bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PR21: DEK is critical for homologous recombination and its loss is synthetic lethal with DNA-PK inhibition
Authors: Smith Eric A. , Gole Boris , Willis Nicholas A. , Eric Krumpelbeck F. , Jegga Anil G. , Ali Abdullah M. , Guo Haihong , Meetei Amom R. , Andreassen Paul R. , Kappes Ferdinand , Scully Ralph , Wiesmüller Lisa , Susanne Wells I. 
Published: April 2017

Abstract
DEK is a highly conserved chromatin-bound protein whose upregulation across different cancer types directly correlates with genotoxic therapy resistance. While DEK loss induces genome instability and sensitizes cells to DNA double strand breaks (DSBs), suggesting defects in DNA repair, the role of DEK remains incompletely understood. To this end we previously determined that loss of DEK moderately attenuates non-homologous end-joining repair (NHEJ). However, the observed partial decrease in NHEJ activity is likely insufficient to fully explain the sensitivity of DEK-deficient cells to radiation and chemotherapy. Thus, we hypothesized that DEK has additional roles in DSB repair, particularly in homologous recombination (HR) DNA repair, a known contributor to chemotherapy resistance. We found that γH2AX activation and HR were strongly compromised in DEK-deficient cells, and that DEK physically interacted with and contributed to RAD51 recruitment. Thus, we hypothesized that DEK-deficient cells likely rely on residual NHEJ for repair of DSBs and survival. Correspondingly, NHEJ inhibition with DNA-PK inhibitors resulted in synthetic lethality in DEK-deficient cells. Together these findings define DEK as an important and multifunctional mediator of homologous recombination.
This abstract is also being presented as Poster A09.
Citation Format: Eric A. Smith, Boris Gole, Nicholas A. Willis, Krumpelbeck F. Eric, Anil G. Jegga, Abdullah M. Ali, Haihong Guo, Amom R. Meetei, Paul R. Andreassen, Ferdinand Kappes, Ralph Scully, Lisa Wiesmüller, Wells I. Susanne. DEK is critical for homologous recombination and its loss is synthetic lethal with DNA-PK inhibition [abstract]. In: Proceedings of the AACR Special Conference on DNA Repair: Tumor Development and Therapeutic Response; 2016 Nov 2-5; Montreal, QC, Canada. Philadelphia (PA): AACR; Mol Cancer Res 2017;15(4_Suppl):Abstract nr PR21.
Anaphase-Promoting Complex Adaptor FZR1/CDH1 Blocks BRAF Signaling Both by Targeting BRAF for Proteolytic Degradation and by Disrupting BRAF Dimerization
Authors: Zhang Chao , Bollag Gideon 
Published: April 2017

Abstract
Summary: Blocking dimerization and stimulating protein degradation are two mechanisms known to inhibit BRAF activity. The study reported by Wan and colleagues identifies BRAF as a substrate of the APC/CFZR1–ubiqutin–proteasome system. The interaction between FZR1 and BRAF also induces a conformational change that disrupts BRAF dimerization. These findings identify a dynamic interplay between FZR1 and BRAF with strong implications for cell-fate determination and the tumor suppressor role of FZR1. Cancer Discov; 7(4); 356–8. ©2017 AACR.
See related article by Wan et al., p. 424.
Exploring the Link between the Germline and Somatic Genome in Cancer
Authors: Geeleher Paul , Huang R. Stephanie 
Published: April 2017

Abstract
Summary: Carter and colleagues propose a systematic analysis of the germline and somatic genome in cancer. They identify interactions that occur between germline and somatic variants. This elucidates the function of the germline genome in the context of cancer risk and development. Cancer Discov; 7(4); 354–5. ©2017 AACR.
See related article by Carter et al., p. 410.
Report on the FDA-AACR Immuno-oncology Drug Development Workshop
Authors: Curran Colleen , Sharon Elad 
Published: April 2017

