Miracle-dz/UniFAR-FTUs huggingface dataset:
Plasma nitrite rather than nitrate reflects regional endothelial nitric oxide synthase activity but lacks intrinsic vasodilator action

The plasma level of NOx, i.e., the sum of NO2− and NO3−, is frequently used to assess NO bioavailability in vivo. However, little is known about the kinetics of NO conversion to these metabolites under physiological conditions. Moreover, plasma nitrite recently has been proposed to represent a delivery source for intravascular NO. We therefore sought to investigate in humans whether changes in NOx concentration are a reliable marker for endothelial NO production and whether physiological concentrations of nitrite are vasoactive. NO2− and NO3− concentrations were measured in blood sampled from the antecubital vein and brachial artery of 24 healthy volunteers. No significant arterial-venous gradient was observed for either NO2− or NO3−. Endothelial NO synthase (eNOS) stimulation with acetylcholine (1–10 μg/min) dose-dependently augmented venous NO2− levels by maximally 71%. This effect was paralleled by an almost 4-fold increase in forearm blood flow (FBF), whereas an equieffective dose of papaverine produced no change in venous NO2−. Intraarterial infusion of NO2− had no effect on FBF. NOS inhibition (NG-monomethyl-l-arginine; 4–12 μmol/min) dose-dependently reduced basal NO2− and FBF and blunted acetylcholine-induced vasodilation and NO release by more than 80% and 90%, respectively. In contrast, venous NO3− and total NOx remained unchanged as did systemic arterial NO2− and NO3− levels during all these interventions. FBF and NO release showed a positive association (r = 0.85; P < 0.001). These results contradict the current paradigm that plasma NO3− and/or total NOx are generally useful markers of endogenous NO production and demonstrate that only NO2− reflects acute changes in regional eNOS activity. Our results further demonstrate that physiological levels of nitrite are vasodilator-inactive.
Intelligence and specific cognitive functions in intellectual disability: implications for assessment and classification

Purpose of review Current diagnostic criteria for intellectual disability categorize ability as measured by IQ tests. However, this does not suit the new conceptualization of intellectual disability, which refers to a range of neuropsychiatric syndromes that have in common early onset, cognitive impairments, and consequent deficits in learning and adaptive functioning. A literature review was undertaken on the concept of intelligence and whether it encompasses a range of specific cognitive functions to solve problems, which might be better reported as a profile, instead of an IQ, with implications for diagnosis and classification of intellectual disability. Recent findings Data support a model of intelligence consisting of distinct but related processes. Persons with intellectual disability with the same IQ level have different cognitive profiles, based on varying factors involved in aetiopathogenesis. Limitations of functioning and many biopsychological factors associated with intellectual disability are more highly correlated with impairments of specific cognitive functions than with overall IQ. Summary The current model of intelligence, based on IQ, is of limited utility for intellectual disability, given the wide range and variability of cognitive functions and adaptive capacities. Assessing level of individual impairment in executive and specific cognitive functions may be a more useful alternative. This has considerable implications for the revision of the International Classification of Diseases and for the cultural attitude towards intellectual disability in general.
Stochastic Methods in Asset Pricing

This book presents a self-contained, comprehensive, and yet concise and condensed overview of the theory and methods of probability, integration, stochastic processes, optimal control, and their connections to the principles of asset pricing. The book is broader in scope than other introductory-level graduate texts on the subject, requires fewer prerequisites, and covers the relevant material at greater depth, mainly without rigorous technical proofs. The book brings to an introductory level certain concepts and topics that are usually found in advanced research monographs on stochastic processes and asset pricing, and it attempts to establish greater clarity on the connections between these two fields. The book begins with measure-theoretic probability and integration, and then develops the classical tools of stochastic calculus, including stochastic calculus with jumps and Levy processes. For asset pricing, the book begins with a brief overview of risk preferences and general equilibrium in incomplete finite endowment economies, followed by the classical asset pricing setup in continuous time. The goal is to present a coherent single overview. For example, the text introduces discrete-time martingales as a consequence of market equilibrium considerations and connects them to the stochastic discount factors before offering a general definition. It covers concrete option pricing models (including stochastic volatility, exchange options, and the exercise of American options), Merton’s investment–consumption problem, and several other applications. The book includes more than 450 exercises (with detailed hints). Appendixes cover analysis and topology and computer code related to the practical applications discussed in the text.
Tree imbalance causes a bias in phylogenetic estimation of evolutionary timescales using heterochronous sequences

