Suche nach einem leichten Higgs-Boson im Kanal WH ev e bb in pp-Kollisionen bei s=1.96 TeV am DO-Detektor des Tevatron

Eine wichtige Komponente des Standardmodells der Teilchenphysik bildet der Higgs-Mechanismus, der benötigt wird um den vom Standardmodell beschriebenen Teilchen Masse zu verleihen. Dieser Mechanismus beinhaltet jedoch ein weiteres schweres Elementarteilchen das bislang noch nich beobachtet werden konnte. Die Suche nach diesem Teilchen ist eines Hauptziele der derzeitigen Forschung an Teilchenbeschleunigern. Diese Arbeit untersucht die vom D0-Detektor am Tevatron des Fermi National Accelerator Laboratory (FNAL) aufgezeichneten Daten von ppbar-Kollisionen bei einer Schwerpunktsenergie von sqrt{s}=1.96 TeV, um im Kanal WH -> enu bb nach einem leichten Higgs-Boson zu suchen. Darüber hinaus wird der Produktionswirkungsquerschnitt der Wbb-Produktion ermittelt. Für die Analyse stand eine integrierte Luminosität von L=255pb^{-1} zur Verfügung. Zur Selektion dieser Prozesse, werden Ereignisse ausgewählt, die Elektronen und fehlenden Transversalimpuls enthalten, sowie mindestens zwei Jets, die sich als b-Jets identifizieren lassen. Um eine effiziente Selektion zu erhalten, wurden Schnitte auf verschiedene Kenngrößen entwickelt, getestet und optimiert. Aus den selektierten Ereignissen wird der Wbb-Wirkungsquerschnitt ermittelt, der für Ereignisse angegeben wird, in denen die b-Quarks p_T>8 GeV und |eta|<3 erfüllen. Der unter Berücksichtigung des Verzweigungsverhältnisses BR(W->enu)=0.108 errechnete Wert ist sigma(Wbb)=21.8 pb (+15.5; -20.0 pb(sys+stat)). Wegen der geringen Signifikanz der Messung von etwa 1.2sigma wurden die Ereigniszahlen auch zur Berechnung einer oberen Grenze auf den Wirkungsquerschnitt verwendet, die sich bei einem Konfidenzniveau von 95% zu sigma^95(Wbb)=60.9pb ergibt. Ebenso wurden Grenzen auf den WH-Produktionswirkungsquerschnitt ermittelt. Dafür wurde die statistische Methode von Feldman und Cousins angewandt, nachdem sie nach den Vorschlägen von Conrad et al. erweitert worden war, um systematische Unsicherheiten zu berücksichtigen. Für ein Standardmodell Higgs-Boson der Masse 115 GeV kann eine obere Grenze auf den Produktionswirkungsquerschnitt von sigma^{95} (WH)=12.2pb angegeben werden. Für höhere Massen bis 135 GeV werden ähnliche Grenzen ermittelt.

Ultrasuoni focalizzati guidati da imaging di risonanza magnetica: studio delle potenziali applicazioni in campo scheletrico, esempio n.1 - osteoma osteoide

