bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cross-strike structures controlling magmatism emplacement in a flat-slab setting (Precordillera, Central Andes of Argentina)
Authors: Oriolo S. , Japas M. S. , Cristallini E. O. , Giménez M. 
Published: November 2013

Abstract
Detailed structural, kinematic and geophysical data on the foreland of the Pampean flat-slab segment (Hualilán area, Andean Precordillera of Argentina) have shown that cross-strike structures have had an important role in the evolution of this Andean segment since Miocene times. These structures represent pre-existing crustal fabrics reactivated during the Andean orogeny and could have controlled the emplacement of the Miocene arc-magmatism migrating into foreland due to the flattening of the slab. Likewise, kinematic results obtained for these structures support a similar stress frame to that obtained elsewhere in the Precordillera but showing different motions as a consequence of their high obliquity to the orogen trend. Moreover, they record a reorientation of kinematic axes during Late Miocene–Pliocene times.
Volcanic markers for dating the onset of the Anthropocene
Authors: Smith Victoria C. 
Published: November 2013

Abstract
Volcanic ash is dispersed over thousands of kilometres during large-scale eruptions, forming sedimentary layers. These ash (tephra) deposits are increasingly being used as unique marker layers in a variety of sedimentary archives including ice cores, and terrestrial and marine records. Tephra dispersed during large explosive eruptions that coincide with the defined beginning of the Anthropocene could therefore be used to help identify this event in various archives, and assess the relative spatial differences in marked anthropogenic change. The 1815 eruption of Tambora, Indonesia, was the largest in historical time and occurred in the middle of Europe's Industrial Revolution. Volatile emissions injected into the atmosphere during this eruption caused widespread effects including the ‘year without a summer’ during which there were anomalously cooler temperatures recorded across much of North America and Europe. Sulphate aerosols associated with the eruption were dispersed by stratospheric and tropospheric winds across the entire globe. Deposits of these are clearly recorded in the Earth's key palaeoclimatic records: polar ice cores. Significantly, the Tambora eruption occurred immediately prior to substantial increases in greenhouse gases, a defining feature of the Anthropocene.
The Role of Polo-like Kinase 1 in Carcinogenesis: Cause or Consequence?
Authors: Cholewa Brian D. , Liu Xiaoqi , Ahmad Nihal 
Published: November 2013

Abstract
Polo-like kinase 1 (Plk1) is a well-established mitotic regulator with a diverse range of biologic functions continually being identified throughout the cell cycle. Preclinical evidence suggests that the molecular targeting of Plk1 could be an effective therapeutic strategy in a wide range of cancers; however, that success has yet to be translated to the clinical level. The lack of clinical success has raised the question of whether there is a true oncogenic addiction to Plk1 or if its overexpression in tumors is solely an artifact of increased cellular proliferation. In this review, we address the role of Plk1 in carcinogenesis by discussing the cell cycle and DNA damage response with respect to their associations with classic oncogenic and tumor suppressor pathways that contribute to the transcriptional regulation of Plk1. A thorough examination of the available literature suggests that Plk1 activity can be dysregulated through key transformative pathways, including both p53 and pRb. On the basis of the available literature, it may be somewhat premature to draw a definitive conclusion on the role of Plk1 in carcinogenesis. However, evidence supports the notion that oncogene dependence on Plk1 is not a late occurrence in carcinogenesis and it is likely that Plk1 plays an active role in carcinogenic transformation. Cancer Res; 73(23); 6848–55. ©2013 AACR.
MAP Kinase Pathway Alterations in BRAF-Mutant Melanoma Patients with Acquired Resistance to Combined RAF/MEK Inhibition
Authors: Wagle Nikhil , Van Allen Eliezer M. , Treacy Daniel J. , Frederick Dennie T. , Cooper Zachary A. , Taylor-Weiner Amaro , Rosenberg Mara , Goetz Eva M. , Sullivan Ryan J. , Farlow Deborah N. , Friedrich Dennis C. , Anderka Kristin , Perrin Danielle , Johannessen Cory M. , McKenna Aaron , Cibulskis Kristian , Kryukov Gregory , Hodis Eran , Lawrence Donald P. , Fisher Sheila , Getz Gad , Gabriel Stacey B. , Carter Scott L. , Flaherty Keith T. , Wargo Jennifer A. , Garraway Levi A. 
Published: November 2013

