bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chapter 8 The rock coast of Canada
Authors: Trenhaile A. S. 
Published: July 2014

Abstract
Canada's coasts, which are primarily rocky, extend along three oceans and four Great Lakes. Many processes operate here in the same way as in other places, but glacio-isostatic uplift, coastal permafrost and ground and sea ice assume particular importance in the Canadian context. Only small amounts of wave erosion have occurred on the very resistant rocks of the Canadian Shield, where rapid changes in relative sea-level have limited the time that marine processes operated at any particular level. The Pacific coast and most of the northern Atlantic coast consist of fiords and most steep coastal slopes have been cut by glaciers. Marine processes have been more effective on weaker substrates in southern Canada, where there are a variety of stacks, arches, wave-eroded cliffs and wide shore platforms. Most work has been conducted on the southern Great Lakes, where rapid erosion and recession of glacial clay cliffs threaten human populations and infrastructure, and on the subhorizontal and sloping shore platforms of Atlantic Canada and eastern Québec.
ADAM9 Promotes Lung Cancer Metastases to Brain by a Plasminogen Activator-Based Pathway
Authors: Lin Chen-Yuan , Chen Hung-Jen , Huang Cheng-Chung , Lai Liang-Chuan , Lu Tzu-Pin , Tseng Guan-Chin , Kuo Ting-Ting , Kuok Qian-Yu , Hsu Jennifer L. , Sung Shian-Ying , Hung Mien-Chie , Sher Yuh-Pyng 
Published: July 2014

Abstract
The transmembrane cell adhesion protein ADAM9 has been implicated in cancer cell migration and lung cancer metastasis to the brain, but the underpinning mechanisms are unclear and clinical support has been lacking. Here, we demonstrate that ADAM9 enhances the ability of tissue plasminogen activator (tPA) to cleave and stimulate the function of the promigratory protein CDCP1 to promote lung metastasis. Blocking this mechanism of cancer cell migration prolonged survival in tumor-bearing mice and cooperated with dexamethasone and dasatinib (a dual Src/Abl kinase inhibitor) treatment to enhance cytotoxic treatment. In clinical specimens, high levels of ADAM9 and CDCP1 correlated with poor prognosis and high risk of mortality in patients with lung cancer. Moreover, ADAM9 levels in brain metastases derived from lung tumors were relatively higher than the levels observed in primary lung tumors. Our results show how ADAM9 regulates lung cancer metastasis to the brain by facilitating the tPA-mediated cleavage of CDCP1, with potential implications to target this network as a strategy to prevent or treat brain metastatic disease. Cancer Res; 74(18); 5229–43. ©2014 AACR.
Armed Oncolytic Virus Enhances Immune Functions of Chimeric Antigen Receptor–Modified T Cells in Solid Tumors
Authors: Nishio Nobuhiro , Diaconu Iulia , Liu Hao , Cerullo Vincenzo , Caruana Ignazio , Hoyos Valentina , Bouchier-Hayes Lisa , Savoldo Barbara , Dotti Gianpietro 
Published: July 2014

Abstract
The clinical efficacy of chimeric antigen receptor (CAR)-redirected T cells remains marginal in solid tumors compared with leukemias. Failures have been attributed to insufficient T-cell migration and to the highly immunosuppressive milieu of solid tumors. To overcome these obstacles, we have combined CAR-T cells with an oncolytic virus armed with the chemokine RANTES and the cytokine IL15, reasoning that the modified oncolytic virus will both have a direct lytic effect on infected malignant cells and facilitate migration and survival of CAR-T cells. Using neuroblastoma as a tumor model, we found that the adenovirus Ad5Δ24 exerted a potent, dose-dependent, cytotoxic effect on tumor cells, whereas CAR-T cells specific for the tumor antigen GD2 (GD2.CAR-T cells) were not damaged. When used in combination, Ad5Δ24 directly accelerated the caspase pathways in tumor cells exposed to CAR-T cells, whereas the intratumoral release of both RANTES and IL15 attracted CAR-T cells and promoted their local survival, respectively, increasing the overall survival of tumor-bearing mice. These preclinical data support the use of this innovative biologic platform of immunotherapy for solid tumors. Cancer Res; 74(18); 5195–205. ©2014 AACR.
Obesity, Cholesterol Metabolism, and Breast Cancer Pathogenesis
Authors: McDonnell Donald P. , Park Sunghee , Goulet Matthew T. , Jasper Jeff , Wardell Suzanne E. , Chang Ching-yi , Norris John D. , Guyton John R. , Nelson Erik R. 
Published: July 2014