Abstract
The FDA-AACR Immuno-oncology Drug Development Workshop was held in Washington, DC, from October 13 to 14, 2016. This interdisciplinary forum included government, industry, and academic leaders in pharmacology and oncology. The aim of the meeting was to discuss methodologies in nonclinical and clinical research, safety monitoring, efficacy endpoints, and statistical evaluation of cancer immunotherapy products. This summary highlights topics and viewpoints raised by the presenters and discussants and should not be viewed as the conclusions or recommendations of the workshop as a whole. Cancer Immunol Res; 5(4); 282–5. ©2017 AACR.
Fire Simulation and Cardiovascular Health in Firefighters
Authors: Hunter Amanda L. , Shah Anoop S.V. , Langrish Jeremy P. , Raftis Jennifer B. , Lucking Andrew J. , Brittan Mairi , Venkatasubramanian Sowmya , Stables Catherine L. , Stelzle Dominik , Marshall James , Graveling Richard , Flapan Andrew D. , Newby David E. , Mills Nicholas L. 
Published: April 2017

Background:
Rates of myocardial infarction in firefighters are increased during fire suppression duties, and are likely to reflect a combination of factors including extreme physical exertion and heat exposure. We assessed the effects of simulated fire suppression on measures of cardiovascular health in healthy firefighters.

Methods:
In an open-label randomized crossover study, 19 healthy firefighters (age, 41±7 years; 16 males) performed a standardized training exercise in a fire simulation facility or light duties for 20 minutes. After each exposure, ex vivo thrombus formation, fibrinolysis, platelet activation, and forearm blood flow in response to intra-arterial infusions of endothelial-dependent and -independent vasodilators were measured.

Results:

After fire simulation training, core temperature increased (1.0±0.1°C) and weight reduced (0.46±0.14 kg,
P
<0.001 for both). In comparison with control, exposure to fire simulation increased thrombus formation under low-shear (73±14%) and high-shear (66±14%) conditions (
P
<0.001 for both) and increased platelet-monocyte binding (7±10%,
P
=0.03). There was a dose-dependent increase in forearm blood flow with all vasodilators (
P
<0.001), which was attenuated by fire simulation in response to acetylcholine (
P
=0.01) and sodium nitroprusside (
P
=0.004). This was associated with a rise in fibrinolytic capacity, asymptomatic myocardial ischemia, and an increase in plasma cardiac troponin I concentrations (1.4 [0.8–2.5] versus 3.0 [1.7–6.4] ng/L,
P
=0.010).

Conclusions:
Exposure to extreme heat and physical exertion during fire suppression activates platelets, increases thrombus formation, impairs vascular function, and promotes myocardial ischemia and injury in healthy firefighters. Our findings provide pathogenic mechanisms to explain the association between fire suppression activity and acute myocardial infarction in firefighters.

Clinical Trial Registration:

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01812317.
Tropical Cyclone Characterization via Nocturnal Low-Light Visible Illumination
Authors: Hawkins Jeffrey D. , Solbrig Jeremy E. , Miller Steven D. , Surratt Melinda , Lee Thomas F. , Bankert Richard L. , Richardson Kim 
Published: April 2017

AbstractGlobal monitoring of tropical cyclones (TC) is enhanced by the unique capabilities provided by the day–night band (DNB), a sensor included on the Visible Infrared Imaging Radiometer Suite (VIIRS) flying on board the Suomi National Polar-Orbiting Partnership (SNPP) satellite. The DNB, a low-light visible–near-infrared-band passive radiometer, can leverage unconventional (i.e., nonsolar) sources of visible light illumination such as moonlight to infer storm structure at night. The DNB provides an unprecedented capability to resolve moonlit clouds at high resolution, offering numerous potential benefits to both operational TC analysts and researchers developing new methods of monitoring TCs occurring within the largely data-void tropical oceanic basins. DNB digital data provide significant enhancements over older nighttime visible data from the Defense Meteorological Satellite Program’s (DMSP) Operational Linescan System (OLS) by leveraging accurate calibration, high sensitivity, and sub-kilometer-scale imagery that covers 2–3 times the moon’s lunar cycle than the OLS. By leveraging these attributes, DNB data can enable the use of automated objective applications instead of subjective image interpretation. Here, the authors detail ways in which critical information about TC structure, location, intensity changes, shear environment, lightning, and other characteristics can be extracted when the DNB data are used in isolation or in a multichannel approach with coincident infrared (IR) channels.
A Climatological Study of Extreme Cold Surges along the African Highlands
Authors: Crossett Caitlin C. , Metz Nicholas D. 
Published: April 2017

