Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of Tetrahydrobiopterin Therapy with Large Neutral Amino Acid Supplementation in Phenylketonuria: Effects on Potential Peripheral Biomarkers, Melatonin and Dopamine, for Brain Monoamine Neurotransmitters

Background Phenylketonuria (PKU) is due to a defective hepatic enzyme, phenylalanine (Phe) hydroxylase. Transport of the precursor amino acids from blood into the brain for serotonin and dopamine synthesis is reported to be inhibited by high blood Phe concentrations. Deficiencies of serotonin and dopamine are involved in neurocognitive dysfunction in PKU. Objective (1) To evaluate the effects of sapropterin (BH4) and concurrent use of large neutral amino acids (LNAA) on the peripheral biomarkers, melatonin and dopamine with the hypothesis they reflect brain serotonin and dopamine metabolism. (2) To evaluate synergistic effects with BH4 and LNAA. (3) To determine the effects of blood Phe concentrations on the peripheral biomarkers concentrations. Methods Nine adults with PKU completed our study consisting of four 4-week phases: (1) LNAA supplementation, (2) Washout, (3) BH4 therapy, and (4) LNAA with BH4 therapy. An overnight protocol measured plasma amino acids, serum melatonin, and 6-sulfatoxymelatonin and dopamine in first void urine after each phase. Results (1) Three out of nine subjects responded to BH4. A significant increase of serum melatonin levels was observed in BH4 responders with decreased blood Phe concentration. No significant change in melatonin, dopamine or Phe levels was observed with BH4 in the subjects as a whole. (2) Synergistic effects with BH4 and LNAA were observed in serum melatonin in BH4 responders. (3) The relationship between serum melatonin and Phe showed a significant negative slope (p = 0.0005) with a trend toward differing slopes among individual subjects (p = 0.066). There was also a negative association overall between blood Phe and urine 6-sulfatoxymelatonin and dopamine (P = 0.040 and 0.047). Conclusion Blood Phe concentrations affected peripheral monoamine neurotransmitter biomarker concentrations differently in each individual with PKU. Melatonin levels increased with BH4 therapy only when blood Phe decreased. Monitoring peripheral neurotransmitter metabolites may assist in optimizing individualized treatment in PKU.
New insights from serranid fishes on the role of trade-offs in suction-feeding diversification

SUMMARY Suction feeding is central to prey capture in the vast majority of ray-finned fishes and has been well studied from a detailed, mechanistic perspective. Several major trade-offs are thought to have shaped the diversification of suction-feeding morphology and behavior, and have become well established in the literature. We revisited several of these expectations in a study of prey capture morphology and kinematics in 30 species of serranid fishes, a large, ecologically variable group that exhibits diverse combinations of suction and forward locomotion. We find that: (1) diversity among species in the morphological potential to generate suction changes drastically across the range of attack speeds that species use, with all species that use high-speed attacks having low capacity to generate suction, whereas slow-speed attackers exhibit the full range of suction abilities (this pattern indicates a more complex ‘ram–suction continuum’ than previously recognized); (2) there is no trade-off between the mechanical advantage of the lower jaw opening lever and the speed of jaw depression, revealing that this simple interpretation of lever mechanics fails to predict kinematic diversity; (3) high-speed attackers show increased cranial excursions, potentially to compensate for a decrease in accuracy; (4) the amount of jaw protrusion is positively related to attack speed, but not suction capacity; and (5) a principal component analysis revealed three significant multivariate axes of kinematic variation among species. Two of the three axes were correlated with the morphological potential to generate suction, indicating important but complex relationships between kinematics and suction potential. These results are consistent with other recent studies that show that trade-offs derived from simple biomechanical models may be less of a constraint on the evolutionary diversification of fish feeding systems than previously thought.
Surface relocation of alpha 6 beta 4 integrins and assembly of hemidesmosomes in an in vitro model of wound healing

