Miracle-dz/UniFAR-FTUs huggingface dataset:
Determinants of Human B Cell Migration Across Brain Endothelial Cells1

Circulating B cells enter the CNS as part of normal immune surveillance and in pathologic states, including the common and disabling illness multiple sclerosis. However, little is known about the molecular mechanisms that mediate human B cell interaction with the specialized brain endothelial cells comprising the blood-brain barrier (BBB). We studied the molecular mechanisms that regulate the migration of normal human B cells purified ex vivo, across human adult brain-derived endothelial cells (HBECs). We found that B cells migrated across HBECs more efficiently than T cells from the same individuals. B cell migration was significantly inhibited by blocking Abs to the adhesion molecules ICAM-1 and VLA-4, but not VCAM-1, similar to the results previously reported for T cells. Blockade of the chemokines monocyte chemoattractant protein-1 and IL-8, but not RANTES or IFN-γ-inducible protein-10, significantly inhibited B cell migration, and these results were correlated with the chemokine receptor expression of B cells measured by flow cytometry and by RNase protection assay. Tissue inhibitor of metalloproteinase-1, a natural inhibitor of matrix metalloproteinases, significantly decreased B cell migration across the HBECs. A comprehensive RT-PCR comparative analysis of all known matrix metalloproteinases and tissue inhibitors of metalloproteinases in human B and T cells revealed distinct profiles of expression of these molecules in the different cell subsets. Our results provide insights into the molecular mechanisms that underlie human B cell migration across the BBB. Furthermore, they identify potential common, and unique, therapeutic targets for limiting CNS B cell infiltration and predict how therapies currently developed to target T cell migration, such as anti-VLA-4 Abs, may impact on B cell trafficking.
Multiplex PCR Assay for Simultaneous Detection of Nine Clinically Relevant Antibiotic Resistance Genes in Staphylococcus aureus

ABSTRACT In this study we describe a multiplex PCR assay for the detection of nine clinically relevant antibiotic resistance genes of Staphylococcus aureus. Conditions were optimized to amplify fragments of mecA (encoding methicillin resistance), aacA-aphD (aminoglycoside resistance), tetK, tetM (tetracycline resistance), erm(A), erm(C) (macrolide-lincosamide-streptogramin B resistance), vat(A), vat(B), and vat(C) (streptogramin A resistance) simultaneously in one PCR amplification. An additional primer pair for the amplification of a fragment of the staphylococcal 16S rDNA was included as a positive control. The multiplex PCR assay was evaluated on 30 different S. aureus isolates, and the PCR results correlated with the phenotypic antibiotic resistance data obtained by the broth microdilution assay. The multiplex PCR assay offers a rapid, simple, and accurate identification of antibiotic resistance profiles and could be used in clinical diagnosis as well as for the surveillance of the spread of antibiotic resistance determinants in epidemiological studies.
Transformation-specific tyrosine phosphorylation of a novel cellular protein in chicken cells expressing oncogenic variants of the avian cellular src gene

We used myristylated and nonmyristylated c-src-based variants and phosphotyrosine-specific antibodies to reevaluate the role of tyrosine phosphorylation in cellular transformation by pp60src. Prior methods used to detect tyrosine-phosphorylated proteins failed to discriminate predicted differences in tyrosine phosphorylation which are clearly observed with phosphotyrosine-specific antibodies and Western blotting (immunoblotting). Here we report the observation of a 120,000-Mr protein whose phosphorylation on tyrosine correlates with the induction of morphological transformation. p120 was not observed in cells overexpressing the regulated, nononcogenic pp60c-src, whereas phosphorylation of p120 was greatly enhanced in cells expressing activated, oncogenic pp60527F. Furthermore, phosphorylation of p120 was not induced by expression of the activated but nonmyristylated src variant pp602A/527F, which is transformation defective. p120 partitioned preferentially with cellular membranes, consistent with the observation that transforming src proteins are membrane associated. Although a number of additional putative substrates were identified and partially characterized with respect to intracellular localization, tyrosine phosphorylation of these proteins was not tightly linked to transformation.
Friends in the Delaware Valley: Philadelphia Yearly Meeting, 1681–1981 . Edited by John M. Moore. Haverford, Pennsylvania: Friends Historical Association, 1981. 273 pp. $8.95 hard cover; $4.95 soft cover.

