Miracle-dz/UniFAR-FTUs huggingface dataset:
Alternative Pathway Activation of Complement by Shiga Toxin Promotes Exuberant C3a Formation That Triggers Microvascular Thrombosis

Shiga toxin (Stx)-producing E.coli O157:H7 has become a global threat to public health; it is a primary cause of diarrhea-associated hemolytic uremic syndrome (HUS), a disorder of thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure with thrombi occluding renal microcirculation. In this study, we explored whether Stx triggers complement-dependent microvascular thrombosis in in vitro and in vivo experimental settings of HUS. Stx induced on human microvascular endothelial cell surface the expression of P-selectin, which bound and activated C3 via the alternative pathway, leading to thrombus formation under flow. In the search for mechanisms linking complement activation and thrombosis, we found that exuberant complement activation in response to Stx generated an increased amount of C3a that caused further endothelial P-selectin expression, thrombomodulin (TM) loss, and thrombus formation. In a murine model of HUS obtained by coinjection of Stx2 and LPS and characterized by thrombocytopenia and renal dysfunction, upregulation of glomerular endothelial P-selectin was associated with C3 and fibrin(ogen) deposits, platelet clumps, and reduced TM expression. Treatment with anti–P-selectin Ab limited glomerular C3 accumulation. Factor B-deficient mice after Stx2/LPS exhibited less thrombocytopenia and were protected against glomerular abnormalities and renal function impairment, indicating the involvement of complement activation via the alternative pathway in the glomerular thrombotic process in HUS mice. The functional role of C3a was documented by data showing that glomerular fibrin(ogen), platelet clumps, and TM loss were markedly decreased in HUS mice receiving C3aR antagonist. These results identify Stx-induced complement activation, via P-selectin, as a key mechanism of C3a-dependent microvascular thrombosis in diarrhea-associated HUS.
Die Kriterien fiir die deutsche Genuszuweisung bei substantivischen Anglizismen

Einfiihrung Der vorliegende Aufsatz macht es sich zur Aufgabe, die von der Interferenzlinguistik im Lauf der Jahre erkannten 'Regeln' oder Kriterien zusammenzustellen, die fiir die Zuweisung eines deutschen Genus an englische Lehnsubstantive Giultigkeit haben. ' Der Beitrag ist somit nicht historisch oder diachronisch orientiert, denn die Grinde, aus denen ein substantivischer Anglizismus einem bestimmten grammatischen Geschlecht im Deutschen zugeordnet wird, gelten fiir Lehnw6rter aus allen Zeiten (vgl. TESCH: 37). 2 Englische Hauptw6rter sind seit Jahrhunderten in die deutsche Sprache eingeflossen, und Boot (um 1260) soll "das erste engl. Lehnwort in der dt. Sprache" gewesen sein.3 Seither hat es verschiedentlich Wellen der Entlehnung aus dem Englischen gegeben, so im 19. Jahrhundert, als sich eine Abwendung vom Franz6sischen bemerkbar machte (u. a. durch den Deutsch-Franz6sischen Krieg). Zu keiner friheren Zeit aber war die Einwirkung auf lexikalischer Ebene so stark wie in den Jahrzehnten seit 1945. Aus den reichlich vorhandenen statistischen Angaben fiber das stiindige Anwachsen der "Fremdw6rterflut" seit Kriegsende4 seien hier nur einige exemplarische Zahlen ausgewdihlt, die alle eine beredte Sprache sprechen: Ein Taschenbuch des Jahres 1972 bucht etwa 3000 englische Neologismen
Which EEG Patterns Warrant Treatment in the Critically Ill? Reviewing the Evidence for Treatment of Periodic Epileptiform Discharges and Related Patterns

Continuous electroencephalographic monitoring in critically ill patients has improved detection of nonconvulsive seizures and periodic discharges, but when and how aggressively to treat these electrographic patterns is unclear. A review of the literature was conducted to understand the nature of periodic discharges and the strength of the data on which management recommendations have been based. Periodic discharges are seen from a wide variety of etiologies, and the discharges themselves are electrographically heterogeneous. This spectrum suggests a need to consider these phenomena along a continuum between interictal and ictal, but more important clinically is the need to consider the likelihood of neuronal injury from each type of discharge in a given clinical setting. Recommendations for treatment are given, and a modification to current criteria for the diagnosis of nonconvulsive seizures is suggested.
Geometry Optimization of Sub-100nm Node RF CMOS Utilizing Three Dimensional TCAD Simulation

