Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional models of Parkinson's disease: A valuable tool in the development of novel therapies

Functional models of Parkinson's disease (PD) have led to effective treatment for the motor symptoms. Toxin‐based models, such as the 6‐hydroxydopamine–lesioned rat and 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine–treated primate, have resulted in novel dopaminergic therapies and new therapeutic strategies. They have also been used to study processes underlying motor complications, particularly dyskinesia, and for developing pharmacological approaches to dyskinesia avoidance and suppression. Symptomatic models of PD based on nigrostriatal degeneration have a high degree of predictability of clinical effect of dopaminergic drugs on motor symptoms in humans. However, the effects of nondopaminergic drugs in these models do not translate effectively into clinical efficacy. Newer experimental models of PD have attempted to reproduce the pathogenic process and to involve all areas of the brain pathologically affected in humans. In addition, models showing progressive neuronal death have been sought but so far unsuccessfully. Pathogenic modeling has been attempted using a range of toxins, as well as through the use of transgenic models of gene defects in familial PD and mutant rodent strains. However, there are still no accepted progressive models of PD that mimic the processes known to occur during cell death and that result in the motor deficits, pathology, biochemistry, and drug responsiveness as seen in humans. Nevertheless, functional models of PD have led to many advances in treating the motor symptoms of the disorder, and we have been fortunate to have them available. They are an important reason the treatment of PD is so much better compared with treatments for related illnesses. Ann Neurol 2008;64 (suppl):S16–S29
Characterization of potent Na+/H+ exchange inhibitors from the amiloride series in A431 cells.

Na+/H+ exchange is stimulated in a variety of cell types by addition of mitogenic polypeptides such as epidermal growth factor or platelet-derived growth factor. In order to assess the importance of Na+/H+ exchange in the mitogenic response, it is desirable to have available inhibitors of this process which exhibit high affinity and good specificity. We characterize in this report a number of 5-alkylamino-substituted derivatives of amiloride [3,5-diamino-6-chloro-N-(diaminomethylene)pyrazinecarboxamide++ +] which show much higher affinity than the parent compound for the Na+/H+ antiporter in A431 cells. High affinity is conferred by substitution with two alkyl groups and is increased by introducing a branched alkyl chain. An analogue bearing a 5-anilino group is also very potent. These analogues effectively inhibit the elevation of intracellular pH upon stimulation of Na+/H+ exchange by growth factors. We have assessed other potential inhibitory effects of these compounds on cellular metabolism. In agreement with previous reports, we find that amiloride inhibits protein synthesis both in cells and in cell-free translation systems. While amiloride and its analogues show similar inhibition of protein synthesis in a cell-free system, most analogues inhibit cellular protein synthesis at much lower concentrations than does amiloride. These analogues are also potent inhibitors of purified Na,K-ATPase and cause a profound decrease in intracellular K+ as well as ATP content. These latter effects, however, require analogue concentrations which are 5-7 times higher than those inhibiting cellular protein synthesis. (ABSTRACT TRUNCATED AT 250 WORDS)
Video Tracking via Tensor Neighborhood Preserving Discriminant Embedding

In a real surveillance scenario, tracking an object usually interfered by the background information. To deal with this problem, this paper proposed a video tracking algorithm based on tensor neighborhood preserving discriminant embedding. The neighborhood relationships of an object within object class and background class are reasonable described by the object image patches similarities which are defined by histograms of oriented gradients. In order to distinguish between the object and background, we formulate an discriminant objective function that maximizing the scatters of object within object class while minimizing the scatters of object with background class, meanwhile maintaining the same neighborhood topological structure in lower dimensional tensor subspace. Finally, we can get the optimal estimate of the object state through Bayesian estimation framework. Experimental evaluations against two state-of-the-art tracking methods demonstrate the robustness and effectiveness of the proposed algorithm.
Inducible Nitric Oxide Synthase in the Rat Testis: Evidence for Potential Roles in Both Normal Function and Inflammation-Mediated Infertility1

