score called P‐RANK. This score allows highlighting small backbone distortions by comparing these RMSD between mutated and native positions to the RMSD at the same positions in the absence of a mutation. It results from the P‐RANK that 38% of all mutations produce a significant effect on the displacement. When compared with a random distribution of RMSD at un‐mutated positions, we show that, even if the RMSD is greater when the mutation is in loops than in regular secondary structure, the relative effect is more important for regular secondary structures and for buried positions. We confirm the absence of correlation between RMSD and the predicted variation of free energy of folding but we found a small correlation between high RMSD and the error in the prediction of ΔΔG.
The impact of the diamond reinforcing particle size on their interaction with the aluminum matrix of composites in the course of heating
Authors: Popov Vladimir 
Published: March 2018

In aluminum matrix composites, the formation of aluminum carbide may occur during heating on contact between aluminum and the carbon reinforcing particles. Samples of composites with an aluminum matrix and various diamond reinforcing particles were prepared to determine the influence of the size of the diamond particles on this process. The composites were obtained via mechanical alloying. Annealing shows that the outcome is different for cases of contact with diamond nanoparticles and microparticles. Differential scanning calorimetry has shown that the reaction between the components to produce aluminum carbide starts at 400°C to 450°C in composite materials made of aluminum and nanodiamond reinforcing particles with a size of 4 to 6 nm. The reaction with diamond microparticles starts at higher temperatures. The studies have shown that the temperature range for the use of composites with an aluminum matrix and nanodiamond reinforcing particles does not exceed 450°C.
A Comparative In Vivo Study of Albumin‐Coated Paclitaxel Nanocrystals and Abraxane
Authors: Park Joonyoung , Park Ji Eun , Hedrick Victoria E. , Wood Karl V. , Bonham Connie , Lee Wooin , Yeo Yoon 
Published: March 2018

AbstractNanoparticulate drug carriers exploit the enhanced permeability of tumor vasculature to achieve selective delivery of chemotherapeutic drugs. For this purpose, nanoparticles (NPs) need to circulate with a long half‐life, enter tumors via the permeable vasculature and stay in tumors via favorable interactions with tumor cells. To fulfill these requirements, albumin‐coated nanocrystal formulation of paclitaxel (PTX), Cim‐F‐alb, featuring high drug loading content, physical stability in serum, and surface‐bound albumin in its native conformation is prepared. The pharmacokinetic and biodistribution (PK/BD) profiles of Cim‐F‐alb in a mouse model of B16F10 melanoma show that Cim‐F‐alb exhibits a longer plasma half‐life and a greater PTX deposition in tumors than Abraxane by ≈1.5 and ≈4.6 fold, respectively. Biolayer interferometry analysis indicates that Cim‐F‐alb has less interaction with serum proteins than nanocrystals lacking albumin coating, indicating the protective effect of the surface‐bound albumin against opsonization in the initial deposition phase. With the advantageous PK/BD profiles, Cim‐F‐alb shows greater and longer‐lasting anticancer efficacy than Abraxane at the equivalent dose. This study demonstrates the significance of controlling circulation stability and surface property of NPs in efficient drug delivery to tumors and enhanced anticancer efficacy.
Defect Engineering in Few‐Layer Phosphorene
Authors: Sharma Ankur , Wen Bo , Liu Boqing , Myint Ye Win , Zhang Han , Lu Yuerui 
Published: March 2018

AbstractDefect engineering in 2D phosphorene samples is becoming an important and powerful technique to alter their properties, enabling new optoelectronic applications, particularly at the infrared wavelength region. Defect engineering in a few‐layer phosphorene sample via introduction of substrate trapping centers is realized. In a three‐layer (3L) phosphorene sample, a strong photoluminescence (PL) emission peak from localized excitons at ≈1430 nm is observed, a much lower energy level than free excitonic emissions. An activation energy of ≈77 meV for the localized excitons is determined in temperature‐dependent PL measurements. The relatively high activation energy supports the strong stability of the localized excitons even at elevated temperature. The quantum efficiency of localized exciton emission in 3L phosphorene is measured to be approximately three times higher than that of free excitons. These results could enable exciting applications in infrared optoelectronics.
In Vitro Fusion of Normal and Neoplastic Breast Epithelial Cells with Human Mesenchymal Stroma/Stem Cells Partially Involves Tumor Necrosis Factor Receptor Signaling
Authors: Melzer Catharina , von der Ohe Juliane , Hass Ralf 
Published: March 2018

