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Showing papers by "University of Valencia published in 2006"


Journal ArticleDOI
TL;DR: In this article, the authors investigated the dimensionality of consumer value in a travel-related context (students' travel behavior), adopting Holbrook's typology, and combining it with negative inputs of value.

1,231 citations


Journal ArticleDOI
Jörg Kämper1, Regine Kahmann1, Michael Bölker2, Li-Jun Ma3, Thomas Brefort1, Barry J. Saville4, Barry J. Saville5, Flora Banuett6, James W. Kronstad7, Scott E. Gold8, Olaf Müller1, Michael H. Perlin9, Han A. B. Wösten10, Ronald P. de Vries10, Jose Ruiz-Herrera, Cristina G. Reynaga-Peña, Karen M. Snetselaar11, Michael P. McCann11, José Pérez-Martín12, Michael Feldbrügge1, Christoph W. Basse1, Gero Steinberg1, José I. Ibeas12, William K. Holloman13, Plinio Guzmán14, Mark L. Farman15, Jason E. Stajich16, Rafael Sentandreu17, Juan Manuel González-Prieto, John C. Kennell18, Lazaro Molina1, Jan Schirawski1, Artemio Mendoza-Mendoza1, Doris Greilinger1, Karin Münch1, Nicole Rössel1, Mario Scherer1, Miroslav Vranes1, Oliver Ladendorf1, Volker Vincon1, Uta Fuchs1, Björn Sandrock2, Shaowu Meng5, Eric C.H. Ho5, Matt J. Cahill5, Kylie J. Boyce7, Jana Klose7, Steven J. Klosterman8, Heine J. Deelstra10, Lucila Ortiz-Castellanos, Weixi Li15, Patricia Sánchez-Alonso14, Peter Schreier19, Isolde Häuser-Hahn19, Martin Vaupel19, Edda Koopmann19, Gabi Friedrich19, Hartmut Voss, Thomas Schlüter, Jonathan Margolis20, Darren Mark Platt20, Candace Swimmer20, Andreas Gnirke20, Feng Chen20, Valentina Vysotskaia20, Gertrud Mannhaupt1, Ulrich Güldener, Martin Münsterkötter, Dirk Haase, Matthias Oesterheld, Hans-Werner Mewes21, Evan Mauceli3, David DeCaprio3, Claire M. Wade3, Jonathan Butler3, Sarah Young3, David B. Jaffe3, Sarah E. Calvo3, Chad Nusbaum3, James E. Galagan3, Bruce W. Birren3 
02 Nov 2006-Nature
TL;DR: The discovery of the secreted protein gene clusters and the functional demonstration of their decisive role in the infection process illuminate previously unknown mechanisms of pathogenicity operating in biotrophic fungi.
Abstract: Ustilago maydis is a ubiquitous pathogen of maize and a well-established model organism for the study of plant-microbe interactions. This basidiomycete fungus does not use aggressive virulence strategies to kill its host. U. maydis belongs to the group of biotrophic parasites (the smuts) that depend on living tissue for proliferation and development. Here we report the genome sequence for a member of this economically important group of biotrophic fungi. The 20.5-million-base U. maydis genome assembly contains 6,902 predicted protein-encoding genes and lacks pathogenicity signatures found in the genomes of aggressive pathogenic fungi, for example a battery of cell-wall-degrading enzymes. However, we detected unexpected genomic features responsible for the pathogenicity of this organism. Specifically, we found 12 clusters of genes encoding small secreted proteins with unknown function. A significant fraction of these genes exists in small gene families. Expression analysis showed that most of the genes contained in these clusters are regulated together and induced in infected tissue. Deletion of individual clusters altered the virulence of U. maydis in five cases, ranging from a complete lack of symptoms to hypervirulence. Despite years of research into the mechanism of pathogenicity in U. maydis, no 'true' virulence factors had been previously identified. Thus, the discovery of the secreted protein gene clusters and the functional demonstration of their decisive role in the infection process illuminate previously unknown mechanisms of pathogenicity operating in biotrophic fungi. Genomic analysis is, similarly, likely to open up new avenues for the discovery of virulence determinants in other pathogens.

