pinecone/core-2020-05-10-deduplication huggingface dataset:
ORAI1 Ca2+ Channels Control Endothelin-1-Induced Mitogenesis and Melanogenesis in Primary Human Melanocytes

UV radiation of the skin triggers keratinocytes to secrete endothelin-1 (ET-1) that binds to endothelin receptors on neighboring melanocytes. Melanocytes respond with a prolonged increase in intracellular Ca2+ concentration ([Ca2+]i), which is necessary for proliferation and melanogenesis. A major fraction of the Ca2+ signal is caused by entry through Ca2+-permeable channels of unknown identity in the plasma membrane. ORAI Ca2+ channels are molecular determinants of Ca2+ release-activated Ca2+ (CRAC) channels and are expressed in many tissues. Here, we show that ORAI1–3 and their activating partners stromal interaction molecules 1 and 2 (STIM1 and STIM2) are expressed in human melanocytes. Although ORAI1 is the predominant ORAI isoform, STIM2 mRNA expression exceeds STIM1. Inhibition of ORAI1 by 2-aminoethoxydiphenyl borate (2-APB) or downregulation of ORAI1 by small interfering RNA (siRNA) reduced Ca2+ entry and CRAC current amplitudes in activated melanocytes. In addition, suppression of ORAI1 caused reduction in the ET-1-induced cellular viability, melanin synthesis, and tyrosinase activity. Our results imply a role for ORAI1 channels in skin pigmentation and their potential involvement in UV-induced stress responses of the human skin
Vascular E-Selectin Expression Correlates with CD8 Lymphocyte Infiltration and Improved Outcome in Merkel Cell Carcinoma

Merkel cell carcinoma (MCC) is an aggressive, polyomavirus-linked skin cancer. Although CD8 lymphocyte infiltration into the tumor is strongly correlated with improved survival, these cells are absent or sparse in most MCCs. We investigated whether specific mechanisms of T-cell migration may be commonly disrupted in MCC tumors with poor CD8 lymphocyte infiltration. Intratumoral vascular E-selectin, critical for T-cell entry into skin, was downregulated in the majority (52%) of MCCs (n=56), and its loss was associated with poor intratumoral CD8 lymphocyte infiltration (P<0.05; n=45). Importantly, survival was improved in MCC patients whose tumors had higher vascular E-selectin expression (P<0.05). Local nitric oxide (NO) production is one mechanism of E-selectin downregulation and it can be tracked by quantifying nitrotyrosine, a stable biomarker of NO-induced reactive nitrogen species (RNS). Indeed, increasing levels of nitrotyrosine within MCC tumors were associated with low E-selectin expression (P<0.05; n=45) and decreased CD8 lymphocyte infiltration (P<0.05, n=45). These data suggest that one mechanism of immune evasion in MCC may be restriction of T-cell entry into the tumor. Existing therapeutic agents that modulate E-selectin expression and/or RNS generation may restore T-cell entry and could potentially synergize with other immune-stimulating therapies
Consensus mutagenesis reveals that non-helical regions influence thermal stability of horseradish peroxidase

The enzyme horseradish peroxidase has many uses in biotechnology but a stabilized derivative would have even wider applicability. To enhance thermal stability, we applied consensus mutagenesis (used successfully with other proteins) to recombinant horseradish peroxidase and generated five single-site mutants. Unexpectedly, these mutations had greater effects on steady-state kinetics than on thermal stability. Only two mutants (T102A, T110V) marginally exceeded the wild type's thermal stability (4% and 10% gain in half-life at 50 °C respectively); the others (Q106R, Q107D, I180F) were less stable than wild type. Stability of a five-fold combination mutant matched that of Q106R, the least-stable single mutant. These results were perplexing: the Class III plant peroxidases display wide differences in thermal stability, yet the consensus mutations failed to reflect these natural variations. We examined the sequence content of Class III peroxidases to determine if there are identifiable molecular reasons for the stability differences observed. Bioinformatic analysis validated our choice of sites and mutations and generated an archetypal peroxidase sequence for comparison with extant sequences. It seems that both genetic variation and differences in protein stability are confined to non-helical regions due to the presence of a highly conserved alpha-helical structural scaffold in these enzymes
Phloem sap intricacy and interplay with aphid feeding