Abstract
Formation of hybrid cells by “accidental cell fusion” of normal and neoplastic breast epithelial cells with local tissue-associated mesenchymal stroma/stem-like cells (MSC) in an inflammatory microenvironment can generate new cancer cell populations whereby molecular signaling mechanisms of this process remain unclear. Fusions of lentiviral enhanced green fluorescent protein-labeled MSC with mcherry-labeled breast epithelial cells were quantified and effects of tumor necrosis factor alpha (TNF-α) and receptor downstream signaling were investigated. Cocultures of MSC with normal human mammary epithelial cells, with neoplastic MCF10A, or with MDA-MB-231 or MCF7 breast cancer cells demonstrated hybrid cell formation between 0.1% and about 2% of the populations within 72 hours, whereby the fusion process occurred in less than 5 minutes. Addition of the pro-inflammatory cytokine TNF-α significantly enhanced MCF10A-MSC cell fusion. Small-interfering RNA (siRNA) knockdown experiments revealed an involvement of tumor necrosis factor (TNF) receptor-1 and -2 in this process. This was also substantiated by siRNA knockdown of tumor necrosis factor receptor type 1-associated death domain which abolished TNF-α-stimulated fusion. While TNF receptor signaling can be relayed via the Mitogen-activated protein kinase 8 (MAPK8), NF-κB or cell death pathways, examination of further downstream signaling exhibited little if any effects of MAPK8 or RelA (p65) on TNF-α-mediated cell fusion, respectively. These data suggested that cell fusion between MSC and MCF10A breast epithelial cells can be stimulated by TNF-α involving TNF receptor-activated cell death pathways or additional NF-κB signaling.
Novel diagnostic approach on the identification of Brucella melitensis Greek endemic strains‐discrimination from the vaccine strain Rev.1 by PCR‐RFLP assay
Authors: Christoforidou Sofia , Boukouvala Evridiki , Zdragas Antonios , Malissiova Eleni , Sandalakis Vassilios , Psaroulaki Anna , Petridou Evanthia , Tsakos Panagiotis , Ekateriniadou Loukia , Hadjichristodoulou Christos 
Published: March 2018

AbstractDespite the intensive implementation of control programmes goat, sheep and human brucellosis remains endemic in Greece. As the discrimination between field endemic strains and vaccine strain Rev.1 is not feasible, it is essential to develop new diagnostic tools for brucellosis diagnosis. Moreover, effective disease control requires enhanced epidemiological surveillance in both humans and animals including robust laboratory support. Two new multiplex (duplex) polymerase chain reactions (PCRs) were developed and the results were compared with those obtained by real‐time PCR and bacteriological biotyping. A total of 71 Brucella spp. Greek endemic strains were identified at species and biovar level, using both molecular and conventional techniques. Their discrimination from the vaccine strain Rev.1 was achieved, using polymerase chain reaction‐restriction fragment length polymorphism assay (PCR‐RFLP). All 71 strains were identified as Brucella melitensis by multiplex PCR as well as by real‐time PCR and conventional biotyping. Sixty‐two (87.3%) out of 71 strains were identified as B. melitensis biovar 3, eight (11,3%) strains as biovar 1 and only one (1,4%) as biovar 2. Digestion with PstI restriction enzyme revealed that all strains were field endemic strains, as they gave different patterns from the vaccine strain Rev.1. Brucella melitensis biovar 3 appears to be the predominant type in Greece. The novel multiplex PCR produced results concordant to ones obtained by real‐time PCR and conventional biotyping. This technique could support and facilitate the surveillance of Brucellosis in Greece contributing in the control of the disease.
Condition monitoring of spar‐type floating wind turbine drivetrain using statistical fault diagnosis
Authors: Ghane Mahdi , Rasekhi Nejad Amir , Blanke Mogens , Gao Zhen , Moan Torgeir 
Published: March 2018