A transmembrane extracellular matrix receptor of the integrin family, alpha 6 beta 4, is a component of the hemidesmosome, an adhesion complex of importance in epithelial cell-connective tissue attachment (Stepp, M. A., S. Spurr-Michaud, A. Tisdale, J. Elwell, and I. K. Gipson. 1990. Proc. Natl. Acad. Sci. USA. 87:8970-8974; Jones, J. C. R., M. A. Kurpakus, H. M. Cooper, and V. Quaranta. 1991. Cell Regulation. 2:427-438). Cytosolic components of hemidesmosomes include bullous pemphigoid (BP) antigens while extracellular components include a 125-kD component of anchoring filaments (CAF) and collagen type VII- containing anchoring fibrils. We have monitored the incorporation of the alpha 6 beta 4 integrins into forming hemidesmosomes in an in vitro wound-healing explant model. In epithelial cells recently migrated from the edges of unwounded sites over bare connective tissue, alpha 6 beta 4 first appears along the entire cell surface. At this stage, these cells contain little or no cytosolic hemidesmosomal components, at least as detectable by immunofluorescence using BP autoantibodies, whereas they are already positive for laminin and CAF. At a later stage, as cells become positive for cytosolic hemidesmosome components such as BP antigens as well as collagen type VII, alpha 6 beta 4 becomes concentrated along the basal pole of the epithelial cell where it abuts the connective tissue of the explant. Polyclonal antibodies to beta 4 do not interfere with the migration of epithelial cells in the explant. However, they prevent assembly of hemidesmosomal complexes and inhibit expression of collagen type VII in cells that have migrated over wound areas. In addition, they induce disruption of established hemidesmosomes in nonmigrating cells of the unwounded area of the explant. Monoclonal antibodies to alpha 6 have a more dramatic effect, since they completely detach epithelial cells in the unwounded area of the explant. Antibodies to CAF also detach epithelial cells in unwounded areas, apparently by inducing separation between epithelium and connective tissue at the lamina lucida of the basement membrane zone. These results suggest a model whereby polarization of alpha 6 beta 4 to the basal surface of the cells, perhaps induced by a putative anchoring filament-associated ligand, triggers assembly of hemidesmosome plaques.
OCCAM: a flexible, multi-purpose and extendable HPC cluster

The Open Computing Cluster for Advanced data Manipulation (OCCAM) is a multipurpose flexible HPC cluster designed and operated by a collaboration between the University of Torino and the Sezione di Torino of the Istituto Nazionale di Fisica Nucleare. It is aimed at providing a flexible, reconfigurable and extendable infrastructure to cater to a wide range of different scientific computing use cases, including ones from solid-state chemistry, high-energy physics, computer science, big data analytics, computational biology, genomics and many others. Furthermore, it will serve as a platform for R&D activities on computational technologies themselves, with topics ranging from GPU acceleration to Cloud Computing technologies. A heterogeneous and reconfigurable system like this poses a number of challenges related to the frequency at which heterogeneous hardware resources might change their availability and shareability status, which in turn affect methods and means to allocate, manage, optimize, bill, monitor VMs, containers, virtual farms, jobs, interactive bare-metal sessions, etc. This work describes some of the use cases that prompted the design and construction of the HPC cluster, its architecture and resource provisioning model, along with a first characterization of its performance by some synthetic benchmark tools and a few realistic use-case tests.
Matrix metalloproteinases promote motor axon fasciculation in the Drosophila embryo

