bluuebunny/crossref_metadata_2025_split huggingface dataset:
Model-based testing of probabilistic systems
Authors: Gerhold Marcus , Stoelinga Mariëlle 
Published: January 2018

Abstract
This work presents an executable model-based testing framework for probabilistic systems with non-determinism. We provide algorithms to automatically generate, execute and evaluate test cases from a probabilistic requirements specification. The framework connects input/output conformance-theory with hypothesis testing: our algorithms handle functional correctness, while statistical methods assess, if the frequencies observed during the test process correspond to the probabilities specified in the requirements. At the core of our work lies the conformance relation for probabilistic input/output conformance, enabling us to pin down exactly when an implementation should pass a test case. We establish the correctness of our framework alongside this relation as soundness and completeness; Soundness states that a correct implementation indeed passes a test suite, while completeness states that the framework is powerful enough to discover each deviation from a specification up to arbitrary precision for a sufficiently large sample size. The underlying models are probabilistic automata that allow invisible internal progress. We incorporate divergent systems into our framework by phrasing four rules that each well-formed system needs to adhere to. This enables us to treat divergence as the absence of output, or quiescence, which is a well-studied formalism in model-based testing. Lastly, we illustrate the application of our framework on three case studies.
Detecting rater bias using a&nbsp;person-fit statistic: a&nbsp;Monte Carlo simulation study
Authors: Aubin André-Sébastien , St-Onge Christina , Renaud Jean-Sébastien 
Published: January 2018

Introduction With the Standards voicing concern for the appropriateness of response processes, we need to explore strategies that would allow us to identify inappropriate rater response processes. Although certain statistics can be used to help detect rater bias, their use is complicated by either a lack of data about their actual power to detect rater bias or the difficulty related to their application in the context of health professions education. This exploratory study aimed to establish the worthiness of pursuing the use of l z to detect rater bias.
Methods We conducted a Monte Carlo simulation study to investigate the power of a specific detection statistic, that is: the standardized likelihood l z person-fit statistics (PFS). Our primary outcome was the detection rate of biased raters, namely: raters whom we manipulated into being either stringent (giving lower scores) or lenient (giving higher scores), using the l z statistic while controlling for the number of biased raters in a sample (6 levels) and the rate of bias per rater (6 levels).
Results Overall, stringent raters (M = 0.84, SD = 0.23) were easier to detect than lenient raters (M = 0.31, SD = 0.28). More biased raters were easier to detect then less biased raters (60% bias: 62, SD = 0.37; 10% bias: 43, SD = 0.36).
Theoretical prediction of a charge-transfer phase transition
Authors: Tokoro Hiroko , Namai Asuka , Yoshikiyo Marie , Fujiwara Rei , Chiba Kouji , Ohkoshi Shin-ichi 
Published: January 2018

AbstractPhase transition materials are attractive from the viewpoints of basic science as well as practical applications. For example, optical phase transition materials are used for optical recording media. If a phase transition in condensed matter could be predicted or designed prior to synthesizing, the development of phase transition materials will be accelerated. Herein we show a logical strategy for designing a phase transition accompanying a thermal hysteresis loop. Combining first-principles phonon mode calculations and statistical thermodynamic calculations considering cooperative interaction predicts a charge-transfer phase transition between the A–B and A+–B− phases. As an example, we demonstrate the charge-transfer phase transition on rubidium manganese hexacyanoferrate. The predicted phase transition temperature and the thermal hysteresis loop agree well with the experimental results. This approach will contribute to the rapid development of yet undiscovered phase transition materials.
Thin and Dense Solid-solid Heterojunction Formation Promoted by Crystal Growth in Flux on a Substrate
Authors: Zettsu Nobuyuki , Shiiba Hiromasa , Onodera Hitoshi , Nemoto Kazune , Kimijima Takeshi , Yubuta Kunio , Nakayama Masanobu , Teshima Katsuya 
Published: January 2018

