bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Millstone Grit Group (Pennsylvanian) of the Northumberland–Solway Basin and Alston Block of northern England
Authors: Waters C. N. , Millward D. , Thomas C. W. 
Published: June 2014

Summary
In the Northumberland–Solway Basin and Alston Block of northern England, some aspects of the stratigraphical and sedimentological relationships between the Millstone Grit Group, the Stainmore Formation (Namurian part of the Yoredale Group) and the Westphalian Pennine Coal Measures Group are uncertain. Also, confusion has resulted from discontinuation of Millstone Grit as a formal lithostratigraphical term north of the Stainmore Basin. This paper presents the evidence for, and describes the nature of, a Kinderscoutian (early Pennsylvanian) abrupt transition from typical ‘Yoredale cyclicity’, characterized by marine limestones in a dominantly siliciclastic succession but including marked fluvial channels, to a sandstone-dominated fluvial succession recognizable as the Millstone Grit Group. Sandbodies present in this region are probably the fluvial feeder systems to many of the fluvio-deltaic successions recorded farther south in the Central Pennine Basin. However, onset of the Millstone Grit Group occurs much earlier to the south, during the Pendleian (late Mississippian), despite the entry of fluvial systems into the Central Pennines Basin from the north. In addition to explaining this counter-intuitive relationship, the paper also recognizes continuation of the fluvial regime into the lowermost part of the Pennine Coal Measures Group.
Faulted craters as indicators for thrust motions on Mercury
Authors: Galluzzi Valentina , Di Achille Gaetano , Ferranti Luigi , Popa Ciprian , Palumbo Pasquale 
Published: June 2014

Abstract
Craters cross-cut by faults are used as markers to obtain fault geometric and kinematic properties. Assuming that the shape of these craters was originally circular, it is possible to measure the horizontal and vertical components of fault displacement as well as the slip trend. By applying trigonometric relations, slip plunge, displacement magnitude, fault true dip and fault rake can be derived from the observed values. An example application of this method on craters faulted by lobate scarps on Mercury shows that most of these inferred reverse faults have moderate oblique-slip trends. Moreover, the derived dips of thrusts vary over a wide range of angles. Some preliminary results in terms of fault rake compared with fault dip, strike and latitude are presented together with a pilot study to test and discriminate global tectonic models suggested for the evolution of Mercury. The possibility of estimating quantitative fault parameters through remotely sensed data provides significant assistance in the structural characterization of faults on planetary surfaces.
ASC-J9 Suppresses Renal Cell Carcinoma Progression by Targeting an Androgen Receptor–Dependent HIF2α/VEGF Signaling Pathway
Authors: He Dalin , Li Lei , Zhu Guodong , Liang Liang , Guan Zhenfeng , Chang Luke , Chen Yuan , Yeh Shuyuan , Chang Chawnshang 
Published: June 2014

Abstract
Males have a higher incidence of renal cell carcinoma (RCC) than females, but the reason for this gender difference is unknown. Addressing this question, we report the discovery of an androgen receptor (AR)–induced HIF2α/VEGF signal that drives RCC progression. AR attenuation or augmentation in RCC cells altered their proliferation, migration, and invasion in multiple models in vitro and in vivo. Mechanistic investigations revealed that AR targeting inhibited RCC cell migration and invasion by modulating HIF2α/VEGF signals at the level of mRNA and protein expression. Interrupting HIF2α/VEGF signals with inhibitors of either HIF2α or VEGF was sufficient to suppress RCC progression. Similarly, the specific AR degradation enhancer ASC-J9 was sufficient to suppress AR-induced HIF2α/VEGF signaling and RCC progression in multiple models in vitro and in vivo. Taken together, our results revealed a novel role for AR in RCC initiation and progression with implications for novel therapeutic strategies. Cancer Res; 74(16); 4420–30. ©2014 AACR.
Risk of Hospitalization for Survivors of Childhood and Adolescent Cancer
Authors: Kirchhoff Anne C. , Fluchel Mark N. , Wright Jennifer , Ying Jian , Sweeney Carol , Bodson Julia , Stroup Antoinette M. , Smith Ken R. , Fraser Alison , Kinney Anita Y. 
Published: June 2014

