bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the quantitative determination of hole-concentration in high-temperature cuprate superconductors
Authors: Honma Tatsuya , Hor Pei-Herng 
Published: September 2015

We compared four hole-scales that have been used to determine the hole-concentration in high-temperature cuprate superconductors. We show that the hole-scale, [Formula: see text]-scale, based on the thermoelectric power [T. Honma et al., Phys. Rev. B 70, (2004) 214517.] is quantitatively consistent with spectroscopic probes for many different cuprate materials, while the other hole-scales, based on a well-known dome-shaped [Formula: see text]-curve [M. R. Presland et al., Physica C 176, 95 (1991)], the [Formula: see text]-axis lattice parameter [R. Liang et al., Phys. Rev. B 73, (2006) 180505(R).] and Hall coefficient [Y. Ando et al., Phys. Rev. B 61, (2000) 14956(R).], are not. We show that the quantitatively different hole-scales resulted in opposite conclusion of the same experimental observations. It can also lead to different interpretations of the electronic phase diagram when comparing different physical properties in different high-[Formula: see text] systems. We suggest that the [Formula: see text]-scale is the correct universal scale that works for all high-[Formula: see text] cuprates and it should be used for all quantitative doping dependence studies of cuprates.
CAFFEINE
Authors: Panda Biswabandan , Balachandran Shankar 
Published: September 2015

Aggressive prefetching improves system performance by hiding and tolerating off-chip memory latency. However, on a multicore system, prefetchers of different cores contend for shared resources and aggressive prefetching can degrade the overall system performance. The role of a prefetcher aggressiveness engine is to select appropriate aggressiveness levels for each prefetcher such that shared resource contention caused by prefetchers is reduced, thereby improving system performance. State-of-the-art prefetcher aggressiveness engines monitor metrics such as prefetch accuracy, bandwidth consumption, and last-level cache pollution. They use carefully tuned thresholds for these metrics, and when the thresholds are crossed, they trigger aggressiveness control measures. These engines have three major shortcomings: (1) thresholds are dependent on the system configuration (cache size, DRAM scheduling policy, and cache replacement policy) and have to be tuned appropriately, (2) there is no single threshold that works well across all the workloads, and (3) thresholds are oblivious to the phase change of applications.
To overcome these shortcomings, we propose CAFFEINE, a model-based approach that analyzes the effectiveness of a prefetcher and uses a metric called net utility to control the aggressiveness. Our metric provides net processor cycles saved because of prefetching by approximating the cycles saved across the memory subsystem, from last-level cache to DRAM.
We evaluate CAFFEINE across a wide range of workloads and compare it with the state-of-the-art prefetcher aggressiveness engine. Experimental results demonstrate that, on average (geomean), CAFFEINE achieves 9.5% (as much as 38.29%) and 11% (as much as 20.7%) better performance than the best-performing aggressiveness engine for four-core and eight-core systems, respectively.
Affinity-Tuned ErbB2 or EGFR Chimeric Antigen Receptor T Cells Exhibit an Increased Therapeutic Index against Tumors in Mice
Authors: Liu Xiaojun , Jiang Shuguang , Fang Chongyun , Yang Shiyu , Olalere Devvora , Pequignot Edward C. , Cogdill Alexandria P. , Li Na , Ramones Melissa , Granda Brian , Zhou Li , Loew Andreas , Young Regina M. , June Carl H. , Zhao Yangbing 
Published: September 2015

Abstract
Target-mediated toxicity is a major limitation in the development of chimeric antigen T-cell receptors (CAR) for adoptive cell therapy of solid tumors. In this study, we developed a strategy to adjust the affinities of the scFv component of CAR to discriminate tumors overexpressing the target from normal tissues that express it at physiologic levels. A CAR-expressing T-cell panel was generated with target antigen affinities varying over three orders of magnitude. High-affinity cells recognized target expressed at any level, including at levels in normal cells that were undetectable by flow cytometry. Affinity-tuned cells exhibited robust antitumor efficacy similar to high-affinity cells, but spared normal cells expressing physiologic target levels. The use of affinity-tuned scFvs offers a strategy to empower wider use of CAR T cells against validated targets widely overexpressed on solid tumors, including those considered undruggable by this approach. Cancer Res; 75(17); 3596–607. ©2015 AACR.
Toxicity Attribution in Phase I Trials: Evaluating the Effect of Dose on the Frequency of Related and Unrelated Toxicities
Authors: Eaton Anne , Iasonos Alexia , Gounder Mrinal M. , Pamer Erika G. , Drilon Alexander , Vulih Diana , Smith Gary L. , Ivy S. Percy , Spriggs David R. , Hyman David M. 
Published: September 2015