1,120 citations


Journal ArticleDOI
TL;DR: An analysis of links among GSH, adaptive responses to stress, molecular mechanisms of invasive cancer cell survival and death, and sensitization of metastatic cells to therapy shows that acceleration of GSH efflux facilitates selective GSH depletion in metastasis cells.
Abstract: The glutathione (GSH) content of cancer cells is particularly relevant in regulating mutagenic mechanisms, DNA synthesis, growth, and multidrug and radiation resistance. In malignant tumors, as compared with normal tissues, that resistance associates in most cases with higher GSH levels within these cancer cells. Thus, approaches to cancer treatment based on modulation of GSH should control possible growth-associated changes in GSH content and synthesis in these cells. Despite the potential benefits for cancer therapy of a selective GSH-depleting strategy, such a methodology has remained elusive up to now.Metastatic spread, not primary tumor burden, is the leading cause of cancer death. For patient prognosis to improve, new systemic therapies capable of effectively inhibiting the outgrowth of seeded tumor cells are needed. Interaction of metastatic cells with the vascular endothelium activates local release of proinflammatory cytokines, which act as signals promoting cancer cell adhesion, extravasation, a...

884 citations


Journal ArticleDOI
TL;DR: In this article, the core burnout and engagement dimensions can be seen as opposites of each other along two distinct bipolar dimensions dubbed energy and identification, and the results obtained by means of the nonparametric Mokken scaling method in three different samples (Ns = 477, 507, and 381) supported their proposal.

833 citations


Journal ArticleDOI
03 Feb 2006-Science
TL;DR: It is shown that neuroblast migration parallels cerebrospinal fluid (CSF) flow, and results suggest that polarized epithelial cells contribute important vectorial information for guidance of young, migrating neurons.
Abstract: In the adult brain, neuroblasts born in the subventricular zone migrate from the walls of the lateral ventricles to the olfactory bulb. How do these cells orient over such a long distance and through complex territories? Here we show that neuroblast migration parallels cerebrospinal fluid (CSF) flow. Beating of ependymal cilia is required for normal CSF flow, concentration gradient formation of CSF guidance molecules, and directional migration of neuroblasts. Results suggest that polarized epithelial cells contribute important vectorial information for guidance of young, migrating neurons.

763 citations


Journal ArticleDOI
TL;DR: Psychological IPV is as detrimental as physical IPV, with the exception of effects on suicidality, which emphasizes that psychological IPV should be considered a major type of violence by all professionals involved.
Abstract: Objective: This study aimed to determine the impact of lifetime physical, psychological, and sexual intimate male partner violence (IPV) on the mental health of women, after controlling for the contribution of lifetime victimization. The comorbidity of depressive symptoms and posttraumatic stress disorder (PTSD) and their relation to state anxiety and suicide were also assessed. Methods: Physically/psychologically (n = 75) and psychologically abused women (n = 55) were compared with nonabused control women (n = 52). Information about sociodemographic characteristics, lifetime victimization, and mental health status (depressive and state anxiety symptoms, PTSD, and suicide) was obtained through face-to-face structured interviews. Results: Women exposed to physical/psychological and psychological IPV had a higher incidence and severity of depressive and anxiety symptoms, PTSD, and thoughts of suicide than control women, with no differences between the two abused groups. The concomitance of sexual violence w...

756 citations


Journal ArticleDOI
TL;DR: Evidence is reported that, after a stroke, subventricular zone GFAP-expressing cells are capable of producing new neurons outside the olfactory bulbs, and long-term tracing of the green fluorescent-labeled cells revealed that the SVZ-derived neuroblasts differentiated into mature neurons in the striatum, in which they expressed neuronal-specific nuclear protein and formed synapses with neighboring striatal cells.
Abstract: Recent studies have revealed that the adult mammalian brain has the capacity to regenerate some neurons after various insults. However, the precise mechanism of insult-induced neurogenesis has not been demonstrated. In the normal brain, GFAP-expressing cells in the subventricular zone (SVZ) of the lateral ventricles include a neurogenic cell population that gives rise to olfactory bulb neurons only. Herein, we report evidence that, after a stroke, these cells are capable of producing new neurons outside the olfactory bulbs. SVZ GFAP-expressing cells labeled by a cell-type-specific viral infection method were found to generate neuroblasts that migrated toward the injured striatum after middle cerebral artery occlusion. These neuroblasts in the striatum formed elongated chain-like cell aggregates similar to those in the normal SVZ, and these chains were observed to be closely associated with thin astrocytic processes and blood vessels. Finally, long-term tracing of the green fluorescent-labeled cells with a Cre-loxP system revealed that the SVZ-derived neuroblasts differentiated into mature neurons in the striatum, in which they expressed neuronal-specific nuclear protein and formed synapses with neighboring striatal cells. These results highlight the role of the SVZ in neuronal regeneration after a stroke and its potential as an important therapeutic target for various neurological disorders.

