Miracle-dz/UniFAR-FTUs huggingface dataset:
Virtual screening on an α‐helix to β‐strand switchable region of the FGFR2 extracellular domain revealed positive and negative modulators

The secondary structure of some protein segments may vary between α‐helix and β‐strand. To predict these switchable segments, we have developed an algorithm, Switch‐P, based solely on the protein sequence. This algorithm was used on the extracellular parts of FGF receptors. For FGFR2, it predicted that β4 and β5 strands of the third Ig‐like domain were highly switchable. These two strands possess a high number of somatic mutations associated with cancer. Analysis of PDB structures of FGF receptors confirmed the switchability prediction for β5. We thus evaluated if compound‐driven α‐helix/β‐strand switching of β5 could modulate FGFR2 signaling. We performed the virtual screening of a library containing 1.4 million of chemical compounds with two models of the third Ig‐like domain of FGFR2 showing different secondary structures for β5, and we selected 32 compounds. Experimental testing using proliferation assays with FGF7‐stimulated SNU‐16 cells and a FGFR2‐dependent Erk1/2 phosphorylation assay with FGFR2‐transfected L6 cells, revealed activators and inhibitors of FGFR2. Our method for the identification of switchable proteinic regions, associated with our virtual screening approach, provides an opportunity to discover new generation of drugs with under‐explored mechanism of action. Proteins 2014; 82:2982–2997. © 2014 Wiley Periodicals, Inc.
GigaWaM—Next-Generation WDM-PON Enabling Gigabit Per-User Data Bandwidth

The “Gigabit access passive optical network using wavelength division multiplexing” project aims to implement 64-Gb/s data transmission over 20-km single-mode fiber. Per-user symmetric data rates of 1-Gb/s will be achieved using wavelength division multiplexing passive optical network (WDM-PON) architecture with a 1:64 user split per PON segment. Enabling technologies being developed within the scope of the project include tunable transceivers and athermal 50-GHz array waveguide grating multiplexer devices. The future-proof WDM architecture will enable convergence triple-play (telephony, TV, and broadband internet) service over existing optical infrastructure, and also facilitate cost-effective dense wavelength division multiplexing for metro aggregation and mobile backhaul networks.
Peroxisome Proliferator-Activated Receptor–γ Agonist Induces Regulatory T Cells in a Murine Model of Allergic Rhinitis

Objective. To evaluate the effects of peroxisome proliferator-activated receptor (PPAR)–γ agonist on the induction of regulatory T cells (Tregs) in a murine model of allergic rhinitis. Study Design. Randomized controlled trial. Setting. Animal study. Subjects and Methods. BALB/c mice that received ovalbumin sensitization and challenge served as the ovalbumin group (n = 6). Two separate groups of 6 mice received intragastric administration with PPAR-γ agonist pioglitazone (30 mg/kg/d) or pioglitazone plus PPAR-γ antagonist GW9662 (0.5 mg/d) before each ovalbumin challenge. The control group (n = 6) was treated with drug vehicle alone. Various allergic responses were assessed. Real-time polymerase chain reaction was performed to investigate the mRNA expression of forkhead box P3 (Foxp3), T-bet, and GATA-3. Flow cytometry was used to determine the percentage of Tregs. Results. Mice developed typical pathophysiological allergic rhinitis features after the ovalbumin challenge. The frequencies of sneezing and scratching were significantly decreased by pioglitazone treatment (P < .0001). Eosinophils infiltration and the levels of interleukin-5 and interferon-γ in nasal cavity lavage fluid and sera immunoglobulin E were also markedly decreased by pioglitazone (P < .001). The expression of Foxp3 mRNA and the population of Tregs were significantly increased by pioglitazone (P < .05). Cotreatment with GW9662 reversed the anti-inflammatory effects of pioglitazone. The effects of PPAR-γ agonist on Foxp3 mRNA expression and Tregs induction were abrogated by administration of GW9662. Conclusion. PPAR-γ agonist attenuates upper airway allergic inflammation in a PPAR-γ-dependent fashion, and the beneficial effects of pioglitazone in airway allergic inflammation may be mediated by induction of Tregs.
An inquiry into quasi‐credit contracts: The role of reciprocal credit and interlinked deals in small‐scale fishing communities

