bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4070: Functional differences of actinin isoforms in the formation of invadopodia by invasive cancer cells
Authors: Ito Yuumi , Yamaguchi Hideki , Fukami Kiyoko , Honda Kazufumi , Miura Nami , Yamada Tesshi , Sakai Ryuichi 
Published: May 2015

Abstract
Invadopodia are ventral membrane protrusions that are formed by invasive cancer cells cultured on physiological substrates. They are actin-based structures and promote the degradation of the extracellular matrix by focally localizing matrix metalloproteinases. Accumulating evidence suggests that invadopodia play an important role in local invasion and distant metastasis of malignant tumors. Actinin is an actin-binding protein that forms dimers and crosslinks actin filaments. There are four isoforms of actinin in mammals and they are divided into the muscle type (actinin-2 and -3) and the non-muscle type (actinin-1 and -4). Actinin-1 is ubiquitously expressed and involved in the formation of focal adhesions, while actinin-4 is strongly expressed at the invading front of advanced cancers and its expression is correlated with poor prognosis. Although actinin-4 is thought to regulate cell motility and invasion, the detailed molecular mechanisms remain unclear. Moreover, functional differences between the two isoforms have yet to be fully defined. In this study, we studied the roles of and functional differences between actinin-1 and -4 in invadopodia formation to determine the impact of actinin-4 expression on cancer cells. Immunofluorescence analysis showed that both actinin-1 and -4 clearly localized at invadopodia in RPMI-7951 human melanoma cells and there was no obvious difference in their localization patterns. Likewise, invadopodia formation and degradation of fluorescent gelatin matrix were blocked by siRNA-mediated knockdown of either actinin-1 or -4. In contrast, only actinin-4, but not actinin-1, promoted invadopodia-mediated gelatin degradation activity when overexpressed in RPMI7951 cells. Similar results were obtained when MDA-MB-231 human breast cancer cells and SCC61 human head and neck squamous cell carcinoma cells were analyzed in the same manner. These results indicate that both actinin-1 and -4 are essential components of invadopodia, but only actinin-4 possesses an ability to promote invadopodia formation. Therefore, further analysis is conducted now to identify the unique functions actinin-4 in invadopodia formation.
Citation Format: Yuumi Ito, Hideki Yamaguchi, Kiyoko Fukami, Kazufumi Honda, Nami Miura, Tesshi Yamada, Ryuichi Sakai. Functional differences of actinin isoforms in the formation of invadopodia by invasive cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4070. doi:10.1158/1538-7445.AM2014-4070
Abstract 4084: NKG2D receptor activation of mTOR and NFκB enhances antitumor immunity in effector CD8+ T cells
Authors: Whitman Emily , Barber Amorette E. 
Published: May 2015

Abstract
To induce strong anti-tumor immune responses, naïve CD8+ T cells require stimulation through the TCR and costimulatory receptors. Each costimulatory molecule can have a unique effect on the function of T cells due to differential activation of downstream signaling pathways and gene expression. However, the effect of stimulating costimulatory receptors on activated T cells is still unclear. One costimulation receptor that is likely to be engaged in the tumor microenvironment is NKG2D since the ligands for this receptor are expressed on over 80% of tumors. In order to determine how activation of costimulatory receptors in the tumor microenvironment affects CD8+ T cell functions, this study investigated the differential activation of signaling pathways by two costimulatory receptors, CD28 and NKG2D. Specifically, this study focused on the activation of mTORC1 and mTORC2 along with NFκB, all of which have been shown to have important roles in anti-tumor functions of CD8+ T cells. Stimulation through the CD3 and NKG2D receptors differentially activated the mTOR and NFκB pathways compared to the other receptors in our study. Activation of CD8+ T cells through CD3 and NKG2D lead to increased phosphorylation of signal transduction pathway members upstream of mTOR, including AKT, p70 S6K, and GSK3β. Also, expression of genes upstream and downstream of mTORC1 and mTORC2 were differentially activated after stimulation through NKG2D, indicating that activation of mTOR pathways are altered after CD3/NKG2D stimulation as compared to stimulation through CD3 or CD3/CD28. In addition, IKKα, IκBα, and NFκB phosphorylation and IκBα degradation was increased after CD3/NKG2D stimulation. This increased activation of the NFκB pathway also lead to increased gene expression and secretion of pro-inflammatory cytokines, including IFN-alpha and IFN-gamma, and decreased gene expression and secretion of anti-inflammatory cytokines, including IL-10 and VEGF-alpha. Together, these data show that stimulation through NKG2D leads to the differential activation of signaling pathways and alters the anti-tumor functions of effector CD8+ T cells.
Citation Format: Emily Whitman, Amorette E. Barber. NKG2D receptor activation of mTOR and NFκB enhances antitumor immunity in effector CD8+ T cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4084. doi:10.1158/1538-7445.AM2014-4084
Incremental Value of Platelet Reactivity Over a Risk Score of Clinical and Procedural Variables in Predicting Bleeding After Percutaneous Coronary Intervention via the Femoral Approach
Authors: Mangiacapra Fabio , Ricottini Elisabetta , Barbato Emanuele , Demartini Chiara , Peace Aaron , Patti Giuseppe , Vizzi Vincenzo , De Bruyne Bernard , Wijns William , Di Sciascio Germano 
Published: May 2015