Matrix metalloproteinases (MMPs) are a large conserved family of extracellular proteases, a number of which are expressed during neuronal development and upregulated in nervous system diseases. Primarily on the basis of studies using pharmaceutical inhibitors, MMPs have been proposed to degrade the extracellular matrix to allow growth cone advance during development and hence play largely permissive roles in axon extension. Here we show that MMPs are not required for axon extension in the Drosophila embryo, but rather are specifically required for the execution of several stereotyped motor axon pathfinding decisions. The Drosophila genome contains only two MMP homologs, Mmp1 and Mmp2. We isolated Mmp1 in a misexpression screen to identify molecules required for motoneuron development. Misexpression of either MMP inhibits the regulated separation/defasciculation of motor axons at defined choice points. Conversely, motor nerves in Mmp1 and Mmp2 single mutants and Mmp1 Mmp2 double mutant embryos are loosely bundled/fasciculated, with ectopic axonal projections. Quantification of these phenotypes reveals that the genetic requirement for Mmp1 and Mmp2 is distinct in different nerve branches, although generally Mmp2 plays the predominant role in pathfinding. Using both an endogenous MMP inhibitor and MMP dominant-negative constructs, we demonstrate that MMP catalytic activity is required for motor axon fasciculation. In support of the model that MMPs promote fasciculation, we find that the defasciculation observed when MMP activity is compromised is suppressed by otherwise elevating interaxonal adhesion - either by overexpressing Fas2 or by reducing Sema-1a dosage. These data demonstrate that MMP activity is essential for embryonic motor axon fasciculation.
Kulfi: Robust Traffic Engineering Using Semi-Oblivious Routing

Wide-area network traffic engineering enables network operators to reduce congestion and improve utilization by balancing load across multiple paths. Current approaches to traffic engineering can be modeled in terms of a routing component that computes forwarding paths, and a load balancing component that maps incoming flows onto those paths dynamically, adjusting sending rates to fit current conditions. Unfortunately, existing systems rely on simple strategies for one or both of these components, which leads to poor performance or requires making frequent updates to forwarding paths, significantly increasing management complexity. This paper explores a different approach based on semi-oblivious routing, a natural extension of oblivious routing in which the system computes a diverse set of paths independent of demands, but also dynamically adapts sending rates as conditions change. Semi-oblivious routing has a number of important advantages over competing approaches including low overhead, nearly optimal performance, and built-in protection against unexpected bursts of traffic and failures. Through in-depth simulations and a deployment on SDN hardware, we show that these benefits are robust, and hold across a wide range of topologies, demands, resource budgets, and failure scenarios.
Influence of hydrogen peroxide in drinking water on diazepam pharmacokinetics in chicks

Aim: Stressful conditions affect drug pharmacokinetics and pharmacodynamics. This study examines the effect of hydrogen peroxide (H O ) in drinking water on the pharmacokinetics of diazepam in a chick model of oxidative stress. 2 2 Materials and Methods: Day old chicks were either provided with plane tap water (control group) or H O in tap water as 2 2 0.5% v/v drinking solution for two weeks in order to produce oxidative stress. On treatment days 7–14, the chicks were treated with a sedative dose of diazepam at 10 mg/kg, intramuscularly. Blood samples were obtained from chicks (5/each sampling time) at times of between 0.17 to 4 h. The concentrations of diazepam in the plasma were determined by an HPLC method with UV-detector. Pharmacokinetic parameters of diazepam were calculated from the mean drug concentrations in the plasma by a non-compartmental analysis using a Windows-based computer program. Results: Injection of diazepam resulted in the appearance of the drug in the plasma of control and H O -treated chicks at mean 2 2 concentrations ranging between 0.11 to 0.444 and 0.131 to 0.535 µg/ml, respectively when measured between 0.17 to 4 h after administration. Diazepam concentrations of the H O -treated chicks were significantly higher than those of the control group 2 2 at the sampling times 0.5, 0.75, 1 and 4 h. The highest concentration of diazepam in the plasma of both the control and H O 2 2 treated chicks occurred one h after the injection. The elimination half-life, mean residence time, maximum plasma concentration, area under the moment curve and area under plasma concentration-time curve in the H O -treated chicks were 2 2 higher than those of the control group by 35, 28, 23, 91 and 49%, respectively. Correspondingly, the steady state volume of distribution, elimination rate constant and total body clearance in the H O -treated chicks decreased from those of the 2 2 respective control values by 15, 24 and 33%. Conclusion: The data suggest that oral exposure of chicks to H O influences the pharmacokinetics of diazepam by 2 2
Hemophilia and Its Genetic Qualities

