Performance of CMS muon reconstruction in cosmic-ray events

The performance of muon reconstruction in CMS is evaluated using a large data sample of cosmic-ray muons recorded in 2008. Efficiencies of various high-level trigger, identification, and reconstruction algorithms have been measured for a broad range of muon momenta, and were found to be in good agreement with expectations from Monte Carlo simulation. The relative momentum resolution for muons crossing the barrel part of the detector is better than 1% at 10 GeV/c and is about 8% at 500 GeV/c, the latter being only a factor of two worse than expected with ideal alignment conditions. Muon charge misassignment ranges from less than 0.01% at 10GeV/c to about 1% at 500 GeV/c. © 2010 IOP Publishing Ltd and SISSA.

Manipulação do contexto da tarefa A-não-B: efeitos no comportamento perseverativo no olhar

Pós-graduação em Ciências da Motricidade - IBRC

Infestação e parasitismo natural de ninfas de Bemisia tabaci biótipo b (Hemiptera: Aleyrodidae) em soja-hortaliça e elaboração de chave de identificação de Encarsia spp. (Hymenoptera: Aphelinidae)

Pós-graduação em Agronomia (Entomologia Agrícola) - FCAV

Perfil de proteínas séricas em cães com linfoma multicêntrico de imunofenótipo B ou T: correlação com fatores prognósticos

Pós-graduação em Medicina Veterinária - FCAV

Observation of the rare B-s(0)->mu(+)mu(-) decay from the combined analysis of CMS and LHCb data

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Estudo in vitro da efetividade do hidróxido de cálcio e da polimixina B na eliminação das endotoxinas presentes nos canais radiculares

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Does anti-obsessional pharmacotherapy treat so-called comorbid depressive and anxiety states?

Background: Obsessive-compulsive disorder (OCD) is a chronic condition that normally presents high rates of psychiatric comorbidity. Depression, tic disorders and other anxiety disorders are among the most common comorbidities in OCD adult patients. There is evidence that the higher the number of psychiatric comorbidities, the worse the OCD treatment response. However, little is known about the impact of OCD treatment on the outcome of the psychiatric comorbidities usually present in OCD patients. The aim of this study was to investigate the impact of exclusive, conventional treatments for OCD on the outcome of additional psychiatric disorders of OCD patients, detected at baseline. Methods: Seventy-six patients with primary OCD admitted to the treatment protocols of the Obsessive-Compulsive Spectrum Disorders Program between July 2007 and December 2009 were evaluated at pre-treatment and after 12 months. Data were analyzed to verify possible associations between,OCD treatment response and the outcome of psychiatric comorbidities. Results: Results showed a significant association between OCD treatment response and improvement of major depression and dysthymia (p-value = 0.002), other anxiety disorders (generalized anxiety disorder, social phobia, specific phobia, posttraumatic stress disorder, panic disorder, agoraphobia and anxiety disorder not otherwise specified) (p-value = 0.054) and tic disorders (p-value = 0.043). Limitations: This is an open, non-blinded study, without rating scales for comorbid conditions. Further research is necessary focusing on the possible mechanisms by which OCD treatment could improve these specific disorders. Conclusions: Our results suggest that certain comorbid disorders may benefit from OCD-targeted treatment. (C) 2012 Elsevier B.V. All rights reserved.

Probing the interaction of brain fatty acid binding protein (B-FABP) with model membranes

Brain fatty acid-binding protein (B-FABP) interacts with biological membranes and delivers polyunsaturated fatty acids (FAs) via a collisional mechanism. The binding of FAs in the protein and the interaction with membranes involve a motif called "portal region", formed by two small α-helices, A1 and A2, connected by a loop. We used a combination of site-directed mutagenesis and electron spin resonance to probe the changes in the protein and in the membrane model induced by their interaction. Spin labeled B-FABP mutants and lipidic spin probes incorporated into a membrane model confirmed that BFABP interacts with micelles through the portal region and led to structural changes in the protein as well in the micelles. These changes were greater in the presence of LPG when compared to the LPC models. ESR spectra of B-FABP labeled mutants showed the presence of two groups of residues that responded to the presence of micelles in opposite ways. In the presence of lysophospholipids, group I of residues, whose side chains point outwards from the contact region between the helices, had their mobility decreased in an environment of lower polarity when compared to the same residues in solution. The second group, composed by residues with side chains situated at the interface between the α-helices, experienced an increase in mobility in the presence of the model membranes. These modifications in the ESR spectra of B-FABP mutants are compatible with a less ordered structure of the portal region inner residues (group II) that is likely to facilitate the delivery of FAs to target membranes. On the other hand, residues in group I and micelle components have their mobilities decreased probably as a result of the formation of a collisional complex. Our results bring new insights for the understanding of the gating and delivery mechanisms of FABPs.

