Miracle-dz/UniFAR-FTUs huggingface dataset:
On the presence and absence of behavioural traits in sport: an example from championship squash match-play.

Here we report two experiments that analysed sport (squash) competition as a non-linear system that transits intermittently between different behavioural states. The first experiment involved a perceptual analysis of 60 rallies in which stable behaviour and unstable behaviour, delineated by behavioural transitions (i.e. shot perturbations), were reliably (kappa = 0.930) and validly (kappa = 0.844) identified by independent observers. In addition, experts were better than non-experts at identifying the type of system behaviour (P < 0.01). These results provide for three alternative descriptions: (a) the system is multi-stable and transits between states via the mechanism of instability; (b) the system is bi-stable and abruptly transits between two states, labelled stable and unstable; or (c) the system is mono-stable and displays variability, marked by transient instability, as a result of system perturbations. The second experiment analysed squash behaviour as expressed in the phase relation between the two players from time-motion analysis. The data, from four rallies, yielded evidence of a tight anti-phase coupling with transient phase shifts, or perturbations, that were quickly damped. These data suggest a mono-stable system with a single (anti-phase) attractor onto which system fluctuations are occasionally written. However, these fluctuations failed to correspond with the short perturbations that were identified from perceptual analysis. Together, these results affirm the presence of transient behaviours in squash match-play, although the information that forms these perceptual judgements has yet to be identified.
Affinity, Avidity, and Kinetics of Target Sequence Binding to LC8 Dynein Light Chain Isoforms*

LC8 dynein light chain (DYNLL) is a highly conserved eukaryotic hub protein with dozens of binding partners and various functions beyond being a subunit of dynein and myosin Va motor proteins. Here, we compared the kinetic and thermodynamic parameters of binding of both mammalian isoforms, DYNLL1 and DYNLL2, to two putative consensus binding motifs (KXTQTX and XG(I/V)QVD) and report only subtle differences. Peptides containing either of the above motifs bind to DYNLL2 with micromolar affinity, whereas a myosin Va peptide (lacking the conserved Gln) and the noncanonical Pak1 peptide bind with Kd values of 9 and 40 μm, respectively. Binding of the KXTQTX motif is enthalpy-driven, although that of all other peptides is both enthalpy- and entropy-driven. Moreover, the KXTQTX motif shows strikingly slower off-rate constant than the other motifs. As most DYNLL partners are homodimeric, we also assessed the binding of bivalent ligands to DYNLL2. Compared with monovalent ligands, a significant avidity effect was found as follows: Kd values of 37 and 3.5 nm for a dimeric myosin Va fragment and a Leu zipper dimerized KXTQTX motif, respectively. Ligand binding kinetics of DYNLL can best be described by a conformational selection model consisting of a slow isomerization and a rapid binding step. We also studied the binding of the phosphomimetic S88E mutant of DYNLL2 to the dimeric myosin Va fragment, and we found a significantly lower apparent Kd value (3 μm). We conclude that the thermodynamic and kinetic fine-tuning of binding of various ligands to DYNLL could have physiological relevance in its interaction network.
Persistent Spin Helix Spin Polarizer

The persistent spin helix (PSH) occurs in 2-D nanosystems where the Rashba and Dresselhaus spin orbit interactions (RSOI/DSOI) are both present and of equal strength. The spin orbit interaction effective field experienced by the charge carriers due to RSOI and/or DSOI generally depends on the direction of the charge carrier momenta. The PSH is unique in that the direction of this effective magnetic field is independent of the momentum direction. We find that this results in the spin accumulation in a PSH system assuming only the PSH eigenspinor directions of ±(1, -1, 0) without any intermediate directions in between, when spin unpolarized electrons are injected into the PSH system. This can be explained by the accumulation of the spin up and spin down carriers about the PSH eigenspinor axis occurring in opposite directions, resulting in the the spin components perpendicular to ±(1, -1, 0) averaging to zero. In particular, the spin accumulation for an infinitely wide PSH segment connected to a narrow spin unpolarized source lead is partitioned between the (1, -1, 0) and (-1, 1, 0) directions along the upper and lower halves of the segment about the source lead-PSH interface. This partitioning of the spin accumulation motivates the proposal of a finite-sized PSH spin polarizer for generating ±(1, -1, 0) spin polarized currents. The spin polarization of the current can be optimized by reducing the length and increasing the width of the spin polarizer.
Analysis of intention to use transjakarta bus

