Miracle-dz/UniFAR-FTUs huggingface dataset:
Dopaminergic modulation of cortical function in patients with Parkinson's disease

Patients with idiopathic Parkinson's disease suffer not only from classic motor symptoms, but from deficits in cognitive function, primarily those subserved by the prefrontal cortex as well. The aim of the current study was to investigate the modulatory effects of dopaminergic therapy on neural systems subserving working memory and motor function in patients with Parkinson's disease. Ten patients with stage I and II Parkinson's disease were studied with functional magnetic resonance imaging, during a relatively hypodopaminergic state (ie, 12 hours after a last dose of dopamimetic treatment), and again during a dopamine‐replete state. Functional magnetic resonance imaging was performed under three conditions: a working memory task, a cued sensorimotor task and rest. Consistent with prior data, the cortical motor regions activated during the motor task showed greater activation during the dopamine‐replete state; however, the cortical regions subserving working memory displayed greater activation during the hypodopaminergic state. Interestingly, the increase in cortical activation during the working memory task in the hypodopaminergic state positively correlated with errors in task performance, and the increased activation in the cortical motor regions during the dopamine‐replete state was positively correlated with improvement in motor function. These results support evidence from basic research that dopamine modulates cortical networks subserving working memory and motor function via two distinct mechanisms: nigrostriatal projections facilitate motor function indirectly via thalamic projections to motor cortices, whereas the mesocortical dopaminergic system facilitates working memory function via direct inputs to prefrontal cortex. The results are also consistent with evidence that the hypodopaminergic state is associated with decreased efficiency of prefrontal cortical information processing and that dopaminergic therapy improves the physiological efficiency of this region.
Lysophospholipid acyltransferases: 1-acylglycerol-3-phosphate O-acyltransferases. From discovery to disease

Purpose of review Over the past several years, many more isoforms for the same enzymes, specifically for 1-acylglycerol-3-phosphate O-acyltransferases (AGPATs), have been cloned and studied. In this review, we summarize their biochemical features and discuss their functional role. Recent findings The most significant role of these AGPATs appeared from our observation of AGPAT2 in the biology of adipose tissue (adipocytes) in humans and mice. Other isoforms are shown to be implicated in lung, reproductive and cardiac muscle function and in the cause of cancer. In-vitro substrate specificities of these AGPATs also suggest the in-vivo role of these AGPATs in remodeling of several of the glycerophospholipids. Summary Despite significant progress in understanding the role of these AGPATs, much is still to be discovered in terms of how each of these AGPATs function in the presence or absence of other AGPATs and what their functional role might be.
Influencia del bloqueo del factor de necrosis tumoral-alfa sobre los niveles del factor reumatoide y anticuerpos anti-péptidos cíclicos citrulinados en pacientes con artritis reumatoide

La respuesta clinica a los anti-TNF-α en los pacientes con Artritis Reumatoide (AR) es muy variable, en muchos casos se logra la remision de la enfermedad, sin embargo una cantidad sustancial de pacientes no responden y persisten con actividad de la enfermedad o presentan recaidas a pesar del tratamiento. Los marcadores clinicos, radiologicos, serologicos y geneticos disponibles para el diagnostico y seguimiento de la enfermedad tienen un valor limitado a la hora de predecir de manera precisa la respuesta al tratamiento y las recaidas. El factor reumatoide (FR) y los anticuerpos anti-peptidos ciclicos citrulinados (anti-PCC) son los principales marcadores biologicos en la AR y forman parte de los criterios de clasificacion de la enfermedad, sin embargo, la relacion entre los cambios en la concentracion de estos autoanticuerpos y la respuesta a los anti-TNF- es variable en los diferentes estudios y no se aceptan como factores de prediccion y de seguimiento de la respuesta a estos farmacos. Las concentraciones sericas del farmaco y los anticuerpos anti-farmaco (ADAb anti-drug antibodies) han sido estudiados como marcadores sericos relacionados con la actividad del enfermedad. Diferentes investigadores han demostrado que la perdida de eficacia a los anti-TNF-α esta asociada con el desarrollo de ADAb, que a su vez se correlaciona con la ausencia de concentraciones sericas adecuadas del farmaco.
Cutaneous Vascular Response to Local Warming: A Response to Letter from Cracowski and Roustit