Abstract
Obesity and altered lipid metabolism are risk factors for breast cancer in pre- and post-menopausal women. These pathologic relationships have been attributed in part to the impact of cholesterol on the biophysical properties of cell membranes and to the influence of these changes on signaling events initiated at the membrane. However, more recent studies have indicated that the oxysterol 27-hydroxycholesterol (27HC), and not cholesterol per se, may be the primary biochemical link between lipid metabolism and cancer. The enzyme responsible for production of 27HC from cholesterol, CYP27A1, is expressed primarily in the liver and in macrophages. In addition, significantly elevated expression of this enzyme within breast tumors has also been observed. It is believed that 27HC, acting through the liver X receptor in macrophages and possibly other cells, is involved in maintaining organismal cholesterol homeostasis. It has also been shown recently that 27HC is an estrogen receptor agonist in breast cancer cells and that it stimulates the growth and metastasis of tumors in several models of breast cancer. These findings provide the rationale for the clinical evaluation of pharmaceutical approaches that interfere with cholesterol/27HC synthesis as a means to mitigate the impact of cholesterol on breast cancer pathogenesis. Cancer Res; 74(18); 4976–82. ©2014 AACR.
“Companion Diagnostics”: Has Their Time Come and Gone?
Authors: Hirsch Fred R. , Bunn Paul A. , Herbst Roy S. 
Published: July 2014

Abstract
Rapid development of molecularly targeted drugs requires a “companion diagnostic” that could delay drug development and limit availability of active drugs for relevant patients. Were the negative results from MetMab studies in patients with advanced non–small cell lung cancer due to drug failure or failure of the right companion diagnostic? Clin Cancer Res; 20(17); 4422–4. ©2014 AACR.
Cytoskeletal Regulatory Gene Expression and Migratory Properties of B-cell Progenitors Are Affected by the ETV6–RUNX1 Rearrangement
Authors: Palmi Chiara , Fazio Grazia , Savino Angela M. , Procter Julia , Howell Louise , Cazzaniga Valeria , Vieri Margherita , Longinotti Giulia , Brunati Ilaria , Andrè Valentina , Della Mina Pamela , Villa Antonello , Greaves Mel , Biondi Andrea , D'Amico Giovanna , Ford Anthony , Cazzaniga Giovanni 
Published: July 2014

Abstract
Although the ETV6–RUNX1 fusion is a frequent initiating event in childhood leukemia, its role in leukemogenesis is only partly understood. The main impact of the fusion itself is to generate and sustain a clone of clinically silent preleukemic B-cell progenitors (BCP). Additional oncogenic hits, occurring even several years later, are required for overt disease. The understanding of the features and interactions of ETV6–RUNX1–positive cells during this “latency” period may explain how these silent cells can persist and whether they could be prone to additional genetic changes. In this study, two in vitro murine models were used to investigate whether ETV6–RUNX1 alters the cellular adhesion and migration properties of BCP. ETV6–RUNX1–expressing cells showed a significant defect in the chemotactic response to CXCL12, caused by a block in CXCR4 signaling, as demonstrated by inhibition of CXCL12-associated calcium flux and lack of ERK phosphorylation. Moreover, the induction of ETV6–RUNX1 caused changes in the expression of cell-surface adhesion molecules. The expression of genes regulating the cytoskeleton was also affected, resulting in a block of CDC42 signaling. The abnormalities described here could alter the interaction of ETV6–RUNX1 preleukemic BCP with the microenvironment and contribute to the pathogenesis of the disease.
Implications: Alterations in the expression of cytoskeletal regulatory genes and migration properties of BCP represent early events in the evolution of the disease, from the preleukemic phase to the clinical onset, and suggest new strategies for effective eradication of leukemia. Mol Cancer Res; 12(12); 1796–806. ©2014 AACR.
Induction of Lysosomal Biogenesis in Atherosclerotic Macrophages Can Rescue Lipid-Induced Lysosomal Dysfunction and Downstream Sequelae
Authors: Emanuel Roy , Sergin Ismail , Bhattacharya Somashubhra , Turner Jaleisa N. , Epelman Slava , Settembre Carmine , Diwan Abhinav , Ballabio Andrea , Razani Babak 
Published: July 2014

