bluuebunny/crossref_metadata_2025_split huggingface dataset:
A CubeSat for Calibrating Ground-Based and Sub-Orbital Millimeter-Wave Polarimeters (CalSat)
Authors: Johnson Bradley R. , Vourch Clement J. , Drysdale Timothy D. , Kalman Andrew , Fujikawa Steve , Keating Brian , Kaufman Jon 
Published: October 2015

We describe a low-cost, open-access, CubeSat-based calibration instrument that is designed to support ground-based and sub-orbital experiments searching for various polarization signals in the cosmic microwave background (CMB). All modern CMB polarization experiments require a robust calibration program that will allow the effects of instrument-induced signals to be mitigated during data analysis. A bright, compact and linearly polarized astrophysical source with polarization properties known to adequate precision does not exist. Therefore, we designed a space-based millimeter-wave calibration instrument, called CalSat, to serve as an open-access calibrator, and this paper describes the results of our design study. The calibration source on board CalSat is composed of five “tones” with one each at 47.1, 80.0, 140, 249 and 309[Formula: see text]GHz. The five tones we chose are well matched to (i) the observation windows in the atmospheric transmittance spectra, (ii) the spectral bands commonly used in polarimeters by the CMB community and (iii) the Amateur Satellite Service bands in the Table of Frequency Allocations used by the Federal Communications Commission. CalSat would be placed in a polar orbit allowing visibility from observatories in the Northern Hemisphere, such as Mauna Kea in Hawaii and Summit Station in Greenland, and the Southern Hemisphere, such as the Atacama Desert in Chile and the South Pole. CalSat also would be observable by balloon-borne instruments launched from a range of locations around the world. This global visibility makes CalSat the only source that can be observed by all terrestrial and sub-orbital observatories, thereby providing a universal standard that permits comparison between experiments using appreciably different measurement approaches.
Effect of a Smac Mimetic (TL32711, Birinapant) on the Apoptotic Program and Apoptosis Biomarkers Examined with Validated Multiplex Immunoassays Fit for Clinical Use
Authors: Srivastava Apurva K. , Jaganathan Soumya , Stephen Laurie , Hollingshead Melinda G. , Layhee Adam , Damour Eric , Govindharajulu Jeevan Prasaad , Donohue Jennifer , Esposito Dominic , Mapes James P. , Kinders Robert J. , Takebe Naoko , Tomaszewski Joseph E. , Kummar Shivaani , Doroshow James H. , Parchment Ralph E. 
Published: October 2015

Abstract
Purpose: To support clinical pharmacodynamic evaluation of the Smac mimetic TL32711 (birinapant) and other apoptosis-targeting drugs, we describe the development, validation, and application of novel immunoassays for 15 cytosolic and membrane-associated proteins indicative of the induction, onset, and commitment to apoptosis in human tumors.
Experimental Design: The multiplex immunoassays were constructed on the Luminex platform with apoptosis biomarkers grouped into three panels. Panel 1 contains Bak, Bax, total caspase-3, total lamin-B (intact and 45 kDa fragment), and Smac; panel 2 contains Bad, Bax–Bcl-2 heterodimer, Bcl-xL, Bim, and Mcl1; and panel 3 contains active (cleaved) caspase-3, Bcl-xL–Bak heterodimer, Mcl1–Bak heterodimer, pS99-Bad, and survivin. Antibody specificity was confirmed by immunoprecipitation and Western blot analysis.
Results: Two laboratories analytically validated the multiplex immunoassays for application with core-needle biopsy samples processed to control preanalytical variables; the biologic variability for each biomarker was estimated from xenograft measurements. Studies of TL32711 in xenograft models confirmed a dose-dependent increase in activated caspase-3 6 hours after dosing and provided assay fit-for-purpose confirmation. Coincident changes in cytosolic lamin-B and subsequent changes in Bcl-xL provided correlative evidence of caspase-3 activation. The validated assay is suitable for use with clinical specimens; 14 of 15 biomarkers were quantifiable in patient core-needle biopsies.
Conclusions: The validated multiplex immunoassays developed for this study provided proof of mechanism data for TL32711 and are suitable for quantifying apoptotic biomarkers in clinical trials. Clin Cancer Res; 22(4); 1000–10. ©2015 AACR.
Germline Variants in Asporin Vary by Race, Modulate the Tumor Microenvironment, and Are Differentially Associated with Metastatic Prostate Cancer
Authors: Hurley Paula J. , Sundi Debasish , Shinder Brian , Simons Brian W. , Hughes Robert M. , Miller Rebecca M. , Benzon Benjamin , Faraj Sheila F. , Netto George J. , Vergara Ismael A. , Erho Nicholas , Davicioni Elai , Karnes R. Jeffrey , Yan Guifang , Ewing Charles , Isaacs Sarah D. , Berman David M. , Rider Jennifer R. , Jordahl Kristina M. , Mucci Lorelei A. , Huang Jessie , An Steven S. , Park Ben H. , Isaacs William B. , Marchionni Luigi , Ross Ashley E. , Schaeffer Edward M. 
Published: October 2015