As Cracowski and Roustit admirably review in their letter and papers, the cutaneous vascular response to local warming in healthy individuals is now well characterised and the mechanism contributing to both the early and later components of the local hyperaemic response extensively investigated [3,4]. It is for these reasons that we chose to use thermal provocation as our tool to investigate microvascular control in our study. We do agree with Cracowski and Roustit that our use of mean heated flux during the plateau phase of the response and area under the response curve (AUC) during 10 minutes of skin warming may disadvantage an interpretation of the physiological factors modulating the response. However our clearly stated aims were to explore associations between smoking habit, age and cutaneous blood flow and flow motion using the dynamic approach of power spectral density (PSD) analysis of the very low component frequencies of the laser Doppler flux trace to explore deficits in control rather than pharmacological intervention. PSD analysis was undertaken using the final 350 seconds of the 600 seconds recording acquired during the plateau phase of the response; i.e., commencing 150 seconds (2.5 minutes) after the start of warming and excluding the early phase of the thermally induced hyperaemia. In this way we were able to avoid biasing our spectral estimates though inclusion of the initial transient response—attributed to increased neurogenic axonreflex mediated activity—and to focus on the sustained largely endothelium-dependent response that we hypothesized would be influenced by age and smoking history. To maintain consistency in our analyses in the spectral and time domains, we used mean plateau flux (excluding the early response) as our flux measure. We also report the AUC of the total response above baseline as this has previously been shown to be a sensitive integrated indicator of the total response [6,7].
Development of a Yellow Flag Assessment Tool for Orthopaedic Physical Therapists: Results From the Optimal Screening for Prediction of Referral and Outcome (OSPRO) Cohort.

Study Design Clinical measurement, cross-sectional. Background Pain-associated psychological distress adversely influences outcomes for patients with musculoskeletal pain. However, assessment of pain-associated psychological distress (ie, yellow flags) is not routinely performed in orthopaedic physical therapy practice. A standardized yellow flag assessment tool will better inform treatment decision making related to psychologically informed practice. Objectives To describe the development of a concise, multidimensional yellow flag assessment tool for application in orthopaedic physical therapy clinical practice. Methods A 136-item yellow flag item bank was developed from validated psychological questionnaires across domains related to pain vulnerability (negative mood, fear avoidance) and resilience (positive affect/coping). Patients seeking physical therapy with neck, back, knee, or shoulder pain completed the item bank. Iterative statistical analyses determined minimal item sets meeting thresholds for identifying elevated vulnerability or low resilience (ie, upper or lower quartile, as indicated). Further item reduction yielded a concise yellow flag assessment tool to assess 11 psychological constructs measuring pain-associated psychological distress. Correlations between the assessment tool and individual psychological questionnaires were measured and compared between anatomical regions. Concurrent validity was assessed by determining variance explained in pain and disability scores by the assessment tool. Results Subjects with elevated vulnerability and decreased resilience were identified with a high degree of accuracy (minimum of 85%) using a 17-item tool. Correlations were moderate to high between the 17-item tool and individual psychological questionnaires, with no significant differences in correlations between different anatomical regions. Shorter 10- and 7-item versions of the assessment tool allow clinicians the flexibility to assess for yellow flags quickly with acceptable trade-offs in accuracy (81% and 75%, respectively). All versions of the tool explained significant additional variance in pain and disability scores (range, 19.3%-36.7%) after accounting for demographics, historical variables, and anatomical region of pain. Conclusion Concise assessment of yellow flags is feasible in outpatient physical therapy settings. This multidimensional tool advances assessment of pain-associated psychological distress through the addition of positive affect/coping constructs and estimation of full questionnaire scores. Further study is warranted to determine how this tool complements established risk-assessment tools by providing the option for efficient treatment monitoring. J Orthop Sports Phys Ther 2016;46(5):327-345. Epub 21 Mar 2016. doi:10.2519/jospt.2016. 6487.
The detection of human finger movement is not facilitated by input from receptors in adjacent digits