690 citations


Journal ArticleDOI
TL;DR: High HIF-2alpha protein levels were correlated with advanced clinical stage and high VEGF expression and predicted poor prognosis in a clinical neuroblastoma material and have general tumor biological implications.

681 citations


Journal ArticleDOI
21 Dec 2006-Proteins
TL;DR: The protein structure validation software suite (PSVS) is developed, for assessment of protein structures generated by NMR or X‐ray crystallographic methods, and is particularly useful in assessing protein structures determined by N MR methods, but is also valuable for assessing X-ray crystal structures or homology models.
Abstract: Structural genomics projects are providing large quantities of new 3D structural data for proteins. To monitor the quality of these data, we have developed the protein structure validation software suite (PSVS), for assessment of protein structures generated by NMR or X-ray crystallographic methods. PSVS is broadly applicable for structure quality assessment in structural biology projects. The software integrates under a single interface analyses from several widely-used structure quality evaluation tools, including PROCHECK (Laskowski et al., J Appl Crystallog 1993;26:283-291), MolProbity (Lovell et al., Proteins 2003;50:437-450), Verify3D (Luthy et al., Nature 1992;356:83-85), ProsaII (Sippl, Proteins 1993;17: 355-362), the PDB validation software, and various structure-validation tools developed in our own laboratory. PSVS provides standard constraint analyses, statistics on goodness-of-fit between structures and experimental data, and knowledge-based structure quality scores in standardized format suitable for database integration. The analysis provides both global and site-specific measures of protein structure quality. Global quality measures are reported as Z scores, based on calibration with a set of high-resolution X-ray crystal structures. PSVS is particularly useful in assessing protein structures determined by NMR methods, but is also valuable for assessing X-ray crystal structures or homology models. Using these tools, we assessed protein structures generated by the Northeast Structural Genomics Consortium and other international structural genomics projects, over a 5-year period. Protein structures produced from structural genomics projects exhibit quality score distributions similar to those of structures produced in traditional structural biology projects during the same time period. However, while some NMR structures have structure quality scores similar to those seen in higher-resolution X-ray crystal structures, the majority of NMR structures have lower scores. Potential reasons for this "structure quality score gap" between NMR and X-ray crystal structures are discussed.

648 citations


Journal ArticleDOI
TL;DR: Transgenic approaches demonstrate that polyamines play essential roles in stress tolerance and open up the possibility to exploit this strategy to improve plant tolerance to multiple environmental stresses.
Abstract: Environmental stresses are the major cause of crop loss worldwide Polyamines are involved in plant stress responses However, the precise role(s) of polyamine metabolism in these processes remain ill-defined Transgenic approaches demonstrate that polyamines play essential roles in stress tolerance and open up the possibility to exploit this strategy to improve plant tolerance to multiple environmental stresses The use of Arabidopsis as a model plant enables us to carry out global expression studies of the polyamine metabolic genes under different stress conditions, as well as genome-wide expression analyses of insertional-mutants and plants over-expressing these genes These studies are essential to dissect the polyamine mechanism of action in order to design new strategies to increase plant survival in adverse environments

551 citations


Journal ArticleDOI
20 Jul 2006-Neuron
TL;DR: It is demonstrated that PDGFRalpha signaling occurs early in the adult stem cell lineage and may help regulate the balance between oligodendrocyte and neuron production and the work demonstrates that PDGF activation in the SVZ in stem cells is sufficient to induce hallmarks associated with early stages of tumor formation.