Background—
Growing evidence suggests that platelet reactivity (PR) may predict bleeding. We investigate the incremental value of PR in predicting bleeding after percutaneous coronary intervention (PCI) via the femoral approach over a validated bleeding risk score (BRS) of clinical and procedural variables.

Methods and Results—

A total of 800 patients undergoing elective PCI via the femoral approach were included. PR was measured before PCI with the VerifyNow P2Y12 assay and low PR was defined as a P2Y12 reaction unit value ≤178. Calculation of the BRS included the following: age, sex, intra-aortic balloon pump, glycoprotein IIb/IIIa inhibitors, chronic kidney disease, anemia, and low-molecular-weight heparin within 48-hour pre-PCI. A new risk score including low PR (BRS-PR) was developed and validated in an independent cohort of patients (n=310). Bleeding events at 30 days after PCI were defined according to the thrombolysis in myocardial infarction, Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2, and Bleeding Academic Research Consortium criteria. Both BRS and PR showed high discriminatory power for bleeding (area under the curve [AUC] >0.7 for all definitions). Discriminatory power of BRS-PR (AUC=0.809 for thrombolysis in myocardial infarction bleeding; AUC=0.814 for Bleeding Academic Research Consortium class ≥2 bleeding; AUC=0.708 for Bleeding Academic Research Consortium class ≥3 bleeding; and AUC=0.813 for REPLACE-2 bleeding) was significantly higher than that of BRS alone (
P
<0.001 for all bleeding definitions). In the validation set, BRS-PR showed higher discriminatory power for thrombolysis in myocardial infarction bleeding than BRS alone (AUC=0.788 versus 0.709;
P
=0.036).

Conclusions—
PR has incremental predictive value on bleeding events after elective PCI via the femoral approach over a validated risk score of clinical and procedural variables. A risk score including PR yields significantly better prognostic performance compared with the original BRS.
Interpolation of Global Monthly Rain Gauge Observations for Climate Change Analysis
Authors: Grieser Jürgen 
Published: May 2015

AbstractLong-term global gridded datasets of observed precipitation are essential for the analysis of the global water and energy cycle, its variability, and possible changes. Several institutions provide those datasets. In 2005 the Global Precipitation Climatology Centre (GPCC) published the so-called Variability Analysis of Surface Climate Observations (VASClimO) dataset. This dataset is especially designed for the investigation of temporal change and variability. To date, however, the GPCC has not published how this dataset has been produced. This paper aims to fill this gap. It provides detailed information on how stations are selected and how data are quality controlled and interpolated. The dataset is based only on station records covering at least 90% of the period 1951–2000. The time series of 9343 stations were used. However, these stations are distributed very inhomogeneously around the globe; 4094 of these stations are within Germany and France. The VASClimO dataset is interpolated from relative deviations of observed monthly precipitation, leading to considerably lower interpolation errors than direct interpolation or the interpolation of absolute deviations. The retransformation from interpolated relative deviations to precipitation is done with local long-term averages of precipitation interpolated from data of the Food and Agriculture Organization of the United Nations. The VASClimO dataset has been interpolated with a method that is based on local station correlations (LSC) that is introduced here. It is compared with ordinary kriging and three versions of Shepard’s method. LSC outperforms these methods, especially with respect to the spatial maxima of interpolation errors.
Dissipation of Internal Wave Energy Generated on a Critical Slope
Authors: Gemmrich Johannes , Klymak Jody M. 
Published: May 2015