Abstract
Background: Childhood cancer survivors may be at increased risk of hospitalization because of cancer-related late effects.
Methods: Using data from population-based research resources in Utah, we identified childhood and adolescent cancer survivors who were diagnosed from 1973 to 2005 (N = 2,571). We selected a comparison cohort based on birth year and sex (N = 7,713). Hospitalizations from 1996 to 2010, excluding pregnancy and delivery, were determined from discharge records. Multivariable regressions were used to evaluate hospitalization admissions, length of stay, and diagnosis for survivors starting five years from diagnosis versus the comparison cohort.
Results: When follow-up began in 1996, there were N = 1,499 survivors and N = 7,219 comparisons who were alive and eligible for follow-up. Average follow-up for survivors was 13.5 years (SD = 8.5) and for the comparison 14.0 years (SD = 8.7; P = 0.05). Survivors were hospitalized, on average, 1.62 (SD = 3.37) times contrasted to 0.79 (SD = 1.73) for the comparison cohort. In multivariable analyses, the hazard ratio (HR) of any hospitalization since 1996 was higher for survivors than the comparison cohort [HR, 1.52, 95% confidence interval (CI), 1.31–1.66]. Survivors experienced a higher hospital admission rate [rate ratio (RR) = 1.67; 95% CI, 1.58–1.77] than the comparison cohort. The number of hospitalizations was highest for neuroblastoma (RR = 2.21; 95% CI, 1.84–2.66) and bone tumors (RR = 2.55; 95% CI, 2.14–3.02) in reference to the comparison cohort. Survivors were hospitalized because of blood disorders more often (HR, 14.2; 95% CI, 6.3–32.0).
Conclusions: The risk of hospitalization and lengths of stay are elevated among childhood cancer survivors.
Impact: Research to identify strategies to prevent and manage survivors' health problems in outpatient settings is needed. Cancer Epidemiol Biomarkers Prev; 23(7); 1280–9. ©2014 AACR.
Androgen Receptor CAG Repeat Polymorphism and Risk of TMPRSS2:ERG–Positive Prostate Cancer
Authors: Yoo Sun , Pettersson Andreas , Jordahl Kristina M. , Lis Rosina T. , Lindstrom Sara , Meisner Allison , Nuttall Elizabeth J. , Stack Edward C. , Stampfer Meir J. , Kraft Peter , Brown Myles , Loda Massimo , Giovannucci Edward L. , Kantoff Philip W. , Mucci Lorelei A. 
Published: June 2014

Abstract
Background: The androgen receptor (AR) is an essential gene in prostate cancer pathogenesis and progression. Genetic variation in AR exists, including a polymorphic CAG repeat sequence that is inversely associated with transcriptional activity. Experimental data suggest that heightened AR activity facilitates formation of TMPRSS2:ERG, a gene fusion present in approximately 50% of tumors of patients with prostate cancer.
Methods: We undertook a nested case–control study to investigate the hypothesis that shorter CAG repeat length would be associated with prostate cancer risk defined by TMPRSS2:ERG status. The study included 291 men with prostate cancer (147 ERG-positive) and 1,221 cancer-free controls. ORs and 95% confidence intervals (CI) were calculated using logistic regression.
Results: Median CAG repeat length (interquartile range) among controls was 22 (20–24). Men with shorter CAG repeats had an increased risk of ERG-positive (OR, 1.07 per 1 repeat decrease; 95% CI, 1.00–1.14), but not ERG-negative prostate cancer (OR, 0.99 per 1 repeat decrease; 95% CI, 0.93–1.05).
Conclusions: These data suggest that shorter CAG repeats are specifically associated with development of TMPRSS2:ERG–positive prostate cancer.
Impact: Our results provide supportive evidence that androgen signaling underlies the development of prostate tumors that harbor TMPRSS2:ERG. Moreover, these results suggest that TMPRSS2:ERG may represent a unique molecular subtype of prostate cancer with an etiology distinct from TMPRSS2:ERG–negative disease. Cancer Epidemiol Biomarkers Prev; 23(10); 2027–31. ©2014 AACR.
Molecular Pathways: PI3K Pathway Phosphatases as Biomarkers for Cancer Prognosis and Therapy
Authors: Chen Muhan , Nowak Dawid G. , Trotman Lloyd C. 
Published: June 2014

