bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Sensitivity Analysis for Resistant Malignancies (DISARM) Identifies Common Candidate Therapies across Platinum-Resistant Cancers
Authors: Gay Carl M. , Tong Pan , Cardnell Robert J. , Sen Triparna , Su Xiao , Ma Jun , Bara Rasha O. , Johnson Faye M. , Wakefield Chris , Heymach John V. , Wang Jing , Byers Lauren A. 
Published: September 2018

Abstract

Purpose:
Despite a growing arsenal of approved drugs, therapeutic resistance remains a formidable and, often, insurmountable challenge in cancer treatment. The mechanisms underlying therapeutic resistance remain largely unresolved and, thus, examples of effective combinatorial or sequential strategies to combat resistance are rare. Here, we present Differential Sensitivity Analysis for Resistant Malignancies (DISARM), a novel, integrated drug screen analysis tool designed to address this dilemma.

Experimental Design:
DISARM, a software package and web-based application, analyzes drug response data to prioritize candidate therapies for models with resistance to a reference drug and to assess whether response to a reference drug can be utilized to predict future response to other agents. Using cisplatin as our reference drug, we applied DISARM to models from nine cancers commonly treated with first-line platinum chemotherapy including recalcitrant malignancies such as small cell lung cancer (SCLC) and pancreatic adenocarcinoma (PAAD).

Results:
In cisplatin-resistant models, DISARM identified novel candidates including multiple inhibitors of PI3K, MEK, and BCL-2, among other classes, across unrelated malignancies. Additionally, DISARM facilitated the selection of predictive biomarkers of response and identification of unique molecular subtypes, such as contrasting ASCL1-low/cMYC-high SCLC targetable by AURKA inhibitors and ASCL1-high/cMYC-low SCLC targetable by BCL-2 inhibitors. Utilizing these predictions, we assessed several of DISARM's top candidates, including inhibitors of AURKA, BCL-2, and HSP90, to confirm their activity in cisplatin-resistant SCLC models.

Conclusions:
DISARM represents the first validated tool to analyze large-scale in vitro drug response data to statistically optimize candidate drug and biomarker selection aimed at overcoming candidate drug resistance.
Combining Homologous Recombination and Phosphopeptide-binding Data to Predict the Impact ofBRCA1BRCT Variants on Cancer Risk
Authors: Petitalot Ambre , Dardillac Elodie , Jacquet Eric , Nhiri Naima , Guirouilh-Barbat Josée , Julien Patrick , Bouazzaoui Isslam , Bonte Dorine , Feunteun Jean , Schnell Jeff A. , Lafitte Philippe , Aude Jean-Christophe , Noguès Catherine , Rouleau Etienne , Lidereau Rosette , Lopez Bernard S. , Zinn-Justin Sophie , Caputo Sandrine M. 
Published: September 2018

AbstractBRCA1 mutations have been identified that increase the risk of developing hereditary breast and ovarian cancers. Genetic screening is now offered to patients with a family history of cancer, to adapt their treatment and the management of their relatives. However, a large number of BRCA1 variants of uncertain significance (VUS) are detected. To better understand the significance of these variants, a high-throughput structural and functional analysis was performed on a large set of BRCA1 VUS. Information on both cellular localization and homology-directed DNA repair (HR) capacity was obtained for 78 BRCT missense variants in the UMD-BRCA1 database and measurement of the structural stability and phosphopeptide-binding capacities was performed for 42 mutated BRCT domains. This extensive and systematic analysis revealed that most characterized causal variants affect BRCT-domain solubility in bacteria and all impair BRCA1 HR activity in cells. Furthermore, binding to a set of 5 different phosphopeptides was tested: all causal variants showed phosphopeptide-binding defects and no neutral variant showed such defects. A classification is presented on the basis of mutated BRCT domain solubility, phosphopeptide-binding properties, and VUS HR capacity. These data suggest that HR-defective variants, which present, in addition, BRCT domains either insoluble in bacteria or defective for phosphopeptide binding, lead to an increased cancer risk. Furthermore, the data suggest that variants with a WT HR activity and whose BRCT domains bind with a WT affinity to the 5 phosphopeptides are neutral. The case of variants with WT HR activity and defective phosphopeptide binding should be further characterized, as this last functional defect might be sufficient per se to lead to tumorigenesis.Implications:The analysis of the current study on BRCA1 structural and functional defects on cancer risk and classification presented may improve clinical interpretation and therapeutic selection.
Comparison of beach profiles conducive for turtle nesting in Andaman
Authors: Narayani Subramanian , Venu Sasidharan , D'Silva Andrea Joan 
Published: September 2018