Abstract
Treatment of BRAF-mutant melanoma with combined dabrafenib and trametinib, which target RAF and the downstream MAP–ERK kinase (MEK)1 and MEK2 kinases, respectively, improves progression-free survival and response rates compared with dabrafenib monotherapy. Mechanisms of clinical resistance to combined RAF/MEK inhibition are unknown. We performed whole-exome sequencing (WES) and whole-transcriptome sequencing (RNA-seq) on pretreatment and drug-resistant tumors from five patients with acquired resistance to dabrafenib/trametinib. In three of these patients, we identified additional mitogen-activated protein kinase (MAPK) pathway alterations in the resistant tumor that were not detected in the pretreatment tumor, including a novel activating mutation in MEK2 (MEK2Q60P). MEK2Q60P conferred resistance to combined RAF/MEK inhibition in vitro, but remained sensitive to inhibition of the downstream kinase extracellular signal–regulated kinase (ERK). The continued MAPK signaling-based resistance identified in these patients suggests that alternative dosing of current agents, more potent RAF/MEK inhibitors, and/or inhibition of the downstream kinase ERK may be needed for durable control of BRAF-mutant melanoma.
Significance: This study represents an initial clinical genomic study of acquired resistance to combined RAF/MEK inhibition in BRAF-mutant melanoma, using WES and RNA-seq. The presence of diverse resistance mechanisms suggests that serial biopsies and genomic/molecular profiling at the time of resistance may ultimately improve the care of patients with resistant BRAF-mutant melanoma by specifying tailored targeted combinations to overcome specific resistance mechanisms. Cancer Discov; 4(1); 61–8. ©2013 AACR.
See related commentary by Solit and Rosen, p. 27
This article is highlighted in the In This Issue feature, p. 1
Deficiency of Endogenous Acute Phase Serum Amyloid A Does Not Affect Atherosclerotic Lesions in Apolipoprotein E–Deficient Mice
Authors: De Beer Maria C. , Wroblewski Joanne M. , Noffsinger Victoria P. , Rateri Debra L. , Howatt Deborah A. , Balakrishnan Anju , Ji Ailing , Shridas Preetha , Thompson Joel C. , van der Westhuyzen Deneys R. , Tannock Lisa R. , Daugherty Alan , Webb Nancy R. , De Beer Frederick C. 
Published: November 2013

Objective—
Although elevated plasma concentrations of serum amyloid A (SAA) are associated strongly with increased risk for atherosclerotic cardiovascular disease in humans, the role of SAA in the pathogenesis of lesion formation remains obscure. Our goal was to determine the impact of SAA deficiency on atherosclerosis in hypercholesterolemic mice.

Approach and Results—

Apolipoprotein E–deficient (apoE
−/−
) mice, either wild type or deficient in both major acute phase SAA isoforms, SAA1.1 and SAA2.1, were fed a normal rodent diet for 50 weeks. Female mice, but not male apoE−/− mice deficient in SAA1.1 and SAA2.1, had a modest increase (22%;
P
≤0.05) in plasma cholesterol concentrations and a 53% increase in adipose mass compared with apoE−/− mice expressing SAA1.1 and SAA2.1 that did not affect the plasma cytokine levels or the expression of adipose tissue inflammatory markers. SAA deficiency did not affect lipoprotein cholesterol distributions or plasma triglyceride concentrations in either male or female mice. Atherosclerotic lesion areas measured on the intimal surfaces of the arch, thoracic, and abdominal regions were not significantly different between apoE−/− mice deficient in SAA1.1 and SAA2.1 and apoE−/− mice expressing SAA1.1 and SAA2.1 in either sex. To accelerate lesion formation, mice were fed a Western diet for 12 weeks. SAA deficiency had effect neither on diet-induced alterations in plasma cholesterol, triglyceride, or cytokine concentrations nor on aortic atherosclerotic lesion areas in either male or female mice. In addition, SAA deficiency in male mice had no effect on lesion areas or macrophage accumulation in the aortic roots.