AbstractTwo-dimensional simulations of stratified flow over an isolated ridge are used to evaluate energy dissipation associated with barotropic tidal flow over topography with critical or near-critical slope. In the midslope region, a shallow borelike flow forms along the bottom in a layer where dissipation rates are increased by several orders of magnitude, and the flow speed is about twice the barotropic background velocity. The height and turbulence in this layer depend on predictable functions of stratification, rotation, and the characteristic forcing speed. A physically sound power-law parameterization of the total energy dissipation associated with this turbulent layer is presented. This simple parameterization is also applicable to coarser-resolution models, where it may be included to compute energy dissipation above continental slopes, even for cases where the slope angle differs somewhat from criticality.
Documenting a Rare Tornado Merger Observed in the 24 May 2011 El Reno–Piedmont, Oklahoma, Supercell*
Authors: French Michael M. , Skinner Patrick S. , Wicker Louis J. , Bluestein Howard B. 
Published: May 2015

Abstract
Unique observations of the interaction and likely merger of two cyclonic tornadoes are documented. One of the tornadoes involved in the interaction was the enhanced Fujita scale (EF5) El Reno–Piedmont, Oklahoma, tornado from 24 May 2011 and the other was a previously undocumented tornado. Data from three S-band radars: Twin Lakes, Oklahoma (KTLX); Norman, Oklahoma (KOUN); and the multifunction phased-array radar (MPAR), are used to detail the formation of the second tornado, which occurred to the northwest of the original tornado in an area of strong radial convergence. Radar data and isosurfaces of azimuthal shear provide evidence that both tornadoes formed within an elongated area of mesocyclone-scale cyclonic rotation. The path taken by the primary tornado and the formation location of the second tornado are different from previous observations of simultaneous cyclonic tornadoes, which have been most often observed in the cyclic tornadogenesis process. The merger of the two tornadoes occurred during the sampling period of a mobile phased-array radar—the Mobile Weather Radar, 2005 X-Band, Phased Array (MWR-05XP). MWR-05XP electronic scanning in elevation allowed for the merger process to be examined up to 4 km above radar level every 11 s. The tornadic vortex signatures (TVSs) associated with the tornadoes traveled around each other in a counterclockwise direction then merged in a helical manner up through storm midlevels. Upon merging, both the estimated intensity and size of the TVS associated with the resulting tornado increased dramatically. Similarities between the merger observed in this case and in previous cases also are discussed.
Predictors of acute kidney injury after coronary artery surgery in Jordanians
Authors: Ibrahim Khalid , Kherallah Khalid , AlWaqfi Nizar , Mayyas Fadia , Abdallat Sager , Alawami Murtada 
Published: May 2015