ment of polygamy is especially notable, as he follows it carefully through both the formative period under Joseph Smith and its later development under Brigham Young. Through all of this, he maintains a lively narrative with balanced attention to personalities as well as social issues. In short, Religion and Sexuality is a superb monograph, insightful in its specific interpretations and its commentary on nineteenth-century America; for, as Foster points out, these communities were not bizarre fanatics, but point directly to the soul of antebellum American culture.
Evaluación de la eficacia de un protocolo transfusional en el trasplante hepático

De forma tradicional, el Trasplante Hepatico se ha asociado con grandes perdidas de sangre perioperatorias derivado del delicado y complejo estado basal del sistema hemostatico, las complejas alteraciones hemostaticas que acontecen durante el propio procedimiento y el traumatismo quirurgico. En las ultimas decadas se ha experimentado un descenso en el sangrado y en el empleo de hemoderivados durante el Trasplante Hepatico y ya no es infrecuente la realizacion de THO sin la necesidad de transfusiones alogenicas, aunque esto debiera convertirse en la norma. Esta tendencia a la reduccion transfusional se debe a varios factores como la seleccion mas precoz de los pacientes a trasplantar, mejoras en la preservacion de los injertos, mejoras en las tecnicas quirurgicas y mejoras en los cuidados anestesicos, asi como un mejor entendimiento del sistema hemostatico del paciente hepatopata y elaboracion de protocolos transfusionales mas restrictivos. Reducir los requerimientos transfusionales es esencial ya que estudios recientes han demostrado que las transfusiones, especialmente de plasma y plaquetas, se asocian con un descenso significativo de la supervivencia a un ano y un ascenso de la morbilidad del paciente sometido a Trasplante Hepatico, pero se ha puesto de manifiesto que existe una gran heterogeneidad interhospitalaria en cuanto a la tasa de enfermos transfundidos y el volumen medio transfundido y que no puede ser explicada exclusivamente por determinadas caracteristicas preoperatorias del paciente y por las tecnicas quirurgicas sino que en gran parte se debe a diferencias en los cuidados anestesicos de cada institucion, determinado principalmente por el manejo de los fluidos, los indicadores y criterios de transfusion empleados y la utilizacion de agentes farmacologicos pro-hemostaticos.
Fibrin formation by staphylothrombin facilitates Staphylococcus aureus-induced platelet aggregation

Summary Interactions of Staphylococcus aureus (S. aureus) and platelets play an important role in the pathogenesis of intravascular infections such as infective endocarditis (IE). A typical feature of S. aureus is the ability to generate thrombin activity through the secretion of two prothrombin activating molecules, staphylocoagulase and von Willebrand factor-binding protein (vWbp), which bind to human prothrombin to form the enzymatically active staphylothrombin complex. The role of staphylothrombin in the interaction between S. aureus and platelets has not yet been studied. We found that in contrast with thrombin, staphylothrombin did not directly activate human platelets. However, the staphylothrombin-mediated conversion of fibrinogen to fibrin initiated platelet aggregation and secondary activation and facilitated S. aureus-platelet interactions. Both the genetic absence of staphylocoagulase and vWbp and pharmacological inhibition of staphylothrombin increased the lag time to aggregation, and reduced platelet trapping by S. aureus in high shear stress conditions. The combined inhibition of staphylothrombin and immunoglobulin binding to platelets completely abolished the ability of S. aureus to aggregate platelets in vitro. In conclusion, although staphylothrombin did not directly activate platelets, the formation of a fibrin scaffold facilitated bacteria-platelet interaction, and the inhibition of staphylothrombin resulted in a reduced activation of platelets by S. aureus.
Ingénierie de l'interaction multimodale en entréeApproche à composants ICARE. (Multimodal Input Interaction ICARE Component-based Approach)

