bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exon‐skipped dystrophins for treatment of Duchenne muscular dystrophy: Mass spectrometry mapping of most exons and cooperative domain designs based on single molecule mechanics
Authors: Krieger Christine Carag , Bhasin Nishant , Tewari Manorama , Brown Andre E. X. , Safer Daniel , Sweeney H. Lee , Discher Dennis E. 
Published: September 2010

AbstractForce‐bearing linkages between the cytoskeleton and extracellular matrix are clearly important to normal cell viability—as is evident in a disease such as Duchenne muscular dystrophy (DMD) which arises in the absence of the linkage protein dystrophin. Therapeutic approaches to DMD include antisense‐mediated skipping of exons to delete nonsense mutations while maintaining reading frame, but the structure and stability of the resulting proteins are generally unclear. Here we use mass spectrometry to detect most dystrophin exons, and we express and physically characterize dystrophin “nano”‐constructs based on multiexon deletions that might find use in a large percentage of DMD patients. The primary structure challenge is addressed first with liquid chromatography tandem mass spectrometry (LC‐MS/MS) which can detect tryptic peptides from 53 of dystrophin's 79 exons; equivalent information from immunodetection would require 53 different high‐specificity antibodies. Folding predictions for the nano‐constructs reveal novel helical bundle domains that arise out of exon‐deleted “linkers,” while secondary structure studies confirm high helicity and also melting temperatures well above physiological. Extensional forces with an atomic force microscope nonetheless unfold the constructs, and the ensemble of unfolding trajectories reveal the number of folded domains, proving consistent with structure predictions. A mechanical cooperativity parameter for unfolding of tandem domains is also introduced as the best predictor of a multiexon deletion that is asymptomatic in humans. The results thereby provide insight and confidence in exon‐skipped designs. © 2010 Wiley‐Liss, Inc.
Pulmonary tuberculosis increases the risk of lung cancer
Authors: Wu Chen‐Yi , Hu Hsiao‐Yun , Pu Cheng‐Yun , Huang Nicole , Shen Hsi‐Che , Li Chung‐Pin , Chou Yiing‐Jeng 
Published: September 2010

AbstractBACKGROUND:The possible effect of pulmonary tuberculosis (TB) on subsequent lung cancer development has been suspected, but the evidence remains inconsistent. The purpose of this study was to perform a nationwide population‐based cohort study to investigate the risk of lung cancer after pulmonary TB infection.METHODS:This nationwide population‐based cohort study was based on data obtained from the Taiwan National Health Insurance Database. In total, 5657 TB patients and 23,984 controls matched for age and sex were recruited for the study from 1997 to 2008.RESULTS:The incidence rate of lung cancer (269 of 100,000 person‐years) was significantly higher in the pulmonary TB patients than that in controls (153 of 100,000 person‐years) (incidence rate ratio [IRR], 1.76; 95% confidence interval [CI], 1.33‐2.32; P < .001). Compared with the controls, the IRRs of lung cancer in the TB cohort were 1.98 at 2 to 4 years, 1.42 at 5 to 7 years, and 1.59 at 8 to 12 years after TB infections. The multivariate Cox proportional hazards model revealed pulmonary TB infections (hazard ratio [HR], 1.64; 95% CI, 1.24‐2.15; P < .001) and chronic obstructive pulmonary disease (HR, 1.09; 95% CI, 1.03‐1.14; P = .002) to be independent risk factors for lung cancer.CONCLUSIONS:Pulmonary infection with TB is associated with an increased risk of lung cancer. Cancer 2011. © 2010 American Cancer Society.
Surgical treatment of breast cancer among the elderly in the United States
Authors: Alderman Amy K. , Bynum Julie , Sutherland Jason , Birkmeyer Nancy , Collins E. Dale , Birkmeyer John 
Published: September 2010