AbstractOperation and maintenance costs are significant for large‐scale wind turbines and particularly so for offshore. A well‐organized operation and maintenance strategy is vital to ensure the reliability, availability, and cost‐effectiveness of a system. The ability to detect, isolate, estimate, and perform prognoses on component degradation could become essential to reduce unplanned maintenance and downtime. Failures in gearbox components are in focus since they account for a large share of wind turbine downtime. This study considers detection and estimation of wear in the downwind main‐shaft bearing of a 5‐MW spar‐type floating turbine. Using a high‐fidelity gearbox model, we show how the downwind main bearing and nacelle axial accelerations can be used to evaluate the condition of the bearing. The paper shows how relative acceleration can be evaluated using statistical change‐detection methods to perform a reliable estimation of wear of the bearing. It is shown in the paper that the amplitude distribution of the residual accelerations follows a t‐distribution and a change‐detection test is designed for the specific changes we observe when the main bearing becomes worn. The generalized likelihood ratio test is extended to fit the particular distribution encountered in this problem, and closed‐form expressions are derived for shape and scale parameter estimation, which are indicators for wear and extent of wear in the bearing. The results in this paper show how the proposed approach can detect and estimate wear in the bearing according to desired probabilities of detection and false alarm.
Dual Frobenius manifolds of minimal gravity on disk
Authors: Bawane Aditya , Muraki Hisayoshi , Rim Chaiho 
Published: March 2018

Abstract

Liouville field theory approach to 2-dimensional gravity possesses the duality (b ↔ b
−1). The matrix counterpart of minimal gravity ℳ(q, p) (q < p co-prime) is effectively described on A

q−1 Frobenius manifold, which may exhibit a similar duality p ↔ q, and allow a description on A

p−1 Frobenius manifold. We have positive results from the bulk one-point and the bulk-boundary two-point correlations on disk that the dual description of the Frobenius manifold works for the unitary series ℳ(q, q + 1). However, for the Lee-Yang series ℳ(2, 2q + 1) on disk the duality is checked only partially. The main difficulty lies in the absence of a canonical description of trace in the continuum limit.
The impact of physician‐hospital integration on hospital supply management
Authors: Abdulsalam Yousef , Gopalakrishnan Mohan , Maltz Arnold , Schneller Eugene 
Published: March 2018

AbstractThis study examines how organizational alignment between professionals—who act as surrogate buyers‐‐ and the organizations in which they work, influence the supply management efficiency of the organization. Based on a cross‐sectional sample of hospital data, we estimate random effects regression models to investigate the association between physician‐hospital integration mechanisms and hospital supply efficiency. The results suggest that either professional hierarchy or bureaucratic pressures can improve supply management efficiency. In a sector of the economy characterized by escalating costs and uncertainty, the findings provide potential guidance for professional relationship strategy design to improve sector performance.
A preclinical study to model taurine pharmokinetics in the undernourished rat
Authors: Catalán-Latorre Ana , Nácher Amparo , Merino Virginia , Díez Octavio , Merino Sanjuán Matilde 
Published: March 2018