In agrarian village societies beset with many hazards and uncertainties, people evolve various means of coping with risk. What is perhaps less known is that credit transactions can sometimes serve the function of reducing risk in such societies. This article is concerned with examining several insurance‐motivated credit arrangements in small‐scale fishing communities. A hunger insurance mechanism of ‘reciprocal credit’ and a system of interlinked contracts aimed at insuring against risks in the spheres of labour and marketing relations will be extensively dealt with. Moreover, the concept of ‘triadic’ relationships will be shown to have special relevance in the case of traditional insurance arrangements aiming at controlling problems of ‘moral hazard’.
Thymosin beta 4 is associated with collateral development in coronary artery disease

Abstract Objectives: Thymosin beta 4 (Tβ4) plays an essential role in cardiac vessel development and is currently being developed as a therapeutic agent for the treatment of coronary artery disease (CAD) in some experimental studies. Thus, we aimed to investigate the association of serum Tβ4 levels and collateral formation in patients presenting with severely stenotic CAD. Methods: Thirteen patients with poor collateral development and 16 age- and sex-matched patients with good collateral development who had ≥ 95% stenosis in at least one major coronary artery on coronary angiogram (CAG) were enrolled in the study. The Gensini score was calculated for each patient by using CAG results. Collateral development was classified according to the Cohen-Rentrop method. Serum Tβ4 levels were measured with enzyme-linked immune sorbent assay. Results: There were no statistically significant differences between the two groups in regard to clinical and laboratory characteristics of the patients except for Tβ4 levels. The Tβ4 levels in the well-collateralized study group were found to be significantly higher than those of the poorly collateralized study group and serum Tβ4 levels were positively correlated with the collateral development. Conclusions: Our findings suggest that serum Tβ4 levels are significantly associated with the collateral development in severe CAD.
BVAR models in the context of cointegration: A Monte Carlo experiment

The kind of prior typically employed in Bayesian vector autoregression (BVAR) analysis has aroused widespread suspicion about the ability of these models to capture long-run patterns. This paper specifies a bivariate cointegrated stochastic process and conducts a Monte Carlo experiment to assess the small sample performance of two classical and two Bayesian estimation methods commonly applied to VAR models. In addition, a proposal to introduce a new dimension to the prior information in order to allow for explicit account of long-run restrictions is suggested and evaluated in the light of the experiment. The results of the experiment show that: the Minnesota -type prior with hyperparameter search performs well, suggesting that the prevalent suspicion about the inability of this prior to capture long-run patterns is not well-grounded; the fine-tunning of the prior is crucial; and adding long-run restrictions to the prior does not provide improvements in the case analyzed.
Performance of Junctional Tourniquets in Normal Human Volunteers

Abstract Background. Inguinal bleeding is a common and preventable cause of death on the battlefield. Four FDA-cleared junctional tourniquets (Combat Ready Clamp [CRoC], Abdominal Aortic and Junctional Tourniquet [AAJT], Junctional Emergency Treatment Tool [JETT], and SAM Junctional Tourniquet [SJT]) were assessed in a laboratory on volunteers in order to describe differential performance of models. Objective. To examine safety and effectiveness of junctional tourniquets in order to inform the discussions of device selection for possible fielding to military units. Methods. The experiment measured safety and effectiveness parameters over timed, repeated applications. Lower extremity pulses were measured in 10 volunteers before and after junctional tourniquet application aimed at stopping the distal pulse assessed by Doppler auscultation. Safety was determined as the absence of adverse events during the time of application. Results. The CRoC, SJT, and JETT were most effective; their effectiveness did not differ (p > 0.05). All tourniquets were applied safely and successfully in at least one instance each, but pain varied by model. Subjects assessed the CRoC as most tolerable. The CRoC and SJT were the fastest to apply. Users ranked CRoC and SJT equally as performing best. Conclusion. The CRoC and SJT were the best-performing junctional tourniquets using this model.
A Reversible Early Oxidized Redox State That Precedes Macromolecular ROS Damage in Aging Nontransgenic and 3xTg-AD Mouse Neurons