AbstractBACKGROUND:Breast‐conserving therapy (BCT) has emerged as the preferred treatment for most women with early stage breast cancer. However, there is concern for underuse in the elderly, with previously documented low rates of BCT and large variations in practice patterns. The authors' purpose was to examine patterns and correlates of BCT for breast cancer in the elderly US population.METHODS:The primary outcome was receipt of BCT. The 2003 to 2004 Medicare inpatient, outpatient, and carrier files were used to identify incident breast cancer patients and the American Medical Association to ascertain surgeon information. The primary independent variables were US state where treatment was performed along with patient and surgeon sociodemographic information. Multivariate logistic regression was used for the analyses.RESULTS:BCT was performed in 81.8% of patients (N = 20,032). Variation in use of BCT across states was low, ranging from 74.2% in Utah to 84.0% in New Mexico. Several factors were significantly associated with low use of BCT: advanced patient age (>85 vs <70 years: odds ratio [OR], 0.50; 95% confidence interval [CI], 0.42‐0.59); comorbidities (>3 vs ≤3: OR, 0.26; 95% CI, 0.24‐0.28), and low socioeconomic status (SES) (lowest quintile vs highest quintile SES: OR, 0.60; 95% CI, 0.52‐0.68). Variation in use of BCT by surgeon was low, although female surgeons aged 40 to 49 years and ≥60 years had significantly higher use compared with younger men.CONCLUSIONS:BCT has become the primary management among elderly breast cancer patients. Despite earlier studies to the contrary, there is now little variation in BCT use among Medicare patients. Cancer 2011. © 2010 American Cancer Society.
Hyperthermia combined with radiation for the treatment of locally advanced prostate cancer
Authors: Hurwitz Mark D. , Hansen Jorgen L. , Prokopios‐Davos Savina , Manola Judith , Wang Qian , Bornstein Bruce A. , Hynynen Kullervo , Kaplan Irving D. 
Published: September 2010

AbstractBACKGROUND:The authors present long‐term results from a phase 2 study that assessed the efficacy of transrectal ultrasound hyperthermia plus radiation with or without androgen suppression for the treatment of locally advanced prostate cancer.METHODS:Patients with clinical T2b‐T3bN0M0 disease (according to 1992 American Joint Committee on Cancer [AJCC] criteria) received radiation plus 2 transrectal ultrasound hyperthermia treatments. After the first 4 patients, 6 months of androgen suppression were allowed. The study was designed to assess absolute improvement in the 2‐year disease‐free survival rate compared with the short‐term androgen suppression arm in Radiation Therapy Oncology Group (RTOG) study 92‐02.RESULTS:Thirty‐seven patients received a total of 72 hyperthermia treatments. The mean cumulative equivalent minutes (CEM) T9043°C was 8.4 minutes. According to the 1992 AJCC classification, there were 19 patients with T2b tumors, 8 patients with T2c tumors, 5 patients with T3a tumors, and 5 patients with T3b tumors. The median Gleason score was 7 (range, 6‐9), and the median prostate‐specific antigen (PSA) level was 13.3 ng/mL (range, 2‐65 ng/mL). Thirty‐three patients received androgen suppression. At a median follow‐up of 70 months (range, 18‐110 months), the 7‐year overall survival rate was 94%, and 61% of patients remained failure free (according to the American Society for Therapeutic Radiology and Oncology definition for failure free survival). The absolute rate of disease‐free survival at 2 years, which was the primary study endpoint, improved significantly (84%) compared with a rate of 64% for similar patients on the 4‐month androgen suppression arm of RTOG 92‐02. When Phoenix criteria (PSA nadir + 2 ng/mL) were used to define biochemical failure, 89% of patients were failure free at 2 years.CONCLUSIONS:Hyperthermia combined with radiation for the treatment of locally advanced prostate cancer appeared to be promising. The current results indicated that further study of hyperthermia for the treatment of prostate cancer with optimal radiation and systemic therapy is warranted. Cancer 2010. © 2010 American Cancer Society.
PDX‐1
Authors: Liu Shi‐He , Patel Sanjeet , Gingras Marie‐Claude , Nemunaitis John , Zhou Guisheng , Chen Changyi , Li Min , Fisher William , Gibbs Richard , Brunicardi F. Charles 
Published: September 2010