Phylogenetic estimation of evolutionary timescales has become routine in biology, forming the basis of a wide range of evolutionary and ecological studies. However, there are various sources of bias that can affect these estimates. We investigated whether tree imbalance, a property that is commonly observed in phylogenetic trees, can lead to reduced accuracy or precision of phylogenetic timescale estimates. We analysed simulated data sets with calibrations at internal nodes and at the tips, taking into consideration different calibration schemes and levels of tree imbalance. We also investigated the effect of tree imbalance on two empirical data sets: mitogenomes from primates and serial samples of the African swine fever virus. In analyses calibrated using dated, heterochronous tips, we found that tree imbalance had a detrimental impact on precision and produced a bias in which the overall timescale was underestimated. A pronounced effect was observed in analyses with shallow calibrations. The greatest decreases in accuracy usually occurred in the age estimates for medium and deep nodes of the tree. In contrast, analyses calibrated at internal nodes did not display a reduction in estimation accuracy or precision due to tree imbalance. Our results suggest that molecular‐clock analyses can be improved by increasing taxon sampling, with the specific aims of including deeper calibrations, breaking up long branches and reducing tree imbalance.
Intelligent Connection Agent for Three-Phase Grid-Connected Microgrids

The high penetration of distributed generation power plants, based on renewable energy sources (RESs), is boosting the connection of power converters to the electrical network. This generation concept would permit to form local networks, microgrids, when the main grid falls due to any kind of contingency in the network. However, the connection and disconnection of these local networks may give rise to undesired transient overcurrents that should be avoided. In order to solve this drawback, this paper presents a method oriented to carry out a stable intentional disconnection/reconnection of local grids from the main electrical network under grid-fault conditions. This control method has been implemented in a grid-connected power converter that acts as an intelligent connection agent (ICA) and adapts its operation mode according to its connection state. The proposed control also manages the operation of a controlled switch, which is responsible of disconnecting/reconnecting the microgrid from the mains. In this paper, the behavior of the ICA under transient conditions will be discussed, and finally, its simulated and experimental performance will be shown.
Timing optimization for multisource nets: characterization andoptimal repeater insertion

This paper presents new results in the area of timing optimization for multisource nets. The augmented RC-diameter (ARD) is suggested as a natural and practical performance measure and a linear time algorithm for computing the ARD of a multisource net is presented. Building on the ARD measure, we characterize the multisource optimization problem in terms of operations on piece-wise linear functions. This characterization is then used to develop an algorithm for optimal repeater insertion: for a given multisource topology the algorithm efficiently identifies an optimal assignment of repeaters to prescribed insertion points under the "min cost timing feasible" problem formulation. The algorithm has been implemented and computational results demonstrate the viability of the approach.
Grid Study on the Basis of Reciprocal Power Losses Calculation

It was found that the losses of some supplierconsumer pairs in a grid (reciprocal losses) can be negative. Upon exploring this issue, it turned out that this phenomenon is not rare and is a result of a certain distribution of the power of electricity suppliers between consumers. Negative reciprocal losses indicate that the overall grid losses are increased. They can be eliminated by redistributing the suppliers’ power. Computing the reciprocal losses, additional properties of a power system can be defined, which facilitates the determination of its more economical operation mode.
National surveillance of occupational fatalities in agriculture.

Agriculture is one of the most hazardous industries in the United States. Although estimates vary, all reporting agencies show agriculture having an occupational fatality rate three to five times higher than that of the general private sector. The National Institute for Occupational Safety and Health (NIOSH), Division of Safety Research's National Traumatic Occupational Fatalities (NTOF) data base monitors occupational fatal injuries in all industries in the United States through death certificates. Uniform case-selection criteria are applied nationwide. NTOF shows that for the years 1980 through 1985, agriculture had a work-related fatality rate of 20.7 deaths per 100,000 workers compared with 7.9 deaths per 100,000 workers for the private sector U.S. work force. Age-specific rates indicate that the risk of fatal occupational injury increases with age for agricultural workers. Workers over 64 years old have an average annual rate of 55.7 deaths per 100,000 workers. Other uses of the surveillance system, as well as its limitations, are discussed.
tRNA-dependent Aminoacyl-adenylate Hydrolysis by a Nonediting Class I Aminoacyl-tRNA Synthetase*