For the purpose of 90nm technology node RF CMOS geometry optimization, the effect of geometrical variations on the high frequency characteristics are precisely analyzed utilizing a three dimensional TCAD device simulator. After showing the accuracy of small-signal 3D TCAD simulation, the dependence of MOSFET's gate resistance on gate width is analyzed with the results showing that when gate width becomes shorter than 1mum gate resistance begins to increase dramatically. 3D TCAD is then applied to achieve a more practical CMOS design. The effects and trade-offs of geometrical factors, such as number, width and pitch size of gate fingers of comb-shaped transistors, are analyzed to attain an optimum combination
Drug-induced valvular heart disease

Drug-induced valvular heart disease (DIVHD) was first described in the 1960s. Initially, associations with ergot derivatives used for migraine prevention, or with anorectic drugs, were described. Drugs used for the treatment of Parkinson’s disease and endocrine diseases, like hyperprolactinemia, may also induce VHD. More recently, the use of 3,4-methylendioxymetamphetamine (MDMA, ‘Ecstasy’) and benfluorexhave been found to be associated with DIVHD. Although some of these drugs were withdrawn from the market, several cases of patients requiring valve surgery even years after the cessation of therapy have been reported. DIVHD is not infrequent, may be severe, and has been described in association with several drugs. Even after drug cessation, long-term implications of this type of VHD may persist. The present review underlines the need for a careful evaluation of the associated clinical and echocardiographic risk factors to allow early recognition so as not to delay appropriate management.
Hemifacial Microsomia: Assessment of Classification Systems

Hemifacial microsomia (HFM) represents a spectrum of congenital malformations involving embryological derivatives of the first and second branchial arches. The multiple anomalies that may exist in HFM present considerable variability in patients with the diagnosis. Numerous classification systems have been devised to facilitate the individualized components of this complex condition. Because multiple HFM classification systems exist, their utility is frequently confusing and selection of a particular system is indeterminate. Several of the better known systems are evaluated using patients with variable expressivity of HFM. This review suggests that there currently exists no ideal classification system for this association of developmental malformations. The systems that were found to be most complete are acknowledged and recommendations or modifications are suggested.
Routes and types of infection in the fetus and the newborn.

This morning it is my task to review with you the routes by which infection may reach the fetus and newborn infant, and, further, to consider the principal types of infection which we see in this period of life. I will start out by saying that the baby may become infected before birth, during delivery, and in the neonatal period. In this presentation I will limit my discussion chiefly to prenatal infections because they have occupied more of my attention and because they are less well understood and appreciated than are the infections which are acquired in neonatal life. This does not necessarily imply, though, that numerically these infections are more important than those which the baby acquires during delivery or in the neonatal period, of which we will hear more in the subsequent presentation. As I go along this morning it will become evident that two principal classes of
Mindfulness and Behavioral Parent Training: Commentary

We review the description of mindfulness-based parent training (MBPT) and the argument that mindfulness practice offers a way to bring behavioral parent training (BPT) in line with current empirical knowledge. The strength of the proposed MBPT model is the attention it draws to process issues in BPT. We suggest, however, that it may not be necessary to posit automatized transactional procedures in the parent–child interaction to justify the need for better delineation of therapist-parent communication in treatment. Empirically established behavioral processes may be used within BPT to accomplish parent-training goals similar to those proposed for mindfulness training. Yet, Dumas (2005) offers refreshing ideas for enhancing the therapeutic alliance and success with the parents of disruptive children.
Lurasidone in the treatment of acute schizophrenia: a double-blind, placebo-controlled trial.