Objective—
Recent reports of a proatherogenic phenotype in mice with macrophage-specific autophagy deficiency have renewed interest in the role of the autophagy-lysosomal system in atherosclerosis. Lysosomes have the unique ability to process both exogenous material, including lipids and autophagy-derived cargo such as dysfunctional proteins/organelles. We aimed to understand the effects of an atherogenic lipid environment on macrophage lysosomes and to evaluate novel ways to modulate this system.

Approach and Results—
Using a variety of complementary techniques, we show that oxidized low-density lipoproteins and cholesterol crystals, commonly encountered lipid species in atherosclerosis, lead to profound lysosomal dysfunction in cultured macrophages. Disruptions in lysosomal pH, proteolytic capacity, membrane integrity, and morphology are readily seen. Using flow cytometry, we find that macrophages isolated from atherosclerotic plaques also display features of lysosome dysfunction. We then investigated whether enhancing lysosomal function can be beneficial. Transcription factor EB (TFEB) is the only known transcription factor that is a master regulator of lysosomal biogenesis although its role in macrophages has not been studied. Lysosomal stress induced by chloroquine or atherogenic lipids leads to TFEB nuclear translocation and activation of lysosomal and autophagy genes. TFEB overexpression in macrophages further augments this prodegradative response and rescues several deleterious effects seen with atherogenic lipid loading as evidenced by blunted lysosomal dysfunction, reduced secretion of the proinflammatory cytokine interleukin-1β, enhanced cholesterol efflux, and decreased polyubiquitinated protein aggregation.

Conclusions—
Taken together, these data demonstrate that lysosomal function is markedly impaired in atherosclerosis and suggest that induction of a lysosomal biogenesis program in macrophages has antiatherogenic effects.
Multisensory Integration: The Case of a Time Window of Gesture–Speech Integration
Authors: Obermeier Christian , Gunter Thomas C. 
Published: July 2014

AbstractThis experiment investigates the integration of gesture and speech from a multisensory perspective. In a disambiguation paradigm, participants were presented with short videos of an actress uttering sentences like “She was impressed by the BALL, because the GAME/DANCE….” The ambiguous noun (BALL) was accompanied by an iconic gesture fragment containing information to disambiguate the noun toward its dominant or subordinate meaning. We used four different temporal alignments between noun and gesture fragment: the identification point (IP) of the noun was either prior to (+120 msec), synchronous with (0 msec), or lagging behind the end of the gesture fragment (−200 and −600 msec). ERPs triggered to the IP of the noun showed significant differences for the integration of dominant and subordinate gesture fragments in the −200, 0, and +120 msec conditions. The outcome of this integration was revealed at the target words. These data suggest a time window for direct semantic gesture–speech integration ranging from at least −200 up to +120 msec. Although the −600 msec condition did not show any signs of direct integration at the homonym, significant disambiguation was found at the target word. An explorative analysis suggested that gesture information was directly integrated at the verb, indicating that there are multiple positions in a sentence where direct gesture–speech integration takes place. Ultimately, this would implicate that in natural communication, where a gesture lasts for some time, several aspects of that gesture will have their specific and possibly distinct impact on different positions in an utterance.
Predicting the Semantic Category of Internally Generated Words from Neuromagnetic Recordings
Authors: Simanova Irina , van Gerven Marcel A. J. , Oostenveld Robert , Hagoort Peter 
Published: July 2014