Congestion is a common problem in big cities, including Jakarta as a capital of Indonesia. Increasing the number of vehicles in Jakarta is not proportional to the growth of roads. This makes the road become inconducive. The use of public transportation is a solution to solve this problem. While public intention in using public transportation is still considered low. Research on the intention of using public transport is still less. Based on this, further research is needed that focuses on the intention to use public transportation. This study explores the intention to use public transport that focus on Transjakarta busway while considering several factors in Jakarta, Indonesia. This study describe intention behavior of Transjakarta potential user, study and explores the relationship between intention to use Transjakarta and other latent factors, including personal norms, social influence, environment impact, and perceived quality. The empirical data were drawn from 190 potential users of Transjakarta in Jabodetabek that still use private vehicle, car or motorbike in daily activity using questionnaire method. Structural equation model (SEM) technique is used to analyze the conceptualized relationship model. The result reveal that personal norms, social influence, and perceived quality significantly affect potential users’ intention behavior. From the empirical result, managerial implications were discussed.
Classification for imbalanced dataset based on biased empirical feature mapping

It is shown that an imbalanced datasets can pose serious problems to many real-world classification tasks when support vector machines is used as the learning machine. To solve this problem, we propose a modified method based on biased empirical feature mapping. In the new method, biased discriminant analysis was applied to make all majority samples far away from center of minority samples in empirical feature space, so that generalization ability of the classifier for minority samples can be improved. Through theoretical analysis and empirical study on synthetic datasets and UCI datasets, we show that our method augments the classification accuracy rate effectively.
Volumetric analysis of white matter, gray matter, and CSF using fractional volume analysis

Quantitative cerebral tissue volumes may be useful for an objective assessment of pathological changes in brain. Accurate determination of tissue volumes is complicated, however, by the partial volume averaging (PVA) effect. We have, therefore, developed a new pulse sequence that minimizes the PVA through the use of inversion‐recovery (IR) and double inversion‐recovery (DIR) techniques. This pulse sequence simultaneously acquires four different sets of images to provide the necessary information for volumetric analysis and reduces potential spatial misregistration of images due to patient motion. The image sets acquired from the proposed pulse sequence are 1) gray matter visible, 2) white matter visible, 3) FLAIR, and 4) fast spin‐echo proton‐density weighted images. An algorithm has been implemented to correct for differential T1‐weighting and for tissue quantitation.
Efficacy and safety of saxagliptin in combination with metformin compared with sitagliptin in combination with metformin in adult patients with type 2 diabetes mellitus

Dipeptidyl peptidase‐4 inhibitors improve glycaemic control in patients with type 2 diabetes mellitus when used as monotherapy or in combination with other anti‐diabetic drugs (metformin, sulphonylurea, or thiazolidinedione). This 18‐week, phase 3b, multicentre, double‐blind, noninferiority trial compared the efficacy and safety of two dipeptidyl peptidase‐4 inhibitors, saxagliptin and sitagliptin, in patients whose glycaemia was inadequately controlled with metformin.
Ranolazine enhances the efficacy of amiodarone for conversion of recent-onset atrial fibrillation.

