bluuebunny/crossref_metadata_2025_split huggingface dataset:
Architecture of rifted continental margins and break-up evolution: insights from the South Atlantic, North Atlantic and Red Sea–Gulf of Aden conjugate margins
Authors: Mohriak Webster Ueipass , Leroy Sylvie 
Published: August 2012

Abstract
The tectonosedimentary development of the South Atlantic is compared with the Central Atlantic margins, which are associated with major episodes of magmatism during the Mesozoic continental break-up. Subsequently, the Cenozoic break-up in the North Atlantic led to the formation of the volcanic Norwegian–Greenland conjugate margins. The DSDP boreholes in the magma-poor Iberian–Newfoundland margins have confirmed the occurrence of exhumed mantle at the ocean–continent transition. This possibility has been suggested for the South Atlantic margins, but still lacks confirmation from drilling.
The Red Sea and the Gulf of Aden may be considered as natural laboratories to study the break-up processes and formation of divergent continental margins. Using key geological and geophysical data, we compare some of the structures observed in incipient stages of basin formation between the African and the Arabian plates with the structures observed in older sedimentary basins associated with the Gondwana break-up. We also analyse deep seismic reflection profiles and potential field data at the continent–ocean boundary of these conjugate margins, using palinspastic reconstructions to define the corresponding seismic pairs. We conclude that the Red Sea and the Gulf of Aden display remarkable differences to the Iberian–Newfoundland margins, and notable similarities with the South Atlantic margins.
End-member modelling as an aid to diagnose remagnetization: a brief review
Authors: Dekkers Mark J. 
Published: August 2012

Abstract

Remagnetization of a palaeomagnetic signal is difficult to recognize independently of directional information. The situation becomes more complex when remagnetized rocks pass palaeomagnetic field tests, for example when the remagnetization of a rock sequence has occurred before folding. It is evident that palaeogeographic reconstructions are seriously flawed when actually remagnetized rocks are not identified as such. Here we discuss the merits and pitfalls of so-called end-member modelling of acquisition curves of the isothermal remanent magnetization (IRM) to recognize remagnetized strata. The technique requires no
a priori
information about the IRM acquisition curves. The algorithm unmixes a set of IRM acquisition curves into a number of invariant curves termed end members and calculates the mixing proportions of the end members for each sample. Since primary natural remanent magnetization (NRM) and remagnetized NRM are acquired by different processes, their signatures can be recognized from subtle differences in the magnetic properties. We illustrate the potential of the approach by three case studies, one from Spain and two from Turkey, in which the magnetic properties of remagnetized and non-remagnetized rocks are evaluated.
Proteomic Identification of a Direct Role for Cyclin D1 in DNA Damage Repair
Authors: Jirawatnotai Siwanon , Hu Yiduo , Livingston David M. , Sicinski Piotr 
Published: August 2012

Abstract
The human CCND1 gene, which encodes the cell-cycle protein cyclin D1, is one of the most frequently amplified genes in human cancers. Cyclin D1 activates the cyclin-dependent kinases CDK4 and CDK6 and drives cell proliferation. Beyond the cell-cycle role, the full repertoire of cyclin D1 functions in cancer cells is still unclear. Emerging evidence indicates that cyclin D1 may play a role in DNA damage response. In this review, we discuss observations linking cyclin D1 to DNA damage repair and summarize our recent findings, which show a cyclin D1 function in homologous recombination-mediated DNA repair. Cancer Res; 72(17); 4289–93. ©2012 AACR.
Differential Protein Stability and ALK Inhibitor Sensitivity of EML4-ALK Fusion Variants
Authors: Heuckmann Johannes M. , Balke-Want Hyatt , Malchers Florian , Peifer Martin , Sos Martin L. , Koker Mirjam , Meder Lydia , Lovly Christine M. , Heukamp Lukas C. , Pao William , Küppers Ralf , Thomas Roman K. 
Published: August 2012

