bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of lattice in YBCO superconductors studied by Raman spectroscopy
Authors: Li L. , Guo C. Q. , Han J. X. , Yan Y. , Jin W. T. , Hao S. J. , Lin F. , Wei K. , Zhang H. 
Published: August 2015

In this paper, we systematically studied Ca–YBCO [Formula: see text] and CaLa–YBCO [Formula: see text] systems by Raman spectroscopy. It is found that [Formula: see text] is closely related to the vibration of lattice. In the Ca–YBCO system, the phonons around 115 and 335 cm[Formula: see text] harden as the [Formula: see text] decreases. Oppositely, the 140 cm[Formula: see text] mode and the 220 cm[Formula: see text] mode soften. In the CaLa–YBCO system, the [Formula: see text] decreases gradually with the content of Ca and La. The Raman peak of 140 cm[Formula: see text] mode hardens and the 360 cm[Formula: see text] mode softens. Besides, the fluctuations of phonons of 210 cm[Formula: see text] mode and 575 cm[Formula: see text] mode were observed.
FDA Approval: Ibrutinib for Patients with Previously Treated Mantle Cell Lymphoma and Previously Treated Chronic Lymphocytic Leukemia
Authors: de Claro R. Angelo , McGinn Karen M. , Verdun Nicole , Lee Shwu-Luan , Chiu Haw-Jyh , Saber Haleh , Brower Margaret E. , Chang C.J. George , Pfuma Elimika , Habtemariam Bahru , Bullock Julie , Wang Yun , Nie Lei , Chen Xiao-Hong , Lu Donghao (Robert) , Al-Hakim Ali , Kane Robert C. , Kaminskas Edvardas , Justice Robert , Farrell Ann T. , Pazdur Richard 
Published: August 2015

Abstract
On November 13, 2013, the FDA granted accelerated approval to ibrutinib (IMBRUVICA capsules; Pharmacyclics, Inc.) for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. On February 12, 2014, the FDA granted accelerated approval for the treatment of patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy. Ibrutinib is a first-in-class Bruton's tyrosine kinase (BTK) inhibitor that received all four expedited programs of the FDA: Fast-Track designation, Breakthrough Therapy designation, Priority Review, and Accelerated Approval. Both approvals were based on overall response rate (ORR) and duration of response (DOR) in single-arm clinical trials in patients with prior treatment. In MCL (N = 111), the complete and partial response rates were 17.1% and 48.6%, respectively, for an ORR of 65.8% [95% confidence interval (CI), 56.2%–74.5%]. The median DOR was 17.5 months (95% CI, 15.8–not reached). In CLL (N = 48), the ORR was 58.3% (95% CI, 43.2%–72.4%), and the DOR ranged from 5.6 to 24.2 months. The most common adverse reactions (≥30% in either trial) were thrombocytopenia, diarrhea, neutropenia, bruising, upper respiratory tract infection, anemia, fatigue, musculoskeletal pain, peripheral edema, and nausea. Clin Cancer Res; 21(16); 3586–90. ©2015 AACR.
Integrating Murine and Clinical Trials with Cabozantinib to Understand Roles of MET and VEGFR2 as Targets for Growth Inhibition of Prostate Cancer
Authors: Varkaris Andreas , Corn Paul G. , Parikh Nila U. , Efstathiou Eleni , Song Jian H. , Lee Yu-Chen , Aparicio Ana , Hoang Anh G. , Gaur Sanchaika , Thorpe Lynnelle , Maity Sankar N. , Bar Eli Menashe , Czerniak Bogdan A. , Shao Yiping , Alauddin Mian , Lin Sue-Hwa , Logothetis Christopher J. , Gallick Gary E. 
Published: August 2015