OBJECTIVE Lurasidone is a novel psychotropic agent with high affinity for D(2) and 5-HT(2A) receptors, as well as for receptors implicated in the enhancement of cognition and mood and the reduction of negative symptoms (5-HT(7), 5-HT(1A), and alpha(2c)). The objective of the study was to evaluate the safety and efficacy of lurasidone in patients hospitalized for an acute exacerbation of DSM-IV-defined schizophrenia. METHOD Patients were randomly assigned to 6 weeks of double-blind treatment with a fixed dose of lurasidone 80 mg (N = 90, 75.6% male, mean age = 39.7 years, mean baseline score on the Brief Psychiatric Rating Scale derived from the Positive and Negative Syndrome Scale [BPRSd] = 55.1) or placebo (N = 90, 77.8% male, mean age = 41.9 years, mean BPRSd score = 56.1). The primary efficacy measure was the BPRSd. The study was conducted from May to December 2004. RESULTS At day 42, last-observation-carried-forward endpoint, treatment with lurasidone was associated with significant improvement compared to placebo on the BPRSd (least squares mean +/- SE = -8.9 +/- 1.3 vs. -4.2 +/- 1.4; p = .012), as well as on all secondary efficacy measures, including the PANSS total score (-14.1 +/- 2.1 vs. -5.5 +/- 2.2; p = .004) and the PANSS positive (-4.3 +/- 0.7 vs. -1.7 +/- 0.7; p = .006), negative (-2.9 +/- 0.5 vs. -1.3 +/- 0.5; p = .025), and general psychopathology (-7.0 +/- 1.1 vs. -2.7 +/- 1.2; p = .0061) subscales. Significant improvement was seen as early as day 3, based on BPRSd, PANSS, and Clinical Global Impressions-Severity of Illness assessments. Treatment with lurasidone was generally well tolerated and was not associated with adverse changes in metabolic or electrocardiogram parameters. There were no clinically significant differences between lurasidone and placebo in objective measures of extrapyramidal symptoms. CONCLUSIONS The results of this study suggest that the novel psychotropic agent lurasidone is a safe and effective treatment for patients with an acute exacerbation of schizophrenia. TRIAL REGISTRATION (ClinicalTrials.gov) Identifier: NCT00088634.
Analysis of hardlimiting parallel interference cancellation (PIC) for synchronous CDMA communication

Parallel interference cancellation (PIC) is a widely considered approach to multiuser detection in CDMA communication. While PIC receivers normally involve nonlinear functions, previous performance analyses mainly addressed linear PIC. We find that the performance of purely hardlimiting PIC may not improve after the second stage. In addition, for the two-user case, one stage usually suffices. Further, the performance of hardlimiting PIC does not approach the single-user limit. We also develop approximate expressions for numerical evaluation of the hardlimiting PIC performance. Simulation results agree well with the analysis.
The role of H pylori in gastrointestinal disease

PREVIEW Helicobacter pylori, which is responsible for the most common infection worldwide, has been implicated in several gastrointestinal diseases, such as peptic ulcer disease, gastric adenocarcinoma, and mucosa-associated lymphoid tissue (MALT) lymphoma. In this article, Dr Knigge discusses the unique adaptation of H pylori to the acidic gastric environment and describes diagnostic tests to identify the organism, treatment recommendations, and tools to confirm eradication of infection.
A Rickettsia WASP‐like protein activates the Arp2/3 complex and mediates actin‐based motility

Spotted fever group Rickettsia are obligate intracellular pathogens that exploit the host cell actin cytoskeleton to promote motility and cell‐to‐cell spread. Although other pathogens such as Listeria monocytogenes use an Arp2/3 complex‐dependent nucleation mechanism to generate comet tails consisting of Y‐branched filament arrays, Rickettsia polymerize tails consisting of unbranched filaments by a previously unknown mechanism. We identified genes in several Rickettsia species encoding proteins (termed RickA) with similarity to the WASP family of Arp2/3‐complex activators. Rickettsia rickettsii RickA activated both the nucleation and Y‐branching activities of the Arp2/3 complex like other WASP‐family proteins, and was sufficient to direct the motility of microscopic beads in cell extracts. Actin tails generated by RickA‐coated beads consisted of Y‐branched filament networks. These data suggest that Rickettsia use an Arp2/3 complex‐dependent actin‐nucleation mechanism similar to that of other pathogens. We propose that additional Rickettsia or host factors reorganize the Y‐branched networks into parallel arrays in a manner similar to a recently proposed model of filopodia formation.
Pathophysiology of contrast medium-induced nephropathy.

