A Compact Gas Cerenkov Detector with Novel Optics

We discuss the design and performance of a threshold Cerenkov counter for identification of charged hadrons. The radiator is pressurized gas, which is contained in thin-walled cylindrical modules. A mirror system of novel design transports Cerenkov photons to photomultiplier tubes. This system is compact, contains relatively little material, and has a large fraction of active volume. A prototype of a module designed for the proposed CLEO III detector has been studied using cosmic rays. Results from these studies show good agreement with a detailed Monte Carlo simulation of the module and indicate that it should achieve separation of pions and kaons at the 2.5-3.0sigma level in the momentum range 0.8-2.8 GeV/c. We predict performance for specific physics analyses using a GEANT-based simulation package.Comment: Submitted to NIM. 23 pages, 11 postscript figures. Postscript file is also available at http://w4.lns.cornell.edu/public/CLNS/199

Evidence for the immobile bipolaron formation in the paramagnetic state of the magnetoresistive manganites

Recent research suggests that the charge carriers in the paramagnetic state of the magnetoresistive manganites are small polarons. Here we report studies of the oxygen-isotope effects on the intrinsic resistivity and thermoelectric power in several ferromagnetic manganites. The precise measurements of these isotope effects allow us to make a quantitative data analysis. Our results do not support a simple small-polaron model, but rather provide compelling evidence for the presence of small immobile bipolarons, i.e., pairs of small polarons. Since the bipolarons in the manganites are immobile, the present result alone appears not to give a positive support to the bipolaronic superconductivity theory for the copper-based perovskites.Comment: 6 pages, 5 figures, monor correction

Prognostic and therapeutic significance of carbohydrate antigen 19-9 as tumor marker in patients with pancreatic cancer

In pancreatic cancer ( PC) accurate determination of treatment response by imaging often remains difficult. Various efforts have been undertaken to investigate new factors which may serve as more appropriate surrogate parameters of treatment efficacy. This review focuses on the role of carbohydrate antigen 19- 9 ( CA 19- 9) as a prognostic tumor marker in PC and summarizes its contribution to monitoring treatment efficacy. We undertook a Medline/ PubMed literature search to identify relevant trials that had analyzed the prognostic impact of CA 19- 9 in patients treated with surgery, chemoradiotherapy and chemotherapy for PC. Additionally, relevant abstract publications from scientific meetings were included. In advanced PC, pretreatment CA 19- 9 levels have a prognostic impact regarding overall survival. Also a CA 19- 9 decline under chemotherapy can provide prognostic information for median survival. A 20% reduction of CA 19- 9 baseline levels within the first 8 weeks of chemotherapy appears to be sufficient to define a prognostic relevant subgroup of patients ('CA 19- 9 responder'). It still remains to be defined whether the CA 19- 9 response is a more reliable method for evaluating treatment efficacy compared to conventional imaging. Copyright (c) 2006 S. Karger AG, Basel

First-in-Human Studies of MW01-6-189WH, a Brain-Penetrant, Antineuroinflammatory Small-Molecule Drug Candidate: Phase 1 Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Studies in Healthy Adult Volunteers

MW01-6-189WH (MW189) is a novel central nervous system-penetrant small-molecule drug candidate that selectively attenuates stressor-induced proinflammatory cytokine overproduction and is efficacious in intracerebral hemorrhage and traumatic brain injury animal models. We report first-in-human, randomized, double-blind, placebo-controlled phase 1 studies to evaluate the safety, tolerability, and pharmacokinetics (PK) of single and multiple ascending intravenous doses of MW189 in healthy adult volunteers. MW189 was safe and well tolerated in single and multiple doses up to 0.25 mg/kg, with no clinically significant concerns. The most common drug-related treatment-emergent adverse event was infusion-site reactions, likely related to drug solution acidity. No clinically concerning changes were seen in vital signs, electrocardiograms, physical or neurological examinations, or safety laboratory results. PK analysis showed dose-proportional increases in plasma concentrations of MW189 after single or multiple doses, with approximately linear kinetics and no significant drug accumulation. Steady state was achieved by dose 3 for all dosing cohorts. A pilot pharmacodynamic study administering low-dose endotoxin to induce a systemic inflammatory response was done to evaluate the effects of a single intravenous dose of MW189 on plasma cytokine levels. MW189 treatment resulted in lower levels of the proinflammatory cytokine TNF-α and higher levels of the anti-inflammatory cytokine IL-10 compared with placebo treatment. The outcomes are consistent with the pharmacological mechanism of MW189. Overall, the safety profile, PK properties, and pharmacodynamic effect support further development of MW189 for patients with acute brain injury

Electrophysiological Evidence of Atypical Spatial Attention in Those with a High Level of Self-reported Autistic Traits