Abstract
Purpose: We performed parallel investigations in cabozantinib-treated patients in a phase II trial and simultaneously in patient-derived xenograft (PDX) models to better understand the roles of MET and VEGFR2 as targets for prostate cancer therapy.
Experimental Design: In the clinical trial, radiographic imaging and serum markers were examined, as well as molecular markers in tumors from bone biopsies. In mice harboring PDX intrafemurally or subcutaneously, cabozantinib effects on tumor growth, MET, PDX in which MET was silenced, VEGFR2, bone turnover, angiogenesis, and resistance were examined.
Results: In responsive patients and PDX, islets of viable pMET-positive tumor cells persisted, which rapidly regrew after drug withdrawal. Knockdown of MET in PDX did not affect tumor growth in mice nor did it affect cabozantinib-induced growth inhibition but did lead to induction of FGFR1. Inhibition of VEGFR2 and MET in endothelial cells reduced the vasculature, leading to necrosis. However, each islet of viable cells surrounded a VEGFR2-negative vessel. Reduction of bone turnover was observed in both cohorts.
Conclusions: Our studies demonstrate that MET in tumor cells is not a persistent therapeutic target for metastatic castrate-resistant prostate cancer (CRPC), but inhibition of VEGFR2 and MET in endothelial cells and direct effects on osteoblasts are responsible for cabozantinib-induced tumor inhibition. However, vascular heterogeneity represents one source of primary therapy resistance, whereas induction of FGFR1 in tumor cells suggests a potential mechanism of acquired resistance. Thus, integrated cross-species investigations demonstrate the power of combining preclinical models with clinical trials to understand mechanisms of activity and resistance of investigational agents. Clin Cancer Res; 22(1); 107–21. ©2015 AACR.
Downregulation of Critical Oncogenes by the Selective SK2 Inhibitor ABC294640 Hinders Prostate Cancer Progression
Authors: Schrecengost Randy S. , Keller Staci N. , Schiewer Matthew J. , Knudsen Karen E. , Smith Charles D. 
Published: August 2015

Abstract
The bioactive sphingolipid sphingosine-1-phosphate (S1P) drives several hallmark processes of cancer, making the enzymes that synthesize S1P, that is, sphingosine kinase 1 and 2 (SK1 and SK2), important molecular targets for cancer drug development. ABC294640 is a first-in-class SK2 small-molecule inhibitor that effectively inhibits cancer cell growth in vitro and in vivo. Given that AR and Myc are two of the most widely implicated oncogenes in prostate cancer, and that sphingolipids affect signaling by both proteins, the therapeutic potential for using ABC294640 in the treatment of prostate cancer was evaluated. This study demonstrates that ABC294640 abrogates signaling pathways requisite for prostate cancer growth and proliferation. Key findings validate that ABC294640 treatment of early-stage and advanced prostate cancer models downregulate Myc and AR expression and activity. This corresponds with significant inhibition of growth, proliferation, and cell-cycle progression. Finally, oral administration of ABC294640 was found to dramatically impede xenograft tumor growth. Together, these pre-clinical findings support the hypotheses that SK2 activity is required for prostate cancer function and that ABC294640 represents a new pharmacological agent for treatment of early stage and aggressive prostate cancer.
Implications: Sphingosine kinase inhibition disrupts multiple oncogenic signaling pathways that are deregulated in prostate cancer. Mol Cancer Res; 13(12); 1591–601. ©2015 AACR.
Adaptive Immune Resistance: How Cancer Protects from Immune Attack
Authors: Ribas Antoni 
Published: August 2015

Abstract
Adaptive immune resistance is a process in which the cancer changes its phenotype in response to a cytotoxic or proinflammatory immune response, thereby evading it. This adaptive process is triggered by the specific recognition of cancer cells by T cells, which leads to the production of immune-activating cytokines. Cancers then hijack mechanisms developed to limit inflammatory and immune responses and protect themselves from the T-cell attack. Inhibiting adaptive immune resistance is the mechanistic basis of responses to PD-1 or PD-L1–blocking antibodies, and may be of relevance for the development of other cancer immunotherapy strategies.
Significance: Several new immunotherapy strategies to treat cancer are based on inhibiting processes through which cancer adapts and evades from an immune response. Recognizing the specific adaptive resistance mechanisms in each case is likely to allow the personalized development of immunotherapies tailored to block how a particular cancer protects itself from the immune system. Cancer Discov; 5(9); 915–9. ©2015 AACR.
The D173G mutation in ADAMTS-13 causes a severe form of congenital thrombotic thrombocytopenic purpura
Authors: Pagliari Maria Teresa , Cairo Andrea , Abdel-Azeim Safwat , Chermak Edrisse , Lazzareschi Ilaria , Mastrangelo Stefano , Cavallo Luigi , Oliva Romina , Lancellotti Stefano , Peyvandi Flora , Cristofaro Raimondo De 
Published: August 2015