AbstractEquatorward-moving cold surges occur along the lee of high terrain during the cold season. Even though the east coast of Africa features high terrain, little research exists on cold surges along the African highlands despite the fact that these surges could have potentially large agricultural and societal effects. This paper examines a 5-yr climatology of the most extreme African-highlands cold surges spanning the 2008–12 period. During these years, 186 cold surges occurred to the lee of the African highlands, with 84 events extending between 30° and 35°S (type 1), 27 extending between 25° and 30°S (type 2), and 75 extending equatorward of 25°S (type 3) based on the 1000–850-hPa thickness pattern. This climatology reveals that extreme African-highlands cold surges have a climatological maximum in September. Cold surges of type 1 and type 2 tend to occur throughout the Southern Hemisphere winter and spring, whereas surges of type 3 are generally confined to the winter months. These cold surges can last from 2 to 8 days, with the highest frequency of events spanning a 3-day period. A typical cold-surge event features maximum 925-hPa meridional flow of 30.0–39.9 kt (1 kt = 0.51 m s−1) that most frequently advects cold Antarctic air to between 15.0° and 24.9°S and at times as far as the equator.
Direct and Diffuse Radiation in the Shallow Cumulus–Vegetation System: Enhanced and Decreased Evapotranspiration Regimes
Authors: Pedruzo-Bagazgoitia X. , Ouwersloot H. G. , Sikma M. , van Heerwaarden C. C. , Jacobs C. M. J. , Vilà-Guerau de Arellano J. 
Published: April 2017

Abstract
Guided by a holistic approach, the combined effects of direct and diffuse radiation on the atmospheric boundary layer dynamics over vegetated land are investigated on a daily scale. Three numerical experiments are designed that are aimed at disentangling the role of diffuse and direct radiation below shallow cumulus at the surface and on boundary layer dynamics. A large-eddy simulation (LES) model coupled to a land surface model is used, including a mechanistically immediate response of plants to radiation, temperature, and water vapor deficit changes. The partitioning in direct and diffuse radiation created by clouds and farther inside the canopy is explicitly accounted for. LES results are conditionally averaged as a function of the cloud optical depth. The findings show larger photosynthesis under thin clouds than under clear sky, due to an increase in diffuse radiation and a slight decrease in direct radiation. The reduced canopy resistance is the main driver for the enhanced carbon uptake by vegetation, while the carbon gradient and aerodynamic effects at the surface are secondary. Because of the coupling of CO2 and water vapor exchange through plant stomata, evapotranspiration is also enhanced under thin clouds, albeit to a lesser extent. This effect of diffuse radiation increases the water use efficiency and evaporative fraction under clouds. The dynamic perturbations of the surface fluxes by clouds do not affect general boundary layer or cloud characteristics because of the limited time and space where these perturbations occur. It is concluded that an accurate radiation partitioning calculation is necessary to obtain reliable estimations on local surface processes.
Generation of High-Resolution Wind Fields from the WegenerNet Dense Meteorological Station Network in Southeastern Austria
Authors: Schlager Christoph , Kirchengast Gottfried , Fuchsberger Jürgen 
Published: April 2017

Abstract
An operational weather diagnostics application for automatic generation of wind fields in near–real time from observations delivered by the high-density WegenerNet meteorological station network in the Feldbach region of Austria is introduced. The purpose of the application is to empirically provide near-surface wind fields of very high spatial and temporal resolution for evaluating convection-permitting climate models as well as investigating weather and climate variability on a local scale. The diagnostic California Meteorological Model (CALMET) is used as the core tool. This model computes 3D wind fields based on observational weather data, a digital elevation model, and land-use categories. The application first produces the required input files from the WegenerNet stations and subsequently runs the CALMET model based on this input. In a third step the modeled wind fields are stored in the WegenerNet data archives every 30 min with a spatial resolution of 100 m × 100 m, while also generating averaged weather and climate products during postprocessing. The performance of the modeling against station observations, for which wind speeds were classified into weak and strong wind speeds, is evaluated and reasonably good results were found for both wind speed classes. The statistical agreement for the vector-mean wind speed is slightly better for weak wind speeds than for strong ones while the difference between modeled and observed wind directions is smaller for strong wind speeds than for weak ones. The application is also a valuable tool for other high-density networks.
Improving quality of life and physical health in patients with schizophrenia: A 30-month program carried out in a real-life setting
Authors: Hjorth Peter , Medici Clara Reece , Juel Anette , Madsen Nikolaj Juul , Vandborg Kirsten , Munk-Jørgensen Povl 
Published: April 2017

