bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neogene landscape evolution in the Andes of north-central Chile between 28 and 32°S: interplay between tectonic and erosional processes
Authors: Rodríguez María Pía , Aguilar Germán , Urresty Constanza , Charrier Reynaldo 
Published: April 2014

Abstract
We combine geomorphological analysis of palaeosurfaces and U–Pb zircon geochronology of overlying tuffs to reconstruct the Neogene landscape evolution in north-central Chile (28–32°S). Prior to the Early Miocene, a pediplain dominated the landscape of the present-day Coastal Cordillera. The pediplain was offset during the Early (Middle?) Miocene, leading to uplift of the present-day eastern Coastal Cordillera and to the formation of a secondary topographic front. During the Late Miocene, the entire Coastal Cordillera was uplifted, with resulting deposition taking place within river valleys similar to those of the present day. A new pediplain developed on top of these deposits between the Early to Middle Pleistocene and was finally uplifted post-500 ka. These three major uplift stages correlate with episodes of increased deformation widely recognized throughout the Central Andes, starting after a Late Oligocene–Early Miocene episode of increased plate convergence. North of 30°S, the previous palaeotopography along the western Coastal Cordillera probably influenced Neogene landscape evolution. The presence of an inherited palaeotopography together with a strong decrease of precipitation to the north of 30°S would have determined differences in landscape development between this area and the area to the south of 30°S since the Early Miocene.
Hydrothermal fluids in epithermal and porphyry Au deposits in the Central Slovakia Volcanic Field
Authors: Koděra Peter , Lexa Jaroslav , Fallick Anthony E. , Wälle Markus , Biroň Adrián 
Published: April 2014

Abstract

The Neogene Central Slovakia Volcanic Field in the Carpathian arc contains various Au deposits, hosted by central zones of large andesite stratovolcanoes. Fluids involved in mineralization have been studied at three different types of deposit, mostly by fluid inclusion and stable isotope techniques. The Rozália mine in the Štiavnica stratovolcano hosts intermediate sulphidation-style Au–Ag epithermal mineralization in subhorizontal veins related to hydrothermal activity during an early stage of caldera collapse. Associated fluids of low salinity underwent extensive boiling at 280–330 °C on transition from suprahydrostatic towards hydrodynamic conditions at shallow depths (
c.
550 m) from fluids of mixed magmatic and meteoric origin. The Kremnica ore field hosts a large system of low sulphidation-style Au–Ag veins contemporaneous with rhyolite magmatism and situated on resurgent horst faults. Fluids were of low salinity, predominantly of meteoric origin, and showed gradual decrease in temperature along the system (
c.
270–140 °C) related to a decrease in erosion level from
c.
500 to
c.
50 m. The Biely Vrch Au-porphyry deposit in the Javorie stratovolcano is associated with quartz stockwork in diorite porphyry intrusion. The major type of ore-bearing fluid was high temperature magmatic vapour (720–<380 °C) accompanied by Fe-rich salt melt. Gold precipitated in a high-temperature but low-pressure subvolcanic environment.

Supplementary material:

Stable isotope data and fluid inclusion microthermometric data are available at
http://www.geolsoc.org.uk/SUP18752
.
Investigating the occurrence of hierarchies of cyclicity in platform carbonates
Authors: Pollitt D. A. , Burgess P. M. , Wright V. P. 
Published: April 2014