Abstract
Purpose: Phase I studies rely on investigators to accurately attribute adverse events as related or unrelated to study drug. This information is ultimately used to help establish a safe dose. Attribution in the phase I setting has not been widely studied and assessing the accuracy of attribution is complicated by the lack of a gold standard. We examined dose–toxicity relationships as a function of attribution and toxicity category to evaluate for evidence of toxicity misattribution.
Experimental Design: Individual patient records from 38 phase I studies activated between 2000 and 2010 were used. Dose was defined as a percentage of maximum dose administered on each study. Relationships between dose and patient-level toxicity were explored graphically and with logistic regression. All P values were two-sided.
Results: 11,909 toxicities from 1,156 patients were analyzed. Unrelated toxicity was not associated with dose (P = 0.0920 for grade ≥3, P = 0.4194 for grade ≥1), whereas related toxicity increased with dose (P &lt; 0.0001, both grade ≥3 and ≥1). Similar results were observed across toxicity categories. In the five-tier system, toxicities attributed as “possibly,” “probably,” or “definitely” related were associated with dose (all P &lt; 0.0001), whereas toxicities attributed as “unlikely” or “unrelated” were not (all P &gt; 0.1).
Conclusions: Reassuringly, we did not observe an association between unrelated toxicity rate and dose, an association that could only have been explained by physician misattribution. Our findings also confirmed our expectation that related toxicity rate increases with dose. Our analysis supports simplifying attribution to a two-tier system by collapsing “possibly,” “probably,” and “definitely” related. Clin Cancer Res; 22(3); 553–9. ©2015 AACR.
See related commentary by Sharma and Ratain, p. 527
Molecular Pathways: Anticancer Activity by Inhibition of Nucleocytoplasmic Shuttling
Authors: Conforti Fabio , Wang Yisong , Rodriguez Jose A. , Alberobello Anna Teresa , Zhang Yu-Wen , Giaccone Giuseppe 
Published: September 2015

Abstract
A dynamic distribution between nucleus and cytoplasm (nucleocytoplasmic shuttling) is one of the control mechanisms adapted by normal cells to regulate the activity of a variety of molecules. Growing evidence suggests that dysregulation of the nucleocytoplasmic shuttling is involved in promoting abnormal cell survival, tumor progression, and drug resistance, and is associated with poor cancer prognosis. Aberrant nucleocytoplasmic shuttling in cancer cells may result from a hyperactive status of diverse signal-transduction pathways, such as the PI3K–AKT and MAPK pathways, or from alterations in the general nuclear import/export machinery. Among the large number of molecules involved in the shuttling process, exportin XPO1, also known as chromosome region maintenance 1, appears to play a particularly prominent role in pathogenesis of both hematological malignancies and solid tumors. Given the importance of nucleocytoplasmic shuttling in cancer pathogenesis and the rapidly expanding knowledge in this field, attempts have been made to develop compounds able to revert the aberrant nucleocytoplasmic shuttling. A promising new drug, KPT-330 (Selinexor), which belongs to the class of XPO1 inhibitors called selective inhibitors of nuclear export, is now being tested in phase I/II clinical trials. Clin Cancer Res; 21(20); 4508–13. ©2015 AACR.
Indole-3-Carbinol Synergizes with and Restores Fludarabine Sensitivity in Chronic Lymphocytic Leukemia Cells Irrespective of p53 Activity and Treatment Resistances
Authors: Perez-Chacon Gema , Martinez-Laperche Carolina , Rebolleda Nerea , Somovilla-Crespo Beatriz , Muñoz-Calleja Cecilia , Buño Ismael , Zapata Juan M. 
Published: September 2015