Aphididae feed upon the plant sieve elements (SE), where they ingest sugars, nitrogen compounds and other nutrients. For ingestion, aphid stylets penetrate SE, and because of the high hydrostatic pressure in SE, phloem sap exudes out into the stylets. Severing stylets to sample phloem exudates (i.e. stylectomy) has been used extensively for the study of phloem contents. Alternative sampling techniques are spontaneous exudation upon wounding that only works in a few plant species, and the popular EDTA-facilitated exudation technique. These approaches have allowed fundamental advances on the understanding of phloem sap composition and sieve tube physiology, which are surveyed in this review. A more complete picture of metabolites, ions, proteins and RNAs present in phloem sap is now available, which has provided large evidence for the phloem role as a signalling network in addition to its primary role in partitioning of photo-assimilates. Thus, phloem sap sampling methods can have remarkable applications to analyse plant nutrition, physiology and defence responses. Since aphid behaviour is suspected to be affected by phloem sap quality, attempts to manipulate phloem sap content were recently undertaken based on deregulation in mutant plants of genes controlling amino acid or sugar content of phloem sap. This opens up new strategies to control aphid settlement on a plant host
Stability Analysis in Spanwise-Periodic Double-Sided Lid-Driven Cavity Flows With Complex Cross-Sectional Profiles

Three-dimensional linear instability analyses are presented of steady two-dimensional laminar flows in the lid-driven cavity defined by [15] and further analyzed in the present volume [1], as well as in a derivative of the same geometry. It is shown that in both of the geometries considered three-dimensional BiGlobal instability leads to deviation of the flow from the two-dimensional solution; the analysis results are used to define low- and high-Reynolds number solutions by reference to the flow physics. Critical conditions for linear global instability and neutral loops are presented in both geometries
Comparison of natural and forced amplification regimes in plasma-based soft-x-ray lasers seeded by high-order harmonic

The amplification of high-order harmonics (HOH) in a plasma-based amplifier is a multiscale, temporal phenomenon that couples plasma hydrodynamics, atomic processes, and HOH electromagnetic fields. We use a one-dimensional, time-dependent Maxwell-Bloch code to compare the natural amplification regime and another regime where plasma polarization is constantly forced by the HOH. In this regime, a 10-MW (i.e., 100 times higher than current seeded soft x-ray laser power), 1.5-μJ, 140-fs pulse free from the parasitic temporal structures appearing on the natural amplification regime can be obtained
Two Novel Methods For The Determination Of The Number Of Components In Independent Components Analysis Models

Independent Components Analysis is a Blind Source Separation method that aims to find the pure source signals mixed together in unknown proportions in the observed signals under study. It does this by searching for factors which are mutually statistically independent. It can thus be classified among the latent-variable based methods. Like other methods based on latent variables, a careful investigation has to be carried out to find out which factors are significant and which are not. Therefore, it is important to dispose of a validation procedure to decide on the optimal number of independent components to include in the final model. This can be made complicated by the fact that two consecutive models may differ in the order and signs of similarly-indexed ICs. As well, the structure of the extracted sources can change as a function of the number of factors calculated. Two methods for determining the optimal number of ICs are proposed in this article and applied to simulated and real datasets to demonstrate their performance
Automatic lateral control for unmanned vehicles via genetic algorithms

It is known that the techniques under the topic of Soft Computing have a strong capability of learning and cognition, as well as a good tolerance to uncertainty and imprecision. Due to these properties they can be applied successfully to Intelligent Vehicle Systems; ITS is a broad range of technologies and techniques that hold answers to many transportation problems. The unmannedcontrol of the steering wheel of a vehicle is one of the most important challenges facing researchers in this area. This paper presents a method to adjust automatically a fuzzy controller to manage the steering wheel of a mass-produced vehicle; to reach it, information about the car state while a human driver is handling the car is taken and used to adjust, via iterative geneticalgorithms an appropriated fuzzy controller. To evaluate the obtained controllers, it will be considered the performance obtained in the track following task, as well as the smoothness of the driving carried out
The paradox of Happiness: towards an alternative explanation