Abstract
Cancer research has seen tremendous changes over the past decade. Fast progress in sequencing technology has afforded us with landmark genetic alterations, which had immediate impact on clinical science and practice by pointing to new kinase targets, such as phosphoinositide 3-kinase (PI3K), the EGF receptor, or BRAF. The PI3K pathway for growth control has emerged as a prime example for both oncogene activation and tumor suppressor loss in cancer. Here, we discuss how therapy using PI3K pathway inhibitors could benefit from information on specific phosphatases, which naturally antagonize the kinase targets. This PI3K pathway is found mutated in most cancer types, including prostate, breast, colon, and brain tumors. The tumor-suppressing phosphatases operate at two levels. Lipid-level phosphatases, such as PTEN and INPP4B, revert PI3K activity to keep the lipid second messengers inactive. At the protein level, PHLPP1/2 protein phosphatases inactivate AKT kinase, thus antagonizing mTOR complex 2 activity. However, in contrast with their kinase counterparts the phosphatases are unlikely drug targets. They would need to be stimulated by therapy and are commonly deleted and mutated in cancer. Yet, because they occupy critical nodes in preventing cancer initiation and progression, the information on their status has tremendous potential in outcome prediction, and in matching the available kinase inhibitor repertoire with the right patients. Clin Cancer Res; 20(12); 3057–63. ©2014 AACR.
Lim Domain Binding 2
Authors: Shang Ming-Mei , Talukdar Husain A. , Hofmann Jennifer J. , Niaudet Colin , Asl Hassan Foroughi , Jain Rajeev K. , Rossignoli Aranzazu , Cedergren Cecilia , Silveira Angela , Gigante Bruna , Leander Karin , de Faire Ulf , Hamsten Anders , Ruusalepp Arno , Melander Olle , Ivert Torbjörn , Michoel Tom , Schadt Eric E. , Betsholtz Christer , Skogsberg Josefin , Björkegren Johan L.M. 
Published: June 2014

Objective—
Using a multi-tissue, genome-wide gene expression approach, we recently identified a gene module linked to the extent of human atherosclerosis. This atherosclerosis module was enriched with inherited risk for coronary and carotid artery disease (CAD) and overlapped with genes in the transendothelial migration of leukocyte (TEML) pathway. Among the atherosclerosis module genes, the transcription cofactor Lim domain binding 2 (LDB2) was the most connected in a CAD vascular wall regulatory gene network. Here, we used human genomics and atherosclerosis-prone mice to evaluate the possible role of LDB2 in TEML and atherosclerosis.

Approach and Results—

mRNA profiles generated from blood macrophages in patients with CAD were used to infer transcription factor regulatory gene networks;
Ldlr

–/–

Apob
100/100
mice were used to study the effects of
Ldb2
deficiency on TEML activity and atherogenesis.
LDB2
was the most connected gene in a transcription factor regulatory network inferred from TEML and atherosclerosis module genes in CAD macrophages. In
Ldlr

–/–

Apob
100/100
mice, loss of
Ldb2
increased atherosclerotic lesion size ≈2-fold and decreased plaque stability. The exacerbated atherosclerosis was caused by increased TEML activity, as demonstrated in air-pouch and retinal vasculature models in vivo, by ex vivo perfusion of primary leukocytes, and by leukocyte migration in vitro. In THP1 cells, migration was increased by overexpression and decreased by small interfering RNA inhibition of
LDB2
. A functional
LDB2
variant (rs10939673) was associated with the risk and extent of CAD across several cohorts.

Conclusions—
As a key driver of the TEML pathway in CAD macrophages, LDB2 is a novel candidate to target CAD by inhibiting the overall activity of TEML.
Stromal Cell–Derived Factor-1α/C-X-C Chemokine Receptor Type 4 Axis Promotes Endothelial Cell Barrier Integrity via Phosphoinositide 3-Kinase and Rac1 Activation
Authors: Kobayashi Koji , Sato Kanako , Kida Taiki , Omori Keisuke , Hori Masatoshi , Ozaki Hiroshi , Murata Takahisa 
Published: June 2014

Objective—
Although stromal cell–derived factor (SDF)-1αis well known to modulate the mobilization of hematopoietic stem cells and endothelial progenitor cells, its effects on some pre-existing vascular functions remain unknown. We have investigated here the role of SDF-1αsignaling in endothelial barrier function.