Journal ArticleDOI
TL;DR: Recognition and understanding of the role of Candida biofilms in human infection should help in the clinical management of these recalcitrant infections.
Abstract: In recent years there has been an increasing appreciation that microbial biofilms are ubiquitous, which has resulted in a number of studies on infectious diseases from a biofilm perspective. Biofilms are defined as structured microbial communities that are attached to a surface and encased in a matrix of exopolymeric material. A wide range of biomaterials used in clinical practice have been shown to support colonization and biofilm formation by Candida spp., and the increase in Candida infections in the last decades has almost paralleled the increase and widespread use of a broad range of medical implant devices, mainly in populations with impaired host defenses. Formation of Candida biofilms has important clinical repercussions because of their increased resistance to antifungal therapy and the ability of cells within biofilms to withstand host immune defenses. Further recognition and understanding of the role of Candida biofilms in human infection should help in the clinical management of these recalcitrant infections.

Journal ArticleDOI
TL;DR: This work provides a basic description of the organization of the adult human SVZ and provides ultrastructural criteria to identify the different cells types including three distinct types of astrocytes and a group of displaced ependymal cells between Layers II and III.
Abstract: The lateral wall of the lateral ventricle in the human brain contains neural stem cells throughout adult life. We conducted a cytoarchitectural and ultrastructural study in complete postmortem brains (n = 7) and in postmortem (n = 42) and intraoperative tissue (n = 43) samples of the lateral walls of the human lateral ventricles. With varying thickness and cell densities, four layers were observed throughout the lateral ventricular wall: a monolayer of ependymal cells (Layer I), a hypocellular gap (Layer II), a ribbon of cells (Layer III) composed of astrocytes, and a transitional zone (Layer IV) into the brain parenchyma. Unlike rodents and nonhuman primates, adult human glial fibrillary acidic protein (GFAP)+ subventricular zone (SVZ) astrocytes are separated from the ependyma by the hypocellular gap. Some astrocytes as well as a few GFAP-cells in Layer II in the SVZ of the anterior horn and the body of the lateral ventricle appear to proliferate based on proliferating cell nuclear antigen (PCNA) and Ki67 staining. However, compared to rodents, the adult human SVZ appears to be devoid of chain migration or large numbers of newly formed young neurons. It was only in the anterior SVZ that we found examples of elongated Tuj1+ cells with migratory morphology. We provide ultrastructural criteria to identify the different cells types in the human SVZ including three distinct types of astrocytes and a group of displaced ependymal cells between Layers II and III. Ultrastructural analysis of this layer revealed a remarkable network of astrocytic and ependymal processes. This work provides a basic description of the organization of the adult human SVZ. J. Comp. Neurol. 494:415–434, 2006. © 2005 Wiley-Liss, Inc.

Journal ArticleDOI
TL;DR: In this article, the authors examined 1038 single-nucleotide polymorphisms (SNPs) spanning 51 candidate genes involved in the regulation of neurotransmitter pathways, particularly dopamine, norepinephrine and serotonin pathways, in addition to circadian rhythm genes.
Abstract: Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, starting in early childhood and persisting into adulthood in the majority of cases. Family and twin studies have demonstrated the importance of genetic factors and candidate gene association studies have identified several loci that exert small but significant effects on ADHD. To provide further clarification of reported associations and identify novel associated genes, we examined 1038 single-nucleotide polymorphisms (SNPs) spanning 51 candidate genes involved in the regulation of neurotransmitter pathways, particularly dopamine, norepinephrine and serotonin pathways, in addition to circadian rhythm genes. Analysis used within family tests of association in a sample of 776 DSM-IV ADHD combined type cases ascertained for the International Multi-centre ADHD Gene project. We found nominal significance with one or more SNPs in 18 genes, including the two most replicated findings in the literature: DRD4 and DAT1. Gene-wide tests, adjusted for the number of SNPs analysed in each gene, identified associations with TPH2, ARRB2, SYP, DAT1, ADRB2, HES1, MAOA and PNMT. Further studies will be needed to confirm or refute the observed associations and their generalisability to other samples.