BACKGROUND Contrast medium-induced nephropathy (CIN) is a well-known cause of acute renal failure, but the development of CIN remains poorly understood. A number of studies have been performed with the one aim, to shed some light onto the pathophysiology of CIN. These have led to manifold interpretations and sometimes contradicting conclusions. METHODS This review critically surveys mechanisms believed to mediate CIN by highlighting the complex pathophysiologic entity, including altered rheologic properties, perturbation of renal hemodynamics, regional hypoxia, auto- and paracrine factors [adenosine, endothelin, and reactive oxygen species (ROS)], and direct cytotoxic effects. Moreover, the importance of physicochemical properties of contrast media are made clear. RESULTS The more recently developed iso-osmolar contrast media are dimers, not monomers as the widely used nonionic low osmolar contrast media. The dimers have physicochemical features different from other contrast media which may be of clinical importance, not only with respect to osmolality. The viscosity of the commercially available dimers is considerably higher than blood. CONCLUSION Many experimental studies provide evidence for a greater perturbation in renal functions by dimeric contrast media in comparison to nonionic monomeric contrast media. Clinical trials have yielded conflicting results.
Phase I pharmacologic and pharmacodynamic study of the gamma secretase (Notch) inhibitor MK-0752 in adult patients with advanced solid tumors.

PURPOSE Aberrant Notch signaling has been implicated in the pathogenesis of many human cancers. MK-0752 is a potent, oral inhibitor of γ-secretase, an enzyme required for Notch pathway activation. Safety, maximum-tolerated dose, pharmacokinetics (PKs), pharmacodynamics, and preliminary antitumor efficacy were assessed in a phase I study of MK-0752. PATIENTS AND METHODS MK-0752 was administered in three different schedules to patients with advanced solid tumors. Hair follicles were collected at higher dose levels to assess a gene signature of Notch inhibition. RESULTS Of 103 patients who received MK-0752, 21 patients received a continuous once-daily dosing at 450 and 600 mg; 17 were dosed on an intermittent schedule of 3 of 7 days at 450 and 600 mg; and 65 were dosed once per week at 600, 900, 1,200, 1,500, 1,800, 2,400, 3,200, and 4,200 mg. The most common drug-related toxicities were diarrhea, nausea, vomiting, and fatigue. PKs (area under the concentration-time curve and maximum measured plasma concentration) increased in a less than dose proportional manner, with a half-life of approximately 15 hours. Significant inhibition of Notch signaling was observed with the 1,800- to 4,200-mg weekly dose levels, confirming target engagement at those doses. One objective complete response and an additional 10 patients with stable disease longer than 4 months were observed among patients with high-grade gliomas. CONCLUSION MK-0752 toxicity was schedule dependent. Weekly dosing was generally well tolerated and resulted in strong modulation of a Notch gene signature. Clinical benefit was observed, and rational combination trials are currently ongoing to maximize clinical benefit with this novel agent.
Approche fonctionnelle de l’outillage lithique à l'aube de l'Holocène dans le nord-ouest de la France

Apres une simplification significative des methodes de debitage durant l'Azilien, rompant progressivement avec les normes magdaleniennes, le retour au cours du Dryas recent a des productions lamino-lamellaires elaborees marque un tournant abrupt dans la tradition lithique. Bien qu'un certain flou pese sur la chronologie des evenements, les recherches menees depuis quelques annees autour des industries de la transition Pleistocene-Holocene permettent de bien cerner les transformations survenues dans les modalites et les objectifs des productions lithiques. En revanche, malgre le fait que les interrogations des chercheurs soient largement orientees vers des reconstitutions d'ordre palethnographiques, les finalites fonctionnelles des outils, leur modalite d'emploi et les chaines operatoires dans lesquelles ils sont impliques restent des themes de recherche tres peu abordes. C'est afin de pallier ce manque que nous avons explore ces questions a travers l'analyse traceologique des industries lithiques de deux sites du nord-ouest de la France issus d'operations recentes (Le Buhot a Calleville, Eure ; La Fosse a Villiers-Charlemagne, Mayenne). L'apport de ce travail est appreciable a differentes echelles spatio-temporelles. Sur le temps court, les resultats obtenus revelent des contrastes saisissants entre les occupations, tant au regard des activites menees par l'intermediaire des outils que de l'economie des produits des debitages, et enrichissent le modele de complementarite des sites deja propose. Sur le temps long, le croisement des donnees fonctionnelles acquises ces trente dernieres annees entre l'Azilien et le premier Mesolithique et les autres donnees du registre archeologique permet de discuter des inflexions dans les systemes techniques et les economies prehistoriques.
Insulin stimulates the kinase activity of RAC‐PK, a pleckstrin homology domain containing ser/thr kinase.