AbstractBACKGROUND:Pancreatic‐duodenal homeobox 1 (PDX‐1) is a transcription factor that regulates embryologic pancreas development and insulin expression in the adult islet; however, it is overexpressed in many types of cancer, including pancreatic cancer. The purpose of this study was to investigate the role of PDX‐1 in tumorigenesis in human cells.METHODS:In vitro cell proliferation, invasion, and transformation were performed in human embryonic kidney cell line (HEK 293), pancreatic cancer cell line MIA PaCa2, and human pancreatic ductal epithelial (HPDE) cells transiently or stably expressing PDX‐1 or green fluorescent protein (GFP) PDX‐1, with or without cotransfection of PDX‐1 short hairpin RNA (shRNA). In vivo tumor formation was carried out in severe combined immunodeficiency (SCID) mice with subcutaneous injection of HEK 293 and MIA PaCa2 stably transfected cells. Cell cycle was analyzed by Western blot or immunostaining. Microarray of RNA from pancreatic adenocarcinoma cells with and without PDX‐1 shRNA was performed and analyzed.RESULTS:Transient and stable expressing PDX‐1 significantly increased cell proliferation and invasion in HEK 293, human pancreatic ductal epithelial (HPDE), and MIA PaCa2 cells versus controls (P < .05), human PDX‐1 shRNA reversed these effects. Expression of PDX‐1 significantly increased colony formation in HEK 293, HPDE, and MIA PaCa2 cells versus controls in vitro (P < .05). PDX‐1 promoted HEK 293 and MIA PaCa2 tumor formation in SCID mice as compared with that of control (P < .05). PDX‐1 overexpression disrupted cell cycles proteins. PDX‐1 expression was confirmed by Western blot and tracked by viewing of GFP–PDX‐1 expression. Microarray data support an oncogenic role of PDX‐1 in pancreas cancer cells.CONCLUSIONS:PDX‐1 induced increased cell proliferation, invasion, and colony formation in vitro, and resulted in markedly increased HEK 293 and MIA PaCa2 tumor formation in SCID mice. These data suggest that PDX‐1 is a potential oncogene that regulates tumorigenesis. Cancer 2011. © 2010 American Cancer Society.
Theoretical Investigation of the Interaction between Carbon Monoxide and Carbon Nanotubes with Single‐Vacancy Defects
Authors: Xiao Bo , Zhao Jing‐xiang , Ding Yi‐hong , Sun Chia‐chung 
Published: September 2010

AbstractDensity functional theory calculations are used to study the healing process of a defective CNT (i.e. (8,0) CNT) by CO molecules. The healing undergoes three evolutionary steps: 1) the chemisorption of the first CO molecule, 2) the incorporation of the C atom of CO into the CNT, accompanied by the adsorption of the leaving O atom on the CNT surface, 3) the removal of the adsorbed O atom from the CNT surface by a second CO molecule to form CO2 and the perfect CNT. Overall, adsorption of the first CO reveals a barrier of 2.99 kcal mol−1 and is strongly exothermal by 109.11 kcal mol−1, while adsorption of a second CO has an intrinsic barrier of 32.37 kcal mol−1and is exothermal by 62.34 kcal mol−1. In light of the unique conditions of CNT synthesis, that is, high temperatures in a closed container, the healing of the defective CNT could be effective in the presence of CO molecules. Therefore, we propose that among the available CNT synthesis procedures, the good performance of chemical vapor decomposition of CO on metal nanoparticles might be ascribed to the dual role of CO, that is, CO acts both as a carbon source and a defect healer. The present results are expected to help a deeper understanding of CNT growth.
New Method for the Determination of the Electron Temperature from Langmuir Probe Characteristics
Authors: Hannemann M. 
Published: September 2010

AbstractThe electron retarding current collected by a Langmuir probe in a plasma possessing a Maxwellian electron energy distribution function is a an exponential function. If such a current is smoothed by a non‐recursive filter the result is a product of the original current and a factor independent on probe voltage. This leads to a shift between the floating potentials of smoothed and unsmoothed probe current from which the electron temperature Ve may be obtained. A suitable smoothing filter is chosen and all means necessary for the practical realization of the method are given. The influence of the ion current on the determined value of Ve is investigated. The convenience of the method is shown by means of testing calculations and a measuring example (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Short DC Discharge with Wall Probe as a Gas Analytical Detector
Authors: Demidov V. I. , Adams S. F. , Blessington J. , Koepke M. E. , Wiliamson J. M. 
Published: September 2010

AbstractA new approach leading to the development of gas analytical detectors is reported. The approach is based on measurements in the near‐cathode plasma of fine structures associated with atomic and molecular plasma processes of the high energy portion of the electron energy distribution function (EEDF). A short (without positive column) dc discharge with cold cathode and conducting walls was used. The EEDF measurements in a dc discharge are technically simpler and have dramatically better sensitivity than in the afterglow since temporal resolution is not required. Additional increased probe sensitivity is achieved by using a large‐area, larger‐radius‐of‐curvature conducting wall as the probe instead of the more common thin cylindrical Langmuir probe. The wall probe, being almost flat, also greatly reduces the ion current contribution to the measurements. The new approach allows for the development of micro‐analytical, dc plasma electron spectroscopy (PLES) gas detectors that are operational up to atmospheric pressure (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Flow Measurements in the Edge Region of the RFX‐Mod Experiment
Authors: De Masi G. , Spolaore M. , Cavazzana R. , Innocente P. , Lorenzini R. , Martines E. , Momo B. , Munaretto S. , Serianni G. , Spagnolo S. , Terranova D. , Vianello N. , Zuin M. 
Published: September 2010