The brain depends on redox electrons from nicotinamide adenine dinucleotide (reduced form; NADH) to produce ATP and oxyradicals (reactive oxygen species [ROS]). Because ROS damage and mitochondrial dysregulation are prominent in aging and Alzheimer's disease (AD) and their relationship to the redox state is unclear, we wanted to know whether an oxidative redox shift precedes these markers and leads to macromolecular damage in a mouse model of AD. We used the 3xTg-AD mouse model, which displays cognitive deficits beginning at 4 months. Hippocampal/cortical neurons were isolated across the age span and cultured in common nutrients to control for possible hormonal and vascular differences. We found an increase of NAD(P)H levels and redox state in nontransgenic (non-Tg) neurons until middle age, followed by a decline in old age. The 3xTg-AD neurons maintained much lower resting NAD(P)H and redox states after 4 months, but the NADH regenerating capacity continuously declined with age beginning at 2 months. These redox characteristics were partially reversible with nicotinamide, a biosynthetic precursor of NAD+. Nicotinamide also protected against glutamate excitotoxicity. Compared with non-Tg neurons, 3xTg-AD neurons had more mitochondria/neuron and lower glutathione (GSH) levels that preceded age-related increases in ROS levels. These GSH deficits were again reversible with nicotinamide in 3xTg-AD neurons. Surprisingly, low macromolecular ROS damage was only elevated after 4 months in the 3xTg-AD neurons if antioxidants were removed. The present data suggest that a more oxidized redox state and a lower antioxidant GSH defense can be dissociated from neuronal ROS damage, changes that precede the onset of cognitive deficits in the 3xTg-AD model.
Relations between the Neural Bases of Dynamic Auditory Processing and Phonological Processing: Evidence from fMRI

Functional magnetic resonance imaging (fMRI) was used to examine how the brain responds to temporal compression of speech and to determine whether the same regions are also involved in phonological processes associated with reading. Recorded speech was temporally compressed to varying degrees and presented in a sentence verification task. Regions involved in phonological processing were identified in a separate scan using a rhyming judgment task with pseudowords compared to a lettercase judgment task. The left inferior frontal and left superior temporal regions (Broca's and Wernicke's areas), along with the right inferior frontal cortex, demonstrated a convex response to speech compression; their activity increased as compression increased, but then decreased when speech became incomprehensible. Other regions exhibited linear increases in activity as compression increased, including the middle frontal gyri bilaterally. The auditory cortices exhibited compression-related decreases bilaterally, primarily reflecting a decrease in activity when speech became incomprehensible. Rhyme judgments engaged two left inferior frontal gyrus regions (pars triangularis and pars opercularis), of which only the pars triangularis region exhibited significant compression-related activity. These results directly demonstrate that a subset of the left inferior frontal regions involved in phonological processing is also sensitive to transient acoustic features within the range of comprehensible speech.
International Wine Trade: Analyzing the Value of Reputation and Quality Signals

This research examines the factors behind price differentials based on regional origin. For this purpose, we estimate a hedonic pricing model of premium wines sold in the U.S. We hypothesize that numerous quality signals affect wine prices including expert opinions about sensory quality, maturing potential, and special selections as well as derived indicators that signal a high or low quality producer. After correcting for variety, regional origin, and age, the data confirms that a wine's price is related to producer quality signals, which may even negate regional effects. We conclude that it is problematic to interpret regional premiums as brand value (as opposed to quality premiums) without adjusting them for producer quality signals. Estimated brand values may then be biased. Moreover, a strong positive producer quality signal receives a larger percentage price premium than a comparable negative signal which warrants important marketing implications for producers and entire regions.
Neural Differentiation of Incorrectly Predicted Memories