AbstractMalnutrition is a common feature of chronic and acute diseases, often associated with a poor prognosis, including worsening of clinical outcome, owing, among other factors, to dysfunction of the most internal organs and systems affecting the absorption, metabolism and elimination of drugs and nutrients. Taurine is involved in numerous biological processes and is required in increased amounts in response to pathological conditions. The aim of this study was to describe the behaviour of taurine in well-nourished (WN) rats and to analyse the influence of protein–energy undernutrition on the pharmacokinetic (PK) parameters of taurine, using a PK model. Wistar rats were randomly distributed into two groups, WN and undernourished (UN), and taurine was administered intravenously or orally at different doses: 1, 10 and 100 mg. Population pharmacokinetic modelling of plasma levels was performed using the NONMEM 7.2 program. Several distribution and absorption models were explored in combination with dose and/or time covariate effects. Covariates such as nutritional status, serum albumin, body weight and score of undernutrition were used. A two-compartment population pharmacokinetic model with zero-order endogenous formation, passive absorption, first-order kinetics distribution and non-linear elimination with parallel Michaelis–Menten excretion and reabsorption processes best described taurine pharmacokinetics. Undernutrition acted as a covariate reducing theVmaxof the active elimination process. Data analysis showed linear absorption and distribution, and non-linear elimination processes for taurine. Elimination of taurine was reduced in UN animals, suggesting that the reabsorption process via the secretion transporter was modified in that group.
Détresse chez les préposés aux bénéficiaires en centre d’hébergement exposés à des symptômes comportementaux
Authors: Angers Véronique , Vézina Jean 
Published: March 2018

RÉSUMÉLes préposés aux bénéficiaires (PAB), qui travaillent dans les centres d’hébergement avec des personnes atteintes de la maladie d’Alzheimer, sont à risque d’être exposés à des symptômes comportementaux. Étant donné que ces comportements peuvent constituer une source de stress, la présente étude vise à estimer la contribution d’un ensemble de variables sur le niveau de détresse psychologique des PAB. Ces variables comprennent la fréquence d’exposition perçue aux symptômes comportementaux, les évaluations cognitives primaires et secondaires et les stratégies de coping. Au total, 92 PAB détenant des postes de jour ont été recrutés dans les centres de la région de Québec. Une analyse de régression multiple révèle que la fréquence des symptômes comportementaux, l’évaluation cognitive « menace », l’évaluation cognitive secondaire « ne pas être capable de changer la situation » et la recherche de soutien émotionnel contribuent à la détresse psychologique. Les résultats mettent en lumière de considérer les symptômes comportementaux dans le travail des PAB et proposent une réflexion sur certains mécanismes psychologiques utilisés par les PAB.
X-ray focusing with efficient high-NA multilayer Laue lenses
Authors: Bajt Saša , Prasciolu Mauro , Fleckenstein Holger , Domaracký Martin , Chapman Henry N , Morgan Andrew J , Yefanov Oleksandr , Messerschmidt Marc , Du Yang , Murray Kevin T , Mariani Valerio , Kuhn Manuela , Aplin Steven , Pande Kanupriya , Villanueva-Perez Pablo , Stachnik Karolina , Chen Joe PJ , Andrejczuk Andrzej , Meents Alke , Burkhardt Anja , Pennicard David , Huang Xiaojing , Yan Hanfei , Nazaretski Evgeny , Chu Yong S , Hamm Christian E 
Published: March 2018

AbstractMultilayer Laue lenses are volume diffraction elements for the efficient focusing of X-rays. With a new manufacturing technique that we introduced, it is possible to fabricate lenses of sufficiently high numerical aperture (NA) to achieve focal spot sizes below 10 nm. The alternating layers of the materials that form the lens must span a broad range of thicknesses on the nanometer scale to achieve the necessary range of X-ray deflection angles required to achieve a high NA. This poses a challenge to both the accuracy of the deposition process and the control of the materials properties, which often vary with layer thickness. We introduced a new pair of materials—tungsten carbide and silicon carbide—to prepare layered structures with smooth and sharp interfaces and with no material phase transitions that hampered the manufacture of previous lenses. Using a pair of multilayer Laue lenses (MLLs) fabricated from this system, we achieved a two-dimensional focus of 8.4 × 6.8 nm2 at a photon energy of 16.3 keV with high diffraction efficiency and demonstrated scanning-based imaging of samples with a resolution well below 10 nm. The high NA also allowed projection holographic imaging with strong phase contrast over a large range of magnifications. An error analysis indicates the possibility of achieving 1 nm focusing.