AbstractIn this work, we demonstrate the direct growth of cubic Li5La3Nb2O12 crystal layer on the LiCoO2 substrate through the conversion of ultra-thin Nb substrate in molten LiOH flux. The initial thickness of the Nb layer determines that of the crystal layer. SEM and TEM observations reveal that the surface is densely covered with well-defined polyhedral crystals. Each crystal is connected to neighboring ones through the formation of tilted grain boundaries with Σ3 (2–1–1) = (1–21) symmetry which show small degradation in lithium ion conductivity comparing to that of bulk. Furthermore, the sub-phase formation at the interface is naturally mitigated during the growth since the formation of Nb2O5 thin film limits the whole reaction kinetics. Using the newly developed stacking approach for stacking solid electrolyte layer on the electrode layer, the grown crystal layer could be an ideal ceramic separator with a dense thin-interface for all-solid-state batteries.
Benefits of aflibercept treatment for age-related macular degeneration patients with good best-corrected visual acuity at baseline
Authors: Minami Sakiko , Nagai Norihiro , Suzuki Misa , Kurihara Toshihide , Sonobe Hideki , Kamoshita Mamoru , Uchida Atsuro , Shinoda Hajime , Takagi Hitoshi , Sonoda Shozo , Sakamoto Taiji , Tsubota Kazuo , Ozawa Yoko 
Published: January 2018

AbstractCurrently, age-related macular degeneration (AMD) is treated while patients exhibit good best-corrected visual acuity (BCVA). However, previous clinical trials only include patients with poor BCVA. We prospectively analyzed the benefits of intravitreal aflibercept (IVA) treatment for AMD patients exhibiting good BCVA at baseline. Twenty-nine treatment-naive AMD patients (29 eyes) with BCVA better than 0.6 (74 letters in ETDRS chart) were treated with IVA once a month for 3 months and every 2 months thereafter with no additional treatments. Improvement in mean BCVA, measured using the conventional Landolt C chart, contrast VA chart, and functional VA (FVA) system, and reductions in mean central retinal thickness (CRT), central choroidal thickness, macular volume (MV), and choroidal area on optical coherence tomography images were observed at 6 and 12 months. Improvements in contrast VA and FVA scores, in contrast to conventional BCVA, correlated with MV reduction; no VA scores correlated with a reduced CRT. The MV correlated with choroidal area after IVA. No severe adverse events occurred. IVA improved visual function, retinal condition, and quality of life evaluated by Visual Function Questionnaire, and was beneficial in these patients. The contrast VA and FVA scores and MVs, which detect subtle changes, helped demonstrate the benefits.
SCFAs strongly stimulate PYY production in human enteroendocrine cells
Authors: Larraufie P. , Martin-Gallausiaux C. , Lapaque N. , Dore J. , Gribble F. M. , Reimann F. , Blottiere H. M. 
Published: January 2018

AbstractPeptide-YY (PYY) and Glucagon-Like Peptide-1 (GLP-1) play important roles in the regulation of food intake and insulin secretion, and are of translational interest in the field of obesity and diabetes. PYY production is highest in enteroendocrine cells located in the distal intestine, mirroring the sites where high concentrations of short chain fatty acids (SCFAs) are produced by gut microbiota. We show here that propionate and butyrate strongly increased expression of PYY but not GCG in human cell line and intestinal primary culture models. The effect was predominantly attributable to the histone deacetylase inhibitory activity of SCFA and minor, but significant contributions of FFA2 (GPR43). Consistent with the SCFA-dependent elevation of PYY gene expression, we also observed increased basal and stimulated PYY hormone secretion. Interestingly, the transcriptional stimulation of PYY was specific to human-derived cell models and not reproduced in murine primary cultures. This is likely due to substantial differences in PYY gene structure between mouse and human. In summary, this study revealed a strong regulation of PYY production by SCFA that was evident in humans but not mice, and suggests that high fibre diets elevate plasma concentrations of the anorexigenic hormone PYY, both by targeting gene expression and hormone secretion.
Structural Basis for the Enhanced Anti-Diabetic Efficacy of Lobeglitazone on PPARγ
Authors: Jang Jun Young , Bae Hwan , Lee Yong Jae , Choi Young Il , Kim Hyun-Jung , Park Seung Bum , Suh Se Won , Kim Sang Wan , Han Byung Woo 
Published: January 2018

AbstractPeroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor superfamily. It functions as a ligand-activated transcription factor and plays important roles in the regulation of adipocyte differentiation, insulin resistance, and inflammation. Here, we report the crystal structures of PPARγ in complex with lobeglitazone, a novel PPARγ agonist, and with rosiglitazone for comparison. The thiazolidinedione (TZD) moiety of lobeglitazone occupies the canonical ligand-binding pocket near the activation function-2 (AF-2) helix (i.e., helix H12) in ligand-binding domain as the TZD moiety of rosiglitazone does. However, the elongated p-methoxyphenol moiety of lobeglitazone interacts with the hydrophobic pocket near the alternate binding site of PPARγ. The extended interaction of lobeglitazone with the hydrophobic pocket enhances its binding affinity and could affect the cyclin-dependent kinase 5 (Cdk5)-mediated phosphorylation of PPARγ at Ser245 (in PPARγ1 numbering; Ser273 in PPARγ2 numbering). Lobeglitazone inhibited the phosphorylation of PPARγ at Ser245 in a dose-dependent manner and exhibited a better inhibitory effect on Ser245 phosphorylation than rosiglitazone did. Our study provides new structural insights into the PPARγ regulation by TZD drugs and could be useful for the discovery of new PPARγ ligands as an anti-diabetic drug, minimizing known side effects.
Radiogenomic analysis of hypoxia pathway is predictive of overall survival in Glioblastoma
Authors: Beig Niha , Patel Jay , Prasanna Prateek , Hill Virginia , Gupta Amit , Correa Ramon , Bera Kaustav , Singh Salendra , Partovi Sasan , Varadan Vinay , Ahluwalia Manmeet , Madabhushi Anant , Tiwari Pallavi 
Published: January 2018

AbstractHypoxia, a characteristic trait of Glioblastoma (GBM), is known to cause resistance to chemo-radiation treatment and is linked with poor survival. There is hence an urgent need to non-invasively characterize tumor hypoxia to improve GBM management. We hypothesized that (a) radiomic texture descriptors can capture tumor heterogeneity manifested as a result of molecular variations in tumor hypoxia, on routine treatment naïve MRI, and (b) these imaging based texture surrogate markers of hypoxia can discriminate GBM patients as short-term (STS), mid-term (MTS), and long-term survivors (LTS). 115 studies (33 STS, 41 MTS, 41 LTS) with gadolinium-enhanced T1-weighted MRI (Gd-T1w) and T2-weighted (T2w) and FLAIR MRI protocols and the corresponding RNA sequences were obtained. After expert segmentation of necrotic, enhancing, and edematous/nonenhancing tumor regions for every study, 30 radiomic texture descriptors were extracted from every region across every MRI protocol. Using the expression profile of 21 hypoxia-associated genes, a hypoxia enrichment score (HES) was obtained for the training cohort of 85 cases. Mutual information score was used to identify a subset of radiomic features that were most informative of HES within 3-fold cross-validation to categorize studies as STS, MTS, and LTS. When validated on an additional cohort of 30 studies (11 STS, 9 MTS, 10 LTS), our results revealed that the most discriminative features of HES were also able to distinguish STS from LTS (p = 0.003).
Yield and resource use efficiency of Plukenetia volubilis plants at two distinct growth stages as affected by irrigation and fertilization
Authors: Gong He-De , Geng Yan-Jing , Yang Chun , Jiao Dong-Ying , Chen Liang , Cai Zhi-Quan 
Published: January 2018

AbstractThis study is to test how seedlings (vegetative) and large plants (reproductive) of an oilseed crop (Plukenetia volubilis) responded to regulated deficit irrigation techniques (conventional deficit irrigation, DI; alternative partial root-zone irrigation, APRI) in a tropical humid monsoon area. Seedlings were more sensitive to water deficit than large plants. Although APRI did better than DI in saving water for both seedlings and large plants at the same amount of irrigation, full irrigation (FI) is optimal for faster seedling growth at the expense of water-use efficiency (WUE). The seed number per unit area was responsible for the total seed oil yield, largely depending on the active process of carbon and nitrogen storages at the whole-plant level. The magnitude of the increase in total seed and seed oil yield by fertilization was similar under different irrigation regimes. Compared with FI, DI can save water, but reduced the total seed yield and had lower agronomic nutrient-use efficiency (NUEagr); whereas APRI had similar total seed yield and NUEagr, but reduced water use greatly. Although the dual goal of increasing the yield and saving water was not compatible, maintaining a high yield and NUEagr at the cost of WUE is recommended for P. volubilis plantation in t he water-rich areas.
Locking bandwidth of two laterally-coupled semiconductor lasers subject to optical injection
Authors: Li Nianqiang , Susanto H. , Cemlyn B. R. , Henning I. D. , Adams M. J. 
Published: January 2018

