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991.
Ronald J. Quinn Michael J Dooley Andre Escher Fiona A. Harden Hiranthi Jayasuriya 《Nucleosides, nucleotides & nucleic acids》2013,32(5):1121-1124
Abstract Computer graphic analyses on a broad spectrum of adenosine receptor ligands has shown that both the A1 and A2 adenosine receptors have three binding sites. The spatial relationship of these three binding sites has been defined. Adenosine orientation at A1 and A2 is different. 相似文献
992.
Kyle W. Kemp Andre J. Labelle Susanna M. Thon Alexander H. Ip Illan J. Kramer Sjoerd Hoogland Edward H. Sargent 《Liver Transplantation》2013,3(7):917-922
Interface recombination was studied in colloidal quantum dot photovoltaics. Optimization of the TiO2‐PbS interface culminated in the introduction of a thin ZnO buffer layer deposited with atomic layer deposition. Transient photovoltage measurements indicated a nearly two‐fold decrease in the recombination rate around 1 sun operating conditions. Improvement to the recombination rate led to a device architecture with superior open circuit voltage (VOC) and photocurrent extraction. Overall a 10% improvement in device efficiency was achieved with Voc enhancements up to 50 mV being realized. 相似文献
993.
RasGRP proteins are activators of Ras and other related small GTPases by the virtue of functioning as guanine nucleotide exchange factors (GEFs). In vertebrates, four RasGRP family members have been described. RasGRP-1 through -4 share many structural domains but there are also subtle differences between each of the different family members. Whereas SOS RasGEFs are ubiquitously expressed, RasGRP proteins are expressed in distinct patterns, such as in different cells of the hematopoietic system and in the brain. Most studies have concentrated on the role of RasGRP proteins in the development and function of immune cell types because of the predominant RasGRP expression profiles in these cells and the immune phenotypes of mice deficient for Rasgrp genes. However, more recent studies demonstrate that RasGRPs also play an important role in tumorigenesis. Examples are skin- and hematological- cancers but also solid malignancies such as melanoma or prostate cancer. These novel studies bring up many new and unanswered questions related to the molecular mechanism of RasGRP-driven oncogenesis, such as new receptor systems that RasGRP appears to respond to as well as regulatory mechanisms for RasGRP expression that appear to be perturbed in these cancers. Here we will review some of the known aspects of RasGRP biology in lymphocytes and will discuss the exciting new notion that RasGRP Ras exchange factors play a role in oncogenesis downstream of various growth factor receptors. 相似文献
994.
Jason D. Howard Whei F. Moriarty JinSeok Park Katherine Riedy Izabela P. Panova Christine H. Chung Kahp‐Yang Suh Andre Levchenko Rhoda M. Alani 《Pigment cell & melanoma research》2013,26(5):697-707
Stromal and cellular components within the tumor microenvironment significantly influence molecular signals mediating tumor growth and progression. We recently performed a screen to evaluate critical mediators of melanoma–endothelial communication and identified several molecular pathways associated with these cellular networks, including Notch3. Here, we evaluate the nature of melanoma–endothelial communication mediated by Notch3 and its functional significance. We find that Notch3 is specifically upregulated in melanoma–endothelial cell cocultures and is functionally associated with increased Notch signaling in melanoma cells. Furthermore, induced Notch3 signaling in melanoma cell lines leads to enhanced tumor cell migration without associated increases in tumor cell growth. Additionally, Notch3 expression is specifically associated with malignant patient samples and is not evident in benign nevi. We conclude that Notch3 mediates melanoma–endothelial cell communication and tumor cell migration and may serve as a meaningful therapeutic target for this aggressive malignancy. 相似文献
995.