Abstract In vitro data have indicated that nitric oxide (NO) inhibits Leydig cell testosterone production, suggesting that NO may play a role in the suppression of steroidogenesis and spermatogenic function during inflammation. Consequently, we investigated expression of the inflammation-inducible isoform of NO synthase (iNOS) in the inflamed adult rat testis and the ability of a broad-spectrum inhibitor of NO production, l-nitro-l-arginine methyl ester, to prevent Leydig cell dysfunction during inflammation. Unexpectedly, immunohistochemical and mRNA data established that iNOS is expressed constitutively in Leydig cells and in a stage-specific manner in Sertoli, peritubular, and spermatogenic cells in the normal testis. Expression was increased in a dose-dependent manner in all these cell types during lipopolysaccharide (LPS)-induced inflammation. In noninflamed testes, treatment with the NO synthase inhibitor reduced testicular interstitial fluid formation and testosterone production without any effect on serum LH levels. Administration of the inhibitor did not prevent the suppression of testicular interstitial fluid and testosterone production that occurs within 6 h after LPS treatment. Collectively, these data indicate a novel role for iNOS in autocrine or paracrine regulation of the testicular vasculature, Leydig cell steroidogenesis, and spermatogenesis in the normal testis. The data suggest that increased NO is not the major cause of acute Leydig cell dysfunction in the LPS-treated inflammation model, although a role for NO in this process cannot be excluded, particularly at other time points. Moreover, up-regulation of iNOS may contribute to the seminiferous epithelium damage caused by LPS-induced inflammation.
Optimal Contract Pricing of Distributed Generation in Distribution Networks

This paper proposes a bilevel programming approach to determine the optimal contract price of dispatchable distributed generation (DG) units in distribution systems. Two different agents are considered in the model, namely, the distribution company (DisCo) and the owner of the DG. The former seeks the minimization of the payments incurred in attending the forecasted demand, while the latter seeks the maximization of his profit. To meet the expected demand, the DisCo has the option to purchase energy from any DG unit within its network and directly from the wholesale electricity market. A traditional distribution utility model with no competition among DG units is considered. The proposed model positions the DG owner in the outer optimization level and the DisCo in the inner one. This last optimization problem is substituted by its Karush-Kuhn-Tucker optimality conditions, turning the bilevel programming problem into an equivalent single-level nonlinear programming problem which is solved using commercially available software. Tests are performed in a modified IEEE 34-bus distribution network.
Expression of EGFR and c‐kit is associated with the basal‐like phenotype in breast carcinomas of African women  

Epidermal growth factor receptor (EGFR) and c‐kit are tyrosine kinase growth factor receptors which are frequently expressed in basal‐like breast carcinomas, and tyrosine kinase inhibition is now a promising strategy in treatment of breast cancer. The aim of this study was to evaluate the expression of EGFR and c‐kit in breast cancer with special focus on the basal‐like phenotype (BLP) and other prognostic factors in an African population. We analyzed 65 archival tissues immunohistologically. EGFR and/or c‐kit were expressed in 55% of basal‐like tumors. Expression of EGFR and/or c‐kit was strongly associated with high histologic grade (P=0.001), high nuclear grade (P=0.017), high mitotic counts (P=0.002), ER negativity (P=0.003), PR negativity (P=0.007), and HER2 negativity (P=0.014). EGFR and/or c‐kit positive tumors were more likely to express the BLP (OR 9.1, CI 2.6–32.0, P<0.0005) than the negative tumors. In conclusion, there is a high expression of EGFR and/or c‐kit in basal‐like breast carcinoma in this series from Uganda and their expression is associated with features of poor prognosis. More studies are required to assess the clinical significance of EGFR and c‐kit in breast cancer patients in Uganda.
Multiple 32-fiber array connection to silica waveguides on Si