Journal ArticleDOI
TL;DR: Among patients with clinically evident CHD and diabetes, intensive therapy with atorvastatin 80 mg significantly reduced the rate of major cardiovascular events by 25% compared with at ORVastatin 10 mg.
Abstract: OBJECTIVE —The Treating to New Targets study showed that intensive lipid-lowering therapy with atorvastatin 80 mg/day provides significant clinical benefit beyond that afforded by atorvastatin 10 mg/day in patients with stable coronary heart disease (CHD). The objective of our study was to investigate whether similar benefits of high-dose intensive atorvastatin therapy can be achieved in patients with CHD and diabetes. RESEARCH DESIGN AND METHODS —A total of 1,501 patients with diabetes and CHD, with LDL cholesterol levels of <130 mg/dl, were randomized to double-blind therapy with either atorvastatin 10 ( n = 753) or 80 ( n = 748) mg/day. Patients were followed for a median of 4.9 years. The primary end point was the time to first major cardiovascular event, defined as death from CHD, nonfatal non–procedure-related myocardial infarction, resuscitated cardiac arrest, or fatal or nonfatal stroke. RESULTS —End-of-treatment mean LDL cholesterol levels were 98.6 mg/dl with atorvastatin 10 mg and 77.0 mg/dl with atorvastatin 80 mg. A primary event occurred in 135 patients (17.9%) receiving atorvastatin 10 mg, compared with 103 patients (13.8%) receiving atorvastatin 80 mg (hazard ratio 0.75 [95% CI 0.58–0.97], P = 0.026). Significant differences between the groups in favor of atorvastatin 80 mg were also observed for time to cerebrovascular event (0.69 [0.48–0.98], P = 0.037) and any cardiovascular event (0.85 [0.73–1.00], P = 0.044). There were no significant differences between the treatment groups in the rates of treatment-related adverse events and persistent elevations in liver enzymes. CONCLUSIONS —Among patients with clinically evident CHD and diabetes, intensive therapy with atorvastatin 80 mg significantly reduced the rate of major cardiovascular events by 25% compared with atorvastatin 10 mg.

Journal ArticleDOI
TL;DR: The need to understand consumer perceptions in order to correctly design product packing and to achieve the desired position in the minds of consumers is discussed.
Abstract: Purpose – This paper seeks to discuss the need to understand consumer perceptions in order to correctly design product packing and to achieve the desired position in the minds of consumers.Design/methodology/approach – Data collection was divided into two phases. The first, (based on designers' opinions), to determine the key graphic variables in the design of packaging. The second, (based on consumers' opinions), to associate each packaging with a positioning strategy. The seven product‐positioning strategies selected were represented from the consumers' standpoint using multidimensional scaling. Four maps were obtained related to: alternative packaging colours; alternative packaging typography; alternative packaging graphical forms; alternative packaging imagesFindings – Each positioning strategy appears associated with particular packaging dimensions.Research limitations/implications – Consumers have exhibited harmonious perceptions towards products‐packaging strategies, so one can conclude that a gene...

Journal ArticleDOI
S. Schael1, R. Barate, R. Bruneliere, I. De Bonis  +1279 moreInstitutions (141)
TL;DR: In this paper, four LEP collaborations, ALEPH, DELPHI, L3 and OPAL, have searched for the neutral Higgs bosons which are predicted by the minimal supersymmetric standard model (MSSM).
Abstract: The four LEP collaborations, ALEPH, DELPHI, L3 and OPAL, have searched for the neutral Higgs bosons which are predicted by the Minimal Supersymmetric standard model (MSSM). The data of the four collaborations are statistically combined and examined for their consistency with the background hypothesis and with a possible Higgs boson signal. The combined LEP data show no significant excess of events which would indicate the production of Higgs bosons. The search results are used to set upper bounds on the cross-sections of various Higgs-like event topologies. The results are interpreted within the MSSM in a number of “benchmark” models, including CP-conserving and CP-violating scenarios. These interpretations lead in all cases to large exclusions in the MSSM parameter space. Absolute limits are set on the parameter cosβ and, in some scenarios, on the masses of neutral Higgs bosons.