Background: Patients with schizophrenia experience low quality of life (QoL) and poor physical health, which is explained, in part, by unhealthy lifestyle, tobacco smoking, poor diet and sedentary behavior. Aim: To measure QoL and physical health in patients with schizophrenia and to quantify associations between QoL and physical health. Methods: This was a naturalistic longitudinal 30-month follow-up study including individual guidance, group sessions and treatment as usual. Results: We included 190 patients. QoL was low among newly diagnosed patients. Higher body mass index was significantly associated with lower QoL. Newly diagnosed male patients showed lower QoL compared with females. Newly diagnosed patients experienced worsened health during the study period. In contrast, long-term schizophrenic patients started with worse physical health but improved with regard to weight, waist circumferences, intake of fast food and soft drinks, and light physical activity level. Newly diagnosed patients improved their QoL ( p = .056), and the psychological domain improved by 8.0 points ( p = .003). The number of interventions was positively associated with QoL. Conclusion: Patients with schizophrenia presented with low QoL and elevated risk factors for poor physical health. The intervention added onto ‘treatment as usual’ improved some risk factors for poor physical health among long-term patients. The number of interventions had an elevating effect on QoL in patients.
Struggles against Territorial Disqualification: Mobilization for Dignified Housing and Defense of Heritage in Santiago
Authors: Angelcos Nicolás , Méndez María Luisa 
Published: April 2017

A critical analysis of two conflicts associated with the displacement resulting from gentrification in Santiago, Chile, reveals that this displacement affects both the urban poor and the middle classes and that the common adversary is the real estate sector. The subjective experience of the groups involved can be understood in terms of the concept of territorial disqualification, a threat both to their positions in the social structure and to the recognition of the identities, personal and collective, that have been constructed about particular neighborhoods. The subject defended in struggles against territorial disqualification is the community. While class positions, specific demands, and territorial claims differ significantly, the structural framework in which neoliberal urbanism develops makes possible a confluence of class organizations that are susceptible to generating interclass strategies of opposition. El análisis crítico de dos conflictos asociados con el desplazamiento provocado por la gentrificación en Santiago de Chile, revela que el desplazamiento afecta tanto a la población urbana pobre como a las clases medias y que el adversario común es el sector de bienes raíces. La experiencia subjetiva de los grupos involucrados se puede entender si usamos el concepto de descalificación territorial, una amenaza tanto a sus posiciones en la estructura social como al reconocimiento de sus identidades, personales y colectivas, que han sido construidas con relación a ciertos vecindarios. La comunidad es el sujeto que se defiende en las luchas en contra de la descalificación territorial. Aunque las posiciones de clase, las demandas específicas y los reclamos territoriales difieren considerablemente, el marco estructural en el que se desarrolla el urbanismo neoliberal facilita la confluencia de organizaciones de clase que son susceptibles de generar estrategias de oposición interclasistas.
Building Citizenship: The Struggle for Housing in Eastern Mexico City
Authors: Rodríguez Cortés Luisa F. 
Published: April 2017