Conclusions—
The absence of endogenous SAA1.1 and 2.1 does not affect atherosclerotic lipid deposition in apolipoprotein E–deficient mice fed either normal or Western diets.
G-Protein–Coupled Receptor-2–Interacting Protein-1 Is Required for Endothelial Cell Directional Migration and Tumor Angiogenesis via Cortactin-Dependent Lamellipodia Formation
Authors: Majumder Syamantak , Sowden Mark P. , Gerber Scott A. , Thomas Tamlyn , Christie Christine K. , Mohan Amy , Yin Guoyong , Lord Edith M. , Berk Bradford C. , Pang Jinjiang 
Published: November 2013

Objective—
Recent evidence suggests G-protein–coupled receptor-2–interacting protein-1 (GIT1) overexpression in several human metastatic tumors, including breast, lung, and prostate. Tumor metastasis is associated with an increase in angiogenesis. We have showed previously that GIT1 is required for postnatal angiogenesis during lung development. However, the functional role of GIT1 in pathological angiogenesis during tumor growth is unknown.

Approach and Results—
In the present study, we show inhibition of angiogenesis in matrigel implants as well as reduced tumor angiogenesis and melanoma tumor growth in GIT1-knockout mice. We demonstrate that this is a result of impaired directional migration of GIT1-depleted endothelial cells toward a vascular endothelial growth factor gradient. Cortactin-mediated lamellipodia formation in the leading edge is critical for directional migration. We observed a significant reduction in cortactin localization and lamellipodia formation in the leading edge of GIT1-depleted endothelial cells. We specifically identified that the Spa homology domain (aa 250–420) of GIT1 is required for GIT1–cortactin complex localization to the leading edge. The mechanisms involved extracellular signal-regulated kinases 1 and 2–mediated Cortactin-S405 phosphorylation and activation of Rac1/Cdc42. Finally, using gain of function studies, we show that a constitutively active mutant of cortactin restored directional migration of GIT1-depleted cells.

Conclusion—
Our data demonstrated that a GIT1–cortactin association through GIT1-Spa homology domain is required for cortactin localization to the leading edge and is essential for endothelial cell directional migration and tumor angiogenesis.
Within-Day and Weekly Variations of Thrombolysis in Acute Ischemic Stroke
Authors: Lorenzano Svetlana , Ahmed Niaz , Tatlisumak Turgut , Gomis Meritxell , Dávalos Antoni , Mikulik Robert , Sevcik Petr , Ollikainen Jyrki , Wahlgren Nils , Toni Danilo 
Published: November 2013

Background and Purpose—
Temporal variations of thrombolysis delivery and their influence on outcome have been reported with controversial results. In this large cohort study, we evaluated whether thrombolytic treatment has a within-day and weekly variability corresponding to circadian and weekly patterns of ischemic stroke onset, and whether these have impact on clinical outcome.

Methods—
We retrospectively analyzed patients with acute ischemic stroke receiving intravenous alteplase, prospectively included in the Safe Implementation of Treatments in Stroke-International Stroke Thrombolysis Register. Patients were grouped by treatment on day hours (08:00–19:59) or night hours (20:00–07:59) and treatment on weekdays and weekends. For each subgroup, we analyzed frequency of thrombolytic treatments, time intervals, and outcomes (3-month modified Rankin Scale score 0–2 as good functional outcome, mortality, symptomatic intracerebral hemorrhage).

Results—

We included 21 513 patients. Considering the mean expected number of patients treated per hour (0.4) and per day of the week (9.8), if no temporal variations were present, patients were significantly treated more during day hours and weekdays (
P
<0.0001). Median door-to-needle and onset-to-treatment times were longer for patients treated during night hours and on weekends (
P
<0.01). After adjustment for confounding variables, treatment during day hours was an independent predictor of good functional outcome (odds ratio, 1.12; 95% confidence interval, 1.04–1.21;
P
=0.004), and patients treated during weekdays were at risk of higher mortality (odds ratio, 1.15; 95% confidence interval, 1.04–1.28;
P
=0.008).

Conclusions—
Frequency of thrombolytic treatment seems to follow the same circadian pattern of stroke incidence, whereas its correspondence to a weekly pattern is less clear. Time of treatment is an independent predictor of outcome.
Socioeconomic Deprivation and Survival After Stroke
Authors: Chen Ruoling , McKevitt Christopher , Rudd Anthony G. , Wolfe Charles D.A. 
Published: November 2013

Background and Purpose—
Previous findings of the association between socioeconomic deprivation (SED) and survival after stroke are inconsistent. There is less investigation on long-term survival. We assessed the associations in a multi-ethnic population in England.