Journal ArticleDOI
TL;DR: This article constructed a set of meta-estimates of the coefficient of years of schooling in an aggregate Cobb-Douglas production function and found that the value of this parameter is likely to be above 0.60.
Abstract: We construct estimates of educational attainment for a sample of 21 OECD countries. Our series incorporate previously unexploited information and remove sharp breaks in the data that can only reflect changes in classification criteria. We then construct indicators of the information content of our estimates and a number of previously available data sets and examine their performance in several growth specifications. We find a clear positive correlation between data quality and the size and significance of human capital coefficients in growth regressions. Using an extension of the classical errors in variables model to correct for measurement error bias, we construct a set of meta-estimates of the coefficient of years of schooling in an aggregate Cobb-Douglas production function. Our results suggest that the value of this parameter is likely to be above 0.60. (JEL: O40, I20, O30, C19)

Journal ArticleDOI
TL;DR: It is shown that pigment epithelium–derived factor (PEDF) is secreted by components of the murine SVZ and promotes self-renewal of adult NSCs in vitro and provides evidence for a role for PEDF protein in NSC maintenance.
Abstract: Adult stem cells are characterized by self-renewal and multilineage differentiation, and these properties seem to be regulated by signals from adjacent differentiated cell types and by extracellular matrix molecules, which collectively define the stem cell "niche." Self-renewal is essential for the lifelong persistence of stem cells, but its regulation is poorly understood. In the mammalian brain, neurogenesis persists in two germinal areas, the subventricular zone (SVZ) and the hippocampus, where continuous postnatal neuronal production seems to be supported by neural stem cells (NSCs). Here we show that pigment epithelium-derived factor (PEDF) is secreted by components of the murine SVZ and promotes self-renewal of adult NSCs in vitro. In addition, intraventricular PEDF infusion activated slowly dividing stem cells, whereas a blockade of endogenous PEDF decreased their cycling. These data demonstrate that PEDF is a niche-derived regulator of adult NSCs and provide evidence for a role for PEDF protein in NSC maintenance.

Journal ArticleDOI
TL;DR: The investigated system is a unique example of an artificial linear nanomotor that behaves as an autonomous linear motor and operates with a quantum efficiency up to ≈12% and works in mild environmental conditions.
Abstract: Light excitation powers the reversible shuttling movement of the ring component of a rotaxane between two stations located at a 1.3-nm distance on its dumbbell-shaped component. The photoinduced shuttling movement, which occurs in solution, is based on a “four-stroke” synchronized sequence of electronic and nuclear processes. At room temperature the deactivation time of the high-energy charge-transfer state obtained by light excitation is ≈10 μs, and the time period required for the ring-displacement process is on the order of 100 μs. The rotaxane behaves as an autonomous linear motor and operates with a quantum efficiency up to ≈12%. The investigated system is a unique example of an artificial linear nanomotor because it gathers together the following features: (i) it is powered by visible light (e.g., sunlight); (ii) it exhibits autonomous behavior, like motor proteins; (iii) it does not generate waste products; (iv) its operation can rely only on intramolecular processes, allowing in principle operation at the single-molecule level; (v) it can be driven at a frequency of 1 kHz; (vi) it works in mild environmental conditions (i.e., fluid solution at ambient temperature); and (vii) it is stable for at least 103 cycles.

Journal ArticleDOI
TL;DR: It is suggested that ROS may serve as messenger molecules to activate adaptive responses through these redox‐sensitive signaling pathways to maintain cellular oxidant‐antioxidant homeostasis during exercise.
Abstract: Contraction-induced production of reactive oxygen species (ROS) has been shown to cause oxidative stress to skeletal muscle. As an adaptive response, muscle antioxidant defense systems are upregulated after heavy exercise. Nuclear factor (NF) kappaB and mitogen-activated protein kinases (MAPKs) are the major oxidative stress-sensitive signal transduction pathways in mammalian tissues. Activation of NF-kappaB signaling cascade has been shown to enhance the gene expression of important enzymes, such as mitochondrial superoxide dismutase (MnSOD) and inducible nitric oxide synthase (iNOS). MAPK activations are involved in a variety of cellular functions including growth, proliferation, and adaptation. We investigated the effect of an acute bout of exercise on NF-kappaB and MAPK signaling, as well as on the time course of activation, in rat skeletal muscle. In addition, we studied the role of ROS in the exercise-induced upregulation of MnSOD and iNOS, and the potential interactions of NF-kappaB and MAPK in the signaling of these enzymes. Our data suggest that ROS may serve as messenger molecules to activate adaptive responses through these redox-sensitive signaling pathways to maintain cellular oxidant-antioxidant homeostasis during exercise.