Urban social organizations have played a crucial role in the definition of political relations and the transformation of urban space. The practices established by a social organization working under conditions of poverty and vulnerability in the dispute over access to housing in eastern Mexico City produce an urban citizenship that is both weak and precarious, marked by tensions between autonomous practices and bargaining with state institutions, a rift between leaders and the grassroots, and targeted struggles that prevent the development of a shared sense of citizenship on a larger scale. Las organizaciones sociales urbanas han jugado un papel fundamental en la definición de las relaciones políticas y la transformación del espacio urbano. Las prácticas establecidas por una organización social que lucha bajo condiciones de pobreza y vulnerabilidad por el acceso a la vivienda en la zona oriente de la Ciudad de México produce una ciudadanía urbana frágil y precaria, caracterizada por conflictos entre las prácticas autónomas y las negociaciones con las instituciones estatales, una brecha entre los líderes y las bases populares, y por luchas específicas que impiden el desarrollo de un sentido compartido de ciudadanía en gran escala.
The Memory of Inhabiting Modern Architecture: Villa Portales, 1955–2010
Authors: Forray Rosanna , Márquez Francisca 
Published: April 2017

Villa Portales is an icon of modern architecture and urban planning of the 1950s and 1960s in Santiago de Chile. It embodies the political and institutional project of the time, which sought to respond to the need to establish a balance—although tenuous—in a fragile and strained economic and political system. This fact is crucial to understanding its socio-spatial objective, the administrative model it employed, and especially the crisis it has endured. The testimony of current Villa Portales dwellers points to a deterioration of its residents’ quality of life beginning in the 1980s with the changes in the role of the state introduced by the military dictatorship, the privatization of public services, and the termination of the Caja de Previsión de Empleados Particulares (Private Employees’ Pension Fund). Despite all this, the community was able to make this space a place of resistance and new meaning based on the sense of belonging arising from its architecture and its history. Villa Portales es un ícono de la arquitectura moderna y de la planificación urbana de los años 50 y 60 en Santiago de Chile. Encarna el proyecto político e institucional de su tiempo, que trataba de responder a la necesidad de establecer un equilibrio—aunque fuera tenue — en un sistema económico y político frágil y al límite de sus capacidades. Esto es crucial si queremos entender su objetivo socio-espacial, el modelo administrativo que usó y, especialmente, la crisis que experimentó. El testimonio de los residentes actuales de Villa Portales señala un deterioro en la calidad de vida que comenzó en los 80 con los cambios en el rol del estado implantados por la dictadura militar, la privatización de los servicios públicos y la terminación de la Caja de Previsión de Empleados Particulares. A pesar de esto, la comunidad fue capaz de convertir este espacio en un lugar de resistencia con nuevos significados gracias al sentido de pertenencia que surge de su arquitectura y su historia.
Accuracy of Mobile‐Based Audiometry in the Evaluation of Hearing Loss in Quiet and Noisy Environments
Authors: Saliba Joe , Al‐Reefi Mahmoud , Carriere Junie S. , Verma Neil , Provencal Christiane , Rappaport Jamie M. 
Published: April 2017

Objectives(1) To compare the accuracy of 2 previously validated mobile‐based hearing tests in determining pure tone thresholds and screening for hearing loss. (2) To determine the accuracy of mobile audiometry in noisy environments through noise reduction strategies.Study DesignProspective clinical study.SettingTertiary hospital.Subjects and MethodsThirty‐three adults with or without hearing loss were tested (mean age, 49.7 years; women, 42.4%). Air conduction thresholds measured as pure tone average and at individual frequencies were assessed by conventional audiogram and by 2 audiometric applications (consumer and professional) on a tablet device. Mobile audiometry was performed in a quiet sound booth and in a noisy sound booth (50 dB of background noise) through active and passive noise reduction strategies.ResultsOn average, 91.1% (95% confidence interval [95% CI], 89.1%‐93.2%) and 95.8% (95% CI, 93.5%‐97.1%) of the threshold values obtained in a quiet sound booth with the consumer and professional applications, respectively, were within 10 dB of the corresponding audiogram thresholds, as compared with 86.5% (95% CI, 82.6%‐88.5%) and 91.3% (95% CI, 88.5%‐92.8%) in a noisy sound booth through noise cancellation. When screening for at least moderate hearing loss (pure tone average >40 dB HL), the consumer application showed a sensitivity and specificity of 87.5% and 95.9%, respectively, and the professional application, 100% and 95.9%. Overall, patients preferred mobile audiometry over conventional audiograms.ConclusionMobile audiometry can correctly estimate pure tone thresholds and screen for moderate hearing loss. Noise reduction strategies in mobile audiometry provide a portable effective solution for hearing assessments outside clinical settings.