Selective attention is atypical in individuals with autism spectrum conditions. Evidence suggests this is also the case for those with high levels of autistic traits. Here we investigated the neural basis of spatial attention in those with high and low levels of self-reported autistic traits via analysis of ERP deflections associated with covert attention, target selection and distractor suppression (the N2pc, NT and PD). Larger N2pc and smaller PD amplitude was observed in those with high levels of autistic traits. These data provide neural evidence for differences in spatial attention, specifically, reduced distractor suppression in those with high levels of autistic traits, and may provide insight into the experience of perceptual overload often reported by individuals on the autism spectrum

Multi-phonon Raman scattering in semiconductor nanocrystals: importance of non-adiabatic transitions

Multi-phonon Raman scattering in semiconductor nanocrystals is treated taking into account both adiabatic and non-adiabatic phonon-assisted optical transitions. Because phonons of various symmetries are involved in scattering processes, there is a considerable enhancement of intensities of multi-phonon peaks in nanocrystal Raman spectra. Cases of strong and weak band mixing are considered in detail. In the first case, fundamental scattering takes place via internal electron-hole states and is participated by s- and d-phonons, while in the second case, when the intensity of the one-phonon Raman peak is strongly influenced by the interaction of an electron and of a hole with interface imperfections (e. g., with trapped charge), p-phonons are most active. Calculations of Raman scattering spectra for CdSe and PbS nanocrystals give a good quantitative agreement with recent experimental results.Comment: 16 pages, 2 figures, E-mail addresses: [email protected], [email protected], [email protected], accepted for publication in Physical Review

Pattern of mRNA expression of β-defensins in basal cell carcinoma

BACKGROUND: Although the human β-defensins hBDs today seem to have diverse functional activities in innate antimicrobial immunity, a few reports also indicated an altered expression of these antimicrobial peptides (AMPs) in tissues of cancers such as oral squamous cell carcinoma. The present work was aimed on the study of hBD gene expression in basal cell carcinoma (BCC) which is the most common cancer in humans. METHODS: Twenty-two non-ulcerated BCCs (12 nodular type, 10 superficial type) have been analysed for the presence of hBD (1–3) mRNA by quantitative real-time RT-PCR. As controls, non-lesional skin specimens of BCC patients as well as samples of healthy subjects were assessed by RT-PCR. RESULTS: hBD-1 levels in healthy controls and non-lesional skin of BCC patients were significantly (P < 0.05) higher than the levels observed in tumour tissue. Moreover, BCCs showed significantly (P < 0.05) increased mRNA expression of hBD-2 as compared to controls. There was no significant (P > 0.05) difference between lesional mRNA levels for hBD-3 and those levels observed in controls. The mRNA expression of hBDs (1–3) found in nodular and superficial BCCs did not significantly (P > 0.05) differ. CONCLUSION: The gene expression patterns of hBD-1 and hBD-2 are for the first time shown to be significantly altered in non-ulcerated BCCs as compared to intra-individual and inter-individual controls, respectively. The present findings may indicate that beside the antimicrobial activity of AMPs, hBDs may also play a role in the pathogenesis of BCC. However, functional and immunohistological studies investigating hBDs in patients with BCC are needed to confirm our data

Event-Related Potentials Dissociate Effects of Salience and Space in Biased Competition for Visual Representation

BACKGROUND: Selective visual attention is the process by which the visual system enhances behaviorally relevant stimuli and filters out others. Visual attention is thought to operate through a cortical mechanism known as biased competition. Representations of stimuli within cortical visual areas compete such that they mutually suppress each others' neural response. Competition increases with stimulus proximity and can be biased in favor of one stimulus (over another) as a function of stimulus significance, salience, or expectancy. Though there is considerable evidence of biased competition within the human visual system, the dynamics of the process remain unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here, we used scalp-recorded electroencephalography (EEG) to examine neural correlates of biased competition in the human visual system. In two experiments, subjects performed a task requiring them to either simultaneously identify two targets (Experiment 1) or discriminate one target while ignoring a decoy (Experiment 2). Competition was manipulated by altering the spatial separation between target(s) and/or decoy. Both experimental tasks should induce competition between stimuli. However, only the task of Experiment 2 should invoke a strong bias in favor of the target (over the decoy). The amplitude of two lateralized components of the event-related potential, the N2pc and Ptc, mirrored these predictions. N2pc amplitude increased with increasing stimulus separation in Experiments 1 and 2. However, Ptc amplitude varied only in Experiment 2, becoming more positive with decreased spatial separation. CONCLUSIONS/SIGNIFICANCE: These results suggest that N2pc and Ptc components may index distinct processes of biased competition--N2pc reflecting visual competitive interactions and Ptc reflecting a bias in processing necessary to individuate task-relevant stimuli