The present study was undertaken to compare beach characteristics associated with turtle nesting in the Andaman group of islands. Karmatang, Kalipur, Ramnagar, Chidiyatapu, Carbyn’s Cove, and Wandoor were chosen as study sites. Beach slope, sand grain characteristics, and general vegetation patterns were analysed. The angle of inclination of the beach slope ranged from 2.06 to 8.3 degrees. Beaches with a higher angle had a comparatively higher number of nesting sites. The study shows that a single factor does not make a beach more conducive for nesting. Chidiyatapu has the widest beach but lacks other features and so it is not a preferred nesting site. The grain size of sand in Wandoor is highly favourable, but the intertidal region is not long and there are streams that can drown the nests. Karmatang has a long beach and a higher slope angle. Ramnagar has a moderate beach length and a high slope angle. The dominant grains at both the beaches were found to be granules. The absence of streams and artificial light, fewer number of anthropogenic activities, lack of obstacles, the presence of bordering vegetation, and a conducive beach slope with granular sand grains make Ramnagar, Karmatang, and Kalipur ideal for turtle nesting.
The rediscovery of Rurk’s Cat Skink Ristella rurkii Gray, 1839 (Reptilia: Ristellidae) with remarks on distribution and natural history
Authors: Ganesh Sumaithangi Rajagopalan 
Published: September 2018

The description of Rurk’s Cat Skink Ristella rurkii is expanded herein based on recent field sightings and a voucher specimen. Three individuals comprising an adult male, an adult female, and a juvenile were encountered in Kodaikanal, Palni Hills of the southern Western Ghats. Morphological and ecological notes on the voucher specimen and these live sightings are elaborated to enrich the current knowledge on this little-known species. This species is also illustrated in life herein for the first time. The current report forms the rediscovery of this species after nearly 90 years and after a lapse of 175 years since its original description. A review of its past distribution records is compiled and further surveys are recommended to revise the geographic range and conservation status of this Data Deficient species.
Neutrophil Gelatinase–Associated Lipocalin and Contrast-Induced Acute Kidney Injury
Authors: Quintavalle Cristina , Anselmi Chiara Viviani , De Micco Francesca , Roscigno Giuseppina , Visconti Gabriella , Golia Bruno , Focaccio Amelia , Ricciardelli Bruno , Perna Enzo , Papa Laura , Donnarumma Elvira , Condorelli Gerolama , Briguori Carlo 
Published: September 2018

Background—
Neutrophil gelatinase–associated lipocalin (NGAL) is an early marker of acute kidney injury (AKI).

Methods and Results—
Urine NGAL and serum NGAL (sNGAL) were assessed at 2, 6, 24, and 48 hours after contrast media (CM) exposure in 458 high-risk patients (development set). Optimal thresholds in predicting contrast-induced AKI (serum creatinine [sCr] increase ≥0.3 mg/dL at 48 hours after CM administration) were identified. Major adverse events (MAE; death, dialysis, nonfatal myocardial infarction, sustained kidney injury, and myocardial revascularization) at 1 year were assessed. In the development set, optimal thresholds for contrast-induced AKI occurred at 6 hours for both urine NGAL (≥20 ng/mL; 97% negative predictive value and 27% positive predictive value) and sNGAL (≥179 ng/mL; 93% negative predictive value and 20% positive predictive value). Furthermore, sNGAL ≥179 ng/mL at 6 hours was an independent predictor of 1-year MAE. 1-year MAE occurred in 27/198 patients (13.5%) with sNGAL <179 ng/mL and sCr <0.3 mg/dL, in 57/193 (29.5%) patients with only sNGAL ≥179 ng/mL, and in 37/67 (55%) patients with sCr ≥0.3 mg/dL. In additional 253 patients (validation set), no patient with urine NGAL <20 ng/mL or sNGAL <179 ng/mL at 6 hours developed contrast-induced AKI. Furthermore, 6/68 (9%) patients with sNGAL <179 ng/mL and sCr increase <0.3 mg/dL had 1-year MAE versus 17/57 (30%) patients with sNGAL ≥179 ng/mL and sCr increase <0.3 mg/dL and 8/16 (50%) patients with sCr increase ≥0.3 mg/dL.