B-vitamins : past, present and future in the study of the coenzymes that built and maintain a habitable planet

Trabajo realizado por Sergio Sañudo-Wilhelmy, Danielle Monteverde and Laura Gomez-Consarnau

Charakterisierung zellulärer Interaktionspartner des großen Hüllproteins des Hepatitis-B-Virus

Im Mittelpunkt dieser Arbeit stand das große L-Hüllprotein (L) des Hepatitis B - Virus. L bildet eine ungewöhnliche duale Topologie in der ER-Membran aus, welche auch im reifen Viruspartikel erhalten bleibt. In einem partiellen, posttranslationalen Reifungsprozess wird die sogenannte PräS-Region von der zytosolischen Seite der Membran aus in das ER-Lumen transloziert. Aufgrund seiner dualen Topologie und der damit verbundenen Multifunktionalität übernimmt L eine Schlüsselfunktion im viralen Lebenszyklus. Ein Schwerpunkt dieser Arbeit lag deshalb darin, neue zelluläre Interaktionspartner des L-Hüllproteins zu identifizieren. Ihre Analyse sollte helfen, das Zusammenspiel des Virus mit der Wirtszelle besser zu verstehen. Hierfür wurde das Split - Ubiquitin Hefe - Zwei - Hybrid System eingesetzt, das die Interaktionsanalyse von Membranproteinen und Membran-assoziierten Proteinen ermöglicht. Zwei der neu identifizierten Interaktionspartner, der v-SNARE Bet1 und Sec24A, die Cargo-bindende Untereinheit des CoPII-vermittelten vesikulären Transports, wurden weitergehend im humanen Zellkultursystem untersucht. Sowohl für Bet1 als auch für Sec24A konnte die Interaktion mit dem L-Hüllprotein bestätigt und der Bindungsbereich eingegrenzt werden. Die Depletion des endogenen Bet1 reduzierte die Freisetzung L-haltiger, nicht aber S-haltiger subviraler Partikel (SVP) deutlich. Im Gegensatz zu Bet1 interagierte Sec24A auch mit dem mittleren M- und kleinen S-Hüllprotein von HBV. Die Inhibition des CoPII-vermittelten vesikulären Transportweges durch kombinierte Depletion der vier Sec24 Isoformen blockierte die Freisetzung sowohl L- als auch S-haltiger SVP. Dies bedeutet, dass die HBV - Hüllproteine das ER CoPII-vermittelt verlassen, wobei sie aktiv Kontakt zur Cargo-bindenden Untereinheit Sec24A aufnehmen. Der effiziente Export der Hüllproteine aus dem ER ist für die Virusmorphogenese und somit für den HBV - Lebenszyklus essentiell. rnEin weiterer Schwerpunkt dieser Arbeit basierte auf der Interaktion des L-Hüllproteins mit dem ER-luminalen Chaperon BiP. In der vorliegenden Arbeit wurde überprüft, ob BiP, ähnlich wie das zytosolische Chaperon Hsc70, an der Ausbildung der dualen Topologie des L-Hüllproteins beteiligt ist. Hierfür wurde BiP durch die ektopische Expression seiner Ko-Chaperone BAP und ERdj4 in seiner Substrat-bindenen Kapazität manipuliert. ERdj4, ein Mitglied der Hsp40 - Proteinfamilie, stimuliert die ATPase-Aktivität von BiP, was die Substratbindung stabilisiert. Der Nukleotid - Austauschfaktor BAP hingegen vermittelt die Auflösung des BiP - Substrat - Komplexes. Die Auswirkung der veränderten in vivo-Aktivität von BiP auf die posttranslationale PräS-Translokation wurde mit Proteaseschutz - Versuchen untersucht. Die ektopische Expression des positiven als auch des negativen Regulators von BiP resultierte in einer drastischen Reduktion der posttranslationalen PräS-Translokation. Ein vergleichbarer Effekt wurde nach Manipulation des BiP ATPase - Zyklus durch Depletion der zellulären ATP - Konzentration beobachtet. Dies spricht dafür, dass das ER-luminale Chaperon BiP, zusammen mit Hsc70, eine zentrale Rolle in der Ausbildung der dualen Topologie des L-Hüllproteins spielt. rnZwei weitere Proteine, Sec62 und Sec63, die sich für die posttranslationale Translokation in der Hefe als essentiell erwiesen haben, wurden in die Analyse der dualen Topologie des L-Hüllproteins einbezogen. Interessanterweise konnte eine rein luminale Ausrichtung der PräS-Region nach kombinierter Depletion des endogenen Sec62 und Sec63 beobachtet werden. Dies deutet an, dass sowohl Sec62 als auch Sec63 an der Ausbildung der dualen Topologie des L-Hüllproteins beteiligt sind. In Analogie zur Posttranslokation der Hefe könnte Sec62 als Translokon-assoziierter Rezeptor für Substrate der Posttranslokation, und damit der PräS-Region, dienen. Sec63 könnte mit seiner J-Domäne BiP zum Translokon rekrutieren und daraufhin dessen Substrat-bindende Aktivität stimulieren. BiP würde dann, einer molekularen Ratsche gleich, die PräS-Region durch wiederholtes Binden und Freisetzen aktiv in das ER-Lumen hereinziehen, bis eine stabile duale Topologie des L-Hüllproteins ausgebildet ist. Die Bedeutung von Sec62 und Sec63 für den HBV - Lebenszyklus wird dadurch untermauert, dass sowohl die ektopische Expression als auch die Depletion des endogenen Sec63 die Freisetzung L-haltiger SVP deutlich reduziert. rn