Abstract
Purpose: Prostate cancers incite tremendous morbidity upon metastatic growth. We previously identified Asporin (ASPN) as a potential mediator of metastatic progression found within the tumor microenvironment. ASPN contains an aspartic acid (D)-repeat domain and germline polymorphisms in D-repeat-length have been associated with degenerative diseases. Associations of germline ASPN D polymorphisms with risk of prostate cancer progression to metastatic disease have not been assessed.
Experimental Design: Germline ASPN D-repeat-length was retrospectively analyzed in 1,600 men who underwent radical prostatectomy for clinically localized prostate cancer and in 548 noncancer controls. Multivariable Cox proportional hazards models were used to test the associations of ASPN variations with risk of subsequent oncologic outcomes, including metastasis. Orthotopic xenografts were used to establish allele- and stroma-specific roles for ASPN D variants in metastatic prostate cancer.
Results: Variation at the ASPN D locus was differentially associated with poorer oncologic outcomes. ASPN D14 [HR, 1.72; 95% confidence interval (CI), 1.05–2.81, P = 0.032] and heterozygosity for ASPN D13/14 (HR, 1.86; 95% CI, 1.03–3.35, P = 0.040) were significantly associated with metastatic recurrence, while homozygosity for the ASPN D13 variant was significantly associated with a reduced risk of metastatic recurrence (HR, 0.44; 95% CI, 0.21–0.94, P = 0.035) in multivariable analyses. Orthotopic xenografts established biologic roles for ASPN D14 and ASPN D13 variants in metastatic prostate cancer progression that were consistent with patient-based data.
Conclusions: We observed associations between ASPN D variants and oncologic outcomes, including metastasis. Our data suggest that ASPN expressed in the tumor microenvironment is a heritable modulator of metastatic progression. Clin Cancer Res; 22(2); 448–58. ©2015 AACR.
Detection of T790M, the Acquired Resistance EGFR Mutation, by Tumor Biopsy versus Noninvasive Blood-Based Analyses
Authors: Sundaresan Tilak K. , Sequist Lecia V. , Heymach John V. , Riely Gregory J. , Jänne Pasi A. , Koch Walter H. , Sullivan James P. , Fox Douglas B. , Maher Robert , Muzikansky Alona , Webb Andrew , Tran Hai T. , Giri Uma , Fleisher Martin , Yu Helena A. , Wei Wen , Johnson Bruce E. , Barber Thomas A. , Walsh John R. , Engelman Jeffrey A. , Stott Shannon L. , Kapur Ravi , Maheswaran Shyamala , Toner Mehmet , Haber Daniel A. 
Published: October 2015

Abstract
Purpose: The T790M gatekeeper mutation in the EGFR is acquired by some EGFR-mutant non–small cell lung cancers (NSCLC) as they become resistant to selective tyrosine kinase inhibitors (TKI). As third-generation EGFR TKIs that overcome T790M-associated resistance become available, noninvasive approaches to T790M detection will become critical to guide management.
Experimental Design: As part of a multi-institutional Stand-Up-To-Cancer collaboration, we performed an exploratory analysis of 40 patients with EGFR-mutant tumors progressing on EGFR TKI therapy. We compared the T790M genotype from tumor biopsies with analysis of simultaneously collected circulating tumor cells (CTC) and circulating tumor DNA (ctDNA).
Results: T790M genotypes were successfully obtained in 30 (75%) tumor biopsies, 28 (70%) CTC samples, and 32 (80%) ctDNA samples. The resistance-associated mutation was detected in 47% to 50% of patients using each of the genotyping assays, with concordance among them ranging from 57% to 74%. Although CTC- and ctDNA-based genotyping were each unsuccessful in 20% to 30% of cases, the two assays together enabled genotyping in all patients with an available blood sample, and they identified the T790M mutation in 14 (35%) patients in whom the concurrent biopsy was negative or indeterminate.
Conclusions: Discordant genotypes between tumor biopsy and blood-based analyses may result from technological differences, as well as sampling different tumor cell populations. The use of complementary approaches may provide the most complete assessment of each patient's cancer, which should be validated in predicting response to T790M-targeted inhibitors. Clin Cancer Res; 22(5); 1103–10. ©2015 AACR.
High-level secretion of tissue factor-rich extracellular vesicles from ovarian cancer cells mediated by filamin-A and protease-activated receptors
Authors: Ito Shin , Yoshioka Yusuke , Kanayama Tomohiko , Nakamura Yoshiyasu , Yoshihara Mitsuyo , Yamada Roppei , Ochiya Takahiro , Ruf Wolfram , Miyagi Etsuko , Hirahara Fumiki , Koizume Shiro , Miyagi Yohei 
Published: October 2015