SummaryCongenital thrombotic thrombocytopenic purpura (TTP) is a rare form of thrombotic microangiopathy, inherited with autosomal recessive mode as a dysfunction or severe deficiency of ADAMTS-13 (A Disinte-grin And Metalloprotease with ThromboSpondin 1 repeats Nr. 13), caused by mutations in the ADAMTS-13 gene. About 100 mutations of the ADAMTS-13 gene were identified so far, although only a few char-acterised by in vitro expression studies. A new Asp to Gly homozygous mutation at position 173 of ADAMTS-13 sequence was identified in a family of Romanian origin, with some members affected by clinical signs of TTP. In two male sons, this mutation caused a severe (< 3 %) deficiency of ADAMTS-13 activity and antigen level, associated with periodic thrombocytopenia, haemolytic anaemia and mild mental confusion. Both parents, who are cousins, showed the same mutation in heterozygous form. Expression studies of the mutant ADAMTS-13, performed in HEK293 cells, showed a severe decrease of the enzyme’s activity and secretion, although the protease was detected inside the cells. Molecular dynamics found that in the D173G mutant the interface area between the metalloprotease domain and the disintegrin-like domain significantly decreases during the simulations, while the proline-rich 20 residues linker region (LR, 285–304) between them undergoes extensive conformational changes. Inter-domain contacts are also significantly less conserved in the mutant compared to the wild-type. Both a decrease of the inter-domain contacts along with a substantial conformational rearrangement of LR interfere with the proper maturation and folding of the mutant ADAMTS-13, thus impairing its secretion.Supplementary Material to this article is available online at www.thrombosis-online.com.
Antiplatelet drugs in patients with enhanced platelet turnover: biomarkers versus platelet function testing
Authors: Gruber Susanne , Grove Erik , Weiss Thomas , Wojta Johann , Huber Kurt , Freynhofer Matthias 
Published: August 2015

SummaryPlatelets are key players in atherothrombosis. Antiplatelet therapy comprising aspirin alone or with P2Y12-inhibitors are effective for prevention of atherothrombotic complications. However, there is interindividual variability in the response to antiplatelet drugs, leaving some patients at increased risk of recurrent atherothrombotic events. Several risk factors associated with high on-treatment platelet reactivity (HTPR), including elevated platelet turnover, have been identified. Platelet turnover is adequately estimated from the fraction of reticulated platelets. Reticulated platelets are young platelets, characterised by residual messenger RNA. They are larger, haemostatically more active and there is evidence that platelet turnover is a causal and prognostic factor in atherothrombotic disease. Whether platelet turnover per se represents a key factor in pathogenesis, progression and prognosis of atherothrombotic diseases (with focus on acute coronary syndromes) or whether it merely facilitates insufficient platelet inhibition will be discussed in this state-of-the art review.
Drug-Free Platelets Can Act as Seeds for Aggregate Formation During Antiplatelet Therapy
Authors: Hoefer Thomas , Armstrong Paul C. , Finsterbusch Michaela , Chan Melissa V. , Kirkby Nicholas S. , Warner Timothy D. 
Published: August 2015

Objective—
Reduced antiplatelet drug efficacy occurs in conditions of increased platelet turnover, associated with increased proportions of drug-free, that is, uninhibited, platelets. Here, we detail mechanisms by which drug-free platelets promote platelet aggregation in the face of standard antiplatelet therapy.

Approach and Results—

To model standard antiplatelet therapy, platelets were treated in vitro with aspirin, the P2Y
12
receptor blocker prasugrel active metabolite, or aspirin plus prasugrel active metabolite. Different proportions of uninhibited platelets were then introduced. Light transmission aggregometry analysis demonstrated clear positive associations between proportions of drug-free platelets and percentage platelet aggregation in response to a range of platelet agonists. Using differential platelet labeling coupled with advanced flow cytometry and confocal imaging we found aggregates formed in mixtures of aspirin-inhibited platelets together with drug-free platelets were characterized by intermingled platelet populations. This distribution is in accordance with the ability of drug-free platelets to generate thromboxane A
2
and so drive secondary platelet activation. Conversely, aggregates formed in mixtures of prasugrel active metabolite–inhibited or aspirin plus prasugrel active metabolite–inhibited platelets together with drug-free platelets were characterized by distinct cores of drug-free platelets. This distribution is consistent with the ability of drug-free platelets to respond to the secondary activator ADP.