AIMS Amiodarone is used commonly for pharmacological cardioversion of atrial fibrillation (AF), but it is limited by moderate efficacy and delayed action. Ranolazine and amiodarone are markedly synergistic in suppressing experimental AF in vitro, yet the clinical efficacy of ranolazine combined with amiodarone for AF conversion has only undergone minimal investigation. This prospective, single-blinded, randomized study compared the safety and efficacy of ranolazine added to amiodarone vs. amiodarone alone for conversion of recent-onset AF. METHODS AND RESULTS We enroled 121 patients (64 ± 10 years, 45% male) with recent-onset (<48 h duration) AF who were eligible for pharmacological cardioversion. Patients received either 24 h amiodarone infusion (loading dose 5 mg/kg followed by maintenance dose of 50 mg/h; n = 60), or amiodarone infusion at the same dosage plus a single oral dose of ranolazine 1500 mg (n = 61). Patients in the amiodarone plus ranolazine group compared with the amiodarone-only group showed significantly higher conversion rates at 24 h (87 vs. 70%, respectively; P = 0.024) and at 12 h (52 vs. 32%; P = 0.021), and shorter time to conversion (10.2 ± 3.3 vs. 13.3 ± 4.1 h; P = 0.001). Subgroup analysis identified higher 24 h conversion in patients with left atrial (LA) diameter >46 mm who received the combination treatment vs. amiodarone alone (81 vs. 54%; P = 0.02), whereas the efficacy of the two interventions did not differ among patients with LA diameter ≤46 mm (P = 0.77). There was modest QT prolongation in both the groups, no serious adverse reactions, and no pro-arrhythmic events. CONCLUSION Addition of ranolazine to amiodarone was safe and well tolerated in this study, and it demonstrated efficacy superior to amiodarone alone for conversion of recent-onset AF. These findings may have clinical implications by offering a simple therapeutic manoeuvre to enhance amiodarone's effectiveness for conversion of AF.
Dysregulation of diurnal cortisol secretion affects abstinence induction during a lead-in period of a clinical trial for depressed cocaine-dependent patients.

BACKGROUND AND OBJECTIVE Hypothesizing that stress dysregulation may worsen cocaine dependence, we investigated the effect of diurnal cortisol secretion profile, suppression of cortisol secretion, and total cortisol secretion on retention, abstinence-based voucher earnings, days of cravings, and mood status of participants at the end of a 2-week medication-free lead-in prior to randomization in a clinical trial of mirtazapine (60 mg vs. placebo) for depressed cocaine-dependent patients. METHODS We measured saliva cortisol levels at 9 AM, 2 PM, and 5 PM on the first two consecutive days of a 2-week medication-free lead-in period. Results from saliva samples were used to estimate the total daily level of cortisol, the diurnal profile of secretion (typical vs. atypical), and response to dexamethasone suppression (.1 mg). Seventy-seven patients collected saliva samples at baseline, and 65 (85%) were suitable for profile analysis. RESULTS Patients with typical profiles (52%) collected significantly more abstinence-based voucher earnings during the lead-in (U = 299.50, p = .025). Diurnal secretion profile did not significantly affect mood status, days of craving, or retention. There were no significant effects of suppression of cortisol secretion or of total cortisol levels on any outcome measures. CONCLUSION In a subgroup of cocaine-dependent patients, deviation of cortisol secretion away from the homeostatic diurnal pattern was associated with reduced success at achieving early abstinence, an important determinant of treatment success.
Subsidy Bidding Wars and the Structure of Multi-Plant Firms

Governments spend large amounts of money to attract firms to their territory, often resulting from bidding wars against other regions. Previous papers show that such bidding wars can improve social welfare by allocating the investment to the regions that value it the most. In this paper, we depart from the usual assumption of exogenous, single-plant investment. We show that in this context, bidding wars incite the firm to allocate its investment strategically, by investing more and differentiating the plants. In turn, the firm receives larger subsidies. Despite these distortions, bidding wars may remain socially optimal, as in simpler models.
A medical application of electromagnetic fields: The magnetic stimulation of nerve fibers inside a cylindrical tissue