Abstract
Hierarchies of cyclicity have been described from a wide variety of carbonate platform strata and are assumed to be a consequence of Milankovitch-forced variations in accommodation, although descriptions of hierarchical strata, including ‘cycles’ and what they constitute, are typically qualitative, subjective, and in some cases difficult to reproduce. One reason for this is the lack of any detailed definition of what constitutes a hierarchy, as well as the implicit and largely untested nature of the assumptions underpinning most interpretations of hierarchical strata.
In this study we aim to investigate the response of depositional systems if they were to behave in the way implied by sequence stratigraphic (hierarchical) models, to clearly state the assumptions of these models, and illustrate the consequences of these assumptions when they are employed in a simple, internally-consistent forward model with plausible parameters.
We define hierarchies, in both the time-domain (chronostratigraphic) and thickness-domain (stratigraphic), as two or more high-frequency sequences (HFSs) in which there exists a repeated trend of decreasing high-frequency sequence thickness such that within a single low-frequency sequence (LFS) each high-frequency sequence is thinner than the previous sequence.
Based on this definition, results from 110 000 numerical model runs suggest that ordered forcing via cyclical eustatic sea-level oscillations rarely results in an easily identifiable hierarchy of stacked cycles. Hierarchies measured in the chronostratigraphic time-domain occur in only 9% of model run cases, and in 15% of cases when measured in the thickness-domain, suggesting that vertical thickness trends are probably not a useful way to identify products of ordered periodic external forcing. Variability in relative forcing periodicity results in significant variation in both HFS and LFS thickness trends making accurate identification of hierarchy and any forcing controls from thickness data alone very difficult. Comparison between model results and outcrop sections suggests that hierarchies are often assumed to be present despite a lack of adequate supporting evidence and quantitative analysis of these sections suggests that they are not hierarchical in any meaningful sense.
The importance of doing nothing: stasis in sedimentation systems and its stratigraphic effects
Authors: Tipper John C. 
Published: April 2014

Abstract
This paper puts forward the proposition that sedimentation systems generally are in stasis. Three lines of evidence suggest the proposition is largely correct: (1) considerations of how sedimentation systems necessarily operate, (2) observations of active systems, and (3) a re-evaluation of ideas about sedimentation rates. There are of course systems to which the proposition cannot apply. A simulation exercise is used to address questions about the stratigraphic effects of stasis. The results show (1) that sedimentation systems that generally are in stasis can be of a variety of types, (2) that stasis is readily preserved in stratigraphic successions, (3) that successions produced by a system in which the time proportion of stasis is high are markedly more complete than successions produced by other systems of the same type, (4) that the proportion of stasis in a system cannot be estimated reliably from stratigraphic successions produced by that system, and (5) that the stratigraphic succession finally left behind by a system is necessarily a systematically biased and partial record of the history of that system. What is always missing is that part of the history before the oldest preserved horizon, which for systems that are in long-term balance will on average be half of the total time.
Predictive Performance of Microarray Gene Signatures: Impact of Tumor Heterogeneity and Multiple Mechanisms of Drug Resistance
Authors: Ng Charlotte K.Y. , Weigelt Britta , A'Hern Roger , Bidard Francois-Clement , Lemetre Christophe , Swanton Charles , Shen Ronglai , Reis-Filho Jorge S. 
Published: April 2014

Abstract
Gene signatures have failed to predict responses to breast cancer therapy in patients to date. In this study, we used bioinformatic methods to explore the hypothesis that the existence of multiple drug resistance mechanisms in different patients may limit the power of gene signatures to predict responses to therapy. In addition, we explored whether substratification of resistant cases could improve performance. Gene expression profiles from 1,550 breast cancers analyzed with the same microarray platform were retrieved from publicly available sources. Gene expression changes were introduced in cases defined as sensitive or resistant to a hypothetical therapy. In the resistant group, up to five different mechanisms of drug resistance causing distinct or overlapping gene expression changes were generated bioinformatically, and their impact on sensitivity, specificity, and predictive values of the signatures was investigated. We found that increasing the number of resistance mechanisms corresponding to different gene expression changes weakened the performance of the predictive signatures generated, even if the resistance-induced changes in gene expression were sufficiently strong and informative. Performance was also affected by cohort composition and the proportion of sensitive versus resistant cases or resistant cases that were mechanistically distinct. It was possible to improve response prediction by substratifying chemotherapy-resistant cases from actual datasets (non-bioinformatically perturbed datasets) and by using outliers to model multiple resistance mechanisms. Our work supports the hypothesis that the presence of multiple resistance mechanisms in a given therapy in patients limits the ability of gene signatures to make clinically useful predictions. Cancer Res; 74(11); 2946–61. ©2014 AACR.
Inhibition of Akt Reverses the Acquired Resistance to Sorafenib by Switching Protective Autophagy to Autophagic Cell Death in Hepatocellular Carcinoma
Authors: Zhai Bo , Hu Fengli , Jiang Xian , Xu Jun , Zhao Dali , Liu Bing , Pan Shangha , Dong Xuesong , Tan Gang , Wei Zheng , Qiao Haiquan , Jiang Hongchi , Sun Xueying 
Published: April 2014