Conclusions—
Urine NGAL <20 ng/mL and sNGAL <179 ng/mL at 6 hours are reliable markers for ruling out contrast-induced AKI. sNGAL ≥179 ng/mL at 6 hours predicts 1-year MAE.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01098032.
“After These Things” and its Composition in Genesis
Authors: Yoo Philip Y. 
Published: September 2018

Abstract
As a formulaic phrase that appears in Genesis to connect sequential narratives, critics have attributed “after these things” to a single literary stratum or to redactional insertions into developing narrative blocks. Drawing upon the other attestations of “after these things” from the biblical corpus, this article explains that “after these things” in Genesis may be viewed as a stock phrase, one that a composer or a redactor may employ in the absence of quantifiable chronological data to express the passage of an indefinite amount of time between two consecutive events.
The Levite’s Concubine (Judg 19:2) and the Tradition of Sexual Slander in the Hebrew Bible: How the Nature of Her Departure Illustrates a Tradition’s Tendency
Authors: Bembry Jason 
Published: September 2018

Abstract
In explaining a text-critical problem in Judges 19:2 this paper demonstrates that MT attempts to ameliorate the horrific rape and murder of an innocent person by sexual slander, a feature also seen in Balaam and Jezebel. Although Balaam and Jezebel are condemned in the biblical traditions, it is clear that negative portrayals of each have been augmented by later tradents. Although initially good, Balaam is blamed by late biblical tradents (Num 31:16) for the sin at Baal Peor (Numbers 25), where “the people begin to play the harlot with the daughters of Moab.” Jezebel is condemned for sorcery and harlotry in 2 Kgs 9:22, although no other text depicts her harlotry. The concubine, like Balaam and Jezebel, dies at the hands of Israelites, demonstrating a clear pattern among the late tradents of the Hebrew Bible who seek to justify the deaths of these characters at the hands of fellow Israelites.
Light and Space in Genesis 1
Authors: Crawford Cory 
Published: September 2018

Abstract
I address here the still-vexing problem of why the Priestly narrator in Genesis 1 separates the fiat lux that opens the process of creation from the creation of sun, moon, and stars three days later, on day four. I organize ancient and modern explanations under four rubrics (polemical; functional; phenomenological; mystical) and find them relevant but ultimately insufficient to explain the way light operates in the logic of the Priestly creation narrative. I argue instead that we must attend first to the logic and narrative irregularity of the text itself in order to discern compositional motivations. The structure of Genesis 1 points toward an understanding of the nonsolar light (and its separation from darkness) in spatial terms, analogous to the separation of waters on day two and dry land on day 3, the sun, moon, and stars populating their spaces as do the birds, fish, land animals and humans.
The Voices Unwording the Words in Beckett’s All Strange Away and Fizzles
Authors: Langlois Christopher 
Published: September 2018

Abstract
In The Step Not Beyond, Maurice Blanchot suspects that “behind discourse the refusal to discourse speaks, as behind philosophy the refusal to philosophize would speak: speech not speaking, violent, concealing itself, saying nothing and suddenly crying out” (116). One of Blanchot’s concerns in this text is with reaching out to the voices that have been exiled to spaces of invisibility and silence. These voices speak from the outside of language where they are excluded from history and lost to a space beyond words. In view of Blanchot’s insinuation that literature and thought are responsible for the hearing of such voices, this article traces the movements of Beckett’s writing, particularly of All Strange Away and Fizzles, as it traverses the spaces in Beckett’s fiction where such voices are made to dwell. It does so to see if at the end of this movement Beckett has arrived at a space beyond words where the voiceless, disfigured voices of his fiction are always speaking, always unworking the work, always unwording the word: ‘saying nothing and suddenly crying out.’
Le paradoxe de l’ aumône
Authors: Masó Joana 
Published: September 2018

Résumé
‘Le paradoxe de l’ aumône’ est l’ une des premières formules que Charles Baudelaire aurait projetée pour intituler ce qui deviendra l’ un de ses poèmes en prose les plus célèbres, ‘La fausse monnaie’ dans Le Spleen de Paris. L’ une des obsessions qui hantent ce poème, c’ est la présence muette de ceux qui semblent exclus du grand projet du progrès dans le Paris de la deuxième moitié du XIXe siècle. La présence des pauvres et des mendiants y est mise en scène comme un langage sans parole donnée et, par là, comme l’ un des thèmes hypervisibles de la modernité. Les lectures de Jacques Derrida dans Donner le temps. La fausse monnaie nous permettront de penser la permanence de cette écriture moderne de l’ aumône et la rhétorique silencieuse de la mendicité chez Beckett dans En attendant Godot comme le projet d’ une écriture pauvre dans l’ absence de richesse propre à la littérature depuis ce que Jacques Rancière a appelé, à partir de 1800, un nouveau régime de l’ art d’ écrire.
Des harmoniques
Authors: Clément Bruno 
Published: September 2018