AbstractIn this contribution a detailed study of the edge flow properties performed on the outer region of the RFX‐mod experiment using a Gundestrup probe is presented. In particular, both parallel and perpendicular components (with respect to the magnetic field) have been evaluated in several low current discharges providing a complete reconstruction of the edge flow profiles.Different methods based on both magnetized and unmagnetized models have been used to evaluate the averaged plasma flow components and their time variations. Furthermore, configurations involving either ion saturation current signals or floating potential ones have been used to evaluate both parallel and perpendicular flow components and a good agreement has been found between different methods.Finally, the dynamic behaviour of edge flow fluctuations induced by gradient modifications following pellet injection and by varying the edge magnetic topology (the m = 0 islands radial position) have been studied (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A Novel Cylindrical Probe for Measuring the Ion Temperature in Magnetized Plasmas
Authors: Tierens W. , Komm M. , Stöckel J. , Van Oost G. 
Published: September 2010

Abstract2D Particle‐In‐Cell simulations are used to predict the ion current density on the surface of a cylinder whose top is perpendicular to the magnetic field in a magnetized nonthermal plasma. This current density decreases with increasing distance to the probe top, and the rate of decrease is predicted to be a sensitive function of the ion temperature. We consider the possibility of a new kind of probe to use this effect to measure the ion temperature with a relatively high temporal resolution (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Ball‐Pen Probe Measurements in L‐Mode and H‐Mode on ASDEX Upgrade
Authors: Adamek J. , Horacek J. , Müller H.W. , Rohde V. , Ionita C. , Schrittwieser R. , Mehlmann F. , Kurzan B. , Stöckel J. , Dejarnac R. , Weinzettl V. , Seidl J. , Peterka M. , ASDEX Upgrade Team  
Published: September 2010

AbstractExperimental investigations of the plasma potential, poloidal electric field and electron temperature during L‐mode and ELMy H‐mode were performed on ASDEX Upgrade by means of a probe head containing four ball‐pen probes and four Langmuir probes. This allows to measure simultaneously the floating and plasma potential at the same time which are related by the electron temperature. Thus a combination of ball‐pen probes and Langmuir probes offers the possibility to determine the electron temperature directly with high temporal resolution. This novel temperature measurement method is compared to standard techniques. The influence of the electron temperature on the usual calculation of the poloidal electric field from the gradient of the floating potential is determined by a comparison to the poloidal electric field derived from the plasma potential (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A Probe Head for Simultaneous Measurements of Electrostatic and Magnetic Fluctuations in ASDEX Upgrade Edge Plasma
Authors: Schrittwieser R. W. , Ionita C. , Vianello N. , Müller H.W. , Mehlmann F. , Zuin M. , Naulin V. , Rasmussen J. J. , Rohde V. , Cavazzana R. , Lupu C. , Maraschek M. , Maszl Ch. , ASDEX Upgrade Team  
Published: September 2010

AbstractFor ASDEX Upgrade (AUG) a new probe head was developed for simultaneous measurements of electric and magnetic fluctuations in the edge plasma region. The probe head consists of a cylindrical graphite case. On the front side six graphite pins are mounted. With this arrangement the poloidal and radial electric field components, the ion saturation current and the current‐voltage characteristic can be registered simultaneously. Inside the graphite case a magnetic sensor is mounted by which the three components of magnetic field fluctuations are measured. During the AUG discharges the probe head is inserted up to three times for 100 ms each by the midplane manipulator into the scrape‐off layer (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Estimation of Plasma Parameters for Microwave‐Sustained Ar/He Plasma Jets at Atmospheric Pressure
Authors: Razzak M.A. , Takamura S. , Saito S. , Talukder M.R. 
Published: September 2010