Conclusions—
These experiments are the first to image the interactions of inhibited and uninhibited platelets in the formation of platelet aggregates. They demonstrate that a general population of platelets can contain subpopulations that respond strikingly differently to overall stimulation of the population and so act as the seed for platelet aggregation.
Fibroblast Growth Factor 23 Is an Independent and Specific Predictor of Mortality in Patients With Heart Failure and Reduced Ejection Fraction
Authors: Koller Lorenz , Kleber Marcus E. , Brandenburg Vincent M. , Goliasch Georg , Richter Bernhard , Sulzgruber Patrick , Scharnagl Hubert , Silbernagel Günther , Grammer Tanja B. , Delgado Graciela , Tomaschitz Andreas , Pilz Stefan , Berger Rudolf , Mörtl Deddo , Hülsmann Martin , Pacher Richard , März Winfried , Niessner Alexander 
Published: August 2015

Background—
Strategies to improve risk prediction are of major importance in patients with heart failure (HF). Fibroblast growth factor 23 (FGF-23) is an endocrine regulator of phosphate and vitamin D homeostasis associated with an increased cardiovascular risk. We aimed to assess the prognostic effect of FGF-23 on mortality in HF patients with a particular focus on differences between patients with HF with preserved ejection fraction and patients with HF with reduced ejection fraction (HFrEF).

Methods and Results—

FGF-23 levels were measured in 980 patients with HF enrolled in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study including 511 patients with HFrEF and 469 patients with HF with preserved ejection fraction and a median follow-up time of 8.6 years. FGF-23 was additionally measured in a second cohort comprising 320 patients with advanced HFrEF. FGF-23 was independently associated with mortality with an adjusted hazard ratio per 1-SD increase of 1.30 (95% confidence interval, 1.14–1.48;
P
<0.001) in patients with HFrEF, whereas no such association was found in patients with HF with preserved ejection fraction (for interaction,
P
=0.043). External validation confirmed the significant association with mortality with an adjusted hazard ratio per 1 SD of 1.23 (95% confidence interval, 1.02–1.60;
P
=0.027). FGF-23 demonstrated an increased discriminatory power for mortality in addition to N-terminal pro–B-type natriuretic peptide (
C
-statistic: 0.59 versus 0.63) and an improvement in net reclassification index (39.6%;
P
<0.001).

Conclusions—
FGF-23 is independently associated with an increased risk of mortality in patients with HFrEF but not in those with HF with preserved ejection fraction, suggesting a different pathophysiologic role for both entities.
Till Human Voices Wake Us
Authors: White Emily Kidd 
Published: August 2015

The present paper is concerned with the role emotions play with respect to evaluative legal concepts, a class of concepts that require judges to interpret values in their application of the law. The paper focuses on the legal concept of human dignity, a central concept in international human rights law and in the constitutional practice of many states. Nearly every article or book written on the concept of human dignity begins by noting its resonance and the power of its promise. The affective dimension of the concept is, however, soon set aside by most scholars and legal practitioners in order to work out the term’s content. Against this trend, the paper explores the affective dimensions of the legal concept of human dignity.
Situated in the field of comparative human rights, the paper examines the various roles emotions play in judicial interpretations of the concept of human dignity in human rights and constitutional law. The paper begins by offering a working definition of emotion before setting out the challenge to legal theory and practice posed by evaluative legal concepts. It then sketches out the landscape of dignity jurisprudence and various key sites for the study of emotion. The paper then develops a typology of roles that emotions play in judicial interpretations of the legal concept of human dignity. The three roles that emotions play, orientation, tracker, and service, draw upon the unique features of emotions to enliven and direct judicial understandings of the concept. Emotions fulfill orientation roles when they imbue a concept with their own meaning, tracker roles when they react to the subject matter of the concept, and service roles when they guide the use of the concept. Each role contributes an additional layer of meaning to the concept by lending structure, and often a sense of importance and clarity, to judicial interpretations of human dignity.
“As a Father Shows Compassion for His Children”
Authors: Maroney Terry A. , Ackerman-Lieberman Phillip 
Published: August 2015