Methods—
We examined data from 4398 patients (3103 whites, 932 blacks, and 253 Asians/others) with first-ever stroke, collected by a population-based stroke register in South London from 1995 to 2011. SED was measured using the Carstairs index score—the higher score, the more deprived. It was analyzed in multivariate Cox regression models in relation to survival after stroke.

Results—
During 17-year follow-up 2754 patients died. The quartile data of Carstairs score showed no significant association of SED with survival in patients, except for black Caribbeans and Africans. Black patients with the fourth quartile SED had a multivariate adjusted hazard ratio of 1.76 (95% confidence interval, 1.06–2.94) for 3-month mortality and 1.54 (1.00–2.37) for 1-year mortality. After adjustment for acute stroke care provisions, these were no longer significant. However, the sextile data of Carstairs score showed a consistent association of SED with survival after stroke; all patients with the sixth sextile had a fully adjusted hazard ratio of 1.23 (1.05–1.44) for 3-month mortality and 1.13 (1.01–1.25) for 17-year mortality.

Conclusions—
There is a weak but significant association of SED with reduced survival after stroke in England. SED in blacks may have a stronger impact on short-term survival when compared with white patients. Further efforts are required to achieve equality in survival among patients with stroke of different socioeconomic groups.
How Fast Are the Tropics Expanding?
Authors: Quan Xiao-Wei , Hoerling Martin P. , Perlwitz Judith , Diaz Henry F. , Xu Taiyi 
Published: November 2013

AbstractDiagnosing the sensitivity of the tropical belt provides one framework for understanding how global precipitation patterns may change in a warming world. This paper seeks to understand boreal winter rates of subtropical dry zone expansion since 1979, and explores physical mechanisms. Various reanalysis estimates based on the latitude where zonal mean precipitation P exceeds evaporation E and the zero crossing latitude for the zonal mean meridional streamfunction () yield tropical width expansion rates in each hemisphere ranging from near zero to over 1° latitude decade−1. Comparisons with 30-yr trends computed from unforced climate model simulations indicate that the range among reanalyses is nearly an order of magnitude greater than the standard deviation of internal climate variability. Furthermore, comparisons with forced climate models indicate that this range is an order of magnitude greater than the forced change signal since 1979. Rapid widening rates during 1979–2009 derived from some reanalyses are thus viewed to be unreliable.The intercomparison of models and reanalyses supports the prevailing view of a tropical widening, but the forced component of tropical widening has likely been only about 0.1°–0.2° latitude decade−1, considerably less than has generally been assumed based on inferences drawn from observations and reanalyses. Climate model diagnosis indicates that the principal mechanism for forced tropical widening since 1979 has been atmospheric sensitivity to warming oceans. The magnitude of this widening and its potential detectability has been greater in the Southern Hemisphere than in the Northern Hemisphere during boreal winter, in part owing to Antarctic stratospheric ozone depletion.
Impact of Wind Guess on the Tracking of Atmospheric Motion Vectors
Authors: Borde Régis , García-Pereda Javier 
Published: November 2013

Abstract
The goal of this paper is to show the impact of the use of the wind guess (WG) in atmospheric motion vector (AMV) extraction schemes. The study has been performed using the Satellite Application Facility on Support to Nowcasting and Very Short Range Forecasting (NWCSAF) High Resolution Winds AMV software. Target box sizes varying from 8 × 8 to 40 × 40 pixels and temporal gaps varying from 5 to 60 min have been considered for two configurations that use WG and do not use the wind guess (NWG) to locate the search area in the tracking process. AMVs have been extracted for four different Meteosat Second Generation (MSG) Spinning Enhanced Visible and Infrared Imager (SEVIRI) channels [high-resolution visible (HRVIS), visible 0.8 μm (VIS0.8), water vapor 6.2 μm (WV6.2), and infrared 10.8 μm (IR10.8)] over the European and Mediterranean area for a 6-month period (January–June 2010). The AMVs’ performances have been tested against radiosonde wind observations and ECMWF NWP model wind analysis.
The results show an impact on the amount of valid AMVs extracted by each configuration. Not using the wind guess produces more valid AMVs when large target boxes and short temporal gaps are used. It is the opposite when small target boxes and long temporal gaps are used. The results also show a general increase in the mean AMV speed, and a general reduction of the normalized bias and the normalized root-mean-square vector difference for all the tested channels and configurations, when the wind guess is not used to locate the search area.
Evaluation of a health education programme about traumatic brain injury
Authors: Garcia Jane Mertz , Sellers Debra M , Hilgendorf Amy E , Burnett Debra L 
Published: November 2013