AbstractIn this article, we have analyzed the measured probe characteristics of microwave‐sustained Ar and He plasma jets at atmospheric pressure using the high‐pressure probe theory developed by Talukder et al. in order to determine the generated plasma parameters (electron temperature, Te, electron density, Ne, plasma potential, ϕp). The calculation shows some unusual temperature profiles (both axial and radial) as well as provides some over estimation of electron temperature measured from the distorted I‐V characteristic due to a smaller electron to ion saturation current ratio coming from the limited electron saturation current. In order to overcome these limitations, the measured probe characteristics are also analyzed by using the asymmetric double probe theory developed by our group, which provides reasonable value of plasma parameters. The influence of microwave power and gas flow rate on the plasma parameters are also investigated (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A Study of Plasma Parameters in Hollow Cathode Plasma Jet in Pulse Regime
Authors: Kudrna P. , Klusoň J. , Leshkov S. , Chichina M. , Picková I. , Hubička Z. , Tichý M. 
Published: September 2010

AbstractThe pulsed DC hollow cathode discharge has been studied in the low pressure plasma jet sputtering system by means of cylindrical Langmuir probe. Measurements have been performed in pure Ar with the flow rate of 30 sccm. The repetition frequency of the pulses of 1 kHz has been chosen with the pulse width 100 μs (duty cycle 10%) and 50 μs (duty cycle 5 %) and the amplitude of the pulses was approximately 400V. The average discharge current varied between 150 and 250 mA. To obtain better stability of the discharge a 3.8 kΩ resistor was connected across the pulse switch. Consequently, there was a weak continuous DC discharge on the background of the pulsed discharge. From the probe characteristics the plasma and floating potential, electron density and electron temperature have been evaluated. Their dependences on the pressure (in the range of several Pa) and on the radial distance from the central axis of the system are presented. Temporal resolution of the measurements is 0.5 μs (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Electrical Probe Diagnostics for KSTAR
Authors: Bak J. G. , Lee S. G. , Kim J. Y. , KSTAR Project Team  
Published: September 2010

AbstractElectrical probe diagnostics (EPDs) for the Korea Superconducting Tokamak Advanced Research (KSTAR), which consists of three fast reciprocating Langmuir probe assemblies (FRLPAs) and two fixed edge Langmuir probe arrays (ELPAs), are proposed to diagnose edge plasma during a plasma discharge in the KSTAR machine. A FRLPA, which has been upgraded through its performance test, is installed at a horizontal port of the KSTAR vacuum vessel in order to get the radial profile of the plasma parameters in the scrape‐off layer (SOL) region during the experimental campaign of 2009 in the KSTAR machine. The prototype fabricated for the ELPA is mounted on the outboard wall of the KSTAR vacuum vessel in order to investigate its performance during the campaign of 2009, which is required before the installation of one fixed EPLA on the plasma facing component (PFC) tiles inside the KSTAR vacuum vessel. In this work, the description of the KSTAR EPDs and their current activities including the technical issues for the installation in the KSTAR machine are presented (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Ligand binding sensitivity of the extracellular loop two of the cannabinoid receptor 1
Authors: Bertalovitz Alexander C. , Ahn Kwang H. , Kendall Debra A. 
Published: September 2010

AbstractThe cannabinoid receptor one (CB1) is a class A G‐protein‐coupled receptor thought to bind ligands primarily within its helical bundle. Evidence suggests, however, that the extracellular domain may also play a role. We have previously shown that the C‐terminus of the extracellular loop 2 of CB1 is important in binding some compounds; receptors with mutations in this region (F268W, P269A, H270A, and I271A) bound some agonists with severely reduced affinity relative to the wild‐type receptor [Ahn et al.,2009. Mol Pharmacol 76:833–842]. In the present work, we examine the impact of these mutations on binding a chemically diverse set of ligands. The receptors, F268W and I271A, exhibited a greater sensitivity to binding the inverse agonists/antagonists SLV319, AVE1625, NESS0327 relative to P269A and H270A, suggesting that the Pro and His are not involved in binding those compounds. In contrast, binding of the agonists, BAY593074 and WIN55212‐2, was diminished in all four receptors, suggesting the conformational unit contributed by all four residues is important. A more marked loss in binding was observed for agonists of the nonclassical (CP55940) and classical (HU‐210, JWH061, JWH179) cannabinoid classes and for a silent antagonist derivative (O‐2050), pointing to the critical nature of this region for binding both the bicyclic/tricyclic core and the alkyl chain of these derivatives. However, moving the location of the alkyl chain on a series of pyrazole analogues shows it can be better accommodated in certain locations (O‐1255) than others (O‐1302, O‐1690) and underscores the involvement of residues F268 and I271. Drug Dev Res 71: 404–411, 2010. © 2010 Wiley‐Liss, Inc.