Journal ArticleDOI
TL;DR: It is now clear that BBB participates in the active regulation of the AA content of the brain, and may serve to modulate movement of AAs from blood to the brain.
Abstract: Brain capillary endothelial cells form the blood-brain barrier (BBB). They are connected by extensive tight junctions, and are polarized into luminal (blood-facing) and abluminal (brain-facing) plasma membrane domains. The polar distribution of transport proteins mediates amino acid (AA) homeostasis in the brain. The existence of two facilitative transporters for neutral amino acids (NAAs) on both membranes provides the brain access to essential AAs. Four Na(+)-dependent transporters of NAA exist in the abluminal membranes of the BBB. Together these systems have the capability to actively transfer every naturally occurring NAA from the extracellular fluid (ECF) to endothelial cells and from there into circulation. The presence of Na(+)-dependent carriers on the abluminal membrane provides a mechanism by which NAA concentrations in the ECF of brain are maintained at approximately 10% those of the plasma. Also present on the abluminal membrane are at least three Na(+)-dependent systems transporting acidic AAs (EAAT) and a Na(+)-dependent system transporting glutamine (N). Facilitative carriers for glutamine and glutamate are found only in the luminal membrane of the BBB. This organization promotes the net removal of acidic- and nitrogen-rich AAs from the brain and accounts for the low level of glutamate penetration into the central nervous system. The presence of a gamma-glutamyl cycle at the luminal membrane and Na(+)-dependent AA transporters at the abluminal membrane may serve to modulate movement of AAs from blood to the brain. The gamma-glutamyl cycle is expected to generate pyroglutamate (synonymous with oxyproline) within the endothelial cells. Pyroglutamate stimulates secondary active AA transporters at the abluminal membrane, thereby reducing the net influx of AAs to the brain. It is now clear that BBB participates in the active regulation of the AA content of the brain.


Journal ArticleDOI
TL;DR: This review focuses on the methodologies in constructing three main components of QSAR model, namely the methods for describing the molecular structure of compounds, for selection of informative descriptors and for activity prediction.
Abstract: Virtual filtering and screening of combinatorial libraries have recently gained attention as methods complementing the high-throughput screening and combinatorial chemistry. These chemoinformatic techniques rely heavily on quantitative structure-activity relationship (QSAR) analysis, a field with established methodology and successful history. In this review, we discuss the computational methods for building QSAR models. We start with outlining their usefulness in high-throughput screening and identifying the general scheme of a QSAR model. Following, we focus on the methodologies in constructing three main components of QSAR model, namely the methods for describing the molecular structure of compounds, for selection of informative descriptors and for activity prediction. We present both the well-established methods as well as techniques recently introduced into the QSAR domain.

Journal ArticleDOI
TL;DR: Strawberries were treated either with 1% calcium gluconate dips, 1.5% chitosan coatings or with a coating formulation containing 1.1% and 1.2% calcium and stored at 20 °C for up to 4 days as discussed by the authors.

Journal ArticleDOI
TL;DR: This study contributes to innovation management research by providing a set of valid and reliable operational measures that satisfy the criteria for unidimensionality, reliability, and validity.
Abstract: Purpose – The purpose of this paper is to report the results of a study aimed at conceptualising and developing valid measurements for two key dimensions of product innovation performance‐efficacy and efficiency – in the context of firm competition.Design/methodology/approach – Data were collected from French biotechnology firms. Using structural equations modeling, the constructs’ measurement models were tested and the scale was validated.Findings – The results of the study indicate that the operational measures developed here satisfy the criteria for unidimensionality, reliability, and validity.Research limitations/implications – This study contributes to innovation management research by providing a set of valid and reliable operational measures. These measures are expected to help researchers in theory testing. Because of the sample features, final results should be considered with caution.Practical implications – The proposed measurement scale for product innovation performance could be implemented a...