Objective: Our aim was to evaluate a health education programme (TBI options: Promoting Knowledge) designed to increase public awareness and understanding about traumatic brain injury (TBI) through in-person (classroom) and computer-based (electronic) learning environments. Design: We used a pre-post survey design with randomization of participants to classroom ( N = 22) or electronic ( N = 22) delivery of the programme, in classroom and computer laboratory settings on the campus of Kansas State University, Manhattan, KS. Method: Forty-four participants rated areas of knowledge about TBI prior to and after the programme experience. They also rated health programme quality and instructional strategies (e.g. video vignettes). Written responses provided information for qualitative analysis. Results: Participants reported significantly higher ratings of knowledge after the programme experience. Qualitative analysis of written responses provided further evidence to support quantitative outcomes. There were no significant differences in comparing the two methods of delivery (classroom versus electronic learning format). Participants rated the quality of the programme and various instructional strategies very highly. Conclusion: TBI options: Promoting Knowledge offers a health education programme to increase understanding about TBI. Both modes of delivery, classroom and electronic, appeared equally effective in terms of self-report of change.
Could an intergovernmental agreement increase the credibility of Canadian treaty commitments in areas within provincial jurisdiction?
Authors: VanDuzer J Anthony 
Published: November 2013

Canada’s federal government has exclusive authority to commit Canada to international treaties, but, under the Canadian constitution, compliance with treaty obligations that extend into areas of provincial competence is solely within provincial jurisdiction. As well, while Canada is responsible to its treaty partners if provinces act contrary to Canada’s obligations, the provinces are not directly accountable. The absence of a direct legal requirement to fulfil treaty obligations means that incentives for provincial compliance are weakened and, in turn, that the reliability of Canadian obligations relating to matters within provincial jurisdiction is diminished. This paper explores the prospects for using an intergovernmental agreement to address the gap between provincial action and federal responsibility. While such an agreement could express each province’s commitment to comply with Canadian treaty obligations, intergovernmental agreements have some inherent weaknesses that make them an imperfect commitment device.
Diffusion-weighted MRI: usefulness for differentiating intrapancreatic accessory spleen and small hypervascular neuroendocrine tumor of the pancreas
Authors: Kang Bo-Kyeong , Kim Jin Hee , Byun Jae Ho , Lee Seung Soo , Kim Hyoung Jung , Kim So Yeon , Lee Moon-Gyu 
Published: November 2013

Background Image findings of intrapancreatic accessory spleen (IPAS) can closely resemble those of neuroendocrine tumor (NET) of the pancreas. Purpose To investigate the usefulness of diffusion-weighted imaging (DWI) for differentiating IPAS from small (≤3 cm) hypervascular NET of the pancreas. Material and Methods The visually assessed signal intensity of pancreatic lesions compared with the spleen on DWI ( b value of 1000 s/mm2) and the apparent diffusion coefficient (ADC) values were compared in 25 patients with IPAS and 31 patients with small hypervascular NET. Two blinded radiologists independently rated their confidence in differentiating the two conditions and compared the diagnostic performance of contrast-enhanced magnetic resonance imaging (CE-MRI) alone with that of combined CE-MRI and DWI. Results The isointensity of the pancreatic lesions compared with the spleen on DWI was more frequently observed in IPAS than in NET (92% vs. 12.9%, P < 0.001). The mean ADC value was significantly lower in IPAS than in NET (0.90 × 10−3 mm2/s vs. 1.44 × 10−3 mm2/s, P < 0.001). The sensitivity and specificity of ADC quantification for differentiating the two conditions when using 1.07 × 10−3 mm2/s as the cut-off value were 96% and 93.5%, respectively. For both readers, the area under the receiver operating characteristic curve and accuracy in differentiating the two conditions of combined CE-MRI and DWI were significantly greater than those of CE-MRI alone ( P ≤ 0.039). Conclusion Visual assessment of DWI and ADC quantification were useful in differentiating IPAS from small hypervascular NET of the pancreas.