Background Acute kidney injury after coronary artery bypass surgery is associated with increased morbidity and mortality. We investigated the predictors of acute kidney injury in a major hospital in Jordan. Methods A retrospective analysis was conducted of clinical, operative, and outcome data of 867 patients (mean age 59 ± 9.8 years) who underwent isolated coronary bypass surgery with cardiopulmonary bypass. Acute kidney injury postoperatively, defined as ≥100% increase in serum creatinine level, was the outcome variable. Retrospective clinical, laboratory, and demographic data, and medication use, were obtained from electronic medical records. Results Univariate analysis revealed that chronic obstructive pulmonary disease, recent myocardial infarction, emergency surgery, preoperative intraaortic balloon pump use, left atrial size >4 cm, grade 1 mitral regurgitation, pneumonia, intensive care unit stay, prolonged vasopressor support, and stroke or transient ischemic attack were significantly associated with postoperative renal failure. On multivariate logistic regression, emergency surgery (adjusted odds ratio = 2.17, p = 0.017), grade 1 mitral regurgitation (adjusted odds ratio = 2.05, p = 0.020), prolonged support (adjusted odds ratio = 3.16, p = 0.000), and stroke (adjusted odds ratio = 20.1, p = 0.004) were independent predictors of kidney injury following coronary bypass surgery. Conclusion Emergency coronary surgery, mitral regurgitation, prolonged inotropic support, and stroke or transient ischemic attack are independent predictors of acute kidney injury following coronary bypass surgery. Further studies involving patients with isolated coronary bypass surgery as well as valve and combined surgeries may be necessary to complete our understanding of this subject.
Oxygen and glucose deprivation induces widespread alterations in mRNA translation within 20 minutes
Authors: Andreev Dmitry E , O’Connor Patrick BF , Zhdanov Alexander V , Dmitriev Ruslan I , Shatsky Ivan N , Papkovsky Dmitri B , Baranov Pavel V 
Published: May 2015

Abstract
Background
Oxygen and glucose metabolism play pivotal roles in many (patho)physiological conditions. In particular, oxygen and glucose deprivation (OGD) during ischemia and stroke results in extensive tissue injury and cell death.

Results
Using time-resolved ribosome profiling, we assess gene expression levels in a neural cell line, PC12, during the first hour of OGD. The most substantial alterations are seen to occur within the first 20 minutes of OGD. While transcription of only 100 genes is significantly altered during one hour of OGD, the translation response affects approximately 3,000 genes. This response involves reprogramming of initiation and elongation rates, as well as the stringency of start codon recognition. Genes involved in oxidative phosphorylation are most affected. Detailed analysis of ribosome profiles reveals salient alterations of ribosome densities on individual mRNAs. The mRNA-specific alterations include increased translation of upstream open reading frames, site-specific ribosome pauses, and production of alternative protein isoforms with amino-terminal extensions. Detailed analysis of ribosomal profiles also reveals six mRNAs with translated ORFs occurring downstream of annotated coding regions and two examples of dual coding mRNAs, where two protein products are translated from the same long segment of mRNA, but in two different frames.

Conclusions
These findings uncover novel regulatory mechanisms of translational response to OGD in mammalian cells that are different from the classical pathways such as hypoxia inducible factor (HIF) signaling, while also revealing sophisticated organization of protein coding information in certain genes.
Generalized coupled common fixed point results in partially ordered A-metric spaces
Authors: Abbas Mujahid , Ali Bashir , Suleiman Yusuf I 
Published: May 2015

AbstractSedghi et al. (Mat. Vesn. 64(3):258-266, 2012) introduced the notion of a S-metric as a generalized metric in 3-tuples $S:X^{3} \rightarrow[0,\infty)$
S
:

X
3

→
[
0
,
∞
)
, where X is a nonempty set. The aim of this paper is to introduce the concept of an n-tuple metric $A: X^{n} \rightarrow[0,\infty)$
A
:

X
n

→
[
0
,
∞
)
and to study its basic topological properties. We also prove some generalized coupled common fixed point theorems for mixed weakly monotone maps in partially ordered A-metric spaces. Some examples are presented to support the results proved herein. Our results generalize and extend various results in the existing literature.
Convergence and stability theorems for the Picard-Mann hybrid iterative scheme for a general class of contractive-like operators
Authors: Akewe Hudson , Okeke Godwin Amechi 
Published: May 2015

AbstractIn this paper we use the general class of contractive-like operators introduced by Bosede and Rhoades (J. Adv. Math. Stud. 3(2):1-3, 2010) to prove strong convergence and stability results for Picard-Mann hybrid iterative schemes considered in a real normed linear space. We establish the strong convergence and stability of the Picard iterative scheme as a corollary. Our results generalize and improve a multitude of results in the literature, including the recent results of Chidume (Fixed Point Theory Appl. 2014:233, 2014).
Randomized Multicenter Placebo-Controlled Trial of Omega-3 Fatty Acids for the Control of Aromatase Inhibitor–Induced Musculoskeletal Pain: SWOG S0927
Authors: Hershman Dawn L. , Unger Joseph M. , Crew Katherine D. , Awad Danielle , Dakhil Shaker R. , Gralow Julie , Greenlee Heather , Lew Danika L. , Minasian Lori M. , Till Cathee , Wade James L. , Meyskens Frank L. , Moinpour Carol M. 
Published: May 2015