AbstractWe report here for the first time (to our knowledge), a new and universal mechanism by which a two-element laser array is locked to external optical injection and admits stably injection-locked states within a nontrivial trapezoidal region. The rate equations for the system are studied both analytically and numerically. We derive a simple mathematical expression for the locking conditions, which reveals that two parallel saddle-node bifurcation branches, not reported for conventional single lasers subject to optical injection, delimit the injection locking range and its width. Important parameters are the linewidth enhancement factor, the laser separation, and the frequency offset between the two laterally-coupled lasers; the influence of these parameters on locking conditions is explored comprehensively. Our analytic approximations are validated numerically by using a path continuation technique as well as direct numerical integration of the rate equations. More importantly, our results are not restricted by waveguiding structures and uncover a generic locking behavior in the lateral arrays in the presence of injection.
Characterization of the interactions between inhibitor-1 and recombinant PP1 by NMR spectroscopy
Authors: Liang Chu-Ting , Lin Yu-Shan , Huang Yi-Choang , Huang Hsien-Lu , Yang Jia-Qian , Wu Tsung-Hsien , Chang Chi-Fon , Huang Shing-Jong , Huang Hsien-Bin , Lin Ta-Hsien 
Published: January 2018

AbstractInhibitor-1 is converted into a potent inhibitor of native protein phosphatase-1 (PP1) when Thr35 is phosphorylated by cAMP-dependent protein kinase (PKA). However, PKA-phosphorylated form of inhibitor-1 displayed a weak activity in inhibition of recombinant PP1. The mechanism for the impaired activity of PKA-phosphorylated inhibitor-1 toward inhibition of recombinant PP1 remained elusive. By using NMR spectroscopy in combination with site-directed mutagenesis and inhibitory assay, we found that the interaction between recombinant PP1 and the consensus PP1-binding motif of PKA-thiophosphorylated form of inhibitor-1 was unexpectedly weak. Unlike binding to native PP1, the subdomains 1 (residues around and including the phosphorylated Thr35) and 2 (the consensus PP1-binding motif) of PKA-thiophosphorylated form of inhibitor-1 do not exhibit a synergistic effect in inhibition of recombinant PP1. This finding implied that a slight structural discrepancy exists between native and recombinant PP1, resulting in PKA-thiophosphorylated form of inhibitor-1 displaying a different affinity to native and recombinant enzyme.
Lateralized behavior and cardiac activity of dogs in response to human emotional vocalizations
Authors: Siniscalchi Marcello , d’Ingeo Serenella , Fornelli Serena , Quaranta Angelo 
Published: January 2018

AbstractOver the recent years, the study of emotional functioning has become one of the central issues in dog cognition. Previous studies showed that dogs can recognize different emotions by looking at human faces and can correctly match the human emotional state with a vocalization having a negative emotional valence. However, to this day, little is known about how dogs perceive and process human non-verbal vocalizations having different emotional valence. The current research provides new insights into emotional functioning of the canine brain by studying dogs’ lateralized auditory functions (to provide a first insight into the valence dimension) matched with both behavior and physiological measures of arousal (to study the arousal dimension) in response to playbacks related to the Ekman’s six basic human emotions. Overall, our results indicate lateralized brain patterns for the processing of human emotional vocalizations, with the prevalent use of the right hemisphere in the analysis of vocalizations with a clear negative emotional valence (i.e. “fear” and “sadness”) and the prevalent use of the left hemisphere in the analysis of positive vocalization (“happiness”). Furthermore, both cardiac activity and behavior response support the hypothesis that dogs are sensitive to emotional cues of human vocalizations.
Reliable landmarks for precise topographical analyses of pathological structural changes of the ovine tibial plateau in 2-D and 3-D subspaces
Authors: Oláh Tamás , Reinhard Jan , Gao Liang , Goebel Lars K. H. , Madry Henning 
Published: January 2018