SummaryThromboembolic events occur frequently in ovarian cancer patients. Tissue factor (TF) is often overexpressed in tumours, including ovarian clear-cell carcinoma (CCC), a subtype with a generally poor prognosis. TF-coagulation factor VII (fVII) complexes on the cell surface activate downstream coagulation mechanisms. Moreover, cancer cells secrete extracellular vesicles (EVs), which act as vehicles for TF. We therefore examined the characteristics of EVs produced by ovarian cancer cells of various histological subtypes. CCC cells secreted high levels of TF within EVs, while the high-TF expressing breast cancer cell line MDA-MB-231 shed fewer TF-positive EVs. We also found that CCC tumours with hypoxic tissue areas synthesised TF and fVII in vivo, rendering the blood of xenograft mice bearing these tumours hypercoagulable compared with mice bearing MDA-MB-231 tumours. Incorporation of TF into EVs and secretion of EVs from CCC cells exposed to hypoxia were both dependent on the actin-binding protein, filamin-A (filA). Furthermore, production of these EVs was dependent on different protease-activated receptors (PARs) on the cell surface. These results show that CCC cells could produce large numbers of TF-positive EVs dependent upon filA and PARs. This phenomenon may be the mechanism underlying the increased incidence of venous thromboembolism in ovarian cancer patients.Supplementary Material to this article is available online at www.thrombosis-online.com.
Introduction to the analysis of next generation sequencing data and its application to venous thromboembolism
Authors: Meijers Joost C. M. , Middeldorp Saskia , Cunha Marisa L. R. 
Published: October 2015

SummaryDespite knowledge of various inherited risk factors associated with venous thromboembolism (VTE), no definite cause can be found in about 50% of patients. The application of data-driven searches such as GWAS has not been able to identify genetic variants with implications for clinical care, and unexplained heritability remains. In the past years, the development of several so-called next generation sequencing (NGS) platforms is offering the possibility of generating fast, inexpensive and accurate genomic information. However, so far their application to VTE has been very limited. Here we review basic concepts of NGS data analysis and explore the application of NGS technology to VTE. We provide both computational and biological viewpoints to discuss potentials and challenges of NGS-based studies.
Safety and effectiveness of dabigatran and warfarin in routine care of patients with atrial fibrillation
Authors: Bykov Katsiaryna , Bartels Dorothee B. , Huybrechts Krista , Zint Kristina , Schneeweiss Sebastian , Seeger John D. 
Published: October 2015

SummaryThe RE-LY study demonstrated the safety and efficacy of dabigatran relative to warfarin for stroke prevention in non-valvular atrial fibrillation. It is important to further evaluate safety and effectiveness of drugs in routine care. This study used a sequential cohort design with propensity score matching to compare dabigatran with warfarin among patients in two commercial health insurance databases. New users of these anticoagulants were followed from initiation until discontinuation, the end of the study, or the occurrence of a study outcome (primary study outcomes were stroke and major bleeding). Proportional hazards regression was conducted separately within each data source and results were pooled. Among 19,189 matched dabigatran and warfarin initiators (mean age: 68 years, 36 % female), as-treated follow-up (average of 5 months for dabigatran, 4 months for warfarin) identified 62 and 69 strokes, respectively (pooled HR = 0.77; 95 % CI = 0.54 to 1.09), and 354 and 395 major haemorrhages, respectively (HR = 0.75; 0.65 to 0.87). No meaningful heterogeneity was identified across subgroups, but numeric trends suggest more pronounced stroke prevention by dabigatran relative to warfarin among patients age 75+ (HR = 0.57; 0.33 to 0.97) or with < 6 months of use (HR = 0.51; 0.19 to 1.42). Major bleeds were reduced more by dabigatran among patients aged < 55 (HR = 0.51; 0.30 to 0.87) and with CHADS2 < 2 (HR = 0.58; 0.44 to 0.77). In conclusion, in routine care of patients with non-valvular atrial fibrillation, dabigatran treatment resulted in improved health outcomes compared with warfarin.
Risk of peripheral arterial occlusive disease in patients with rheumatoid arthritis
Authors: Chuang Ya-Wen , Yu Mei-Ching , Lin Cheng-Li , Yu Tung-Min , Shu Kuo-Hsiung , Huang Shih-Ting , Kao Chia-Hung 
Published: October 2015