Abstract
Purpose: ALK rearrangement–positive lung cancers can be effectively treated with ALK inhibitors. However, the magnitude and duration of response is heterogeneous. In addition, acquired resistance limits the efficacy of ALK inhibitors, with most upfront resistance mechanisms being unknown.
Experimental Design: By making use of the Ba/F3 cell line model, we analyzed the cytotoxic efficacy of ALK kinase inhibitors as a function of different EML4-ALK fusion variants v1, v2, v3a, and v3b as well as of three artificially designed EML4-ALK deletion constructs and the ALK fusion genes KIF5b-ALK and NPM1-ALK. In addition, the intracellular localization, the sensitivity to HSP90 inhibition and the protein stability of ALK fusion proteins were studied.
Results: Different ALK fusion genes and EML4-ALK variants exhibited differential sensitivity to the structurally diverse ALK kinase inhibitors crizotinib and TAE684. In addition, differential sensitivity correlated with differences in protein stability in EML4-ALK–expressing cells. Furthermore, the sensitivity to HSP90 inhibition also varied depending on the ALK fusion partner but differed from ALK inhibitor sensitivity patterns. Finally, combining inhibitors of ALK and HSP90 resulted in synergistic cytotoxicity.
Conclusions: Our results might explain some of the heterogeneous responses of ALK-positive tumors to ALK kinase inhibition observed in the clinic. Thus, targeted therapy of ALK-positive lung cancer should take into account the precise ALK genotype. Furthermore, combining ALK and HSP90 inhibitors might enhance tumor shrinkage in EML4-ALK–driven tumors. Clin Cancer Res; 18(17); 4682–90. ©2012 AACR.
A Comparative and Integrative Approach Identifies ATPase Family, AAA Domain Containing 2 as a Likely Driver of Cell Proliferation in Lung Adenocarcinoma
Authors: Fouret Robert , Laffaire Julien , Hofman Paul , Beau-Faller Michèle , Mazieres Julien , Validire Pierre , Girard Philippe , Camilleri-Bröet Sophie , Vaylet Fabien , Leroy-Ladurie François , Soria Jean-Charles , Fouret Pierre 
Published: August 2012

Abstract
Purpose: To identify genetic changes that could drive cancer pathogenesis in never and ever smokers with lung adenocarcinoma.
Experimental Design: We analyzed the copy number and gene expression profiles of lung adenocarcinomas in 165 patients and related the alterations to smoking status. Having found differences in the tumor profiles, we integrated copy number and gene expression data from 80 paired samples.
Results: Amplifications at 8q24.12 overlapping MYC and ATAD2 were more frequent in ever smokers. Unsupervised analysis of gene expression revealed two groups: in the group with mainly never smokers, the tumors expressed genes common to normal lung; in the group with more ever smokers, the tumors expressed “proliferative” and “invasive” gene clusters. Integration of copy number and gene expression data identified one module enriched in mitotic genes and MYC targets. Its main associated modulator was ATAD2, a cofactor of MYC. A strong dose–response relationship between ATAD2 and proliferation-related gene expression was noted in both never and ever smokers, which was verified in two independent cohorts. Both ATAD2 and MYC expression correlated with 8q24.12 amplification and were higher in ever smokers. However, only ATAD2, and not MYC, overexpression explained the behavior of proliferation-related genes and predicted a worse prognosis independently of disease stage in a large validation cohort.
Conclusions: The likely driving force behind MYC contribution to uncontrolled cell proliferation in lung adenocarcinoma is ATAD2. Deregulation of ATAD2 is mainly related to gene amplification and is more frequent in ever smokers. Clin Cancer Res; 18(20); 5606–16. ©2012 AACR.
Mutated BCR-ABL Generates Immunogenic T-cell Epitopes in CML Patients
Authors: Cai Ann , Keskin Derin B. , DeLuca David S. , Alonso Anselmo , Zhang Wandi , Zhang Guang Lan , Hammond Naa Norkor , Nardi Valentina , Stone Richard M. , Neuberg Donna , Sidney John , Brusic Vladimir , Wu Catherine J. 
Published: August 2012

Abstract
Purpose: Characterization of an approach to identify leukemia neoantigens arising in the context of drug resistance.
Experimental Design: We assessed whether leukemia neoantigens could be generated from drug-resistant mutations in BCR-ABL after imatinib relapse in patients with chronic myelogenous leukemia (CML).
Results: We computationally predicted that approximately 70 peptides derived from 26 BCR-ABL mutations would bind eight common alleles of MHC class I (IC50 &lt; 1,000 nmol/L). Seven of nine imatinib-resistant CML patients were predicted to generate at least 1 peptide that binds autologous HLA alleles. We predicted and confirmed that an E255K mutation-derived peptide would bind HLA-A3 with high affinity (IC50 = 28 nmol/L), and showed that this peptide is endogenously processed and presented. Polyfunctional E255K-specific CD8+ T cells were detected in two imatinib-resistant HLA-A3+ CML patients concurrent with an effective anti-CML response to further therapy.
Conclusions: Our in vitro studies support the hypothesis that leukemia-driven genetic alterations are targeted by the immune system in association with a clinical response, and suggest the possibility of immunizing relapsed patients with CML against newly acquired tumor neoantigens. Clin Cancer Res; 18(20); 5761–72. ©2012 AACR.
MicroRNA Regulation of Oncolytic Adenovirus 6 for Selective Treatment of Castration-Resistant Prostate Cancer
Authors: Zhang Zhenwei , Zhang Xuemei , Newman Kam , Liu Xinyuan 
Published: August 2012