Current treatment for hemophilic bleeding episodes is limited to the intravenous infusion of intravenous purified and recombinant factor protein. While this is generally effective, it is transient due to the brief lifespan of the proteins. Aside from this, factor protein treatment is costly, constrains the prophylactic use of factors and can potentially lead to degenerative joint disease as well as susceptibility to infectious agents, including HIV virus [1]. Hence, for many years now, attention has been focused on gene therapy as a potential cure for hemophilia. Nevertheless, clinical trials that have been undertaken in this direction have shown that this cure will not be easily achieved. This paper discusses the progress done in the field of research in the context of gene therapy for hemophilia, as well as the challenges that have emerged and how these could possibly be resolved based on research.
Child Abuse and Adolescent Parenting

Abstract Adolescent parents are commonly identified as an at-risk group in the child abuse literature. However, theoretical models specific to the area of child abuse and adolescent parenting are not well developed. This essay reviews established theories on child abuse, abusive parenting, and adolescent parenting to synthesize a proposed child abuse and adolescent parenting model. An ecological perspective is used to organize the theoretical model. The components of this model are supported by existing research on child abuse and adolescent parenting. The new synthesized model on child abuse and adolescent parenting should be viewed as an informed way to organize and conduct future research in this area. Further theory development on child abuse and adolescent parenting should be encouraged.
Energy efficient logic gates using subthreshold adiabatic logic

Adiabatic logic circuits offer significant reduction in power dissipation when compared with static CMOS. Subthreshold adiabatic logic is a new energy recovery logic. In this paper the efficiency of all logic gates with this novel logic is compared with conventional counterpart. The performance of each logic gate circuit and energy consumption is studied in terms of different technologies, supply voltages and operating frequencies. The proposed circuits are designed and simulated using CADENCE technology. The simulation results shows that the subthreshold adiabatic logic saves more than 90% of power compared to static CMOS.
15.3 An a-IGZO asynchronous delta-sigma modulator on foil achieving up to 43dB SNR and 40dB SNDR in 300Hz bandwidth

Amorphous IGZO (a-IGZO) TFTs fabricated on flexible large-area substrates provide better mobility than a-Si or organic counterparts and good uniformity. These features make a-IGZO TFTs an attractive technology for large-area sensing (e.g. strain, pressure, IR), low-cost RFIDs augmented with sensors and monitoring of biopotentials. In this context, it is crucial to accurately transform analogue sensor signals in a robust representation. The most common choice is a synchronous digital word, but a two-level PWM representation is another interesting possibility. Binary PWM can be transmitted on wire or via RF amplitude modulation with high immunity to noise and interferers.
Synthesis of asynchronous circuits using early data validity

Interest in asynchronous circuit design is increasing due to its promise of efficient designs. The quiescent nature of asynchronous circuits allows them to remain in a stable state until necessary wire transitions trigger an event to occur. This avoids synchronizing events using a global clock tree, which can consume a large amount of energy. The need for low power and high performance circuits leads to investigation of various asynchronous design styles. The work presented here provides an overview and novel implementation of synthesizing asynchronous circuits using an early data validity protocol. Conventional asynchronous tools synthesize circuits using a broad data validity protocol, which leads to simple circuits, but non-overlapped sequencing of consecutive operations. The early protocol requires data to be valid for a shorter period, allowing consecutive operations to overlap phases. The resulting circuits have a potential increase in performance by allowing greater concurrency and earlier execution of events.
Better Expanders and Superconcentrators by Kolmogorov Complexity

We show the existence of various versions of expander graphs using Kolmogorov complexity. This method seems superior to the usual “probabilistic construction”. Also, the best known bounds on the size of expanders and superconcentrators can be obtained this way. In the case of (acyclic) superconcentrators we obtain the density 34. Also, we review related graph properties, like magnification, edge-magnification, isolation, and develop bounds based on the Kolmogorov approach.
Smart phone localization method using dual-carrier acoustic waves