Glutaminyl-tRNA synthetase generates Gln-tRNAGln 107-fold more efficiently than Glu-tRNAGln and requires tRNA to synthesize the activated aminoacyl adenylate in the first step of the reaction. To examine the role of tRNA in amino acid activation more closely, several assays employing a tRNA analog in which the 2′-OH group at the 3′-terminal A76 nucleotide is replaced with hydrogen (\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{tRN}\mathrm{A}_{2^{{^\prime}}\mathrm{H}}^{\mathrm{Gln}}\) \end{document}) were developed. These experiments revealed a 104-fold reduction in kcat/Km in the presence of the analog, suggesting a direct catalytic role for tRNA in the activation reaction. The catalytic importance of the A76 2′-OH group in aminoacylation mirrors a similar role for this moiety that has recently been demonstrated during peptidyl transfer on the ribosome. Unexpectedly, tracking of Gln-AMP formation utilizing an α-32P-labeled ATP substrate in the presence of \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{tRN}\mathrm{A}_{2^{{^\prime}}\mathrm{H}}^{\mathrm{Gln}}\) \end{document} showed that AMP accumulates 5-fold more rapidly than Gln-AMP. A cold-trapping experiment revealed that the nonenzymatic rate of Gln-AMP hydrolysis is too slow to account for the rapid AMP formation; hence, the hydrolysis of Gln-AMP to form glutamine and AMP must be directly catalyzed by the \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{GlnRS}{\cdot}\mathrm{tRN}\mathrm{A}_{2^{{^\prime}}\mathrm{H}}^{\mathrm{Gln}}\) \end{document} complex. This hydrolysis of glutaminyl adenylate represents a novel reaction that is directly analogous to the pre-transfer editing hydrolysis of noncognate aminoacyl adenylates by editing synthetases such as isoleucyl-tRNA synthetase. Because glutaminyl-tRNA synthetase does not possess a spatially separate editing domain, these data demonstrate that a pre-transfer editing-like reaction can occur within the synthetic site of a class I tRNA synthetase.
Tunable control of antibody immobilization using electric field

Significance We introduce a novel method for controlling orientation of proteins during immobilization on solid-state surfaces using electric fields. Atomic force microscopy measurements and fluorescence-based readout are used to confirm this phenomenon. This method of immobilization has broad implications for improvement in performance of both affinity-based protein assays and probe-free detection assays. The controlled immobilization of proteins on solid-state surfaces can play an important role in enhancing the sensitivity of both affinity-based biosensors and probe-free sensing platforms. Typical methods of controlling the orientation of probe proteins on a sensor surface involve surface chemistry-based techniques. Here, we present a method of tunably controlling the immobilization of proteins on a solid-state surface using electric field. We study the ability to orient molecules by immobilizing IgG molecules in microchannels while applying lateral fields. We use atomic force microscopy to both qualitatively and quantitatively study the orientation of antibodies on glass surfaces. We apply this ability for controlled orientation to enhance the performance of affinity-based assays. As a proof of concept, we use fluorescence detection to indirectly verify the modulation of the orientation of proteins bound to the surface. We studied the interaction of fluorescently tagged anti-IgG with surface immobilized IgG controlled by electric field. Our study demonstrates that the use of electric field can result in more than 100% enhancement in signal-to-noise ratio compared with normal physical adsorption.
Biodiversity Conservation and the Eradication of Poverty

It is widely accepted that biodiversity loss and poverty are linked problems and that conservation and poverty reduction should be tackled together. However, success with integrated strategies is elusive. There is sharp debate about the social impacts of conservation programs and the success of community-based approaches to conservation. Clear conceptual frameworks are needed if policies in these two areas are to be combined. We review the links between poverty alleviation and biodiversity conservation and present a conceptual typology of these relationships.
Greenwash and green purchase behaviour: the mediation of green brand image and green brand loyalty

This paper discusses the influence of firms’ greenwash on their consumers’ green purchase behaviour and explores the mediation roles of their green brand image and their consumers’ green brand loyalty. This study focuses on Taiwanese consumers who have purchase experience of green products. This study uses structural equation modelling (SEM) to obtain empirical results. The results demonstrate that firms’ greenwash negatively influences their consumers’ green purchase behaviour. Besides, this research proves that firms’ greenwash is negatively related to both their green brand image and their consumers’ green brand loyalty that would positively affect their consumers’ green purchase behaviour. This paper also verifies that firms’ green brand image and their consumers’ green brand loyalty partially mediate the negative relationship between their greenwash and their consumers’ green purchase behaviour. It means that firms’ greenwash does not only have a direct negative effect on their consumers’ green purchase behaviour, but also has an indirect negative effect on it via their green brand image and their consumers’ green brand loyalty. Thus, this research suggests that firms should decrease their greenwash behaviours and increase their green brand image and their consumers’ green brand loyalty to enhance their consumers’ green purchase behaviour.
Fortress Europe Breached: Political And Economic Impact Of The Recent Refugee Crisis On European States