Abstract
Almost all patients with advanced prostate cancer progress to castration-resistant stage with limited treatment options. Oncolytic adenoviruses have been actively pursued as potential agents for cancer treatment. Virtually all clinical trials on oncolytic adenovirus are based on serotype 5. However, viral replication in hepatocytes induces severe liver toxicity and limits its systemic administration for metastatic disease. Moreover, rapid clearance of viral particles injected intravenously further hinders the anticancer efficacy. Adenovirus 6 (Ad6) was previously reported to exhibit less liver toxicity and escape Kupffer cells absorption after systemic administration. To further improve its safety, we generated a novel oncolytic adenovirus Ad6miR, in which four copies of binding sites of a liver-specific microRNA miR122 were incorporated into E1A gene of Ad6. miR122 regulation significantly decreased Ad6 replication in hepatocytes and consequently hepatotoxicity because of the negative regulation of miR122. Cytotoxicity assay using primary or established prostate cancer cell lines showed robust oncolytic activity of Ad6miR. Systemic treatment of established tumors with Ad6miR showed strong antitumor activity, comparable with that of Ad6 or Ad5. Although Ad6 evaded Kupffer cells, its blood clearance rate was as rapid as Ad5. The vast majority of Ad6 particles intravenously injected localized in liver sinusoidal endothelial cells rather than previously reported Kupffer cells. Elevating Ad6miR injection dose increased circulating Ad6miR concentration and its antitumor efficacy. miR122 regulation of Ad6 significantly improves its safety profile after systemic administration, which allows increasing therapeutic doses leading to improved anticancer efficacy of systemic treatment of castration-resistant prostate cancer. Mol Cancer Ther; 11(11); 2410–8. ©2012 AACR.
Haemostatic effects of levothyroxine and selenomethionine in euthyroid patients with Hashimoto’s thyroiditis
Authors: Okopien Boguslaw , Krysiak Robert 
Published: August 2012

SummaryThe aim of this prospective study was to investigate for the first time whether levothyroxine and selenomethionine, administered alone or in combination, affect coagulation and fibrinolysis in Hashimoto’s thyroiditis patients with normal thyroid function tests. A group of 155 ambulatory women with recently diagnosed and previously untreated Hashimoto’s thyroiditis, of whom 149 completed the study, were randomly assigned in a double-blind fashion to six months of treatment with levothyroxine, selenomethionine, levothyroxine plus selenomethionine, or placebo. The control group included 39 matched healthy women. The prothrombin time ratio, the activated partial thromboplastin time, and plasma levels/activities of fibrinogen, factor VII, von Willebrand factor, factor X and plasminogen activator inhibitor-1 (PAI-1) were assessed at baseline and after three and six months of treatment. Compared with the healthy subjects, Hashimoto’s thyroiditis patients exhibited higher plasma levels/activities of all of the parameters studied, as well as were characterised by the abnormal prothrombin time ratio and activated partial thromboplastin time. All these haemostatic disturbances were reduced or normalised by levothyroxine + selenomethionine treatment, while the effect of levothyroxine or selenomethionine was limited to fibrinogen and PAI-1, respectively. Our results demonstrate that euthyroid women with Hashimoto’s thyroiditis are characterised by abnormal coagulation and fibrinolysis. Levothyroxine and selenomethionine, especially if administered together, produce a beneficial effect on haemostasis in euthyroid patients with this disorder.Note: This study was in part a sub-study of another trial (ACTRN 12611000238976), which assessed the effect of levothyroxine and selenomethionine, administered alone or in combination, on monocyte and lymphocyte cytokine release in Hashimoto“s thyroiditis patients. Trial no.: ACTRN12612000271808.
Mitotically Inactivated Embryonic Stem Cells Can Be Used as an In Vivo Feeder Layer to Nurse Damaged Myocardium after Acute Myocardial Infarction
Authors: Burt Richard K. , Chen You-hong , Verda Larissa , Lucena Carolina , Navale Shankararao , Johnson Jesse , Han Xiaoqiang , Lomasney Jon , Baker Jessa M. , Ngai Ka-Leung , Kino Aya , Carr James , Kajstura Jan , Anversa Piero 
Published: August 2012