We describe an indoor localization technique for smart phones. Our new method, called the Frequency Division Multiplexing Phase Accordance Method (FDM-PAM), uses a beat called a sync pattern composed of a pair of sinusoidal waves with slightly different frequencies, which is similar to our original ultrasound ranging technique called the Phase Accordance Method (PAM). By generating multiple sync patterns with different central frequencies and transmitting them from different speakers, FDM-PAM conducts time-difference-of-arrival (TDOA) multilateration for localizing smart phones. In the current implementation of FDM-PAM, the 2D indoor position of a smart phone can be estimated. Three sync patterns are generated by using two out of six sinusoidal waves with frequencies ranging from 14.75 kHz to 17.25 kHz. The transmission of the sync pattern from the speakers lasts 4 ms. Through experiments, we have confirmed that FDM-PAM achieves accuracy of around 10 cm using only a short burst transmission, which indicates that the localization technique is sufficiently rapid and accurate.
Effects of preload alterations on peak early diastolic mitral annulus velocities evaluated by tissue Doppler echocardiography

Background and objective: Tissue Doppler echocardiography is proposed to be a relatively preload independent tool for assessment of diastolic function. No data exist on anaesthetized patients in whom myocardial contractility, vascular tone and baroreceptor reflexes are depressed. The aim of this study was to evaluate the effects of preload alterations on tissue velocities in patients during general anaesthesia for coronary arterial bypass surgery. Methods: Fifteen patients referred for elective aorto‐coronary bypass surgery were examined by tissue Doppler echocardiography. Early diastolic velocities in the septal and lateral portion of the mitral annulus were measured during preload interventions induced by tilting of the operating table in patients during general anaesthesia both before surgery and after chest closure. To verify changes in preload we used right atrial pressure and pulmonary artery occlusion pressure. Results: Tissue velocities in both the septal and lateral portion of the mitral annulus were significantly higher when preload was increased, compared to when it was decreased. Alterations in diastolic velocities in the septal portion of the mitral annulus prior to surgery: 0.8 ± 0.2 cm s−1, P < 0.001, after surgery: 1.1 ± 0.2 cm s−1, P < 0.001. Alterations in diastolic velocities in the lateral portion of the mitral annulus prior to surgery: 1.4 ± 0.2 cm s−1, P < 0.001, after surgery: 1.1 ± 0.3 cm s−1, P < 0.01. Concomitant changes in right atrial pressure and pulmonary artery occlusion pressure were 11 ± 1 and 12 ± 1 mmHg before surgery and 13 ± 1 and 12 ± 1 mmHg after surgery (P < 0.001 for all), respectively. Conclusion: These results show that tissue velocities of the mitral annulus are preload dependent in patients during general anaesthesia both before and after coronary surgery.
¿Democracia 2.0? Un análisis del potencial deliberativo de la blogosfera política

La democracia deliberativa y las tecnologias de la informacion y la comunicacion han asumido un papel central en el debate sobre la profundizacion de nuestras practicas democraticas en las sociedades contemporaneas. Por un lado, la propuesta de Jurgen Habermas y de quienes comparten sus perspectivas apuestan por una revitalizacion del espacio publico y hacen de este ultimo el centro del modelo politico. Por otro lado, la irrupcion de Internet y, en particular, de la Web 2.0 ha impuesto un cambio estructural de este espacio publico dominado por los medios de comunicacion tradicionales. Sin embargo, ? supone este cambio estructural del espacio publico una ventana de oportunidad para la implementacion del modelo deliberativo de Habermas? El proposito de este articulo es mostrar hasta que punto la comunicacion digital articulada en torno al uso de instrumentos interactivos de comunicacion y, en particular, de los blogs se parecen al patron impuesto por la teoria del discurso.
Top-Level Ontology of Knowledge Sharing Criteria

This article presents a generic model and a top-level ontology to represent, organize and combine knowledge from various sources and, in particular, best practices and quality criteria or measures for knowledge sharing. These elements may then also be used by people to compare tools, techniques and knowledge providers. One top-level distinction permitting to organize this ontology is the one between content, medium and containers of descriptions. Various structural, ontological, syntactical and lexical distinctions are then used.