Abstract
In this study, we explore the possibility to predict the semantic category of words from brain signals in a free word generation task. Participants produced single words from different semantic categories in a modified semantic fluency task. A Bayesian logistic regression classifier was trained to predict the semantic category of words from single-trial MEG data. Significant classification accuracies were achieved using sensor-level MEG time series at the time interval of conceptual preparation. Semantic category prediction was also possible using source-reconstructed time series, based on minimum norm estimates of cortical activity. Brain regions that contributed most to classification on the source level were identified. These were the left inferior frontal gyrus, left middle frontal gyrus, and left posterior middle temporal gyrus. Additionally, the temporal dynamics of brain activity underlying the semantic preparation during word generation was explored. These results provide important insights about central aspects of language production.
Dynamics of Self-monitoring and Error Detection in Speech Production: Evidence from Mental Imagery and MEG
Authors: Tian Xing , Poeppel David 
Published: July 2014

Abstract
A critical subroutine of self-monitoring during speech production is to detect any deviance between expected and actual auditory feedback. Here we investigated the associated neural dynamics using MEG recording in mental-imagery-of-speech paradigms. Participants covertly articulated the vowel /a/; their own (individually recorded) speech was played back, with parametric manipulation using four levels of pitch shift, crossed with four levels of onset delay. A nonmonotonic function was observed in early auditory responses when the onset delay was shorter than 100 msec: Suppression was observed for normal playback, but enhancement for pitch-shifted playback; however, the magnitude of enhancement decreased at the largest level of pitch shift that was out of pitch range for normal conversion, as suggested in two behavioral experiments. No difference was observed among different types of playback when the onset delay was longer than 100 msec. These results suggest that the prediction suppresses the response to normal feedback, which mediates source monitoring. When auditory feedback does not match the prediction, an “error term” is generated, which underlies deviance detection. We argue that, based on the observed nonmonotonic function, a frequency window (addressing spectral difference) and a time window (constraining temporal difference) jointly regulate the comparison between prediction and feedback in speech.
Characterizing the Radar Backscatter-Cross-Section Sensitivities of Ice-Phase Hydrometeor Size Distributions via a Simple Scaling of the Clausius–Mossotti Factor
Authors: Hammonds Kevin D. , Mace Gerald G. , Matrosov Sergey Y. 
Published: July 2014

AbstractOne of the challenges that limit the amount of information that can be inferred from radar measurements of ice and mixed-phase precipitating clouds is the variability in ice mass within hydrometeors. The variable amount of ice mass within particles of a given size drives further variability in single-scattering properties that results in uncertainties of forward-modeled remote sensing quantities. Nonspherical ice-phase hydrometeors are often approximated as spheroids to simplify the calculation of single-scattering properties, yet offline calculations remain necessary to quantify these radiative properties as a function of size in discrete increments. In this paper, a simple scaling of the Clausius–Mossotti factor is used that allows for an approximation of the scattering and extinction cross sections for an arbitrary mass–dimensional power-law relationship of a nonspherical particle given a single T-matrix calculation. Using data collected by the University of Wyoming King Air in snow clouds over the Colorado Park Range, the uncertainty in forward-modeled radar reflectivity to assumptions regarding mass–dimensional relationships is examined. This is accomplished by taking advantage of independently measured condensed mass and particle size distributions to estimate the variability of the prefactor in the mass–dimensional power law. Then, calculating the partial derivative of the radar backscatter cross sections using the scaling relationships, an estimate is made of the statistical uncertainty in forward-modeled radar reflectivity. Uncertainties on the order of 4 dB are found in this term for the dataset considered.
The Downward Influence of Stratospheric Sudden Warmings*
Authors: Hitchcock Peter , Simpson Isla R. 
Published: July 2014