The onset of the Syrian civil war, the expansion of the military influence of the Islamic State in the Middle and Near East and the ongoing conflicts in Africa has caused a significant number of refugees from the affected areas to flee towards Europe, generating a migrant crisis that has proven itself a contentious issue among European states as they struggle to find a solution to house the refugees and integrate them within the different host societies while also managing internal political debates and pacifying internal reluctance regarding the immigrants. The recent terrorist attacks in Brussels as well as various incidents associated with areas where refugees are concentrated have worsened the problem as European states fear security issues associated with the mostly Muslim population that seeks asylum within their borders. Beyond humanitarian, political and security concerns, the economic impact of the crisis upon European states has been varied. The immigrants have been seen both as blessings in disguise for the aging workforce of some European states and a potential financial burden on the economies of others in terms of social welfare costs and risks of increasing the local unemployment rates. Not only that, but the refugee problem has given way to a clash between two opposing viewpoints within the European Community: on the one hand, states who have sought to facilitate the accommodation of asylum-seekers on their territories, and on the other, states who have taken a tough approach to stem the flow of refugees within their borders and have rebuked the solutions thus far proposed by the EU. The present paper seeks to investigate the political and economic effects of refugees on host countries in Europe with a focus on the perceived division between countries that have welcomed immigrants versus those who have sought to restrict the number of refugees entering their countries.
Valuing Convertible Bonds: A New Approach

A recent paper by Finnerty expresses the value of a convertible bond as the value of the straight bond component plus the value of the option to exchange the bond component for a specified number of conversion shares and develops a closed-form convertible bond valuation model. This article illustrates how to apply the model to value nonredeemable convertible bonds and callable convertible bonds. The article also compares model and market prices for a sample of 148 corporate convertible bonds issued between 2006 and 2010. The average median and mean pricing errors are −0.18% and 0.21%, respectively, which are within the average bid-ask spread for convertible bonds during the postcrisis sample period.
Optimal Spectrum Sensing Interval in Energy-Harvesting Cognitive Radio Networks

Spectrum efficiency (SE) and energy efficiency (EE) are two key design objectives in future wireless communication networks. In traditional cognitive radio (CR) network, a secondary user (SU) performs spectrum sensing at the start of each time slot, which may waste energy and the transmission opportunities for the SU. In order to improve the SE and EE, a CR network using energy harvesting techniques is considered. A partially observable Markov decision process (MDP) framework and an MDP framework are used to determine the optimal spectrum sensing energy, the transmit energy and spectrum sensing interval to maximize the long-term average weighed sum of the throughput of the SU and the interference caused to the PU. Simulation results show that the proposed algorithm can significantly increase the average throughput of the SU and EE compared with the traditional spectrum scheme, at the cost of the small but tolerable interference caused to the PU.
Two atomic constraints unambiguously position the S4 segment relative to S1 and S2 segments in the closed state of Shaker K channel

It is now well established that the voltage-sensing S4 segment in voltage-dependent ion channels undergoes a conformational change in response to varying membrane potential. However, the magnitude of the movement of S4 relative to the membrane and the rest of the protein remains controversial. Here, by using histidine scanning mutagenesis in the Shaker K channel, we identified mutants I241H (S1 segment) and I287H (S2 segment) that generate inward currents at hyperpolarized potentials, suggesting that these residues are part of a hydrophobic plug that separates the water-accessible crevices. Additional experiments with substituted cysteine residues showed that, at hyperpolarized potentials, both I241C and I287C can spontaneously form disulphide and metal bridges with R362C, the position of the first charge-carrying residue in S4. These results constrain unambiguously the closed-state positions of the S4 segment with respect to the S1 and S2 segments, which are known to undergo little or no movement during gating. To satisfy these constraints, the S4 segment must undergo an axial rotation of ≈180° and a transmembrane (vertical) movement of ≈6.5 Å at the level of R362 in going from the open to the closed state of the channel, moving the gating charge across a focused electric field.
Ki-67 predicts outcome in advanced-stage mantle cell lymphoma patients treated with anti-CD20 immunochemotherapy: results from randomized trials of the European MCL Network and the German Low Grade Lymphoma Study Group.

Clinical outcome of mantle cell lymphoma (MCL) is highly heterogeneous. Tumor cell proliferation as assessed by the Ki-67 index has been shown to yield prognostic information on MCL in many studies using heterogeneously treated patient cohorts. The prognostic value of the Ki-67 index in patients treated with anti-CD20 therapy has not been studied so far. We analyzed the Ki-67 index at primary diagnosis in 249 advanced-stage MCL patients treated within randomized trials. Ki-67 showed high prognostic relevance for overall survival (relative risk 1.27 for 10% higher Ki-67, P < .001), also independently from clinical prognostic factors. The 3 groups with different Ki-67 index of less than 10%, 10% to less than 30%, and 30% or more showed significantly different overall survival in patients treated with CHOP (P = .001) as well as in patients treated with CHOP in combination with anti-CD20 therapy (R-CHOP, P = .013). Thus, the Ki-67 index remains an important prognostic marker in the era of anti-CD20 therapy. The Euro-pean MCL study is registered at www.ClinicalTrials. gov as #NCT00016887.