Résumé
A partir de deux exemples canoniques (extraits de En attendant Godot et Fin de partie), cet article revient sur les fameux “fundamental sounds” dont parle Samuel Beckett à propos de Fin de partie, et tente de jeter un peu de jour sur la notion d’ harmoniques avec laquelle Beckett entretient un rapport manifestement ambigu.
The Role of Polygonal Eyewalls in Rapid Intensification of Typhoon Megi (2010)
Authors: Lee Jae-Deok , Wu Chun-Chieh 
Published: September 2018

Abstract
High-resolution numerical experiments for Typhoon Megi (2010) in the western North Pacific are conducted using the Advanced Research version of the Weather Research and Forecasting (WRF) Model to understand the mechanisms of rapid intensification (RI). With a dynamically initialized vortex, sensitivity experiments are carried out focusing on the planetary boundary layer (PBL) and the following microphysics schemes: WRF single-moment 6-class (WSM6) and WRF double-moment 6-class (WDM6) microphysics with Yonsei University, Mellor–Yamada–Janjić (MYJ), and Mellor–Yamada–Nakanishi–Niino (MYNN) 2.5-level (MN2.5) and 3.0-level (MN3) PBL schemes. The largest differences are found between WSM6-MN3 and WDM6-MN3, and we therefore examine RI mechanisms based on the results of these experiments. Prior to RI, WDM6-MN3 shows a drier environment and stronger downdrafts in the lower troposphere than in WSM6-MN3. As a result, during the RI period, WSM6-MN3 (WDM6-MN3) significantly intensifies with the minimum sea level pressure decreasing by 51 (29) hPa and the maximum surface wind increasing by 28 (12) m s−1 in 24 h. In both experiments, the maximum values of surface heat fluxes, potential vorticity (PV), radial absolute angular momentum advection, inertial stability, supergradient wind, and convective bursts inside the radius of maximum winds are frequently observed at each vertex of polygonal eyewalls in the lower troposphere. In particular, WSM6-MN3 exhibits more convective cells inside the inner-core region, a more persistent and thicker polygonal eyewall in the lower troposphere, and a more robust vertical structure of hydrometeors and vertical velocity than WDM6-MN3. This study suggests that within the inner-core region, polygonal eyewalls like WSM6-MN3 provide favorable conditions for RI.
Flux Correction and Overturning Stability: Insights from a Dynamical Box Model
Authors: Gnanadesikan Anand , Kelson Richard , Sten Michaela 
Published: September 2018

AbstractA recent paper suggested that the global climate models used to project future climate changes may significantly overestimate the stability of the Atlantic meridional overturning circulation under anthropogenic global warming. It further asserted that “flux adjusting” the models (adding offsets to heat and freshwater fluxes to reproduce the observed density field) may reduce model stability. However, temperature, salinity, and density fields in climate models likely deviate from observations because of biases in model physics as well as inaccuracies in fluxes. In such cases it is unclear whether adjusting the fluxes to produce a more realistic density field will result in a model with more realistic stability properties, as flux correction may be compensating for other inaccuracies in model formulation. We investigate this question using a simplified dynamical box model, in which we can flux correct one version of the model to match density gradients within another version of the model. We show that flux adjustment can realistically compensate for biases in stability associated with some processes, such as uncertainty in the value of the vertical diffusivity, but not other processes, such as inaccurate simulation of the relationship between density structure and overturning or the isopycnal tracer diffusivity coefficient. An ability to compensate for biases when the overturning shuts off does not imply an ability to compensate for biases in when it reestablishes itself, and vice versa.
The Role of Eddies in Buoyancy-Driven Eastern Boundary Currents
Authors: Bire Suyash , Wolfe Christopher L. P. 
Published: September 2018