A model is presented that predicts the electric field induced in the arm during magnetic stimulation of a peripheral nerve. The arm is represented as a homogeneous, cylindrical volume conductor. The electric field arises from two sources: the time - varying magnetic field and the accumulation of charge on the tissue - air surface. In magnetic stimulation both of these contributions are significant. A passive cable model describes the response of the nerve fiber to this induced electric field. Once the coil's position, orientation and shape are given, and the resistance, capacitance and the initial voltage of the stimulating circuit are specified, the resulting transmembrane potential of the fiber is calculated as a function of distance and time.
Design and experimental validation of a controller suite for an autonomous, finless airship

This paper describes the design and experimental validation of a controller suite allowing an unmanned, finless airship to track a series of waypoints autonomously. The control architecture consists of a low-level controller providing attitude and velocity control as well as a high-level controller performing the autonomous trajectory tracking task. The airship equations of motion and the design of the low-level controller are described briefly. Subsequently, the high-level controller design is described in more detail and its performance is evaluated in simulation and experiment. It is found to track the desired waypoints well even in the presence of time-varying wind as an external disturbance.
Activation of Autophagic Flux against Xenoestrogen Bisphenol-A-induced Hippocampal Neurodegeneration via AMP kinase (AMPK)/Mammalian Target of Rapamycin (mTOR) Pathways*

Background: The effects of xenoestrogen bisphenol-A on autophagy, and association with oxidative stress and apoptosis are still elusive. Results: Transient activation of autophagy protects against bisphenol-A-induced neurodegeneration via AMPK activation and mTOR down-regulation. Conclusion: Autophagy induction against bisphenol-A is an early cell's tolerance response. Significance: Autophagy provides an imperative biological marker for evaluation of neurotoxicity by xenoestrogen. The human health hazards related to persisting use of bisphenol-A (BPA) are well documented. BPA-induced neurotoxicity occurs with the generation of oxidative stress, neurodegeneration, and cognitive dysfunctions. However, the cellular and molecular mechanism(s) of the effects of BPA on autophagy and association with oxidative stress and apoptosis are still elusive. We observed that BPA exposure during the early postnatal period enhanced the expression and the levels of autophagy genes/proteins. BPA treatment in the presence of bafilomycin A1 increased the levels of LC3-II and SQSTM1 and also potentiated GFP-LC3 puncta index in GFP-LC3-transfected hippocampal neural stem cell-derived neurons. BPA-induced generation of reactive oxygen species and apoptosis were mitigated by a pharmacological activator of autophagy (rapamycin). Pharmacological (wortmannin and bafilomycin A1) and genetic (beclin siRNA) inhibition of autophagy aggravated BPA neurotoxicity. Activation of autophagy against BPA resulted in intracellular energy sensor AMP kinase (AMPK) activation, increased phosphorylation of raptor and acetyl-CoA carboxylase, and decreased phosphorylation of ULK1 (Ser-757), and silencing of AMPK exacerbated BPA neurotoxicity. Conversely, BPA exposure down-regulated the mammalian target of rapamycin (mTOR) pathway by phosphorylation of raptor as a transient cell's compensatory mechanism to preserve cellular energy pool. Moreover, silencing of mTOR enhanced autophagy, which further alleviated BPA-induced reactive oxygen species generation and apoptosis. BPA-mediated neurotoxicity also resulted in mitochondrial loss, bioenergetic deficits, and increased PARKIN mitochondrial translocation, suggesting enhanced mitophagy. These results suggest implication of autophagy against BPA-mediated neurodegeneration through involvement of AMPK and mTOR pathways. Hence, autophagy, which arbitrates cell survival and demise during stress conditions, requires further assessment to be established as a biomarker of xenoestrogen exposure.
Molecular Consequences of Proprotein Convertase 1/3 (PC1/3) Inhibition in Macrophages for Application to Cancer Immunotherapy: A Proteomic Study*