When an item is predicted in a particular context but the prediction is violated, memory for that item is weakened (Kim et al., 2014). Here, we explore what happens when such previously mispredicted items are later reencountered. According to prior neural network simulations, this sequence of events—misprediction and subsequent restudy—should lead to differentiation of the item's neural representation from the previous context (on which the misprediction was based). Specifically, misprediction weakens connections in the representation to features shared with the previous context and restudy allows new features to be incorporated into the representation that are not shared with the previous context. This cycle of misprediction and restudy should have the net effect of moving the item's neural representation away from the neural representation of the previous context. We tested this hypothesis using human fMRI by tracking changes in item-specific BOLD activity patterns in the hippocampus, a key structure for representing memories and generating predictions. In left CA2/3/DG, we found greater neural differentiation for items that were repeatedly mispredicted and restudied compared with items from a control condition that was identical except without misprediction. We also measured prediction strength in a trial-by-trial fashion and found that greater misprediction for an item led to more differentiation, further supporting our hypothesis. Therefore, the consequences of prediction error go beyond memory weakening. If the mispredicted item is restudied, the brain adaptively differentiates its memory representation to improve the accuracy of subsequent predictions and to shield it from further weakening. SIGNIFICANCE STATEMENT Competition between overlapping memories leads to weakening of nontarget memories over time, making it easier to access target memories. However, a nontarget memory in one context might become a target memory in another context. How do such memories get restrengthened without increasing competition again? Computational models suggest that the brain handles this by reducing neural connections to the previous context and adding connections to new features that were not part of the previous context. The result is neural differentiation away from the previous context. Here, we provide support for this theory, using fMRI to track neural representations of individual memories in the hippocampus and how they change based on learning.
Animals and the 3Rs in toxicology research and testing

Despite efforts to eliminate the use of animals in testing and the availability of many accepted alternative methods, animals are still widely used for toxicological research and testing. While research using in vitro and computational models has dramatically increased in recent years, such efforts have not yet measurably impacted animal use for regulatory testing and are not likely to do so for many years or even decades. Until regulatory authorities have accepted test methods that can totally replace animals and these are fully implemented, large numbers of animals will continue to be used and many will continue to experience significant pain and distress. In order to positively impact the welfare of these animals, accepted alternatives must be implemented, and efforts must be directed at eliminating pain and distress and reducing animal numbers. Animal pain and distress can be reduced by earlier predictive humane endpoints, pain-relieving medications, and supportive clinical care, while sequential testing and routine use of integrated testing and decision strategies can reduce animal numbers. Applying advances in science and technology to the development of scientifically sound alternative testing models and strategies can improve animal welfare and further reduce and replace animal use.
Men's attitudes toward prostate cancer and seeking prostate-specific antigen testing.

BACKGROUND Although the Australian Cancer Society recommends against performing PSA tests to screen for prostate cancer, many Australian men currently undergo such screening. This study investigated attitudinal variables that may predict prostate cancer screening behaviors in this context. METHODS A questionnaire was administered by mail in a two-phase procedure, first to a sample of 1,461 men (46% response), then to 919 men from the initial sample. Prostate cancer screening behaviors of men > 40 years old were examined. The questionnaire assessed worry about prostate cancer, perceived vulnerability to prostate cancer, belief in the efficacy of PSA testing for detection, having received a PSA test for detection, and the presence of urologic symptoms at the time of testing. RESULTS Men who had had PSA testing with urologic symptoms at the time of the test were more worried about prostate cancer and perceived themselves as more vulnerable to prostate cancer compared with both asymptomatic tested and untested men. Men who had undergone PSA testing believed the test to be more effective in the detection of prostate cancer than did men who had not. CONCLUSIONS Urologic symptoms act as a risk cue for men to prostate cancer. Asymptomatic men should be considered separately from symptomatic men in the investigation of psychological variables predictive of seeking screening for prostate cancer. These findings are discussed in terms of both the focus and design of interventions to alter prostate cancer screening behavior and their implications for the clinical management of men with urologic symptoms.
Designing Tunable Microstructure Spectroscopic Gas Sensor Using Optofluidic Hollow-Core Photonic Crystal Fiber