A multiple 32-fiber array connection method with low loss and high stability is developed for silica-based planar lightwave circuits (PLCs) on Si. This technique is realized by fabricating a 32-fiber array with high pitch accuracy and reducing the warp of the chip. The average connection loss of a module connected to four 32-fiber arrays is 0.3 dB/point and the average loss change in a temperature cycle between 75 and -40/spl deg/C is less than 0.1 dB. Moreover, the module insertion loss was stable for 1200 h at 75/spl deg/C and 90% RH. These results show that the technique is suitable for practical applications.
Role of neuropeptides in inflammatory bowel disease

Abstract Inflammatory bowel disease (IBD) is a chronic, relapsing condition involving complex interactions between genes and the environment. The mechanisms triggering the initial attack and relapses, however, are not well understood. In the past several years the enteric nervous system (ENS) has been implicated in the pathophysiology of IBD. Both the ENS and the central nervous system (CNS) can amplify or modulate aspects of intestinal inflammation through secretion of neuropeptides that serve as a link between the ENS and CNS. Neuropeptides are defined as any peptide released from the nervous system that serves as an intercellular signaling molecule. Neuropeptides thought to play a potentially key role in IBD include substance P, corticotropin‐releasing hormone, neurotensin, vasoactive intestinal peptide, mu‐opioid receptor agonists, and galanin. This review focuses on the role of these neuropeptides in the pathophysiology of IBD and discusses the cell types and mechanisms involved in this process. The available evidence that neuropeptide blockade may be considered a therapeutic approach in both Crohn's disease and ulcerative colitis will also be discussed. (Inflamm Bowel Dis 2007)
The anxieties of new clinical students

Summary. The specific anxieties of 74 medical students beginning their clinical training were assessed by means of a questionnaire at the start of the clinical introductory course at St Mary's Hospital Medical School, London. Situations differed in the amount of anxiety that they engendered, and students also differed in the number of situations that they found anxiety producing. Students particularly reported that interactions with senior staff on ward rounds were anxiety provoking. The same questionnaire was also distributed to 52 teaching hospital doctors who were asked to complete the questionnaire as they thought the students had done. Compared with students, the doctors considered more situations to be anxiety provoking, and they differed in their rank ordering of the situations. Doctors tended to overestimate anxiety concerning communication problems, and to underestimate anxiety concerning routine clinical tasks such as phlebotomy.
Kar4p, a karyogamy-specific component of the yeast pheromone response pathway

Karyogamy is the process whereby two haploid nuclei fuse to form a diploid nucleus during mating in Saccharomyces cerevisiae. Here, we describe the characterization of the KAR4 gene, previously identified in a screen for new nuclear fusion-defective mutants. During mating, kar4 mutants were defective for the microtubule-dependent movement of nuclei, a phenotype identical to that of mutations in KAR3 and CIK1. Consistent with its mutant phenotype, we found that the kar4 mutation resulted in failure to induce KAR3 and CIK1 mRNA during mating. Expression of KAR3 and CIK1 under independent regulatory control suppressed the kar4 defect, indicating that KAR4 is required primarily for the induction of KAR3 and CIK1. KAR4 was also required for meiosis, during which it may regulate KAR3; however, mitotic expression of KAR3 and CIK1 during S/G2 phase was independent of KAR4. A 30-bp region upstream of KAR3 conferred both KAR4- and STE12-dependent induction by mating pheromone. This region contained one moderate and two weak matches to the consensus pheromone response element to which the Ste12p transcriptional activator binds and five repeats of the sequence CAAA(A). Overproduction of Ste12p suppressed the kar4 defect in KAR3 induction and nuclear fusion. In contrast, Ste12p-independent expression of Kar4p did not alleviate the requirement for Ste12p during KAR3 induction. We propose that Kar4p assists Ste12p in the pheromone-dependent expression of KAR3 and CIK1. KAR4 defines a novel level of regulation for the pheromone response pathway, acting at a subset of Stel2p-inducible genes required for karyogamy.
Psychological stress and susceptibility to the common cold.