SummaryRheumatoid arthritis (RA) is associated with atherosclerosis. However, the relationship between RA and peripheral arterial occlusive disease (PAOD) remains unclear. We used a national health insurance database to identify a cohort of 30,812 patients diagnosed with RA between 2000 and 2011. Each RA patient was frequency-matched according to age and sex with a patient without RA from a control cohort. A multivariate Cox proportional hazards model was used to analyse the adjusted risk of PAOD. The incidence of PAOD was 1.73-fold higher (95 % confidence interval [CI] = 1.57–1.91) in the RA cohort than in the non-RA cohort. The adjusted risk of PAOD was the highest in the patients with RA aged ≤ 49 years (hazard ratio [HR] = 3.39, 95 % CI = 2.66–4.32). Patients with RA and various comorbidities showed a significantly higher risk of PAOD (HR = 9.62, 95 % CI = 4.86–19.1) compared with control patients without comorbidity. The risk of PAOD increased during the first year of follow-up. In conclusion, patients with RA have an independently higher risk of PAOD compared with the general population. Patients with RA and various comorbidities and those at a young age and early stage of the disease have an increased risk of PAOD.
Final 3-Year Outcome of a Randomized Trial Comparing Second-Generation Drug-Eluting Stents Using Either Biodegradable Polymer or Durable Polymer
Authors: Natsuaki Masahiro , Kozuma Ken , Morimoto Takeshi , Kadota Kazushige , Muramatsu Toshiya , Nakagawa Yoshihisa , Akasaka Takashi , Igarashi Keiichi , Tanabe Kengo , Morino Yoshihiro , Ishikawa Tetsuya , Nishikawa Hideo , Awata Masaki , Abe Mitsuru , Okada Hisayuki , Takatsu Yoshiki , Ogata Nobuhiko , Kimura Kazuo , Urasawa Kazushi , Tarutani Yasuhiro , Shiode Nobuo , Kimura Takeshi 
Published: October 2015

Background—
There is a paucity of data reporting the clinical outcomes of biodegradable polymer biolimus-eluting stent (BP-BES) compared with durable polymer everolimus-eluting stent (DP-EES) beyond 1 year after stent implantation when the polymer is fully degraded.

Methods and Results—

The NOBORI Biolimus-Eluting Versus XIENCE/PROMUS Everolimus-Eluting Stent Trial (NEXT) is a prospective, multicenter, randomized, open-label, noninferiority trial comparing BP-BES with DP-EES in patients scheduled for percutaneous coronary intervention using drug-eluting stent (DES) without any exclusion criteria among 98 participating centers in Japan. The trial was designed to evaluate noninferiority of BP-BES relative to DP-EES in terms of any target-lesion revascularization at 1 year and death or myocardial infarction at 3 years. Between May and October 2011, 3235 patients were randomly assigned to receive either BP-BES (1617 patients) or DP-EES (1618 patients). Complete 3-year follow-up was achieved in 97.6% of patients. At 3 years, the primary safety end point of death or myocardial infarction occurred in 159 patients (9.9%) in the BP-BES group and in 166 patients (10.3%) in the DP-EES group, demonstrating noninferiority of BP-BES relative to DP-EES (
P
noninferiority<0.0001 and
P
superiority=0.7). Cumulative incidence of target-lesion revascularization was not significantly different between the 2 groups (7.4% versus 7.1%;
P
=0.8). By a landmark analysis at 1 year, the cumulative incidences of death or myocardial infarction and target-lesion revascularization were also not significantly different between the 2 groups (4.6% versus 5.2%;
P
=0.46 and 3.3% versus 2.7%;
P
=0.39, respectively).