ABSTRACT
There is a common empirical finding in many countries that  substantial increases in real per capita income do not correspond to equivalent increases of individual happiness. These findings have puzzled many economists that some have called the “paradox of happiness”. There have been a number of explanations regarding this paradox. This paper attempts to tackle the paradox of happiness by employing the idea of hierarchical choice. The hierarchical approach  implies that there are some basic human needs which must be satisfied before non-basic needs come into the picture. The paper argues that the hierarchical structure of needs implies that the satisfaction of basic needs provides substantial increases to individual happiness compared to the subsequent satisfaction of  secondary needs. This might also be an alternative explanation of  empirical findings showing a positive relationship between income and happiness up to certain level of income.
The Forward Premium Puzzle And The Euro

This paper evaluates the forward premium puzzle using the Euro exchange rate. Unlike previous studies, our analysis utilizes time-varying parameter methods and is based on two approaches for evaluation of the puzzle; the traditional approach analyzing the sensitivity of interest rate differentials to the forward premium, and the other looking into deviations from the covered interest rate parity (CIRP) condition. Then we provide evidence that the forward premium puzzle indeed became more prominent around the time of the recent crisis periods such as the Lehman Shock and the Euro crisis. This is also shown to be consistent with a deterioration in the CIRP.
Voltammetric Behavior of Antileukemia Drug Glivec. Part II - Redox Processes of Glivec Electrochemical Metabolite

Glivec is a newly developed drug that belongs to the class of 2-phenylaminopyrimidine. It is a potent inhibitor of ABL-kinase, the main clinical manifestation of chronic myelogenous leukemia (CML). Based on its activity on CML, glivec is undergoing extensive evaluation for its activity against other tumor types. Detection and quantitation of glivec in biological fluids or cells is thus very important. The antileukemia drug glivec undergoes oxidation at glassy carbon electrodes and involves the formation of an oxidation product, Pglivec. The adsorption of Pglivec at the GCE surface yields a compact monolayer allowing an electrochemical study of this compound adsorbed at the GCE surface. The reversible redox reaction of the adsorbed Pglivec is pH dependent and occurs with the transfer of 2 electrons and 2 protons. The surface standard potential and the rate constant of the heterogeneous electrochemical reaction were calculated using cyclic voltammetry to be Eθ=+180 mV and k=15.5 s-1, respectively. The total surface concentration of adsorbed Pglivec is 2.5×10-12 mol cm-2. The analytical determination of glivec was carried out by differential pulse voltammetric measurement of the anodic peak current corresponding to either the oxidation peak of glivec or the oxidation peak of Pglivec adsorbed on the GCE surface. The limits of detection of glivec and adsorbed Pglivec based on three times the noise level are 3.3×10-8 M and 2.9×10-10 M, respectively.http://dx.doi.org/10.1002/elan.20060359
Existence of strictly diabatic basis sets for the two-state problem

Some new properties of the nonadiabatic coupling elements are derived, in particular the orthogonality and gauge invariance of their longitudinal and transverse components. A method for constructing a strictly diabatic basis set that makes both the transverse and longitudinal components of the nonadiabatic coupling elements of the two-state problem vanish identically and is based on introducing overlap between the electronic states in the vicinity of the crossing seam is proposed. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2002http://dx.doi.org/10.1002/qua.1029
Optimal Space-time Coverage and Exploration Costs in Groundwater Monitoring Networks

A method to determine the optimal subset of stations from a reference level groundwater monitoring network is proposed. The method considers the redundancy of data from historical time series, the times associated with the total distance required to run through the entire monitoring network, and the sum of the times for each monitoring station. The method was applied to a hypothetical case-study consisting of a monitoring network with 32 stations. Cost-benefit analysis was performed to determine the number of stations to include in the new design versus loss of information. This optimisation problem was solved with simulated annealing. Results showed that the relative reduction in exploration costs more than compensates for the relative loss in data representativeness.http://dx.doi.org/10.1023/B:EMAS.0000016795.91968.1
Local Convergence of a Primal-Dual Method for Degenerate Nonlinear Programming