Expression of Concern
This article has a related Expression of Concern:

10.1161/RES.0000000000000241 (
Circ Res
. 2018; doi: 10.1161/RES.0000000000000241)
Association Between Coronary Vascular Dysfunction and Cardiac Mortality in Patients With and Without Diabetes Mellitus
Authors: Murthy Venkatesh L. , Naya Masanao , Foster Courtney R. , Gaber Mariya , Hainer Jon , Klein Josh , Dorbala Sharmila , Blankstein Ron , Di Carli Marcelo F. 
Published: August 2012

Background—
Diabetes mellitus increases the risk of adverse cardiac outcomes and is considered a coronary artery disease (CAD) equivalent. We examined whether coronary vascular dysfunction, an early manifestation of CAD, accounts for increased risk among diabetics compared with nondiabetics.

Methods and Results—

A total of 2783 consecutive patients (1172 diabetics and 1611 nondiabetics) underwent quantification of coronary flow reserve (CFR; CFR=stress divided by rest myocardial blood flow) by positron emission tomography and were followed up for a median of 1.4 years (quartile 1–3, 0.7–3.2 years). The primary end point was cardiac death. Impaired CFR (below the median) was associated with an adjusted 3.2- and 4.9-fold increase in the rate of cardiac death for diabetics and nondiabetics, respectively (
P
=0.0004). Addition of CFR to clinical and imaging risk models improved risk discrimination for both diabetics and nondiabetics (c index, 0.77–0.79,
P
=0.04; 0.82–0.85,
P
=0.03, respectively). Diabetic patients without known CAD with impaired CFR experienced a rate of cardiac death comparable to that for nondiabetic patients with known CAD (2.8%/y versus 2.0%/y;
P
=0.33). Conversely, diabetics without known CAD and preserved CFR had very low annualized cardiac mortality, which was similar to patients without known CAD or diabetes mellitus and normal stress perfusion and systolic function (0.3%/y versus 0.5%/y;
P
=0.65).

Conclusions—
Coronary vasodilator dysfunction is a powerful, independent correlate of cardiac mortality among both diabetics and nondiabetics and provides meaningful incremental risk stratification. Among diabetic patients without CAD, those with impaired CFR have event rates comparable to those of patients with prior CAD, whereas those with preserved CFR have event rates comparable to those of nondiabetics.
The Dependence of QPF on the Choice of Microphysical Parameterization for Lake-Effect Snowstorms
Authors: Reeves Heather Dawn , Dawson Daniel T. 
Published: August 2012

AbstractSeveral lake-effect-snow forecasts are compared to assess how the choice of microphysical parameterization affects quantitative precipitation forecasting (QPF). Eight different schemes, with different numbers of moments and categories of hydrometeors, are considered. Half of the schemes are in the steady regime (so named because the precipitation rates are nearly constant with time), and the remaining experiments are in the unsteady regime, which has a high temporal variation in precipitation. The steady-regime members have broader precipitation shields and 24-h accumulations that range from 43 to 50 mm. In the unsteady regime, the precipitation shields are narrower, leading to higher accumulations (ranging from 55 to 94 mm). These differences are the result of lower terminal velocities υt in the steady regime, which allows for relofting or suspension of hydrometeors (assuming the vertical velocity is sufficiently large) and, hence, a longer in-cloud residence time and stronger downstream transport. In the six-category experiments, low υt values in the steady regime occur in conjunction with a lower production of graupel, which is primarily due to less accretion of rain by snow. In the five-category experiments, differences are due to the way υt is functionally dependent on environmental temperature and the degree of riming, with the steady regime having a more conservative relation. The steady regime compares better to available observations, although both have notable forecast errors.
Influence of Land Cover Change on Regional Water Cycles in Eastern Siberia
Authors: Yoshida Ryuhei , Sawada Masahiro , Yamazaki Takeshi , Ohta Takeshi , Hiyama Tetsuya 
Published: August 2012