Abstract
Purpose: Chronic lymphocytic leukemia (CLL) still is lacking a cure. Relapse and development of refractoriness to current treatments are common. New therapies are needed to improve patient prognosis and survival.
Experimental design: Indole-3-carbinol (I3C) is a natural product with antitumor properties already clinically tested. The effect of I3C, F-ara-A, and combinations of both drugs on CLL cells from patients representing different Rai stages, IGHV mutation status, cytogenetic alterations, p53 functionality, and treatment resistances was tested, as well as the toxicity of these treatments in mice.
Results: I3C induces cytotoxicity in CLL cells but not in normal lymphocytes. I3C strongly synergized with F-ara-A in all CLL cells tested, including those with p53 deficiency and/or F-ara-A resistance. The mechanism of cell death involved p53-dependent and -independent apoptosis. The combination of I3C + F-ara-A was equally effective in CLL cells irrespective of IGHV mutation stage and patient refractoriness. Moreover, CLL survival and treatment resistance induced by co-culturing CLL cells on stroma cells were overcome by the combinatory I3C + F-ara-A treatment. No toxicity was associated with the combined I3C + fludarabine treatment in mice.
Conclusions: I3C in combination with F-ara-A is highly cytotoxic in CLL cells from refractory patients and those with p53 deficiency. The striking dose reduction index for F-ara-A in combination with I3C would reduce fludarabine toxicity while having a similar or better anti-CLL effectiveness. Moreover, the low toxicity of I3C, already clinically tested, supports its use as adjuvant and combinatory therapy in CLL, particularly for patients with relapsed or refractory disease. Clin Cancer Res; 22(1); 134–45. ©2015 AACR.
Realism and Malarkey: Henry Kissinger's State Department, Détente, and Domestic Consensus
Authors: Allen David 
Published: September 2015

This article uses recently declassified archival documents to reassess public opinion in the United States regarding East-West détente. When Henry Kissinger was U.S. secretary of state during the Nixon and Ford administrations, he made dozens of speeches intended to educate the public in what he considered the proper methods of diplomacy. By analyzing those “heartland” speeches using recently released documents, the article shows that Kissinger and the State Department tried much harder to create a foreign policy consensus behind détente and realism than previously understood. Despite these efforts, Kissinger's message was lost on the public. The article provides the first extended analysis of a series of fact-finding “town meetings” held by the State Department in five locations across the United States—meetings that revealed how badly Kissinger had failed. By February 1976, all those involved in U.S. foreign policymaking—Kissinger's opponents, his advisers, and the wider public—desired a greater role for moral values in foreign policy.
A 6-yr Cloud-to-Ground Lightning Climatology and Its Relationship to Rainfall over Central and Eastern China
Authors: Xia Rudi , Zhang Da-Lin , Wang Bailin 
Published: September 2015

AbstractThe cloud-to-ground (CG) lightning climatology and its relationship to rainfall over central and eastern China is examined, using data from 32 million CG lightning flashes and Tropical Rainfall Measuring Mission measurements during a 6-yr period covering 2008–13. Results show substantial spatial and temporal variations of flash density across China. Flash counts are the highest (lowest) in summer (winter) with the lowest (highest) proportion of positive flashes. CG lightning over northern China is more active only in summer, whereas in winter CG lightning is more active only in the Yangtze River basin. The highest CG lightning densities, exceeding 9 flashes per kilometer squared per year and more than 70 CG lightning days per year, are found in the northern Pearl River delta region, followed by the Sichuan basin, the Yangtze River delta, and the southeastern coast of China in that order. Lower-flash-density days occur over mountainous regions as a result of the development of short-lived afternoon storms, while higher-flash-density days, typically associated with nocturnal thunderstorms, appear over the north China plain and Sichuan basin. The highest number of CG lightning flashes is found in August whereas monthly convective rainfall peaks in May or July. Flash rates during the warm season are typically maximized in the afternoon hours in coincidence with a convective rainfall peak except for the Sichuan basin and its surrounding mountainous areas where a single late-night convective rainfall peak dominates. Much less lightning activity corresponds to a late-night to morning rainfall peak over the plains in eastern China because of the increased proportion of stratiform rainfall during that period.
The Linkage between Upper-Level Jet Streams over East Asia and East Asian Winter Monsoon Variability
Authors: Luo Xiao , Zhang Yaocun 
Published: September 2015