AbstractSelecting identical topographical locations to analyse pathological structural changes of the osteochondral unit in translational models remains difficult. The specific aim of the study was to provide objectively defined reference points on the ovine tibial plateau based on 2-D sections of micro-CT images useful for reproducible sample harvesting and as standardized landmarks for landmark-based 3-D image registration. We propose 5 reference points, 11 reference lines and 12 subregions that are detectable macroscopically and on 2-D micro-CT sections. Their value was confirmed applying landmark-based rigid and affine 3-D registration methods. Intra- and interobserver comparison showed high reliabilities, and constant positions (standard errors < 1%). Spatial patterns of the thicknesses of the articular cartilage and subchondral bone plate were revealed by measurements in 96 individual points of the tibial plateau. As a case study, pathological phenomena 6 months following OA induction in vivo such as osteophytes and areas of OA development were mapped to the individual subregions. These new reference points and subregions are directly identifiable on tibial plateau specimens or macroscopic images, enabling a precise topographical location of pathological structural changes of the osteochondral unit in both 2-D and 3-D subspaces in a region-appropriate fashion relevant for translational investigations.
Local delivery of hormonal therapy with silastic tubing for prevention and treatment of breast cancer
Authors: Park Jeenah , Thomas Scott , Zhong Allison Y. , Wolfe Alan R. , Krings Gregor , Terranova-Barberio Manuela , Pawlowska Nela , Benet Leslie Z. , Munster Pamela N. 
Published: January 2018

AbstractBroad use of germline testing has identified an increasing number of women at risk for breast cancer with a need for effective chemoprevention. We report a novel method to selectively deliver various anti-estrogens at high drug levels to the breast tissue by implanting a device comprised of silastic tubing. Optimized tubing properties allow elution of otherwise poorly bioavailable anti-estrogens, such as fulvestrant, into mammary tissue in vitro and in vivo with levels sufficient to inhibit estrogen receptor activation and tumor cell proliferation. Implantable silastic tubing delivers fulvestrant selectively to mouse mammary fat tissue for one year with anti-tumor effects similar to those achieved with systemic fulvestrant exposure. Furthermore, local delivery of fulvestrant significantly decreases cell proliferation, as assessed by Ki67 expression, most effectively in tumor sections adjacent to tubing. This approach may thereby introduce a potential paradigm shift and offer a promising alternative to systemic therapy for prevention and early interception of breast cancer.
Frequency selectivity of echo responses in the mouse primary auditory cortex
Authors: Wang Meng , Li Ruijie , Li Jingcheng , Zhang Jianxiong , Chen Xiaowei , Zeng Shaoqun , Liao Xiang 
Published: January 2018

AbstractIn the primary auditory cortex (A1), neuronal ensembles are activated relative to anticipated sound events following rhythmic stimulation, but whether the echo responses of the neurons are related to their frequency selectivity remains unknown. Therefore, we used in vivo two-photon Ca2+ imaging to record the neuronal activities in the mouse A1 to elucidate the relationship between their echo responses and frequency selectivity. We confirmed the presence of echo responses in a subgroup of mouse Layer 2/3 A1 neurons following a train of rhythmic pure tone stimulation. After testing with a range of frequencies, we found that these echo responses occurred preferentially close to the best frequencies of the neurons. The local organization of the echo responses of the neurons was heterogeneous in the A1. Therefore, these results indicate that the observed echo responses of neurons within A1 are highly related to their frequency selectivity.
Enhanced growth of large-scale nanostructures with metallic ion precipitation in helium plasmas
Authors: Kajita Shin , Kawaguchi Shota , Ohno Noriyasu , Yoshida Naoaki 
Published: January 2018

AbstractHelium plasma irradiation on metal surfaces leads to the formation of metallic fuzzy nanostructures accompanied by the growth of helium bubbles in metals. The mechanism of the growth process, its impact for fusion devices, and potential application have been explored. Here we show enhanced growth of large-scale fuzz by precipitating additional metallic particles during helium plasma irradiation. The growth rate of the fuzzy structures became orders of magnitude greater than conventional fuzz growth; in an hour of irradiation, 1 mm-thick visible tungsten and molybdenum fuzzy fur structures covered a tungsten metal substrate. Additional precipitation of metallic ions breaks the bottleneck diffusion process; moreover, further acceleration in the growth rate could have occurred if the electric sheath shape was influenced by the grown structure and the electric field that formed around the structure started collecting ions.