Macrophages provide the first line of host immune defense. Their activation triggers the secretion of pro-inflammatory cytokines and chemokines recruiting other immune cells. In cancer, macrophages present an M2 anti-inflammatory phenotype promoting tumor growth. In this way, strategies need to be develop to reactivate macrophages. Previously thought to be expressed only in cells with a neural/neuroendocrine phenotype, the proprotein convertase 1/3 has been shown to also be expressed in macrophages and regulated as a function of the Toll-like receptor immune response. Here, we investigated the intracellular impact of the down-regulation of the proprotein convertase 1/3 in NR8383 macrophages and confirmed the results on macrophages from PC1/3 deficient mice. A complete proteomic study of secretomes and intracellular proteins was undertaken and revealed that inhibition of proprotein convertase 1/3 orient macrophages toward an M1 activated phenotype. This phenotype is characterized by filopodial extensions, Toll-like receptor 4 MyD88-dependent signaling, calcium entry augmentation and the secretion of pro-inflammatory factors. In response to endotoxin/lipopolysaccharide, these intracellular modifications increased, and the secreted factors attracted naïve T helper lymphocytes to promote the cytotoxic response. Importantly, the application of these factors onto breast and ovarian cancer cells resulted in a decrease viability or resistance. Under inhibitory conditions using interleukin 10, PC1/3-knockdown macrophages continued to secrete inflammatory factors. These data indicate that targeted inhibition of proprotein convertase 1/3 could represent a novel type of immune therapy to reactivate intra-tumoral macrophages.
Pregnane X receptor and drug-induced liver injury

Introduction: The liver plays a central role in transforming and clearing foreign substances. The continuous exposure of the liver to xenobiotics sometimes leads to impaired liver function, referred to as drug-induced liver injury (DILI). The pregnane X receptor (PXR) tightly regulates the expression of genes in the hepatic drug-clearance system and its undesired activation plays a role in DILI. Areas covered: This review focuses on the recent progress in understanding PXR-mediated DILI and highlights the efforts made to assess and manage PXR-mediated DILI during drug development. Expert opinion: Future efforts are needed to further elucidate the mechanisms of PXR-mediated liver injury, including the epigenetic regulation and polymorphisms of PXR. Novel in vitro models containing functional PXR could improve our ability to predict and assess DILI during drug development. PXR inhibitors may provide chemical tools to validate the potential of PXR as a therapeutic target and to develop drugs to be used in the clinic to manage PXR-mediated DILI.
Evidence of persistent low-level viremia in long-term HAART-suppressed, HIV-infected individuals

Background:HAART can effectively reduce plasma HIV RNA levels to below the level of detection in most HIV-infected patients. The degree to which residual low-level viremia persists during HAART remains unclear. Methods:We identified 180 individuals (median duration of HIV infection 12 years) who had at least two consecutive plasma HIV-1 RNA levels below the level of detection (<50–75 copies/ml) while taking antiretroviral drugs; 36 of 180 had been virologically suppressed for more than 5 years. Longitudinal plasma samples that were taken from these individuals during periods of viral load suppression were selected and analyzed. The isothermal transcription-mediated amplification (TMA) (limit of detection <3.5 copies RNA/ml) assay was used to measure persistent viremia. A ‘detuned’ EIA assay was used to obtain quantitative HIV antibody levels. Results:A total of 1606 TMA assays were performed on 438 specimens in 180 HAART-suppressed individuals (median 3 replicates per specimen). In the first year of viral suppression, plasma RNA levels declined significantly (P = 0.001), but after month 12 there was no evidence for a continued decline (P = 0.383). In the first year of viral suppression, HIV antibody levels also declined (P = 0.054), but after month 12 there was no evidence for a continued decline (P = 0.988). Conclusion:Viremia continued to decline during the first 12 months after viremia became undetectable using conventional methods, and then remained stable. HIV antibody levels also decreased in the first year of viral suppression and then remained stable. Viremia and the HIV-associated host response appear to achieve a steady-state ‘set-point’ during long-term combination therapy.