In recent work, the local convergence behavior of path-following interior-point methods and sequential quadratic programming methods for nonlinear programming has been investigated for the case in which the assumption of linear independence of the active constraint gradients at the solution is replaced by the weaker Mangasarian–Fromovitz constraint qualification. In this paper, we describe a stabilization of the primal-dual interior-point approach that ensures rapid local convergence under these conditions without enforcing the usual centrality condition associated with path-following methods. The stabilization takes the form of perturbations to the coefficient matrix in the step equations that vanish as the iterates converge to the solution.http://dx.doi.org/10.1023/A:101979850285
Optimal embeddings and compact embeddings of Bessel-potential-type spaces

First, we establish necessary and sufficient conditions for embeddings of Bessel potential spaces H^ σ X(R^n) with order of smoothness less than one, modelled upon rearrangement invariant Banach function spaces X(R^n), into generalized Hölder spaces. To this end, we derive a sharp estimate of modulus of smoothness of the convolution of a function f in X(R^n) with the Bessel potential kernel gσ  , 0 < s < 1. Such an estimate states that if gσ belongs to the associate space of X, then   ω(f* gσ,t) precsim \int\limits_0^{t^n}s^{\frac{\σ}{n}-1}f^*(s)\,ds \quad {\rm for\,all} \quad t\in(0,1) \quad {\rm and\,every}\quad f in X(R^n). Second, we characterize compact subsets of generalized Hölder spaces and then we derive necessary and sufficient conditions for compact embeddings of Bessel potential spaces Hσ X(R^n) into generalized Hölder spaces. We apply our results to the case when X(R^n) is the Lorentz–Karamata space {L_{p,q;b}(R^n)}. In particular, we are able to characterize optimal embeddings of Bessel potential spaces {H^{σ}L_{p,q;b}(R^n)} into generalized Hölder spaces and also compact embeddings of spaces in question. Applications cover both superlimiting and limiting cases.http://dx.doi.org/10.1007/s00209-008-0395-
The Reproducing Kernel Structure Arising from a Combination of Continuous and Discrete Orthogonal Polynomials into Fourier Systems

Abstract  We study mapping properties of operators with kernels defined via a combination of continuous and discrete orthogonal polynomials, which provide an abstract formulation of quantum (q-) Fourier-type systems.We prove Ismail’s conjecture regarding the existence of a reproducing kernel structure behind these kernels, by establishing a link with Saitoh’s theory of linear transformations in Hilbert space. The results are illustrated with Fourier kernels with ultraspherical, their continuous q-extensions and generalizations. As a byproduct of this approach, a new class of sampling theorems is obtained, as well as Neumann-type expansions in Bessel and q-Bessel functions.http://dx.doi.org/10.1007/s00365-006-0657-
Orientation fluctuation-induced spinodal decomposition in polymer–liquid-crystal mixtures

We study the early stages of spinodal decomposition (SD) in polymer–liquid-crystal mixtures by solving linearized time-dependent Landau-Ginzburg equations for concentration (conserved order parameter) and orientation (nonconserved order parameter). The theory takes into account a cross term between concentration and orientation gradients, which becomes an important factor for phase separation kinetics. We calculate structure factors for concentration and for orientation, depending on a quench temperature and concentration. We find a new SD process driven by instability of the orientational order parameter. In this case, the average domain size initially grows as a nontrivial and evolving power of time, which starts as t1/3 in our minimal model. The domain growth is advanced by the coupling between the two order parameters
A case analysis of a sustainable food supply chain distribution system – a multi-objective approach