Conventional wisdom holds that judges ought to be emotionless. Occasional counterclaims, however, have posited compassion as an essential element of judicial wisdom. When compassion is thus privileged, it is understood as uniquely parental.
We use as our lens two examples, one ancient and one modern: the disqualification, in the Babylonian Talmud, of childless men from judging capital cases on the ground that they are “devoid of paternal tenderness,” and Judge Julian Mack’s vision of the early 20th century juvenile court judge as a “wise and merciful father.” In both narratives judges are asked to have the capacity for empathy, which is believed to spark compassion, which in turn is predicted to manifest in mercy. In neither narrative, however, is this empathic arc seen as critical for judging in the ordinary case. A contemporary study showing the jurisprudential impact of fathering daughters represents a modern iteration of the judge-as-caring-parent meme.
Decadal Sea Level Variations in the Indian Ocean Investigated with HYCOM: Roles of Climate Modes, Ocean Internal Variability, and Stochastic Wind Forcing*
Authors: Li Yuanlong , Han Weiqing 
Published: August 2015

Abstract
In this study decadal (≥10 yr) sea level variations in the Indian Ocean (IO) during 1950–2012 are investigated using the Hybrid Coordinate Ocean Model (HYCOM). The solution of the main run agrees well with observations in the western-to-central IO. Results of HYCOM experiments reveal large spatial variations in the mechanisms of decadal sea level variability. Within the tropical IO (north of 20°S), decadal sea level variations achieve maximum amplitude in the south IO thermocline ridge region. They are predominantly forced by decadal fluctuations of surface wind stress associated with climate variability modes, while the impact of other processes is much smaller. The Somali coast and the western Bay of Bengal are two exceptional regions, where ocean internal (unforced) variability has large contribution. Between 28° and 20°S in the subtropical south IO, surface heat flux and ocean internal variability are the major drivers of decadal sea level variability. Heat budget analysis for the upper 300 m of this region suggests that surface heat flux affects regional thermosteric sea level through both local surface heating and heat transport by ocean circulation. In the southwestern IO south of 30°S, where stochastic winds are strong, stochastic wind forcing and its interaction with ocean internal variability generate pronounced decadal variations in sea level. The comprehensive investigation of decadal sea level variability over the IO from an oceanic perspective will contribute to decadal sea level prediction research, which has a high societal demand.
Evaluation of Remotely Sensed Precipitation and Its Performance for Streamflow Simulations in Basins of the Southeast Tibetan Plateau
Authors: Wang Sheng , Liu Suxia , Mo Xingguo , Peng Bin , Qiu Jianxiu , Li Mingxin , Liu Changming , Wang Zhonggen , Bauer-Gottwein Peter 
Published: August 2015

Abstract
Four satellite-based precipitation products [TMPA real time (T-rt), its gauge-adjusted version (T-adj), Climate Prediction Center (CPC) morphing technique (CMORPH) real time (C-rt), and its gauge-adjusted version (C-adj)] were evaluated by a gauge-based synthesis dataset. Further, these products along with the CMORPH gauge–satellite blended version (C-ga), which is virtually C-adj in precipitation ungauged regions and is controlled by gauge analysis over regions of a dense station network, were intercompared with daily streamflow predicted by the distributed vegetation interface processes (VIP) model in the Lhasa and Gongbo basins of the southeast Tibetan Plateau. Results show these satellite-based products perform better in summer than in other seasons. Relative to the gauge-based synthesis dataset, for areal precipitation of the Lhasa basin from 2007 to 2010, biases of C-rt and T-rt are −10.49% and 157.88%, respectively. Biases of C-adj and T-adj are 3.42% and 24.12%, respectively. The C-rt bias is underestimation of the volume of observed rainfall correctly detected and overestimation of the volume of falsely alarmed rainfall, while T-rt bias comes from overestimation of the volume of observed rainfall correctly detected. Simulation efficiencies of stream discharges driven by T-adj and C-adj are better than those by T-rt and C-rt, which are consistent with the accuracies of these products. With benchmarked model parameters using the gauge-based dataset, C-adj presents well for simulation, while T-adj needs parameter recalibration to achieve good skills. Compared to T-adj and C-adj, better simulation could be obtained by C-ga in precipitation-gauged regions.