These experiments were designed to determine whether cutaneous input from a digit provides a general facilitation of the detection of movements applied to an adjacent digit. The ability to detect passive movements at the proximal interphalangeal joint of the right index finger was measured when cutaneous (and joint) input was removed (using local anaesthesia) from the tip of one or both digits adjacent to the test finger (16 subjects). The same parameter was also measured when input was artificially increased by stimulation of the adjacent digits at three intensities: below, above and at perceptual threshold (PT; 15 subjects). Detection of flexion or extension movements was not altered by anaesthesia of one or both adjacent digits. Since it was possible that too few tonically active afferents in the hand had been blocked to reveal an effect, the median nerve was blocked, with movements applied to the little finger, causing no measurable impairment in acuity (three subjects). Simultaneous electrical stimulation of the tips of the adjacent digits at intensities above PT impaired movement detection, but had no effect when delivered at or below PT. To test whether the effect of detectable electrical stimuli was due to a specific interaction between the artificial input and the input evoked by moving the digit, or due to mental distraction, stimuli were delivered above PT to either the left or right little finger, or the test index finger during movement of the index finger. Electrical stimulation of the index finger significantly reduced detection by ∼50%, but stimulation of the remote little fingers did not. Electrical stimulation is a non‐natural stimulus, so a ‘natural’ stimulus was applied by continuously stroking the tips of the adjacent digits with a brush (10 subjects). The natural stimulus also significantly reduced movement detection by ∼50%. Together, these findings suggest that tonic inputs from digital nerve afferents adjacent to, or more remote from the passively moved finger do not facilitate movement detection. However, the reduced detection during stimulation of the adjacent digits shows that there is nevertheless some interaction between the various proprioceptive inputs from the digits.
Asymmetrical hybrid unidirectional T-type rectifier for high-speed gen-set applications

The paper deals with a high efficiency boost rectifier for high rotational speed Gen-Set applications. It is tailored around a permanent magnet synchronous generator (PMSG) featuring an open end winding configuration. According to such a configuration the generator stator windings are connected on one side to a three level T-type unidirectional rectifier, and on the other side, to an auxiliary two-level inverter. The multilevel rectifier is operated at the fundamental frequency, while, the two-level inverter is driven by a standard sine PWM technique, in order to suitably shape the currents produced by the electric generator. The entire system is equivalent to a six-level multilevel converter. As the main stream power is handled by the multilevel rectifier operating at low switching frequency, a higher efficiency is achieved compared to a similar multilevel rectifier driven through a PWM technique, even considering extra losses due to the auxiliary inverter. The last can be supplied through an active source or a floating capacitor, and plays a key role in balancing the voltage across the DC Bus capacitors of the T-type rectifier, making unnecessary additional circuits. Suitable control solutions have been implemented considering either an active source, either a floating capacitor. Simulation results confirm the effectiveness of the proposed configuration.
Signal-dependent Slow Leukocyte Rolling Does Not Require Cytoskeletal Anchorage of P-selectin Glycoprotein Ligand-1 (PSGL-1) or Integrin αLβ2*