Julian W. Tang Andre D. Nicolle Christian A. Klettner Jovan Pantelic Liangde Wang Amin Bin Suhaimi Ashlynn Y. L. Tan Garrett W. X. Ong Ruikun Su Chandra Sekhar David D. W. Cheong Kwok Wai Tham 《PloS one》2013,8(4)
Natural human exhalation flows such as coughing, sneezing and breathing can be considered as ‘jet-like’ airflows in the sense that they are produced from a single source in a single exhalation effort, with a relatively symmetrical, conical geometry. Although coughing and sneezing have garnered much attention as potential, explosive sources of infectious aerosols, these are relatively rare events during daily life, whereas breathing is necessary for life and is performed continuously. Real-time shadowgraph imaging was used to visualise and capture high-speed images of healthy volunteers sneezing and breathing (through the nose – nasally, and through the mouth - orally). Six volunteers, who were able to respond to the pepper sneeze stimulus, were recruited for the sneezing experiments (2 women: 27.5±6.36 years; 4 men: 29.25±10.53 years). The maximum visible distance over which the sneeze plumes (or puffs) travelled was 0.6 m, the maximum sneeze velocity derived from these measured distances was 4.5 m/s. The maximum 2-dimensional (2-D) area of dissemination of these sneezes was 0.2 m2. The corresponding derived parameter, the maximum 2-D area expansion rate of these sneezes was 2 m2/s. For nasal breathing, the maximum propagation distance and derived velocity were 0.6 m and 1.4 m/s, respectively. The maximum 2-D area of dissemination and derived expansion rate were 0.11 m2 and 0.16 m2/s, respectively. Similarly, for mouth breathing, the maximum propagation distance and derived velocity were 0.8 m and 1.3 m/s, respectively. The maximum 2-D area of dissemination and derived expansion rate were 0.18 m2 and 0.17 m2/s, respectively. Surprisingly, a comparison of the maximum exit velocities of sneezing reported here with those obtained from coughing (published previously) demonstrated that they are relatively similar, and not extremely high. This is in contrast with some earlier estimates of sneeze velocities, and some reasons for this difference are discussed. 相似文献
996.
Jun Hata Hisatomi Arima Sophia Zoungas Greg Fulcher Carol Pollock Mark Adams John Watson Rohina Joshi Andre Pascal Kengne Toshiharu Ninomiya Craig Anderson Mark Woodward Anushka Patel Giuseppe Mancia Neil Poulter Stephen MacMahon John Chalmers Bruce Neal 《PloS one》2013,8(2)
Background
Endpoint adjudication committees (EPAC) are widely used in clinical trials. The aim of the present analysis is to assess the effects of the endpoint adjudication process on the main findings of the ADVANCE trial (Trial registration: ClinicalTrials.gov ). NCT00145925Methods and Findings
The ADVANCE trial was a multicentre, 2×2 factorial randomised controlled trial of blood pressure lowering and intensive blood glucose control in 11140 patients with type 2 diabetes. Primary outcomes were major macrovascular (nonfatal myocardial infarction, nonfatal stroke and cardiovascular death) and microvascular (new or worsening nephropathy and retinopathy) events. Suspected primary outcomes were initially reported by the investigators at the 215 sites with subsequent adjudication by the EPAC. The EPAC also adjudicated upon potential events identified directly by ongoing screening of all reported events. Over a median follow-up of 5 years, the site investigators reported one or more primary outcomes among 2443 participants. After adjudication these events were confirmed for 2077 (85%) with 48 further events added through the EPAC-led database screening process. The estimated relative risk reductions (95% confidence intervals) in the primary outcome for the blood pressure lowering comparison were 8% (−1 to 15%) based on the investigator-reported events and 9% (0 to 17%) based on the EPAC-based events (P for homogeneity = 0.70). The corresponding findings for the glucose comparison were 8% (1 to 15%) and 10% (2% to 18%) (P for homogeneity = 0.60). The effect estimates were also highly comparable when studied separately for macrovascular events and microvascular events for both comparisons (all P for homogeneity>0.6).Conclusions
The endpoint adjudication process had no discernible impact on the main findings in ADVANCE. These data highlight the need for careful consideration of the likely impact of an EPAC on the findings and conclusions of clinical trials prior to their establishment. 相似文献997.
Mariel Asbury Marlow Marise da Silva Mattos Maria Ernestina Makowiecky Iriane Eger Andre Luiz Rossetto Edmundo Carlos Grisard Mário Steindel 《PloS one》2013,8(2)
Background
Although known to be highly endemic in the Amazon regions of Brazil, the presence of cutaneous leishmaniasis (CL) in the subtropical southern part of the country has largely been ignored. This study was conducted to demonstrate CL is emerging in the Brazilian state of Santa Catarina, as well as to characterize the epidemiological profile and Leishmania species involved.Methodology/Principal Findings
For this cross-sectional study, data from all CL cases from Santa Catarina, Brazil, reported to the Brazilian National Notifiable Diseases Information System from 2001 to 2009 were investigated. Amplification of the kDNA minicircle conserved region followed by restriction fragment length polymorphism (PCR-RFLP) was conducted to screen for Leishmania species present in patient biopsy. Overall, 542 CL cases were reported, with majority resulting from autochthonous transmission (n = 401, 73.99%) and occurring in urban zones (n = 422, 77.86%). Age, gender, zone of residence, origin of case, clinical form and case outcome were found to differ significantly by region. Imported cases were over seven times more likely to relapse (95% CI 2.56–21.09). Mapping of cases revealed new endemic areas in northeastern Santa Catarina with two species present. With the exception of three L. (Leishmania) amazonensis cases (1.20%), majority of PCR positive samples were found to be L. (Viannia) braziliensis (n = 248, 98.80%).Conclusions/Significance
CL is now endemic in the state of Santa Catarina, Brazil, with case profiles varying significantly by region. L. (V.) braziliensis has been identified as the predominant species in the region. 相似文献998.