The area of multimodal interaction has expanded rapidly since the seminal “Put that there” demonstrator of R. Bolt that combines speech and gesture. In parallel with the development of the Graphical User Interface technology, natural language processing and gesture recognition have made significant progress. In addition, recent interaction paradigms such as tangible and embodied user interfaces as well as augmented reality open a vast world of possibilities for interaction modalities. Significant achievements have been made in terms of both modalities and real multimodal systems. Although several multimodal systems have been built, their design and development still remains a difficult task particularly because of a lack of reusability. In this thesis we address this problem of design and development for input multimodal interfaces (from the user to the system). We describe a conceptual model of multimodality as a unified framework for modalities and combinations of modalities. Based on this conceptual model, we define a generic component-based approach called ICARE which allows the easy and rapid design, development and maintenance of multimodal interfaces. We have developed the ICARE tool to prove the usefulness of our component-based approach. The ICARE tool is a graphical platform that enables the designer/developer to graphically manipulate and assemble ICARE software components in order to specify the multimodal interaction. From this specification, the code of the multimodal interaction is automatically generated. Five multimodal systems with different characteristics (augmented virtuality/ reality, mobile systems) have been developed with the ICARE tool.
Current issues in reactive power management: A critical overview

This paper reviews specific issues and challenges in reactive power management within the competitive electricity market context and increasing requirements of system security. The basic aspects refer to the specific constraints introduced by the capability curves of the generating units, the notion of opportunity costs and the questionable role of obligation to serve concerns. Other key issues are related to the responsibilities of the grid operator in transmission networks, the mechanisms for reactive power procurement with critical concerns about the use of optimization procedures, the importance of obtaining meaningful indicators and suitable sensitivity information to characterize the power system operation, and the needs for developing specific calculations based on the value of reactive support during normal operation and in dynamic conditions.
Effect of relative stimulus validity: learning or performance deficit?

This research examined whether the effect of relative stimulus validity (A.R. Wagner, F.A. Logan, K. Haberlandt, & T. Price, 1968) is a deficit of acquisition or performance. Experiment 1 demonstrated the relative validity effect using rats in a conditioned lick suppression. task. A target cue trained in the presence of another cue that was a more valid predictor of reinforcement exhibited less behavioral control than a target cue that had been trained in the presence of an equally valid predictor of reinforcement. In Experiment 2, the more valid predictor was extinguished after training. This manipulation increased responding to the target cue, thereby attenuating the effect of low relative validity. This outcome suggests that the relative validity effect is a performance deficit. In addition, recovery from the relative validity deficit was specific to the particular target stimulus that was trained in the presence of the subsequently extinguished cue.
Changing interpretation of chromosomal microarray over time in a community cohort with intellectual disability