AbstractAn eastern boundary current (EBC) system driven by a large-scale meridional buoyancy gradient is simulated using an idealized eddy-resolving model. The EBC system consists of a pair of stacked meridional currents that flow poleward near the surface and equatorward at intermediate depths. Buoyancy advection in the EBC is primarily balanced by the shedding of eddies, with anticyclonic, warm-core eddies dominating near the surface and cyclonic, cold-core eddies found at intermediate depths. These boundary eddies play a significant role in both the eastern boundary circulation—by helping to trap the EBC near the coast—and the large-scale circulation through their effect on the downwelling limb of the overturning circulation. Momentum and thickness budgets analyzed using the thickness-weighted average framework highlight the role of eddy form drag in shaping and maintaining the EBC. The efficiency of the form drag increases dramatically at the offshore flank of the EBC. This zonal variation of the form drag is essential for maintaining a swift, narrow EBC. The essential physics of the EBC are illustrated using a simple, semianalytical model.
A Meta-Analysis of Latinx Acculturation and Intimate Partner Violence
Authors: Alvarez Miriam J. , Ramirez Sandra Oviedo , Frietze Gabriel , Field Craig , Zárate Michael A. 
Published: September 2018

Objective: Intimate partner violence (IPV) is a serious public health concern that affects many Latinx couples. The present study conducted a systematic review and meta-analysis to quantitatively assess acculturation as a predictor of IPV among Latinxs and subgroup analyses to evaluate the effect size by gender and type of acculturation measure. Method: The meta-analysis implemented the preferred reporting items for systematic reviews and meta-analyses guidelines to retrieve studies assessing the relationship between acculturation and intimate partner victimization among foreign-born and U.S.-born Latinx adults. A fixed effects model (FEM) and a random effects model (REM) were employed. Additional subgroup analyses examined the strength of the relationship by gender and type of acculturation measure. Results: The meta-analysis included 27 independent effect sizes across 21 studies. An REM yielded a weighted average correlation of .11 (95% confidence interval [.02, .20]). The strength of the correlation differed by scale and ranged from −.003 to .47. For both men and women, higher acculturation was associated with increased IPV. Conclusions: Our results yielded three important findings: (1) the overall effect of acculturation on IPV is relatively small, (2) acculturation differentially influences male-to-female and female-to-male partner violence, and (3) the strength of the correlation between acculturation and IPV differs by scale. This body of work provides evidence for the effect of acculturation on IPV, with potential implications for interventions targeting Latinxs.
Indoles derived from intestinal microbiota act via type I interferon signaling to limit graft-versus-host disease
Authors: Swimm Alyson , Giver Cynthia R. , DeFilipp Zachariah , Rangaraju Sravanti , Sharma Akshay , Ulezko Antonova Alina , Sonowal Robert , Capaldo Christopher , Powell Domonica , Qayed Muna , Kalman Daniel , Waller Edmund K. 
Published: September 2018

Abstract
The intestinal microbiota in allogeneic bone marrow transplant (allo-BMT) recipients modulates graft-versus-host disease (GVHD), a systemic inflammatory state initiated by donor T cells that leads to colitis, a key determinant of GVHD severity. Indole or indole derivatives produced by tryptophan metabolism in the intestinal microbiota limit intestinal inflammation caused by diverse stressors, so we tested their capacity to protect against GVHD in murine major histocompatibility complex–mismatched models of allo-BMT. Indole effects were assessed by colonization of allo-BMT recipient mice with tryptophanase positive or negative strains of Escherichia coli, or, alternatively, by exogenous administration of indole-3-carboxaldehyde (ICA), an indole derivative. Treatment with ICA limited gut epithelial damage, reduced transepithelial bacterial translocation, and decreased inflammatory cytokine production, reducing GVHD pathology and GVHD mortality, but did not compromise donor T-cell-mediated graft-versus-leukemia responses. ICA treatment also led to recipient-strain-specific tolerance of engrafted T cells. Transcriptional profiling and gene ontology analysis indicated that ICA administration upregulated genes associated with the type I interferon (IFN1) response, which has been shown to protect against radiation-induced intestinal damage and reduce subsequent GVHD pathology. Accordingly, protective effects of ICA following radiation exposure were abrogated in mice lacking IFN1 signaling. Taken together, these data indicate that indole metabolites produced by the intestinal microbiota act via type I IFNs to limit intestinal inflammation and damage associated with myeloablative chemotherapy or radiation exposure and acute GVHD, but preserve antitumor responses, and may provide a therapeutic option for BMT patients at risk for GVHD.