In the present study, insulin is shown to rapidly stimulate by 8‐ to 12‐fold the enzymatic activity of RAC‐PK alpha, a pleckstrin homology domain containing ser/thr kinase. In contrast, activation of protein kinase C by phorbol esters had almost no effect on the enzymatic activity of RAC‐PK alpha. Insulin activation was accompanied by a shift in molecular weight of the RAC‐PK alpha protein, and the activated kinase was deactivated by treatment with a phosphatase, indicating that insulin activated the enzyme by stimulating its phosphorylation. This insulin‐induced shift in RAC‐PK was also observed in primary rat epididymal adipocytes, as well as in a muscle cell line called C2C12 cells. The insulin‐stimulated increase in RAC‐PK alpha activity was inhibited by wortmannin (an inhibitor of phosphatidylinositol 3‐kinase) in a dose‐dependent manner with a half‐maximal inhibition of 10 nM, but not by 20 ng/ml of rapamycin. Activation of RAC‐PK alpha activity was also observed in a variant RAC lacking the pleckstrin homology domain. These results indicate that RAC‐PK alpha activity can be regulated by the insulin receptor. RAC‐PK alpha may therefore play a general role in intracellular signaling mediated by receptor tyrosine kinases.
Molecular and cellular basis of chemically induced immunotoxicity.

Immunotoxicology is the study of adverse effects on the immune system resulting from occupational, inadvertent, or therapeutic exposure to drugs, environmental chemicals, and, in some instances, biological materials. For the purpose of this chapter, we refer to these substances collectively as "xenobiotics. " Immunotoxicity is subdivided into three main research areas: (a) studies of altered immunological events associated with exposure of humans and animals to xenobiotics, including altered host resistance to infectious disease; (b) studies of allergy and autoimmunity resulting from xenobiotic exposure; and (c) implementation of analytical immunological methods into toxicology research. This chapter focuses only on chemical­ induced immunomodulation and describes several classes of irnmunotoxic xenobiotics, emphasizing cellular and molecular targets. Laboratory studies, conducted primarily in rodents, have provided evi­ dence that the immune system is very sensitive to chemical injury (reviewed in 1-6). This sensitivity is probably due as much to the general properties of a xenobiotic (e.g. reactivity with macromolecules) as to the complex nature of the immune system, which encompasses antigen recognition and processing;
Social Capital and the Creation of Knowledge

This paper examines the relationship between the social capital and knowledge creation in research, mostly in the context of universities. The analysis is developed considering all of the following critical aspects of social capital: direct ties, strengths of direct ties, density, structural holes, centrality, and external-internal index in terms of fields of knowledge. Two important results arise from this research. First, the overall results suggest that, when controlling for other network variables and individual heterogeneity, the effects of the structural holes variable disappear. This result stands in contrast to the established idea that structural holes is the most important variable to represent social capital and, therefore, is seen as contributing to superior performance. Second, the results show that with this strong set of controls, what matters in social capital is having many direct ties, being in a central position, having partners from different areas of knowledge, and being part of a non dense network.
Hamming distance between partitions , clustering comparison and information

Measuring the distance between partitions is useful for clustering comparison in different fields. For example, in bioinformatics the measuring mostly obtains through a maximum matching distance MMD, although this is algorithmically demanding and hardly fits certain instances. In fact, another distance measure is being tested, namely one based on information theory and termed variation of information VI. Alternatively, this paper proposes the Hamming distance HD, displaying large range and great measurement sensitivity, while also relying on a neat binary string representation of partitions. Novel distance HD is computationally handy and shares with VI important characterizing axioms. Developing from the combinatorial concern to translate the traditional Hamming distance from subset to partition lattices, HD constitutes a valuable computational tool for clustering and information processing where a distance between partitions is to be measured.