Abstract
This study investigates the linkage between East Asian winter monsoon (EAWM) variability and upper-level jets, with particular focus on the East Asian polar front jet (PJ) and its concurrent variation with the subtropical jet located to the south of the Tibetan Plateau (TSJ). The winter upper-level zonal wind variations over the Asian landmass (70°–120°E) are dominated by two principal modes (i.e., meridional displacement of the PJ and out-of-phase variation in the intensity of the TSJ and PJ) and they are closely linked to the EAWM northern mode and southern mode, respectively. Southward shifting of the PJ concurs with northwestward displacement of the Siberian high (SH), an enhanced northern East Asian trough, leading to cold winter in northern East Asia. Meanwhile the simultaneous TSJ intensification and PJ weakening is linked to an amplified SH, a southward shift of the Aleutian low (AL), a strengthened southern East Asian trough, and a wavelike anomaly pattern extending from western Barents Sea downstream to East Asia at the 500-hPa level. Equatorward shift of the PJ is associated with La Niña conditions in the tropics and sea ice anomalies over the Arctic. An intensified TSJ and weakened PJ are preceded by autumn warming over the central and eastern Pacific Ocean and are linked to circulation anomalies induced by the extensions of stationary Rossby waves, as well as synoptic-scale transient eddy activity anomalies. Therefore, a combination of external forcing and internal atmospheric dynamics plays a role in driving the variations of two leading EOFs, and there is potential for seasonal forecasting of both modes.
Formation Mechanism of Barrier Layer in the Subtropical Pacific
Authors: Katsura Shota , Oka Eitarou , Sato Kanako 
Published: September 2015

AbstractSeasonal and interannual variations of the barrier layer (BL) and its formation mechanism in the subtropical North and South Pacific were investigated by using raw and gridded Argo profiling float data and various surface flux data in 2003–12 and hydrographic section data from the World Ocean Circulation Experiment Hydrographic Programme. BLs detected by raw Argo profiles, which existed within the sea surface salinity (SSS) front located on the equator side of SSS maxima, were thickest and most frequent in winter and had a temporal scale shorter than 10 days, indicating their transient nature. Surface and subsurface processes for the BL formation suggested by previous studies were evaluated. Poleward Ekman advection of fresher water was dominant as the surface freshening process but cannot explain the observed seasonal variations of the BL. Subsurface equatorward intrusion of high-salinity tropical water was too deep to produce salinity stratification within isothermal layers. These results strongly suggest that BLs in the subtropical Pacific are formed mainly through tilting of the SSS front due to the poleward Ekman flow near the sea surface and the equatorward geostrophic flow in the subsurface. This idea is supported by the dominant contribution of the meridional SSS gradient to the meridional sea surface density gradient within the SSS front and the correspondence between the seasonal variations of the BL and isothermal layer depth. On an interannual time scale, the winter BL thickness in the North and South Pacific was related to the Pacific decadal oscillation and the El Niño–Southern Oscillation, respectively, through the intensity of trade winds controlling isothermal layer depth.
Determinants of All-Cause Mortality and Incidence of Cardiovascular Disease (2009 to 2013) in Older Adults
Authors: Chrysohoou Christina , Pitsavos Christos , Lazaros George , Skoumas John , Tousoulis Dimitris , Stefanadis Christodoulos 
Published: September 2015