Approach and Results—

Treatment with SDF-1α elevated transendothelial electrical resistance and inhibited the dextran hyperpermeability elicited by thrombin in bovine aortic endothelial cells, both indicating an increase in endothelial barrier function. SDF-1α binds to 2 receptors, C-X-C chemokine receptor types 4 and 7 (CXCR4 and CXCR7). Pretreatment with a CXCR4 antagonist or CXCR4 gene depletion by small interfering RNA (siRNA) eliminated SDF-1α–induced endothelial barrier enhancement. In contrast, CXCR7 antagonist or CXCR7 gene depletion by siRNA did not influence SDF-1α–induced barrier enhancement. Pretreatment with a Gi-protein inhibitor, a phosphoinositide 3-kinase (PI3K) inhibitor, or PI3K p110γsubunit gene depletion by siRNA also inhibited SDF-1α–induced barrier enhancement significantly. Western blot analysis revealed that SDF-1α phosphorylated Akt
Ser473
in endothelial cells, suggesting PI3K activation. Immunostaining showed that treatment with SDF-1αformed a cortical actin rim, which was accompanied by Rac1 activation. In vivo, SDF-1αinhibited croton oil–induced vascular leakage indexed by dye extravasation, which is attenuated by a pretreatment with a CXCR4 antagonist.

Conclusions—
We have identified SDF-1α as a novel suppressor of endothelial permeability. Specifically, SDF-1α stimulates the CXCR4/PI3K/Rac1 signaling pathway and the subsequent cytoskeletal rearrangement.
Phosphodiesterase Type 4 Blockade Prevents Platelet-Mediated Neutrophil Recruitment at the Site of Vascular Injury
Authors: Totani Licia , Piccoli Antonio , Dell’Elba Giuseppe , Concetta Amore , Di Santo Angelomaria , Martelli Nicola , Federico Lorenzo , Pamuklar Zehra , Smyth Susan S. , Evangelista Virgilio 
Published: June 2014

Objective—
Platelet–neutrophil interactions play a key role in cardiovascular disease and inflammatory processes. Src family kinases mediate P-selectin glycoprotein ligand-1–Mac-1 cross talk necessary for firm platelet–neutrophil adhesion. Because Src family kinase activity can be regulated by cAMP-dependent pathways, in this work, we evaluated the role of phosphodiesterases in the signaling events that are required to sustain platelet–neutrophil interactions and neutrophil recruitment at the site of vascular injury.

Approach and Results—
In neutrophils exposed to P-selectin, selective phosphodiesterase 4 (PDE4) inhibition prevented Src family kinase–mediated phosphorylation of the proline-rich tyrosine kinase 2 on Tyr579/Tyr580. The effects of PDE4 inhibition required protein kinase A, likely through protein kinase A–mediated activation of COOH-terminal Src kinase, a major negative regulator of Src family kinases. PDE4, but not other phosphodiesterase inhibitors, reduced platelet–neutrophil conjugates as well as neutrophil firm adhesion on spread platelets under flow conditions. The effect of PDE4 inhibition on neutrophil adhesion was primarily mediated by downregulation of P-selectin–induced activation of Mac-1. In a murine model of endovascular injury, selective inhibition of PDE4 significantly reduced neutrophil recruitment at the site of vascular damage.

Conclusions—
This study identifies PDE4 as a central node in the signaling network that mediates platelet–neutrophil adhesion and suggests that pharmacological inhibition of PDE4 may represent a novel therapeutic avenue for the treatment of cardiovascular disease.
Processed and Unprocessed Red Meat Consumption and Risk of Heart Failure
Authors: Kaluza Joanna , Åkesson Agneta , Wolk Alicja 
Published: June 2014

Background—
Epidemiological studies of red meat consumption in relation to risk of heart failure (HF) are scarce. We examined the associations of unprocessed and processed red meat consumption with HF incidence and mortality in men.