Journal ArticleDOI
TL;DR: This paper provides the main principles and ideas of scatter search and its generalized form path relinking and describes a basic design to give the reader the tools to create relatively simple implementations.

Journal ArticleDOI
TL;DR: In this article, the effect of weather and non-weather variables on CO2 prices is studied. And the results show that the most emission intensive energy sources are the principal factors in the determination of CO2 price, and that only extreme temperatures influence them.
Abstract: One of the main objectives of the European Union Emission Trading Scheme is the establishment of a market price for allowances that show to European CO2 emitting installations the environmental impact of their polluting activities. The aim of this paper is to study the effect of those weather and non-weather variables that academic and market agents consider as the major determinants of CO2 prices. The results show that the most emission intensive energy sources are the principal factors in the determination of CO2 prices, and that only extreme temperatures influence them.

Journal ArticleDOI
TL;DR: From the data presented here, it becomes clear that the composition, structure and synthesis of the cell wall of C. albicans display both subtle and important differences with the wall of different saprophytic fungi, and that some of these differences are of utmost importance for its pathogenic behavior.
Abstract: Candida albicans is one of the most important opportunistic pathogenic fungi. Weakening of the defense mechanisms of the host, and the ability of the microorganism to adapt to the environment prevailing in the host tissues, turn the fungus from a rather harmless saprophyte into an aggressive pathogen. The disease, candidiasis, ranges from light superficial infections to deep processes that endanger the life of the patient. In the establishment of the pathogenic process, the cell wall of C. albicans (as in other pathogenic fungi) plays an important role. It is the outer structure that protects the fungus from the host defense mechanisms and initiates the direct contact with the host cells by adhering to their surface. The wall also contains important antigens and other compounds that affect the homeostatic equilibrium of the host in favor of the parasite. In this review, we discuss our present knowledge of the structure of the cell wall of C. albicans, the synthesis of its different components, and the mechanisms involved in their organization to give rise to a coherent composite. Furthermore, special emphasis has been placed on two further aspects: how the composition and structure of C. albicans cell wall compare with those from other fungi, and establishing the role of some specific wall components in pathogenesis. From the data presented here, it becomes clear that the composition, structure and synthesis of the cell wall of C. albicans display both subtle and important differences with the wall of different saprophytic fungi, and that some of these differences are of utmost importance for its pathogenic behavior.

Journal ArticleDOI
TL;DR: This work presents a new lattice-based perfect reconstruction and critically sampled anisotropic M-DIR WT, which provides an efficient tool for nonlinear approximation of images, achieving the approximation power O(N/sup -1.55/), which, while slower than the optimal rate O-2/, is much better than O-1/ achieved with wavelets, but at similar complexity.
Abstract: In spite of the success of the standard wavelet transform (WT) in image processing in recent years, the efficiency of its representation is limited by the spatial isotropy of its basis functions built in the horizontal and vertical directions. One-dimensional (1-D) discontinuities in images (edges and contours) that are very important elements in visual perception, intersect too many wavelet basis functions and lead to a nonsparse representation. To efficiently capture these anisotropic geometrical structures characterized by many more than the horizontal and vertical directions, a more complex multidirectional (M-DIR) and anisotropic transform is required. We present a new lattice-based perfect reconstruction and critically sampled anisotropic M-DIR WT. The transform retains the separable filtering and subsampling and the simplicity of computations and filter design from the standard two-dimensional WT, unlike in the case of some other directional transform constructions (e.g., curvelets, contourlets, or edgelets). The corresponding anisotropic basis functions (directionlets) have directional vanishing moments along any two directions with rational slopes. Furthermore, we show that this novel transform provides an efficient tool for nonlinear approximation of images, achieving the approximation power O(N/sup -1.55/), which, while slower than the optimal rate O(N/sup -2/), is much better than O(N/sup -1/) achieved with wavelets, but at similar complexity.