Histone deacetylase inhibitors in adult patients with diffuse large b-cell lymphoma relapsed/refractory: a phase II study with Panobinostat

Backgrounds:Treatment of patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) not eligible to high dose therapy represents an unmet medical need. Panobinostat showed encouraging therapeutic activity in studies conducted in lymphoma cell lines and in vivo in patients with advanced hematologic malignancies.Purpose:FIL-PanAL10 (NCT01523834) is a phase II, prospective multicenter trial of the Fondazione Italiana Linfomi (FIL) to evaluate safety and efficacy of single agent Panobinostat as salvage therapy for R/R DLBCL patients and to evaluate a possible relationships between response and any biological features. Patients and Methods:Patients with R/R DLBCL were included. The treatment plan included 6 induction courses with Panobinostat monotherapy followed by other 6 courses of consolidation. The primary objective was to evaluate Panobinostat activity in terms of overall response (OR); secondary objectives were: CR rate, time to response (TTR), progression-free survival (PFS), safety and feasibility of Panobinostat. We included evaluation of the impact of pharmacogenetics, immunohistochemical patterns and patient’s specific gene expression and mutations as potential predictors of response to Panobinostat as explorative objectives. To this aim a pre-enrollment new tissue biopsy was mandatory. ResultsThirty-five patients, 21 males (60%), were enrolled between June 2011 and March 2014. At the end of induction phase, 7 responses (20%) were observed, including 4 CR (11%), while 28 patients (80%) discontinued treatment due to progressive disease (PD) in 21 (60%) or adverse events in 7 (20%). Median TTR in 9 responders was 2.6 months (range 1.8-12). With a median follow up of 6 months (range 1-34), the estimated 12 months PFS and OS were 27% and 30.5%, respectively. Grade 3-4 thrombocytopenia and neutropenia were the most common toxicities (in 29 (83%) and 12 (34%) patients, respectively. Conclusions The results of this study indicate that Panobinostat might be remarkably active in some patients with R/R DLBCL, showing durable CR

Progetto di dizionario interattivo per il pellegrino a Santiago de Compostela (spagnolo-italiano)

Il presente lavoro si concentra sullo svilupo del progetto di un Dizionario interattivo del Pellegrino a Santiago de Compostela. L’idea nasce a fronte dell’esperienza di pellegrinaggio compiuta nell’estate 2014, durante la quale si è potuta toccare con mano la necessità prestare appoggio ai pellegrini attraverso servizi di interpretazione e mediazione. Il Dizionario del Pellegrino ha l’obiettivo di venire in soccorso dei pellegrini che non hanno vicino figure in grado di tradurre, tentando di colmare parzialmente le loro lacune linguistiche attraverso l’elaborazione di un repertorio fraseologico in italiano e in spagnolo che si concentra su un numero limitato di interazioni tipo che potrebbero coinvolgere i pellegrini. Lo strumento cerca di aiutare il suo utente ampliandone le conoscenze specifiche circa gli aspetti pratici relativi al pellegrinaggio a Santiago de Compostela. Il prodotto è strutturato in alberi concettuali nelle due lingue che propongono i termini evidenziando i rapporti fra i diversi concetti. A ogni termine è poi associata una scheda terminologica non convenzionale formata da termine nelle due lingue, immagine, definizione, fraseologia e consigli pratici. L’elaborato segue la creazione del Dizionario: nel primo capitolo si espongono i risultati dello studio della storia e della geografia del Cammino a Santiago; nel secondo si passa all'analisi dell’ambiente linguistico del pellegrinaggio, di cui si evidenziano i tratti relativi al contatto fra parlanti di diverse lingue cercando di studiare gli usi dello spagnolo fra i pellegrini italiani e locali. Nel terzo capitolo tesi si espone la metodologia adottata nello sviluppo del Dizionario mentre nel quarto capitolo si può consultare una versione del prodotto, che è però pensato per essere fruito in formato elettronico e interattivo. Nel quinto capitolo analizziamo brevemente una selezione delle schede terminologiche facenti parte del Dizionario del Pellegrino e riportiamo le risposte date da alcuni pellegrini ai questionari di valutazione che avevamo sottoposto loro.