BACKGROUND It is not known whether psychological stress suppresses host resistance to infection. To investigate this issue, we prospectively studied the relation between psychological stress and the frequency of documented clinical colds among subjects intentionally exposed to respiratory viruses. METHODS After completing questionnaires assessing degrees of psychological stress, 394 healthy subjects were given nasal drops containing one of five respiratory viruses (rhinovirus type 2, 9, or 14, respiratory syncytial virus, or coronavirus type 229E), and an additional 26 were given saline nasal drops. The subjects were then quarantined and monitored for the development of evidence of infection and symptoms. Clinical colds were defined as clinical symptoms in the presence of an infection verified by the isolation of virus or by an increase in the virus-specific antibody titer. RESULTS The rates of both respiratory infection (P less than 0.005) and clinical colds (P less than 0.02) increased in a dose-response manner with increases in the degree of psychological stress. Infection rates ranged from approximately 74 percent to approximately 90 percent, according to levels of psychological stress, and the incidence of clinical colds ranged from approximately 27 percent to 47 percent. These effects were not altered when we controlled for age, sex, education, allergic status, weight, the season, the number of subjects housed together, the infectious status of subjects sharing the same housing, and virus-specific antibody status at base line (before challenge). Moreover, the associations observed were similar for all five challenge viruses. Several potential stress-illness mediators, including smoking, alcohol consumption, exercise, diet, quality of sleep, white-cell counts, and total immunoglobulin levels, did not explain the association between stress and illness. Similarly, controls for personality variables (self-esteem, personal control, and introversion-extraversion) failed to alter our findings. CONCLUSIONS Psychological stress was associated in a dose-response manner with an increased risk of acute infectious respiratory illness, and this risk was attributable to increased rates of infection rather than to an increased frequency of symptoms after infection.
Nucleosome loss activates CUP1 and HIS3 promoters to fully induced levels in the yeast Saccharomyces cerevisiae

We have previously shown that nucleosome loss, obtained by repressing histone H4 mRNA synthesis, activates otherwise inactive PHO5, GAL1, and CYC1 gene promoters (fused to the bacterial beta-galactosidase [lacZ] reporter gene) to moderate levels of activity (approximately 2 to 15% of fully induced levels). We now report that nucleosome loss activates the expression of two additional promoters that are normally induced by independent mechanisms: CUP1 (induced by heavy-metal toxicity) and HIS3 (induced by amino acid starvation). Surprisingly, the level of CUP1-lacZ and HIS3-lacZ activation by nucleosome loss approximates fully induced levels of transcription. These CUP1 and HIS3 promoter activities are increased similarly from either episomal or genomic constructs. Our results emphasize the universality of the mechanism by which nucleosome loss activates yeast promoters. Moreover, a comparison of absolute levels of activation for different promoters suggests that activation by nucleosome loss results in a relatively constant level of activation, while levels obtained by normal induction vary considerably. These data argue that nucleosome loss may play a uniquely dominant role in the regulation of certain promoters.
ERP Mapping in Phonological and Lexical Semantic Monitoring Tasks: A Study Complementing Previous PET Results

Previous PET results identified distinct neural systems involved with phonology (vicinity of the left sylvian fissure) and lexical semantics (left inferior temporal, left superior frontal, bilateral inferior parietal regions). In the time domain, the phonological task was thought to involve serial parsing of pseudo-words, whereas the lexical semantic task would correspond to probabilistic automated access to meaning. Auditory event-related potentials (ERPs) elicited by the same tasks were explored on 32 channels in 12 male volunteers. Subjects had to categorize as target a second element of a pair of pseudo-words or words if a preceding target was detected in the first element. Depending on the absence/presence of target in the first element, a RELEASE condition and a HOLD condition were distinguished. RELEASE and HOLD ERPs split earlier in the semantic task than in the phonological task (300 versus 412 ms after SOT, respectively), although words lasted longer than pseudo-words. Corresponding paired t test maps showed a predominance of differences over left perisylvian regions for the phonological task and posterior bilateral regions for the semantic task. Underlying generators were investigated using BESA (Scherg, 1990) with global task ERPs. Six dipoles-constrained according to PET clusters-brought residual variance down to 0.36%, from 364 to 565 ms after SOT, in both tasks. Relative dipole amplitudes suggested a left-sided functional asymmetry for phonology. These results support the hypothesis of left perisylvian serial processing for phonology contrasting with bihemispheric parallel access for semantics and substantiates BESA for temporally tackling cognitive processes.
Expression, purification, and characterization of EpiC, an enzyme involved in the biosynthesis of the lantibiotic epidermin, and sequence analysis of Staphylococcus epidermidis epiC mutants