Chromosomal microarray (CMA) is the first‐line diagnostic test for individuals with intellectual disability, autism, or multiple congenital anomalies, with a 10–20% diagnostic yield. An ongoing challenge for the clinician and laboratory scientist is the interpretation of variants of uncertain significance (VOUS)—usually rare, unreported genetic variants. Laboratories differ in their threshold for reporting VOUS, and clinical practice varies in how this information is conveyed to the family and what follow‐up is arranged. Workflows, websites, and databases are constantly being updated to aid the interpretation of VOUS. There is a growing literature reporting new microdeletion and duplication syndromes, susceptibility, and modifier copy number variants (CNVs). Diagnostic methods are also evolving with new array platforms and genome builds. In 2010, high‐resolution arrays (Affymetrix 2.7 M Oligo and SNP, 50 kB resolution) were performed on a community cohort of 67 individuals with intellectual disability of unknown aetiology. Three hundred and one CNVs were detected and analyzed using contemporary resources and a simple scoring system. Thirteen (19%) of the arrays were assessed as potentially pathogenic, 4 (6%) as benign and 50 (75%) of uncertain clinical significance. The CNV data were re‐analyzed in 2012 using the contemporary interpretative resources. There was a statistically significant difference in the assessment of individual CNVs (P < 0.0001). An additional eight patients were reassessed as having a potentially pathogenic array (n = 21, 31%) and several additional susceptibility or modifier CNVs were identified. This study highlights the complexity involved in the interpretation of CMA and uniquely demonstrates how, even on the same array platform, it can be subject to change over time. © 2013 Wiley Periodicals, Inc.
Feasibility Study of a Mini, Bone-Attached, Robotic System for Spinal Operations: Analysis and Experiments

Study Design. In this investigation, a new concept of a miniature, bone-attached, medical robotic system for spinal operations is presented. As part of the design parameters of the robot, the forces and moments applied by the physician during insertion of Kirschner wires to soft tissues and drilling in hard tissues were examined. A theoretical model for the expected error of the robotic system due to the applied force has been derived and verified experimentally. The results of a clinical experiment that was carried out on a cadaver support the theoretical model derived and the miniature, bone-attached, robotic concept. Objectives. 1) Examining the concept of attaching a miniature robotic system to the spinous process of the operated vertebra. 2) Measuring the forces applied by the physician during insertion of Kirschner wires to soft tissues and drilling in hard tissues. 3) Evaluating the expected error of the robot due to mechanical and anatomic deflection caused by the forces applied by the physician during operation. 4) Testing and verifying the theoretical background by a clinical experiment. Summary of Background Data. Spinal operations are reported in the literature to have a relatively low success rate (70%–90%). This low success rate is affected by misunderstanding of the disease and its indications, resulting in bad selection of patients. From the technical point of view, the low success rate is greatly affected by the physician’s lack of experience and the complexity of the spinal anatomy. The development of a miniature bone-attached robotic system for spinal operations could improve the success rate of spinal operations, introduce new percutaneous procedures, and shorten recovery and hospitalization time. Moreover, it will reduce the use of fluoroscopic exposure during operation; consequently, it will decrease considerably exposure to radiation during spinal operations. Methods. Forces and moments applied by the physician during operation were measured by a 6-DOF miniature sensor. The measurements were taken during K-wire insertion both to soft and to hard tissues of a sheep and a human cadaver. A theoretical model of the expected location error of a K-wire, inserted to selected vertebralanatomies by the robotic system, was derived and verified experimentally. Results. The theoretical model agreed with the experimental results, meaning that the combination of the spinous process and the robotic structure is rigid enough to guide a K-wire accurately. The forces and moments were measured and analyzed, and the total expected error due to the forces and moments was calculated. The clinical experiments supported the theoretical model and proved the system’s feasibility. Conclusions. The given results support the theoretical model developed. Moreover, a miniature robotic guiding system can be attached to the spinous process of a given vertebra. The deflection and system error resulting from the forces and moments acting during operation are within the allowable errors.
The Microbiome as a Novel Paradigm in Studying Stress and Mental Health

At the intersection between neuroscience, microbiology, and psychiatry, the enteric microbiome has potential to become a novel paradigm for studying the psychobiological underpinnings of mental illness. Several studies provide support for the view that the enteric microbiome influences behavior through the microbiota–gut–brain axis. Moreover, recent findings are suggestive of the possibility that dysregulation of the enteric microbiota (i.e., dysbiosis) and associated bacterial translocation across the intestinal epithelium may be involved in the pathophysiology of stress-related psychiatric disorders, particularly depression. The current article reviews preliminary evidence linking the enteric microbiota and its metabolites to psychiatric illness, along with separate lines of empirical inquiry on the potential involvement of psychosocial stressors, proinflammatory cytokines and neuroinflammation, the hypothalamic–pituitary–adrenal axis, and vagal nerve activation, respectively, in this relationship. Finally, and drawing on these independent lines of research, an integrative conceptual model is proposed in which stress-induced enteric dysbiosis and intestinal permeability confer risk for negative mental health outcomes through immunoregulatory, endocrinal, and neural pathways.
An Extended Active-site Motif Controls the Reactivity of the Thioredoxin Fold*