Andrey V. Khrunin Denis V. Khokhrin Irina N. Filippova T?nu Esko Mari Nelis Natalia A. Bebyakova Natalia L. Bolotova Janis Klovins Liene Nikitina-Zake Karola Rehnstr?m Samuli Ripatti Stefan Schreiber Andre Franke Milan Macek Veronika Kruli?ová Jan Lubinski Andres Metspalu Svetlana A. Limborska 《PloS one》2013,8(3)
Several studies examined the fine-scale structure of human genetic variation in Europe. However, the European sets analyzed represent mainly northern, western, central, and southern Europe. Here, we report an analysis of approximately 166,000 single nucleotide polymorphisms in populations from eastern (northeastern) Europe: four Russian populations from European Russia, and three populations from the northernmost Finno-Ugric ethnicities (Veps and two contrast groups of Komi people). These were compared with several reference European samples, including Finns, Estonians, Latvians, Poles, Czechs, Germans, and Italians. The results obtained demonstrated genetic heterogeneity of populations living in the region studied. Russians from the central part of European Russia (Tver, Murom, and Kursk) exhibited similarities with populations from central–eastern Europe, and were distant from Russian sample from the northern Russia (Mezen district, Archangelsk region). Komi samples, especially Izhemski Komi, were significantly different from all other populations studied. These can be considered as a second pole of genetic diversity in northern Europe (in addition to the pole, occupied by Finns), as they had a distinct ancestry component. Russians from Mezen and the Finnic-speaking Veps were positioned between the two poles, but differed from each other in the proportions of Komi and Finnic ancestries. In general, our data provides a more complete genetic map of Europe accounting for the diversity in its most eastern (northeastern) populations. 相似文献
999.
Javier Adur Lilia DSouza-Li Marcus Vinícius Pedroni Carlos E. Steiner Vitor B. Pelegati Andre A. de Thomaz Hernandes F. Carvalho Carlos L. Cesar 《PloS one》2013,8(7)
Background
The confirmatory diagnosis of Osteogenesis Imperfecta (OI) requires invasive, commonly bone biopsy, time consuming and destructive methods. This paper proposes an alternative method using a combination of two-photon excitation fluorescence (TPEF) and second-harmonic generation (SHG) microscopies from easily obtained human skin biopsies. We show that this method can distinguish subtypes of human OI.Methodology/Principal Findings
Different aspects of collagen microstructure of skin fresh biopsies and standard H&E-stained sections of normal and OI patients (mild and severe forms) were distinguished by TPEF and SHG images. Moreover, important differences between subtypes of OI were identified using different methods of quantification such as collagen density, ratio between collagen and elastic tissue, and gray-level co-occurrence matrix (GLCM) image-pattern analysis. Collagen density was lower in OI dermis, while the SHG/autofluorescence index of the dermis was significantly higher in OI as compared to that of the normal skin. We also showed that the energy value of GLCM texture analysis is useful to discriminate mild from severe OI and from normal skin.Conclusions/Significance
This work demonstrated that nonlinear microscopy techniques in combination with image-analysis approaches represent a powerful tool to investigate the collagen organization in skin dermis in patients with OI and has the potential to distinguish the different types of OI. The procedure outlined in this paper requires a skin biopsy, which is almost painless as compared to the bone biopsy commonly used in conventional methods. The data presented here complement existing clinical diagnostic techniques and can be used as a diagnostic procedure to confirm the disease, evaluate its severity and treatment efficacy. 相似文献1000.
Rudi Wisaksana Quirijn de Mast Bachti Alisjahbana Hadi Jusuf Primal Sudjana Agnes R. Indrati Rachmat Sumantri Dorine Swinkels Reinout van Crevel Andre van der Ven 《PloS one》2013,8(11)