Abstract
Sorafenib is the standard first-line systemic drug for advanced hepatocellular carcinoma (HCC), but the acquired resistance to sorafenib results in limited benefits. Activation of Akt is thought to be responsible for mediating the acquired resistance to sorafenib. The present study aims to examine the underlying mechanism and seek potential strategies to reverse this resistance. Two sorafenib-resistant HCC cell lines, which had been established from human HCC HepG2 and Huh7 cells, were refractory to sorafenib-induced growth inhibition and apoptosis in vitro and in vivo. Sustained exposure to sorafenib activated Akt via the feedback loop of mTOR but independent of protein phosphatase 2A in HCC cells. Autophagy participated in the resistance to sorafenib as inhibition of autophagy reduced the sensitivity of sorafenib-resistant HCC cells to sorafenib, whereas activation of autophagy by rapamycin had the opposite effect. However, rapamycin did not show a synergistic effect with sorafenib to inhibit cell proliferation, while it also activated Akt via a feedback mechanism in sorafenib-resistant HCC cells. Inhibition of Akt reversed the acquired resistance to sorafenib by switching autophagy from a cytoprotective role to a death-promoting mechanism in the sorafenib-resistant HCC cells. Akt inhibition by GDC0068 synergized with sorafenib to suppress the growth of sorafenib-resistant HCC tumors that possessed the sorafenib-resistant feature in vivo. The results have provided evidence for clinical investigation of GDC0068, a novel ATP-competitive pan-Akt inhibitor, as the second-line treatment after the failure of sorafenib-medicated molecular targeted therapy for advanced HCC. Mol Cancer Ther; 13(6); 1589–98. ©2014 AACR.
Epithelial-to-Mesenchymal Transition Activates PERK–eIF2α and Sensitizes Cells to Endoplasmic Reticulum Stress
Authors: Feng Yu-xiong , Sokol Ethan S. , Del Vecchio Catherine A. , Sanduja Sandhya , Claessen Jasper H.L. , Proia Theresa A. , Jin Dexter X. , Reinhardt Ferenc , Ploegh Hidde L. , Wang Qiu , Gupta Piyush B. 
Published: April 2014

Abstract
Epithelial-to-mesenchymal transition (EMT) promotes both tumor progression and drug resistance, yet few vulnerabilities of this state have been identified. Using selective small molecules as cellular probes, we show that induction of EMT greatly sensitizes cells to agents that perturb endoplasmic reticulum (ER) function. This sensitivity to ER perturbations is caused by the synthesis and secretion of large quantities of extracellular matrix (ECM) proteins by EMT cells. Consistent with their increased secretory output, EMT cells display a branched ER morphology and constitutively activate the PERK–eIF2α axis of the unfolded protein response (UPR). Protein kinase RNA-like ER kinase (PERK) activation is also required for EMT cells to invade and metastasize. In human tumor tissues, EMT gene expression correlates strongly with both ECM and PERK–eIF2α genes, but not with other branches of the UPR. Taken together, our findings identify a novel vulnerability of EMT cells, and demonstrate that the PERK branch of the UPR is required for their malignancy.
Significance: EMT drives tumor metastasis and drug resistance, highlighting the need for therapies that target this malignant subpopulation. Our findings identify a previously unrecognized vulnerability of cancer cells that have undergone an EMT: sensitivity to ER stress. We also find that PERK–eIF2α signaling, which is required to maintain ER homeostasis, is also indispensable for EMT cells to invade and metastasize. Cancer Discov; 4(6); 702–15. ©2014 AACR.
This article is highlighted in the In This Issue feature, p. 621
Intralesional Treatment of Stage III Metastatic Melanoma Patients with L19–IL2 Results in Sustained Clinical and Systemic Immunologic Responses
Authors: Weide Benjamin , Eigentler Thomas K. , Pflugfelder Annette , Zelba Henning , Martens Alexander , Pawelec Graham , Giovannoni Leonardo , Ruffini Pier Adelchi , Elia Giuliano , Neri Dario , Gutzmer Ralf , Becker Jürgen C. , Garbe Claus 
Published: April 2014