Aim: Ikaria Island (North-East Aegean, Greece) has been recognized as one of the places with the highest life expectancy around the world (the Blues Zones). Risk factors in relation to 4-year all-cause mortality and cardiovascular disease (CVD) incidence in elders were studied. Methods: From June to October 2009, 330 men and 343 women, aged 65 to 100 years, were enrolled, and in June to July 2013, they were reevaluated. Results: Age-standardized, gender-specific, all-cause mortality rate was 790 deaths per 10 000 inhabitants, and causes of death were CVD (36%), cancer (21%), infection (10%), respiratory disease (2%), and other (31%). Incidence of CVDwas 520 cases per 10 000 men inhabitants and 320 cases per 10 000 women ( P = .03). Age, male gender, heart rate, urea levels, left atrial maximum volume, left ventricular hypertrophy, thyroid-stimulating hormone, and moderate to severe depression were positively associated with mortality, whereas left ventricular ejection fraction as well as coffee and tea drinking, fruit intake, and exclusive olive oil use were inversely associated with CVD. Conclusion: Heart function markers in addition to antioxidant dietary factors were placed in this puzzle of CVD morbidity.
Interventional bronchoscopy in the management of thoracic malignancy
Authors: Hardavella Georgia , George Jeremy 
Published: September 2015

Educational AimsTo highlight the various methods of interventional bronchoscopy.To inform about the indications for palliation and curative bronchoscopy in lung cancer.Interventional bronchoscopy is a rapidly expanding field in respiratory medicine offering minimally invasive therapeutic and palliative procedures for all types of lung neoplasms. This field has progressed over the last couple of decades with the application of new technology. The HERMES European curriculum recommendations include interventional bronchoscopy skills in the modules of thoracic tumours and bronchoscopy [1]. However, interventional bronchoscopy is not available in all training centres and consequently, not all trainees will obtain experience unless they rotate to centres specifically offering such training.In this review, we give an overview of interventional bronchoscopic procedures used for the treatment and palliation of thoracic malignancy. These can be applied either with flexible or rigid bronchoscopy or a combination of both depending on the anatomical location of the tumour, the complexity of the case, bleeding risk, the operator’s expertise and preference as well as local availability. Specialised anaesthetic support and appropriately trained endoscopy staff are essential, allowing a multimodality approach to meet the high complexity of these cases.
The phenotypic signature of adaptation to thermal stress in Escherichia coli
Authors: Hug Shaun M. , Gaut Brandon S. 
Published: September 2015

Abstract
Background
In the short-term, organisms acclimate to stress through phenotypic plasticity, but in the longer term they adapt to stress genetically. The mutations that accrue during adaptation may contribute to completely novel phenotypes, or they may instead act to restore the phenotype from a stressed to a pre-stress condition. To better understand the influence of evolution on the diversity and direction of phenotypic change, we used Biolog microarrays to assay 94 phenotypes of 115 Escherichia coli clones that had adapted to high temperature (42.2 °C). We also assayed these same phenotypes in the clones’ ancestor under non-stress (37.0 °C) and stress (42.2 °C) conditions. We explored associations between Biolog phenotypes and genotypes, and we also investigated phenotypic differences between clones that have one of two adaptive genetic trajectories: one that is typified by mutations in the RNA polymerase β-subunit (rpoB) and another that is defined by mutations in the rho termination factor.

Results
Most (54 %) phenotypic variation was restorative, shifting the phenotype from the acclimated state back toward the unstressed state. Novel phenotypes were more rare, comprising between 5 and 18 % of informative phenotypic variation. Phenotypic variation associated statistically with genetic variation, demonstrating a genetic basis for phenotypic change. Finally, clones with rpoB mutations differed in phenotype from those with rho mutations, largely due to differences in chemical sensitivity.

Conclusions
Our results contribute to previous observations showing that a major component of adaptation in microbial evolution experiments is toward restoration to the unstressed state. In addition, we found that a large deletion strongly affected phenotypic variation. Finally, we demonstrated that the two genetic trajectories leading to thermal adaptation encompass different phenotypes.
Oxygen - a limiting factor for brain recovery
Authors: Hadanny Amir , Efrati Shai 
Published: September 2015

AbstractEffective brain metabolism is highly dependent on a narrow therapeutic window of oxygen. In major insults to the brain (e.g., intracerebral hemorrhage), a slight decrease in oxygen supply, as occurs in a hypobaric environment at high altitude, has devastating effects on the injured brain tissue. Conversely, increasing brain oxygenation, by the use of hyperbaric oxygen therapy, can improve brain metabolism and its dependent regenerative processes.