La chirurgia con ultrasuoni focalizzati guidati da MRI (MR-g-FUS) è un trattamento di minima invasività, guidato dal più sofisticato strumento di imaging a disposizione, che utilizza a scopo diagnostico e terapeutico forme di energia non ionizzante. Le sue caratteristiche portano a pensare un suo possibile e promettente utilizzo in numerose aree della patologia umana, in particolare scheletrica. L'osteoma osteoide affligge frequentemente pazienti di giovane età, è una patologia benigna, con origine ed evoluzione non chiare, e trova nella termoablazione con radiofrequenza continua sotto guida CT (CT-g-RFA) il suo trattamento di elezione. Questo lavoro ha valutato l’efficacia, gli effetti e la sicurezza del trattamento dell’osteoma osteoide con MR-g-FUS. Sono stati presi in considerazione pazienti arruolati per MR-g-FUS e, come gruppo di controllo, pazienti sottoposti a CT-g-RFA, che hanno raggiunto un follow-up minimo di 18 mesi (rispettivamente 6 e 24 pazienti). Due pazienti erano stati esclusi dal trattamento MR-g-FUS per claustrofobia (2/8). Tutti i trattamenti sono stati portati a termine con successo tecnico e clinico. Non sono state registrate complicanze o eventi avversi correlati all’anestesia o alle procedure di trattamento, e tutti i pazienti sono stati dimessi regolarmente dopo 12-24 ore. La durata media dei trattamenti di MR-g-FUS è stata di 40±21 min. Da valori di score VAS pre-trattamento oscillanti tra 6 e 10 (su scala 0-10), i trattamenti hanno condotto tutti i pazienti a VAS 0 (senza integrazioni farmacologiche). Nessun paziente ha manifestato segni di persistenza di malattia o di recidiva al follow-up. Nonostante la neurolisi e la risoluzione dei sintomi, la perfusione del nidus è stata ritrovata ancora presente in oltre il 70% dei casi sottoposti a MR-g-FUS (4/6 pazienti). I risultati derivati da un'analisi estesa a pazienti più recentemente arruolati confermano questi dati. Il trattamento con MR-g-FUS sembra essere efficace e sicuro nel risolvere la sintomatologia dell'osteoma osteoide.

Ten-year results of a three-arm prospective cohort study on implants in periodontally compromised patients. Part 1: implant loss and radiographic bone loss

OBJECTIVES: The aim of this study was to compare the long-term outcomes of implants placed in patients treated for periodontitis periodontally compromised patients (PCP) and in periodontally healthy patients (PHP) in relation to adhesion to supportive periodontal therapy (SPT). MATERIAL AND METHODS: One hundred and twelve partially edentulous patients were consecutively enrolled in private specialist practice and divided into three groups according to their initial periodontal condition: PHP, moderate PCP and severe PCP. Perio and implant treatment was carried out as needed. Solid screws (S), hollow screws (HS) and hollow cylinders (HC) were installed to support fixed prostheses, after successful completion of initial periodontal therapy (full-mouth plaque score <25% and full-mouth bleeding score <25%). At the end of treatment, patients were asked to follow an individualized SPT program. At 10 years, clinical measures and radiographic bone changes were recorded by two calibrated operators, blinded to the initial patient classification. RESULTS: Eleven patients were lost to follow-up. During the period of observation, 18 implants were removed because of biological complications. The implant survival rate was 96.6%, 92.8% and 90% for all implants and 98%, 94.2% and 90% for S-implants only, respectively, for PHP, moderate PCP and severe PCP. The mean bone loss was 0.75 (+/- 0.88) mm in PHP, 1.14 (+/- 1.11) mm in moderate PCP and 0.98 (+/- 1.22) mm in severe PCP, without any statistically significant difference. The percentage of sites, with bone loss > or =3 mm, was, respectively, 4.7% for PHP, 11.2% for moderate PCP and 15.1% for severe PCP, with a statistically significant difference between PHP and severe PCP (P<0.05). Lack of adhesion to SPT was correlated with a higher incidence of bone loss and implant loss. CONCLUSION: Patients with a history of periodontitis presented a lower survival rate and a statistically significantly higher number of sites with peri-implant bone loss. Furthermore, PCP, who did not completely adhere to the SPT, were found to present a higher implant failure rate. This underlines the value of the SPT in enhancing the long-term outcomes of implant therapy, particularly in subjects affected by periodontitis, in order to control reinfection and limit biological complications.

Human TOP1 residues implicated in species specificity of HIV-1 infection are required for interaction with BTBD2, and RNAi of BTBD2 in old world monkey and human cells increases permissiveness to HIV-1 infection