Abstract
The coupling between the stratosphere and the troposphere following two major stratospheric sudden warmings is studied in the Canadian Middle Atmosphere Model using a nudging technique by which the zonal-mean evolution of the reference sudden warmings are artificially induced in an ~100-member ensemble spun off from a control simulation. Both reference warmings are taken from a freely running integration of the model. One event is a displacement, the other is a split, and both are followed by extended recoveries in the lower stratosphere. The methodology permits a statistically robust study of their influence on the troposphere below.
The nudged ensembles exhibit a tropospheric annular mode response closely analogous to that seen in observations, confirming the downward influence of sudden warmings on the troposphere in a comprehensive model. This tropospheric response coincides more closely with the lower-stratospheric annular mode anomalies than with the midstratospheric wind reversal. In addition to the expected synoptic-scale eddy feedback, the planetary-scale eddies also reinforce the tropospheric wind changes, apparently responding directly to the stratospheric anomalies.
Furthermore, despite the zonal symmetry of the stratospheric perturbation, a highly zonally asymmetric near-surface response is produced, corresponding to a strongly negative phase of the North Atlantic Oscillation with a much weaker response over the Pacific basin that matches composites of sudden warmings from the Interim ECMWF Re-Analysis (ERA-Interim). Phase 5 of the Coupled Model Intercomparison Project models exhibit a similar response, though in most models the response’s magnitude is underrepresented.
Robust Forced Response in South Asian Summer Monsoon in a Future Climate
Authors: Srivastava Abhishekh K. , DelSole Timothy 
Published: July 2014

Abstract
A robust response of South Asian summer monsoon precipitation to increasing greenhouse gas concentration during the twenty-first century is identified in 23 models from phase 5 of the Coupled Model Intercomparison Project. The pattern of this response is dominated by two dipole structures, one oriented east–west across the Maritime Continent and another oriented north–south across the equatorial Indian Ocean, and is characterized by enhanced rainfall in South Asia and diminished rainfall over the Maritime Continent. The response is robust in the sense that the same pattern has a trend that is within one standard deviation of the trend of other models. Another robust feature is that the variability of precipitation about this trend decreases in all models, and hence becomes more detectable with time. The response is negligible compared to internal variability during the twentieth century but emerges clearly by the middle of the twenty-first century. Although the pattern as a whole is robust, the response over small land areas such as India has more uncertainty, with some models disagreeing even with the sign of the response.
Angiotensin Converting Enzyme Inhibitor-Related Angioedema
Authors: Chan Norman J. , Soliman Ahmed M.S. 
Published: July 2014

Objective: This study aimed to determine the duration of use, presentation, and management of angiotensin converting enzyme (ACE) inhibitor-related angioedema patients at an urban academic medical center. Methods: Retrospective chart review. Results: Eighty-eight patients who presented with ACE inhibitor-related angioedema between January 1, 2012, and December 31, 2012, were identified. They presented anywhere from 1 day to 20 years after starting an ACE inhibitor. About half the patients (50.7%) presented after taking an ACE inhibitor for at least 1 year. Fifty-five patients were female (62.5%). Twenty-eight patients (31.8%) had an airway intervention with 27 intubated and 1 requiring cricothyroidotomy. Six patients were intubated after more than 1 flexible laryngoscopy. The percentage of patients with involvement of the face, lips, tongue, floor of mouth, soft palate/uvula, and larynx were 12.5%, 60.2%, 39.7%, 6.8%, 17.0%, and 29.5%, respectively. Sixty-eight percent of patients with laryngeal edema were intubated. The majority of patients were treated with a corticosteroid and H1 and H2 receptor antagonists. Conclusion: Angioedema can occur at any time after starting ACE inhibitor use, with nearly half occurring after 1 year of use. Laryngeal involvement occurred in a minority of patients, but most of these patients were felt to require airway protection.
The Boy Who Lost His Smile
Authors: Kopelovich Jonathan C. , Owen Scott , Mathews Katherine D. , Henstrom Douglas K. 
Published: July 2014

Background: Facioscapulohumeral dystrophy is the third most common muscular dystrophy and the one most likely to present primarily in the head and neck. Methods: In this report, we present a case of a young child with subtle progressive bilateral facial weakness whose workup ultimately led to this diagnosis. Paralysis in this disorder is secondary to worsening muscle atrophy, which typically progresses in a cephalad to caudad direction. Despite facial paralysis being a key and early component of this illness, no prior descriptions in the otolaryngology literature exist. Discussion: The case described is unusual in that the patient initially presented to a community otolaryngologist. In addition to workup, the disease characteristics, head and neck manifestations, and prognosis are discussed.