Background: Proteins with a thioredoxin (Trx) fold share several structural features but carry out different reactions. Results: The contribution of the electrostatic environment of the active site to the reactivity of Trx-fold proteins is described. Conclusion: Function and reactivity of the Trx fold depend on an extended active-site motif. Significance: These results are expected to assist with functional prediction for Trx-fold proteins. Proteins belonging to the thioredoxin (Trx) superfamily are abundant in all organisms. They share the same structural features, arranged in a seemingly simple fold, but they perform a multitude of functions in oxidative protein folding and electron transfer pathways. We use the C-terminal domain of the unique transmembrane reductant conductor DsbD as a model for an in-depth analysis of the factors controlling the reactivity of the Trx fold. We employ NMR spectroscopy, x-ray crystallography, mutagenesis, in vivo functional experiments applied to DsbD, and a comparative sequence analysis of Trx-fold proteins to determine the effect of residues in the vicinity of the active site on the ionization of the key nucleophilic cysteine of the -CXXC- motif. We show that the function and reactivity of Trx-fold proteins depend critically on the electrostatic features imposed by an extended active-site motif.
Ethics in Autism Care

Autism and autism spectrum disorders (ASDs) are now recognized as an urgent public health problem [1], as their prevalence continues to increase until now current rates of 11.3 per 1,000 children in US [2]. The social impact of ASDs is highly problematic, as these pathologies negatively affect parent and family life [3]. It has been reported increased stress and mental and physical health problems in parents of autistic children compared with parents of typically developing children [4]. Furthermore, one autistic patient is very expensive for health system, as the estimated total lifetime societal cost of caring is $3.2 million US dollars [1].
Apports et limites d'une enquête internationale: le cas de PISA en Suisse romande : Perspectives élargies

L'enquete PISA est un projet international cyclique qui vise a mesurer les competences des eleves de 15 ans. A travers l'experience de la mise en oeuvre de cette enquete dans un espace restreint (la Suisse romande), la publication des premiers resultats a eu un impact fort sur le monde de l'education en Suisse romande. La richesse, la quantite et la complexite des informations disponibles amene un certain nombre d'interrogations sur l'interpretation, la diffusion et l'utilisation des resultats. On se penchera egalement sur les problemes que posent l'exploitation a un niveau local d'informations dont le recueil est concu dans un but essentiellement de comparaison internationale.
On the electric field simulation in the electrostatic precipitators

This paper analyses the distribution of the electric field in an electrostatic precipitator through simulation techniques. For this reason the finite volume method is used. The computational program, created in MATLAB, considers the nonuniform distribution of the electrical charge density. The technique used to estimate the charge density in every point of the computational domain is similar to that used for the determination of electrostatic potential. This analogy was possible based on the observations made by analyzing the computational and experimental results obtained by other scientists and published in their previous works. So our computational model calculates both charge density and electrical field distributions using almost the same numerical techniques. The results are presented in a comparative manner. Both constant and variable charge density distributions were considered in the electrical potential and the electric field strength calculations. Also they were compared with results obtained by using a commercial program, QuickField Professional, that uses finite element method to calculate the electric field, but only for a constant value of the electrical charge density. Finally the error calculation was done. Its maximum value proved to be less than 1 %; this remark permits to formulate some conclusions. The results obtained by using our program are in good agreement with those obtained and published by other researchers.