Background: The cytoskeleton contributes to receptor-initiated signaling and has been linked to force-regulated integrin activation. Results: Disrupting cytoskeletal interactions of PSGL-1 or αLβ2 does not impair slow rolling of leukocytes on P-selectin and ICAM-1. Conclusion: The cytoskeleton is not required for PSGL-1-initiated signals to extend αLβ2. Significance: Signals can “prime” integrins without the cytoskeleton. In inflamed venules, neutrophils roll on P- or E-selectin, engage P-selectin glycoprotein ligand-1 (PSGL-1), and signal extension of integrin αLβ2 in a low affinity state to slow rolling on intercellular adhesion molecule-1 (ICAM-1). Cytoskeleton-dependent receptor clustering often triggers signaling, and it has been hypothesized that the cytoplasmic domain links PSGL-1 to the cytoskeleton. Chemokines cause rolling neutrophils to fully activate αLβ2, leading to arrest on ICAM-1. Cytoskeletal anchorage of αLβ2 has been linked to chemokine-triggered extension and force-regulated conversion to the high affinity state. We asked whether PSGL-1 must interact with the cytoskeleton to initiate signaling and whether αLβ2 must interact with the cytoskeleton to extend. Fluorescence recovery after photobleaching of transfected cells documented cytoskeletal restraint of PSGL-1. The lateral mobility of PSGL-1 similarly increased by depolymerizing actin filaments with latrunculin B or by mutating the cytoplasmic tail to impair binding to the cytoskeleton. Converting dimeric PSGL-1 to a monomer by replacing its transmembrane domain did not alter its mobility. By transducing retroviruses expressing WT or mutant PSGL-1 into bone marrow-derived macrophages from PSGL-1-deficient mice, we show that PSGL-1 required neither dimerization nor cytoskeletal anchorage to signal β2 integrin-dependent slow rolling on P-selectin and ICAM-1. Depolymerizing actin filaments or decreasing actomyosin tension in neutrophils did not impair PSGL-1- or chemokine-mediated integrin extension. Unlike chemokines, PSGL-1 did not signal cytoskeleton-dependent swing out of the β2-hybrid domain associated with the high affinity state. The cytoskeletal independence of PSGL-1-initiated, αLβ2-mediated slow rolling differs markedly from the cytoskeletal dependence of chemokine-initiated, αLβ2-mediated arrest.
Enhanced oral bioavailability of piperine by self-emulsifying drug delivery systems: in vitro, in vivo and in situ intestinal permeability studies

Abstract The main purpose of this work was to develop and evaluate a self-emulsifying drug delivery system (SEDDS) of piperine to enhance its solubility and bioavailability. The formulation was optimized by solubility test and ternary phase diagrams. Then physiochemical properties and in vitro release of SEDDS were characterized. In vivo pharmacokinetics study and in situ single-pass intestinal perfusion were performed to investigate the effects of SEDDS on the bioavailability and intestinal absorption of piperine. The optimized formulation was composed of ethyl oleate, Tween 80 and Transcutol P (3:5.5:1.5, w/w), with the level of the piperine reached 2.5% (w/w). The in vitro dissolution rates of piperine SEDDS were significantly higher than the self-prepared capsules. In vivo pharmacokinetic study showed Cmax1, Cmax2 and area under the curve of piperine after oral administration of SEDDS in rats were 3.8-, 7.2- and 5.2-fold higher than the self-prepared capsules, respectively, and the relative bioavailability of SEDDS was 625.74%. The in situ intestinal absorption study revealed that the effective permeability and the effective absorption rate values of piperine for SEDDS were significantly improved comparing to solutions (p < 0.01). So SEDDS formulation could improve the oral bioavailability and intestinal absorption of piperine effectively.
Agreement in Detecting Glaucomatous visual Field Progression by using Guided Progression Analysis and Humphrey Overview Printout

Purpose To examine the level of agreement among 3 clinicians in assessing glaucoma visual field progression by using 2 different methods. Methods Each visual field was assessed by Humphrey Field Analyzer (HFA), program SITA standard 30–2 or 24–2. In each printout the first 3 fields were excluded to minimize learning effect: the fourth and fifth full-threshold or SITA Standard examinations were used as baseline. Three clinicians assessed the progression status of each series using both HFA overview printouts and the guided progression analysis (GPA). The level of agreement among the clinicians was evaluated using a weighted kappa statistic (κ). Results A total of 510 tests, comprising 83 eyes with an average of 6.1 tests each, was assessed by the 3 specialists. The mean follow-up time was 5.8±1.75 years (mean ± standard deviation). When the intraobserver intermethod agreement was evaluated, κ ranged from 0.5 to 0.7. When the interobserver agreement was analyzed, if HFA overview printouts were used, κ ranged from 0.4 to 0.7. But when GPA was used, κ ranged from 0.2 to 0.6. The level of agreement on progression status between the clinicians was always higher when they used HFA overview printouts (median κ = 0.54) than when they used GPA (median κ=0.37). Conclusions Agreement among expert clinicians about visual field progression status was moderate when GPA printouts were used. Clinicians’ agreement about patients’ visual field progression status was better when HFA overview printouts were used than with GPA printouts.
Selection of Ground Motion Prediction Equations for the Global Earthquake Model