Methods and Results—

The population-based prospective Cohort of Swedish Men included 37 035 men, aged 45 to 79 years, with no history of HF, ischemic heart disease, or cancer at baseline. Meat consumption was assessed with a self-administered questionnaire in 1997. During a mean follow-up of 11.8 years, 2891 incidences and 266 deaths from HF were ascertained. Consumption of processed meat was statistically significant positively associated with risk of HF in both age- and multivariable-adjusted models. Men who consumed ≥75 g/d processed meat compared with those who consumed <25 g/d had a 1.28 (95% confidence interval, 1.10–1.48,
P
trend=0.01) higher risk of HF incidence and 2.43 (95% confidence interval, 1.52–3.88,
P
trend<0.001) higher risk of HF mortality. The consumption of unprocessed meat was not associated with increased risk of incidence of HF or mortality from HF.

Conclusions—
Findings from this prospective study of men with low to moderate red meat consumption indicate that processed red meat consumption, but not unprocessed red meat, is associated with an increased risk of HF.
Partitioning Internal Variability and Model Uncertainty Components in a Multimember Multimodel Ensemble of Climate Projections
Authors: Hingray Benoit , Saïd Mériem 
Published: June 2014

Abstract
A simple and robust framework is proposed for the partitioning of the different components of internal variability and model uncertainty in an unbalanced multimember multimodel ensemble (MM2E) of climate projections obtained for a suite of statistical downscaling models (SDMs) and global climate models (GCMs). It is based on the quasi-ergodic assumption for transient climate simulations. Model uncertainty components are estimated from the noise-free signals of the different modeling chains using a two-way analysis of variance (ANOVA) framework. The residuals from the noise-free signals are used to estimate the large- and small-scale internal variability components associated with each considered GCM–SDM configuration. This framework makes it possible to take into account all members available from any climate ensemble of opportunity. Uncertainty is quantified as a function of lead time for projections of changes in temperature and precipitation produced for a mesoscale alpine catchment. Internal variability accounts for more than 80% of total uncertainty in the first decades. This proportion decreases to less than 10% at the end of the century for temperature but remains greater than 50% for precipitation. Small-scale internal variability is negligible for temperature; however, it is similar to the large-scale component for precipitation, whatever the projection lead time. SDM uncertainty is always greater than GCM uncertainty for precipitation. It is also greater for temperature in the middle of the century. The response-to-uncertainty ratio is very high for temperature. For precipitation, it is always less than one, indicating that even the sign of change is uncertain.
Estimations of Hazardous Convective Weather in the United States Using Dynamical Downscaling
Authors: Gensini Vittorio A. , Mote Thomas L. 
Published: June 2014

Abstract
High-resolution (4 km; hourly) regional climate modeling is utilized to resolve March–May hazardous convective weather east of the U.S. Continental Divide for a historical climate period (1980–90). A hazardous convective weather model proxy is used to depict occurrences of tornadoes, damaging thunderstorm wind gusts, and large hail at hourly intervals during the period of record. Through dynamical downscaling, the regional climate model does an admirable job of replicating the seasonal spatial shifts of hazardous convective weather occurrence during the months examined. Additionally, the interannual variability and diurnal progression of observed severe weather reports closely mimic cycles produced by the regional model. While this methodology has been tested in previous research, this is the first study to use coarse-resolution global climate model data to force a high-resolution regional model with continuous seasonal integration in the United States for purposes of resolving severe convection. Overall, it is recommended that dynamical downscaling play an integral role in measuring climatological distributions of severe weather, both in historical and future climates.
The Seasonal Effects of ENSO on European Precipitation: Observational Analysis
Authors: Shaman Jeffrey 
Published: June 2014

Abstract
An analysis and characterization of seasonal changes in the atmospheric teleconnection between ENSO and western European precipitation, as well as atmospheric conditions over the North Atlantic and Europe, are presented. Significant ENSO-associated changes in precipitation are evident during the boreal spring and fall seasons, marginal during boreal summer, and absent during boreal winter. The spring and fall precipitation anomalies are accompanied by statistically significant ENSO-related changes in large-scale fields over the North Atlantic and Europe. These seasonal teleconnections appear to be mediated by changes in upper tropospheric conditions along the coast of Europe that project down to the lower troposphere and produce onshore or offshore moisture flux anomalies, depending on the season. Some ENSO-related changes in storm activity are also evident during fall and winter. Analyses during boreal winter reveal little effect of coincident ENSO conditions on either European precipitation or upper tropospheric conditions over Europe.