AbstractThis study evaluated the effect of recent eastern Siberian land surface changes, such as water surface expansion, on water-energy fluxes and precipitation and focused on land surface parameters using a three-dimensional atmospheric model [the Japan Meteorological Agency Nonhydrostatic model (JMA-NHM)]. Five parameters were set (viz., surface albedo, evaporative efficiency, roughness length, heat capacity, and thermal conductivity), and a response of evaporation and precipitation was evaluated. Increased precipitation corresponded to 75% of the increased evaporation on interparameter average, indicating strong land–atmosphere coupling. Water-energy flux and precipitation responses to water surface expansion were evaluated by two methods: JMA-NHM and the parameter sensitivity method. The latter method used a linear combination of parameter sensitivity on the fluxes and precipitation and parameter changes with land surface change. JMA-NHM demonstrated an increase in evaporation and precipitation and a decrease in downward shortwave radiation with low-level cloud increases. The parameter sensitivity method gave the same order as JMA-NHM in the estimation. This method has minimal calculation cost; thus, water-energy flux and precipitation response with further water surface expansion and decreases in forest area were simulated, producing various land surface data. The enhancement of the precipitation response to evaporation was weak for further water surface expansion in the largely expanded water surface area; however, the ratio increased dramatically for the small water surface expanding area, indicating intense water cycle enhancement at the beginning of water surface expansion. Although grassland formation from forest has minimal impact, if incoming downward shortwave radiation were to increase because of the disappearance of the forest shading effect and the water surface formed by permafrost melting, the water cycle would be enhanced intensely.
Wind-Driven Cross-Equatorial Flow in the Indian Ocean
Authors: Pérez-Hernández M. Dolores , Hernández-Guerra Alonso , Joyce Terrence M. , Vélez-Belchí Pedro 
Published: August 2012

Abstract
Meridional velocity, mass, and heat transport in the equatorial oceans are difficult to estimate because of the nonapplicability of the geostrophic balance. For this purpose a steady-state model is utilized in the equatorial Indian Ocean using NCEP wind stress and temperature and salinity data from the World Ocean Atlas 2005 (WOA05) and Argo. The results show a Somali Current flowing to the south during the winter monsoon carrying −11.5 ± 1.3 Sv (1 Sv ≡ 106 m3 s−1) and −12.3 ± 0.3 Sv from WOA05 and Argo, respectively. In the summer monsoon the Somali Current reverses to the north transporting 16.8 ± 1.2 Sv and 19.8 ± 0.6 Sv in the WOA05 and Argo results. Transitional periods are considered together and in consequence, there is not a clear Somali Current present in this period. Model results fit with in situ measurements made around the region, although Argo data results are quite more realistic than WOA05 data results.
“One Can Learn From Other People’s Experiences”
Authors: Baig Arshiya A. , Locklin Cara A. , Wilkes Abigail E. , Oborski Donna Dempsey , Acevedo John C. , Gorawara-Bhat Rita , Quinn Michael T. , Burnet Deborah L. , Chin Marshall H. 
Published: August 2012

Purpose To assess Latino adults’ preferences for peer-based diabetes self-management interventions and the acceptability of the church setting for these interventions. Methods The authors partnered with 2 predominantly Mexican American churches in Chicago and conducted 6 focus groups with 37 adults who had diabetes or had a family member with diabetes. They assessed participant preferences regarding group education and telephone-based one-to-one peer diabetes self-management interventions. Systematic qualitative methods were used to identify the types of programming preferred by participants in the church setting. Results Participants had a mean (SD) age of 53 (11) years. All participants were Latino, and more than half were born in Mexico (60%). Most participants were female (78%), had finished high school (65%), and had health insurance (57%). Sixty-five percent reported having a diagnosis of diabetes. Many participants believed the group-based and telephone-based one-to-one peer support programs could provide opportunities to share diabetes knowledge. Yet, the majority stated the group education model would offer more opportunity for social interaction and access to people with a range of diabetes experience. Participants noted many concerns regarding the one-to-one intervention, mostly involving the impersonal nature of telephone calls and the inability to form a trusting bond with the telephone partner. However, the telephone-based intervention could be a supplement to the group educational sessions. Participants also stated the church would be a familiar and trusted setting for peer-based diabetes interventions. Conclusions Church-based Latinos with diabetes and their family members were interested in peer-based diabetes self-management interventions; however, they preferred group-based to telephone-based one-to-one peer programs.