Purpose Musculoskeletal symptoms are the most common adverse effects of aromatase inhibitors (AIs) and can result in decreased quality of life and discontinuation of therapy. Omega-3 fatty acids (O3-FAs) can be effective in decreasing arthralgia resulting from rheumatologic conditions and reducing serum triglycerides. Patients and Methods Women with early-stage breast cancer receiving an AI who had a worst joint pain/stiffness score ≥ 5 of 10 using the Brief Pain Inventory–Short Form (BPI-SF) were randomly assigned to receive either O3-FAs 3.3 g or placebo (soybean/corn oil) daily for 24 weeks. Clinically significant change was defined as ≥ 2-point drop from baseline. Patients also completed quality-of-life (Functional Assessment of Cancer Therapy–Endocrine Symptoms) and additional pain/stiffness assessments at baseline and weeks 6, 12, and 24. Serial fasting blood was collected for lipid analysis. Results Among 262 patients registered, 249 were evaluable, with 122 women in the O3-FA arm and 127 in the placebo arm. Compared with baseline, the mean observed BPI-SF score decreased by 1.74 points at 12 weeks and 2.22 points at 24 weeks with O3-FAs and by 1.49 and 1.81 points, respectively, with placebo. In a linear regression adjusting for the baseline score, osteoarthritis, and taxane use, adjusted 12-week BPI-SF scores did not differ by arm (P = .58). Triglyceride levels decreased in patients receiving O3-FA treatment and remained the same for those receiving placebo (P = .01). No between-group differences were seen for HDL, LDL, or C-reactive protein. Conclusion We found a substantial (> 50%) and sustained improvement in AI arthralgia for both O3-FAs and placebo but found no meaningful difference between the groups.
Germline BRCA Mutations in a Large Clinic-Based Cohort of Patients With Pancreatic Adenocarcinoma
Authors: Holter Spring , Borgida Ayelet , Dodd Anna , Grant Robert , Semotiuk Kara , Hedley David , Dhani Neesha , Narod Steven , Akbari Mohammad , Moore Malcolm , Gallinger Steven 
Published: May 2015

Purpose The main purpose of this study was to determine the prevalence of pathogenic BRCA1 and BRCA2 mutations in a consecutively ascertained clinic-based cohort of patients with pancreatic ductal adenocarcinoma and describe the clinical and family history characteristics. Patients and Methods Unselected, consecutive, incident patients with pancreatic ductal adenocarcinoma were recruited at a single cancer center over a 2-year period. Participants provided blood for DNA analysis and cancer family history, and cancer treatment records were reviewed. DNA from all patients was analyzed by Sanger sequencing and multiplex ligation-dependent probe amplification for germline variants in BRCA1 and BRCA2. Results Three hundred six patients were eligible for analysis. Pathogenic germline BRCA mutations were identified in 14 patients (4.6%; 95% CI, 2.2% to 6.9%), including 11 patients with a BRCA2 mutation and three patients with a BRCA1 mutation. Having a cancer family history that met genetic testing criteria of the National Comprehensive Cancer Network or the Ontario Ministry of Health and Long-Term Care or self-reporting as Ashkenazi Jewish was significantly associated with BRCA mutation carrier status (P = .02, P < .001, and P = .05, respectively). However, the majority of the BRCA mutation–positive patients did not actually meet these genetic testing criteria. Conclusion Pathogenic BRCA mutations were identified in 4.6% of a large cohort of clinic-based patients. Considering the implications for family members of BRCA carriers, and possibly tailored chemotherapeutic treatment of patients, our finding has implications for broader BRCA genetic testing for patients with pancreatic ductal adenocarcinoma.