Conclusions—
Safety and efficacy outcomes of BP-BES were non inferior to those of DP-EES 3 years after stent implantation.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01303640.
The Right of Children in Accessing Primary Education: Vientiane Province Case Study
Authors: Vongvannasay Khonsavanh , Vongphachanh Khamphang , Langkavong Vilay 
Published: October 2015

The right to education is an important fundamental right for all Lao citizens and is regarded as one of the priorities of development in Lao pdr. The Lao pdr realizes the importance of education for all as a significant tool to help the country graduate from the least developed country status in 2020. Primary and tertiary education is therefore one of the Lao pdr Government’s priorities.
This research analyses the existing rights of children to access primary education in Vientiane Province, the education system in Lao pdr and its education policy for all children. The researchers conducted an in-depth review on the actual implementation of children’s access to education in Vientiane Province, identifying barriers to the full implementation of education policy in the province as well as other important external factors for education. Recommendations are made for increasing children’s access to education, thereby improving the right to education in the state and building a much stronger foundation for the development of Lao pdr.
Connecting Climate Model Projections of Global Temperature Change with the Real World
Authors: Hawkins Ed , Sutton Rowan 
Published: October 2015

Abstract
Current state-of-the-art global climate models produce different values for Earth’s mean temperature. When comparing simulations with each other and with observations, it is standard practice to compare temperature anomalies with respect to a reference period. It is not always appreciated that the choice of reference period can affect conclusions, both about the skill of simulations of past climate and about the magnitude of expected future changes in climate. For example, observed global temperatures over the past decade are toward the lower end of the range of the phase 5 of the Coupled Model Intercomparison Project (CMIP5) simulations irrespective of what reference period is used, but exactly where they lie in the model distribution varies with the choice of reference period. Additionally, we demonstrate that projections of when particular temperature levels are reached, for example, 2 K above “preindustrial,” change by up to a decade depending on the choice of reference period. In this article, we discuss some of the key issues that arise when using anomalies relative to a reference period to generate climate projections. We highlight that there is no perfect choice of reference period. When evaluating models against observations, a long reference period should generally be used, but how long depends on the quality of the observations available. The Intergovernmental Panel on Climate Change (IPCC) Fifth Assessment Report (AR5) choice to use a 1986–2005 reference period for future global temperature projections was reasonable, but a case-by-case approach is needed for different purposes and when assessing projections of different climate variables. Finally, we recommend that any studies that involve the use of a reference period should explicitly examine the robustness of the conclusions to alternative choices.
Identifying and Quantifying Benefits of Meteorological Satellites
Authors: Brown Molly E. , Wooldridge Charles 
Published: October 2015

Abstract
The Coordination Group for Meteorological Satellites (CGMS) provides an international forum for the exchange of technical information on geostationary and polar-orbiting meteorological satellite systems. In 2013, the CMGS established the Socioeconomic Benefits Tiger Team (SETT) to develop a credible methodology and common terminology for articulating the socioeconomic benefits of satellite observing systems, and to explore the most effective ways to communicate the benefits to decision makers and stakeholders. As part of its first years’ activities, the SETT gathered examples of socioeconomic studies across all member organizations. This article describes key elements of these studies, and identified eight key themes that are presented. We welcome additional collaborations to identify opportunities to incorporate socioeconomic best practices, integrate these into additional or subsequent phases of work on new instruments and satellites, and develop recommendations for the way forward for the broader meteorological community.
M2 Internal Tides and Their Observed Wavenumber Spectra from Satellite Altimetry
Authors: Ray R. D. , Zaron E. D. 
Published: October 2015

AbstractA near-global chart of surface elevations associated with the stationary M2 internal tide is empirically constructed from multimission satellite altimeter data. An advantage of a strictly empirical mapping approach is that results are independent of assumptions about ocean wave dynamics and, in fact, can be used to test such assumptions. A disadvantage is that present-day altimeter coverage is only marginally adequate to support mapping such short-wavelength features. Moreover, predominantly north–south ground-track orientations and contamination from nontidal oceanographic variability can lead to deficiencies in mapped tides. Independent data from Cryosphere Satellite-2 (CryoSat-2) and other altimeters are used to test the solutions and show positive reduction in variance except in regions of large mesoscale variability. The tidal fields are subjected to two-dimensional wavenumber spectral analysis, which allows for the construction of an empirical map of modal wavelengths. Mode-1 wavelengths show good agreement with theoretical wavelengths calculated from the ocean’s mean stratification, with a few localized exceptions (e.g., Tasman Sea). Mode-2 waves are detectable in much of the ocean, with wavelengths in reasonable agreement with theoretical expectations, but their spectral signatures grow too weak to map in some regions.