Host determinants of HIV-1 viral tropism include factors from producer cells that affect the efficiency of productive infection and factors in target cells that block infection after viral entry. TRIM5 restricts HIV-1 infection at an early post-entry step through a mechanism associated with rapid disassembly of the retroviral capsid. Topoisomerase I (TOP1) appears to play a role in HIV-1 viral tropism by incorporating into or otherwise modulating virions affecting the efficiency of a post-entry step, as the expression of human TOP1 in African Green Monkey (AGM) virion-producing cells increased the infectivity of progeny virions by five-fold. This infectivity enhancement required human TOP1 residues 236 and 237 as their replacement with the AGM counterpart residues abolished the infectivity enhancement. Our previous studies showed that TOP1 interacts with BTBD1 and BTBD2, two proteins which co-localize with the TRIM5 splice variant TRIM5 in cytoplasmic bodies. Because BTBD1 and BTBD2 interact with one HIV-1 viral tropism factor, TOP1, and co-localize with a splice variant of another, we investigated the potential involvement of BTBD1 and BTBD2 in HIV-1 restriction.

Remodeling of calcium handling in skeletal muscle through PGC-1?: impact on force, fatigability, and fiber type

Regular endurance exercise remodels skeletal muscle, largely through the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). PGC-1α promotes fiber type switching and resistance to fatigue. Intracellular calcium levels might play a role in both adaptive phenomena, yet a role for PGC-1α in the adaptation of calcium handling in skeletal muscle remains unknown. Using mice with transgenic overexpression of PGC-1α, we now investigated the effect of PGC-1α on calcium handling in skeletal muscle. We demonstrate that PGC-1α induces a quantitative reduction in calcium release from the sarcoplasmic reticulum by diminishing the expression of calcium-releasing molecules. Concomitantly, maximal muscle force is reduced in vivo and ex vivo. In addition, PGC-1α overexpression delays calcium clearance from the myoplasm by interfering with multiple mechanisms involved in calcium removal, leading to higher myoplasmic calcium levels following contraction. During prolonged muscle activity, the delayed calcium clearance might facilitate force production in mice overexpressing PGC-1α. Our results reveal a novel role of PGC-1α in altering the contractile properties of skeletal muscle by modulating calcium handling. Importantly, our findings indicate PGC-1α to be both down- as well as upstream of calcium signaling in this tissue. Overall, our findings suggest that in the adaptation to chronic exercise, PGC-1α reduces maximal force, increases resistance to fatigue, and drives fiber type switching partly through remodeling of calcium transients, in addition to promoting slow-type myofibrillar protein expression and adequate energy supply.

IL28B alleles associated with poor hepatitis C virus (HCV) clearance protect against inflammation and fibrosis in patients infected with non-1 HCV genotypes

Genetic polymorphisms near IL28B are associated with spontaneous and treatment-induced clearance of hepatitis C virus (HCV), two processes that require the appropriate activation of the host immune responses. Intrahepatic inflammation is believed to mirror such activation, but its relationship with IL28B polymorphisms has yet to be fully appreciated. We analyzed the association of IL28B polymorphisms with histological and follow-up features in 2335 chronically HCV-infected Caucasian patients. Assessable phenotypes before any antiviral treatment included necroinflammatory activity (n = 1,098), fibrosis (n = 1,527), fibrosis progression rate (n = 1,312), and hepatocellular carcinoma development (n = 1,915). Associations of alleles with the phenotypes were evaluated by univariate analysis and multivariate logistic regression, accounting for all relevant covariates. The rare G allele at IL28B marker rs8099917-previously shown to be at risk of treatment failure-was associated with lower activity (P = 0.04), lower fibrosis (P = 0.02) with a trend toward lower fibrosis progression rate (P = 0.06). When stratified according to HCV genotype, most significant associations were observed in patients infected with non-1 genotypes (P = 0.003 for activity, P = 0.001 for fibrosis, and P = 0.02 for fibrosis progression rate), where the odds ratio of having necroinflammation or rapid fibrosis progression for patients with IL28B genotypes TG or GG versus TT were 0.48 (95% confidence intervals 0.30-0.78) and 0.56 (0.35-0.92), respectively. IL28B polymorphisms were not predictive of the development of hepatocellular carcinoma.

The role of migration and domestic transmission in the spread of HIV-1 non-B subtypes in Switzerland

By analyzing human immunodeficiency virus type 1 (HIV-1) pol sequences from the Swiss HIV Cohort Study (SHCS), we explored whether the prevalence of non-B subtypes reflects domestic transmission or migration patterns.