The plasmid-encoded epidermin biosynthetic gene epiC of Staphylococcus epidermidis Tü3298 was expressed in Escherichia coli by using the T7 RNA polymerase-promoter system, and the gene product EpiC was identified by Western blotting (immunoblotting) with an anti-EpiC-peptide antiserum. EpiC was a hydrophobic but soluble protein. EpiC was purified by hydrophobic-interaction chromatography. The determined amino-terminal amino acid sequence was M I N I N N I . The electrophoretic migration behavior of EpiC depended on the oxidation state of the enzyme, indicating the formation of an intramolecular disulfide bridge between C-274 and C-321. The cysteine residues in the motifs WC-274YG and C-321HG of EpiC are conserved in all lantibiotic enzymes of the C type (so-called LanC proteins) and in the CylM protein. Mutated epiC genes from S. epidermidis epiC mutants were cloned and expressed in E. coli. Sequence analysis revealed that the mutations occurred in the two motifs -S-X-X-X-G-X-X-G- and -N-X-G-X-A-H-G-X-X-G-, which are conserved in all LanC proteins. For the investigation of EpiC-EpiA interactions, precursor peptide EpiA was coupled to N-hydroxysuccinimide-activated Sepharose High Performance Material (HiTrap). Under reducing conditions, EpiC was retarded on the EpiA-HiTrap column. In the incubation experiments, EpiC did not react with EpiA, with proepidermin, or with oxidative decarboxylated peptides.
Isolation and culture of human neuromicrovascular endothelial cells for the study of angiogenesis in vitro

Neovascularization in the adult central nervous system occurs as a response to several pathophysiological conditions such as ischemia, wound repair, or neoplasia. Endothelial cells from different blood vessel types, different organs, and different species are heterogeneous; therefore, the appropriate cell type should be used to study specific aspects of vascular pathology. We have developed a method to isolate human cerebral microvascular endothelial cells (CMECs) from small, freshly obtained specimens of normal brain adherent to human arteriovenous malformations (AVMs). The isolation procedure involves enzymatic digestions and gradient centrifugations, yielding over 95% pure primary cultures. Alternative isolation methods using magnetic beads, panning, or cloning were not superior with regard to cell purity or yield. CMECs were identified by their immunoreactivity for vWF, CD34, EN4, binding of Ulex europeus lectin, and uptake of DiI‐Ac‐LDL. They displayed ultrastructural features characteristic of blood‐brain barrier endothelial cells and expressed GLUT‐1. CMECs were subcultured; however, prolonged culture led to reduced culture purity. Vascular endothelial growth factor, basic fibroblast growth factor and hepatocyte growth factor/scatter factor stimulated the directional motility of CMECs, with dose‐response profiles similar to human umbilical vein endothelial cells (HUVECs). In contrast, to stimulate proliferation, lower concentrations of growth factors tended to be necessary for CMECs than for the large vessel endothelial cells. CMECs formed capillary tube‐like structures in an in vitro angiogenesis assay using matrigel. This study expands the spectrum of available tissue sources for the isolation of human neuromicrovascular endothelial cells, which are essential for the in vitro study of blood‐brain barrier function and cerebral angiogenesis. J. Neurosci. Res. 55:370–381, 1999. © 1999 Wiley‐Liss, Inc.