The great fluid debate: saline or so-called "balanced" salt solutions?

BACKGROUND Intravenous fluids are commonly prescribed in childhood. 0.9 % saline is the most-used fluid in pediatrics as resuscitation or maintenance solution. Experimental studies and observations in adults suggest that 0.9 % saline is a poor candidate for fluid resuscitation. Although anesthesiologists, intensive care specialists, perioperative physicians and nephrologists have been the most active in this debate, this issue deserves some physiopathological considerations also among pediatricians. RESULTS As compared with so-called "balanced" salt crystalloids such as lactated Ringer, administration of large volumes of 0.9 % saline has been associated with following deleterious effects: tendency to hyperchloremic metabolic acidosis (called dilution acidosis); acute kidney injury with reduced urine output and salt retention; damaged vascular permeability and stiffness, increase in proinflammatory mediators; detrimental effect on coagulation with tendency to blood loss; detrimental gastrointestinal perfusion and function; possible uneasiness at the bedside resulting in unnecessary administration of more fluids. Nevertheless, there is no firm evidence that these adverse effects are clinically relevant. CONCLUSIONS Intravenous fluid therapy is a medicine like insulin, chemotherapy or antibiotics. Prescribing fluids should fit the child's history and condition, consider the right dose at the right rate as well as the electrolyte levels and other laboratory variables. It is unlikely that a single type of fluid will be suitable for all pediatric patients. "Balanced" salt crystalloids, although more expensive, should be preferred for volume resuscitation, maintenance and perioperatively. Lactated Ringer appears unsuitable for patients at risk for brain edema and for those with overt or latent chloride-deficiency. Finally, in pediatrics there is a need for new fluids to be developed on the basis of a better understanding of the physiology and to be tested in well-designed trials.

BLyS/BAFF-R signaling pathway in human aggressive non Hodgkin's lymphoma B cell and normal peripheral blood B lymphocytes

B-lymphocyte stimulator (BLyS also called BAFF), is a potent cell survival factor expressed in many hematopoietic cells. BLyS levels are elevated in the serum of non-Hodgkin lymphoma (NHL) patients, and have been reported to be associated with disease progression, and prognosis. To understand the mechanisms involved in BLyS gene expression and regulation, we examined expression, function, and regulation of the BLyS gene in B cell non-Hodgkin's lymphoma (NHL-B) cells. BLyS is constitutively expressed in aggressive NHL-B cells including large B cell lymphoma (LBCL) and mantle cell lymphoma (MCL) contributing to survival and proliferation of malignant B cells. Two important transcription factors, NF-κB and NFAT, were found to be involved in regulating BLyS expression through at least one NF-κB and two NFAT binding sites in the BLyS promoter. Further study indicates that the constitutive activation of NF-κB and BLyS in NHL-B cells forms a positive feedback loop contributing to cell survival and proliferation. In order to further investigate BLyS signaling pathway, we studied the function of BAFF-R, a major BLyS receptor, on B cells survival and proliferation. Initial study revealed that BAFF-R was also found in the nucleus, in addition to its presence on plasma membrane of B cells. Nuclear presentation of BAFF-R can be increased by anti-IgM and soluble BLyS treatment in normal peripheral B lymphocytes. Inhibition of BLyS expression decreases nuclear BAFF-R level in LBCL cells. Furthermore, we showed that BAFF-R translocated to nucleus through the classic karyopherin pathway. A candidate nuclear localization sequence (NLS) was identified in the BAFF-R protein sequence and mutation of this putative NLS can block BAFF-R entering nucleus and LBCL cell proliferation. Further study showed that BAFF-R co-localized with NF-κB family member, c-rel in the nucleus. We also found BAFF-R mediated transcriptional activity, which could be increased by c-rel. We also found that nuclear BAFF-R could bind to the NF-κB binding site on the promoters of NF-κB target genes such as BLyS, CD154, Bcl-xL, Bfl-1/A1 and IL-8. These findings indicate that BAFF-R may also promote survival and proliferation of normal B cells and NHL-B cells by directly functioning as a transcriptional co-factor with NF-κB family member. ^