A tunable slow-light hollow-core photonic crystal fiber (HPCF), applicable to miniaturized microstructure spectroscopic gas sensors is proposed. In the proposed structure, we have taken the advantage of the microfluidic infiltration technique to tune the slow-light regime so as to match the reference absorption line of the target gas sample, which is required for designing miniaturized gas sensors with reconfigurable detection sensitivity. The main feature of this structure is that the enhanced electrical field is strongly localized in the hollow-core of a photonic crystal fiber for any gas samples due to tunability of slow-light modes. We discuss the potential of slow light in HPCF for realizing compact and tunable gas sensor devices with low and high loss material. In particular, we present numerical results showing how this optofluidic microstructure can be used for detecting CO, CO2, H2S, CH4, SO2, and N2O gases.
Towards an integrative framework of strategic international human resource control: the case of Taiwanese subsidiaries in the People's Republic of China

This study integrates the resource-based view of the firm, the resource dependence model, institutionalism theory and the cybernetic system model into a framework to investigate the determinants of international human resource (IHR) control at the subsidiary level. The effects of competitive strategies and the mediating effects of inter-organizational interdependencies on three different dimensions of IHR control (input, behaviour and output) were studied by using a sample of 101 Taiwanese subsidiaries operating in the People's Republic of China (PRC). Four notable associations were found: (1) a robust direct relationship between the adoption of a low-cost strategy and two dimensions of IHR control (behaviour and output) was testified; (2) an indirect effect of a low-cost strategy on IHR input control through dependence on the parent's resources was found; (3) the direct relationship between local differentiation strategy and IHR input control could not be testified because a positive mediating effect of dependence on local resources counteracted the negative mediating effect of dependence on parents resources; (4) the direct effects of dependence on local resources on the IHR input control and dependence on parent's resources on IHR input control and behavioural control were testified.
Brain response to working memory over three years of adolescence: influence of initiating heavy drinking.

OBJECTIVE Many adolescents engage in heavy alcohol use. The aim of this study was to disentangle whether brain abnormalities seen in adolescent heavy drinkers are a consequence of heavy drinking, a preexisting risk factor for initiation of alcohol use, or both. METHOD Study 1 used cross-sectional functional magnetic resonance imaging (fMRI) visual working-memory (VWM) data from 15- to 19-year-olds (20 heavy drinkers, 20 controls) to identify brain regions affected by heavy adolescent alcohol use. Study 2 used longitudinal fMRI VWM data from 12- to 16-year-olds imaged before the onset of drinking and imaged again on the same scanner approximately 3 years later. Those who had transitioned into heavy drinking (n = 20) were matched to continuous nondrinkers (n = 20) on baseline alcohol risk and developmental factors (N = 40; 80 scans). RESULTS Study 1 found that heavy drinkers exhibited more frontal and parietal but less occipital activation than controls, defining the regions of interest for Study 2. In Study 2, adolescents who later transitioned into heavy drinking showed less fMRI response contrast at baseline than continuous nondrinkers, which increased after the onset of heavy drinking, in frontal (1,431 μL, p = .003; η² = .19) and parietal (810 μL, p = .005; η²= .23) regions, as in Study 1. Lower baseline activation in the frontal and parietal regions predicted subsequent substance use, more so than commonly observed predictors of youth drinking (p < .05). CONCLUSIONS Adolescents who initiated heavy drinking showed different brain activation before the onset of drinking, then less efficient information processing after high-dose alcohol use started. This suggests neural response patterns that could be risk factors for future substance use and also supports prior neuropsychological reports indicating that initiating heavy episodic drinking in adolescence may be followed by subtle alterations in brain functioning.