AbstractL19–IL2 is a recombinant protein comprising the cytokine IL2 fused to the single-chain monoclonal antibody L19. In previous studies, intralesional injection with IL2 has shown efficacy for the locoregional treatment of cutaneous/subcutaneous metastases in patients with advanced melanoma. The objectives of this study were to investigate whether (i) intralesional delivery of a targeted form of IL2 would yield similar results, with reduction of injection frequency and treatment duration; and (ii) systemic immune responses were induced by the local treatment. Patients with stage IIIB/IIIC melanoma and cutaneous/subcutaneous injectable metastases received weekly intratumoral injections of L19–IL2 at a maximum dose of 10 MIU/week for 4 consecutive weeks. Tumor response was evaluated 12 weeks after the first treatment. Twenty-four of 25 patients were evaluable for therapy-induced responses. A complete response (CR) by modified immune-related response criteria (irRC) of all treated metastases was achieved in 6 patients (25%), with long-lasting responses in most cases (5 patients for ≥24 months). Objective responses were documented in 53.9% of all index lesions [44.4% CR and 9.5% partial responses (by irRC)], and 36.5% of these remained stable, while 9.5% progressed. Toxicity was comparable with that of free IL2, and no serious adverse events were recorded. A significant temporary increase of peripheral regulatory T cells and natural killer cells, sustained increase of absolute CD4+ lymphocytes, and decrease of myeloid-derived suppressor cells were observed upon treatment. Finally, we recorded encouraging data about the progression time to distant metastases and overall survival. Cancer Immunol Res; 2(7); 668–78. ©2014 AACR.
Role of Tropical SST Variability on the Formation of Subtropical Dipoles
Authors: Morioka Yushi , Masson Sébastien , Terray Pascal , Prodhomme Chloé , Behera Swadhin K. , Masumoto Yukio 
Published: April 2014

Abstract
Interannual variations of sea surface temperature (SST) in the midlatitudes of the Southern Hemisphere play an important role in the rainfall variability over the surrounding countries by modulating synoptic-scale atmospheric disturbances. These are frequently associated with a northeast–southwest-oriented dipole of positive and negative SST anomalies in each oceanic basin, referred to as a subtropical dipole. This study investigates the role of tropical SST variability on the generation of subtropical dipoles by conducting SST-nudging experiments using a coupled general circulation model. In the experiments where the simulated SST in each tropical basin is nudged to the climatology of the observed SST, the subtropical dipoles tend to occur as frequently as the case in which the simulated SST is allowed to freely interact with the atmosphere. It is found that without the tropical SST variability, the zonally elongated atmospheric mode in the mid- to high latitudes, called the Antarctic Oscillation (AAO), becomes dominant and the stationary Rossby waves related to the AAO induce the sea level pressure (SLP) anomalies in the midlatitudes, which, in turn, generate the subtropical dipoles. These results suggest that the tropical SST variability may not be necessary for generating the subtropical dipoles, and hence provide a useful insight into the important role of the AAO in the midlatitude climate variability.
Frailty Measurements and Dysphagia in the Outpatient Setting
Authors: Hathaway Bridget , Vaezi Alec , Egloff Ann Marie , Smith Libby , Wasserman-Wincko Tamara , Johnson Jonas T. 
Published: April 2014