Ground motion prediction equations (GMPEs) relate ground motion intensity measures to variables describing earthquake source, path, and site effects. From many available GMPEs, we select those models recommended for use in seismic hazard assessments in the Global Earthquake Model. We present a GMPE selection procedure that evaluates multidimensional ground motion trends (e.g., with respect to magnitude, distance, and structural period), examines functional forms, and evaluates published quantitative tests of GMPE performance against independent data. Our recommendations include: four models, based principally on simulations, for stable continental regions; three empirical models for interface and in-slab subduction zone events; and three empirical models for active shallow crustal regions. To approximately incorporate epistemic uncertainties, the selection process accounts for alternate representations of key GMPE attributes, such as the rate of distance attenuation, which are defensible from available data. Recommended models for each domain will change over time as additional GMPEs are developed.
Serum Lipid Concentrations and Growth Characteristics in 12-year-old Children Born Small for Gestational Age

According to Barker's hypothesis, children born small for gestational age (SGA) are at increased risk for cardiovascular diseases in adulthood. The aim of our study was to determine whether retarded fetal growth is associated with dyslipidemia in childhood and, if so, to find predictive factors in the growth characteristics of SGA children. We studied the serum lipid concentrations of 55 SGA children and their 55 appropriate for gestational age control subjects at the age of 12 y. Growth variables were recorded at birth, 5 y, and 12 y of age. The study group consisted of all full-term SGA children born at our university hospital during a 22-mo period in 1984–1986. Nearly half of the SGA children (47.3%) were in the highest quartile for serum total cholesterol of the appropriate for gestational age children (p = 0.038). In multiple logistic regression analysis, poor catch-up growth in height (odds ratio, 13.8; 95% confidence interval, 2.0–97.5), female sex (odds ratio, 8.1; 95% confidence interval, 1.3–48.9), and early stage of puberty (odds ratio, 7.5; 95% confidence interval, 1.2–46.5) predicted high cholesterol level in the SGA children. By the age of 5 y, 20 (36.4%) SGA children showed catch-up growth of ≥ 2 SD scores in height, and 21 (38.2%) SGA children showed catch-up growth of ≥ 2 SD scores in weight from birth. At the age of 12 y, the SGA children were still significantly shorter (p < 0.001) and lighter (p < 0.05) than the appropriate for gestational age children, even though their pubertal development was similarly advanced. In conclusion, to be born SGA has long-term consequences for later growth and may already influence the level of serum total cholesterol before the teens. SGA children with poor catch-up growth in height may be at the highest risk for hypercholesterolemia.
Bewertung und Analyse hybrider Systeme

Das Haupteinsatzgebiet für hybride Systeme liegt im Bereich der eingebetteten Systeme, welche beispielsweise in der Telekommunikation, der Avionik und der Automobiltechnik Verwendung finden. Diese Systeme sind unter anderem dadurch charakterisiert, daß sie harten Echtzeitanforderungen genügen müssen. Bei mobilen, batteriegetriebenen eingebetteten Systemen kommt zusätzlich noch der Leistungsverbrauch zum Tragen, der die mobile Verfügbarkeit des Systems entscheidend beeinflußt. Nicht eingehaltene Echtzeitanforderungen oder ein inakzeptabler Leistungsverbrauch führen zu einem zeitund kostenaufwendigen Redesign, bei dem einige Entwurfsentscheidungen revidiert werden müssen. Die Notwendigkeit eines Redesigns kann reduziert werden, wenn der Entwerfer die Auswirkungen aller Entwurfsentscheidungen schon bei der Auswahl einer Alternative kennt. Von Bedeutung ist an dieser Stelle nicht die resultierende Struktur, sondern nur die Auswirkung einer Entscheidung auf die wesentlichen Kenngrößen der Schaltung wie beispielsweise Verzögerungszeit, Leistungsoder Flächen verbrauch. Die Bestimmung der Kenngrößen eines Systems aus der Spezifikation, d.h. ohne explizite Durchführung der Konstruktion, können Bewertungsverfahren ermöglichen. Somit können nach der Partitionierung des Systems, vor einer Konstrukti-