Sustainable supply chain management is a topical area which is continuing to grow and evolve. Within supply chains, downstream distribution from producers to customers plays a significant role in the environmental performance of production supply chains. With consumer consciousness growing in the area of sustainable food supply, food distribution needs to embrace and adapt to improve its environmental performance, while still remaining economically competitive. With a particular focus on the dairy industry, a robust solution approach is presented for the design of a capacitated distribution network for a two-layer supply chain involved in the distribution of milk in Ireland. In particular the green multi-objective optimisation model minimises CO2 emissions from transportation and total costs in the distribution chain. \ud
These distribution channels are analysed to ensure the non-dominated solutions are distributed along the Pareto fronts. A multi-attribute decision-making approach, TOPSIS, has been used to rank the realistic feasible transportation routes resulting from the trade-offs between total costs and CO2 emissions. The refined realistic solution space allows the decision-makers to geographically locate the sustainable transportation routes. In addition to geographical mapping the decision maker is also presented with a number of alternative analysed scenarios which forcibly open closed distribution routes to build resiliency into the solution approach. In terms of model performance, three separate GA based optimisers have been evaluated and reported upon. In the case presented NSGA-II was found to outperform its counterparts of MOGA-II and HYBRID
Primary teachers’ experience of a physical education professional development programme

Professional development (PD) is essential for primary school teachers to meet the demands of the education system. Quality PD is aligned with classroom conditions, school contexts and teachers’ daily experiences. The purpose of the study was to explore primary teachers’ experiences of a 6-week physical education professional development programme (PE-PDP). A single school case study was employed (N =28 teachers, N =780 pupils) and all teachers and a sample of children participated in focus group interviews. Transcripts were categorised and themed using systematic content analysis. Results revealed that post the PE-PDP, teachers’ PE content knowledge had expanded and this encouraged them to use existing classroom paedagogical strategies in the PE context. This developed their confidence in teaching PE and a greater understanding of the PE curriculum and its purpose
Explanation for the dark I-V curve of III-V concentrator solar cells

The measurement of the dark I–V curve is one of the most straightforward methods for characterizing solar cells. Consequently, an accurate knowledge of its meaning is of high relevance for the comprehension and technological feedback of these devices. In this paper, an explanation of the dark I–V curve for concentrator III–V solar cells is presented using a 3D (three-dimensional) model in order to provide a proper data fit that provides meaningful physical parameters that are also compatible and coherent with a data fit from illumination curves. The influence on the dark I–V curve of the most significant series resistance components of concentrator solar cells is also analysed concluding that only the vertical component as well as the front contact-specific resistance can be assessable by means of this characterization method while both emitter and metal sheet resistances cannot be detected. For comparison purposes, the same experimental data have been fitted by means of a traditional two-diode model showing that, although an accurate dark I–V curve fitting can be achieved, the extracted parameters are unable to reproduce illumination data since lumped models assume the same ohmic losses distribution for both dark and illumination conditions
Performance of a direct steam generation solar thermal power plant for electricity production as a function of the solar multiple

This paper describes the influence of the solar multiple on the annual performance of parabolic trough solar thermal power plants with direct steam generation (DSG). The reference system selected is a 50 M We DSG power plant, with thermal storage and auxiliary natural gas-fired boiler. It is considered that both systems are necessary for an optimum coupling to the electricity grid. Although thermal storage is an opening issue for DSG technology, it gives an additional degree of freedom for plant performance optimization. Fossil hybridization is also a key element if a reliable electricity production must be guaranteed for a defined time span. Once the yearly parameters of the solar power plant are calculated, the economic analysis is performed, assessing the effect of the solar multiple in the levelized cost of electricity, as well as in the annual natural gas consumption
Evaluating Conformance to WCAG 2.0: Open Challenges

Web accessibility for people with disabilities is a highly visible area of work in the field of ICT accessibility, including many policy activities in several countries. The commonly accepted guidelines for web accessibility (WCAG 1.0) were published in 1999 and have been extensively used by designers, evaluators and legislators. A new version of these guidelines (WCAG 2.0) was published in 2008. In this paper we point out the main challenges that WCAG 2.0 raises for web accessibility evaluators: the concept of "accessibility supported technologies"; success criteria testability; technique and failure openness, and the aggregation of partial results. We conclude the paper with some recommendations for the future