Objective: Deconditioning and frailty may contribute to dysphagia and aspiration. Early identification of patients at risk of aspiration is important. Aspiration prevention would lead to reduced morbidity and health care costs. We therefore wondered whether objective measurements of frailty could help identify patients at risk for dysphagia and aspiration. Methods: Consecutive patients (n = 183) were enrolled. Patient characteristics and objective measures of frailty were recorded prospectively. Variables tested included age, body mass index, grip strength, and 5 meter walk pace. Statistical analysis tested for association between these parameters and dysphagia or aspiration, diagnosed by instrumental swallowing examination. Results: Of variables tested for association with grip strength, only age category ( P = .003) and ambulatory status ( P < .001) were significantly associated with grip strength in linear regression models. Whereas walk speed was not associated with dysphagia or aspiration, ambulatory status was significantly associated with dysphagia and aspiration in multivariable model building. Conclusion: Nonambulatory status is a predictor of aspiration and should be included in risk assessments for dysphagia. The relationship between frailty and dysphagia deserves further investigation. Frailty assessments may help identify those at risk for complications of dysphagia.
Postural Variability
Authors: Davis Kermit G. , Kotowski Susan E. 
Published: April 2014

Objective: This article investigates whether different interventions aimed at promoting postural change could increase body movement throughout the shift and reduce musculoskeletal discomfort. Background: Many researchers have reported high levels of discomfort for workers that have relatively low-level demands but whose jobs are sedentary in nature. To date, few interventions have been found to be effective in reducing worker discomfort. Methods: Thirty-seven call center operators were evaluated in four different workstation conditions: conventional workstation, sit-stand workstation, conventional workstation with reminder software, and sit-stand workstation with break reminder software–prompt to remind workers to take break. The primary outcome variables consisted of productivity, measured by custom software; posture changes, measured by continuous video recording; and discomfort, measured by simple survey. Each condition was evaluated over a 2-week period. Results: Significant reductions in short-term discomfort were reported in the shoulders, upper back, and lower back when utilizing reminder software, independent of workstation type. Although not significant, many productivity indices were found to increase by about 10%. Conclusions: Posture-altering workstation interventions, specifically sit-stand tables or reminder software with traditional tables, were effective in introducing posture variability. Further, postural variability appears to be linked to decreased short-term discomfort at the end of the day without a negative impact on productivity. Applications: An intervention that can simply induce the worker to move throughout the day, such as a sit-stand table or simple software reminder about making a large posture change, can be effective in reducing discomfort in the worker, while not adversely impacting productivity.
Management of Lateral Frontal Sinus Pathology in the Endoscopic Era
Authors: Conger Bryant T. , Illing Elisa , Bush Benjamin , Woodworth Bradford A. 
Published: April 2014

ObjectivesConsiderable advances in endoscopic technique and experience have allowed an increasing number of patients with complex frontal sinus disease to be treated with endoscopic surgery. The objective of the current study was to evaluate management strategies and outcomes regarding treatment of lateral frontal sinus disease.Study DesignProspective case series.SettingAcademic tertiary medical center.Subjects and MethodsProspectively collected data concerning frontal sinus pathology located lateral to the plane of the lamina papyracea (lateral disease) were reviewed. Data were collected regarding demographics, etiology, surgical technique, revision rate, anatomic considerations, and clinical follow‐up. Only patients with at least 24 weeks of clinical follow‐up and pathology who required removal and dissection in this region were included in the study.ResultsOver 5 years, 156 patients (mean age, 47.9 years; range, 14‐84 years) with 183 lateral frontal sinus pathologies and an average clinical follow up of 76 weeks (range, 24‐237 weeks) were evaluated. Endoscopic or open surgery was attempted in 84 patients (54%) prior to intervention at our institution. Primary pathologies included inflammatory/obstructive diseases (n = 119), skull base defects (n = 33), and tumors (n = 31). Initial interventions included endoscopic (Draf IIA, n = 76; Draf IIB, n = 52; Draf III, n = 23), extended (IIA + trephine, n = 1; III + trephine, n = 2; III + osteoplastic flap, n = 2), and open (osteoplastic flap, n = 3; Reidel, n = 1; cranialization, n = 1) procedures. Seven patients (4%) required a subsequent revision procedure.ConclusionThe vast majority of lateral frontal sinus pathology was managed using endoscopic techniques with excellent outcomes and a low revision rate in the current study.