bluuebunny/crossref_metadata_2025_split huggingface dataset:
A gradual transition to plate tectonics on Earth between 3.2 to 2.7 billion years ago
Authors: Hartnady Michael I. H. , Kirkland Christopher L. 
Published: February 2019

AbstractZircon crystals precipitated from granitoid magmas contain a robust record of the age and chemistry of continental magmatism spanning some 4.375 Ga of Earth history, a record that charts initiation of plate tectonics. However, constraining when exactly plate tectonics began to dominate crustal growth processes is challenging as the geochemical signatures of individual rocks may reflect local subduction processes rather than global plate tectonics. Here we apply counting statistics to a global database of coupled U–Pb and Hf isotope analyses on magmatic zircon grains from continental igneous and sedimentary rocks to quantify changes in the compositions of their source rocks. The analysis reveals a globally significant change in the sources of granitoid magmas between 3.2 and 2.7 Ga. These secular changes in zircon chemistry are driven by a coupling of the deep (depleted mantle) and shallow (crustal) Earth reservoirs, consistent with a geodynamic regime dominated by Wilson cycle style plate tectonics.
Identification of red blood cell antibodies in maternal breast milk implicated in prolonged hemolytic disease of the fetus and newborn
Authors: Leonard Alexis , Hittson Boal Lauren , Pary Philippe , Mo Y. Delores , Jacquot Cyril , Luban Naomi L. , Darbari Deepika S. , Webb Jennifer 
Published: February 2019

BACKGROUNDAlloantibodies against more than 50 non‐ABO blood group antigens have been implicated in hemolytic disease of the fetus and newborn (HDFN) and are expected to wane within weeks after delivery. Persistent anemia leads to the hypothesis of continued exposure to red blood cell (RBC) alloantibodies via breast milk, which has been shown in a murine model and suggested in rare case reports.CASE REPORTWe report three cases of prolonged HDFN in two neonates with anti‐D HDFN and one with anti‐Jka HDFN. Patient 1 demonstrated 4+ anti‐D serologic testing beyond 2 months; therefore, antibody testing was performed on maternal breast milk.METHODSMaternal serum samples were tested for the presence of unexpected antibodies using standard Ortho gel card and 37 °C 60 minutes with anti‐human globulin (AHG) tube saline methods. Antibody titrations were performed using the standard 37 °C 60 minutes to AHG tube saline method. Fresh breast milk samples were tested using the standard 37 °C 60 minutes to AHG tube saline method for both unexpected antibodies and titration study. Fresh breast milk from an O‐positive, antibody‐negative donor was used as control for any reactivity that may have been due to milk solids or proteins alone.RESULTSUsing a known methodology applied in a novel way to test breast milk for RBC alloantibodies, antibodies against fetal RBCs were identified in the maternal breast milk of three patients.CONCLUSIONMaternal RBC alloantibodies are present in breast milk and may be clinically significant in patients with prolonged recovery from HDFN.
Serum vascular endothelial growth factor changes and safety after topical anti‐human VEGF antibody bevacizumab in healthy dogs
Authors: Muellerleile Lisa‐Marie , Tichy Alexander , Nell Barbara 
Published: February 2019

AbstractObjectiveTo evaluate ocular and general safety of topical anti‐human VEGF bevacizumab and the effect on serum vascular endothelial growth factor (VEGF) values in healthy dogs.ProceduresNine university‐owned beagles received 0.05 mL of 0.25% bevacizumab eyedrops (Avastin®, Roche) in one eye and 0.05 mL of 0.9% saline solution in the other eye as a control, administered at 12 hours intervals over a period of 28 days. Continuous monitoring for vital parameters and ocular examinations were conducted. Complete blood counts including hematology and coagulation parameters were performed before trial start as well as 24 hours, 7 days, and 28 days after trial start. Measurements of serum VEGF values were obtained using an ELISA‐based approach at days 0, 7, and 28. The experiment was designed as a masked placebo‐controlled study.ResultsNo clinical signs of ocular toxicity or systemic incompatibility were noted in any dog at any time point of the study. No signs of pain were present in any dog at any time point. All blood count values remained in normal clinical ranges without relevant variation. There was no significant change in mean serum VEGF values between day 0 and day 7 and between day 0 and day 28.ConclusionsThe results indicate that topical bevacizumab treatment is safe in healthy dogs. However, further studies are needed to assess safety and efficacy in diseased dogs with naturally occurring corneal neovascularization.
Comparison of early posttreatment effects of two steroidal anti‐inflammatory ophthalmic drugs on the ocular inflammatory response induced by paracentesis in healthy canine eyes
Authors: Sato Kazuaki , Iwasaki Kiwako , Nagai Noriaki , Yamashita Yohei , Chikazawa Seishiro , Hoshi Fumio , Kanai Kazutaka 
Published: February 2019

AbstractObjectiveWe investigated the early posttreatment effects of two steroidal anti‐inflammatory ophthalmic drugs on blood‐aqueous barrier (BAB) breakdown by paracentesis in dogs.Animal studiesWe studied 21 healthy beagles with normal eyes.ProceduresControlled anterior chamber paracentesis (0.5 mL) was performed in one eye of each dog. Control group dogs (n = 7) received no medication, whereas those in the treatment groups received a topical anti‐inflammatory medication (difluprednate [DFBA] ophthalmic emulsion 0.05% [n = 7] or betamethasone [BMZ] sodium phosphate ophthalmic solution 0.1% [n = 7]) at 0, 15, 30, and 45 minutes after initial paracentesis in the paracentesed eyes. Secondary aqueous humor (AH) was collected 60 minutes after initial paracentesis. Protein and prostaglandin E2(PGE2) concentrations in AH were determined using the bicinchoninic acid assay and commercially available immunoassay kit, respectively. All mean values in the three groups were compared using analysis of variance followed by Tukey's post hoc test.ResultsAqueous protein and PGE2concentrations were markedly increased at 60 minutes following paracentesis. Both concentrations in the secondary AH of the DFBA group were significantly lower than those of the control group; however, treatment with BMZ had no significant effects.ConclusionsEarly postparacentesis treatment with DFBA was more effective than that with BMZ for reducing aqueous protein and PGE2contents in dogs with paracentesis‐induced BAB breakdown. DFBA may be an appropriate treatment during the early stage of anterior uveitis caused by intraocular surgery in dogs.
Limits on Transformation Strains for Non-Negative
Dissipation
Authors: Vasoya Manish , Kondori Babak , Benzerga Ahmed Amine , Needleman Alan 
Published: February 2019

Abstract
We consider the maximum value of the magnitude of transformation strain for an Eshelby inclusion set by the requirement of non-negative dissipation. The general formulation for a linear elastic solid shows that the dissipation associated with a strain transformation can be calculated as an integral over the transformed inclusion. Closed-form expressions are given for the maximum transformation strain magnitude in an isotropic linear elastic solid for both cylindrical and spherical inclusions that have undergone transformations corresponding to either a pure volume (or area) change or a pure shear. Most results presented are for transformations in an infinite solid and presume uniform material properties. Examples of the effect of a finite boundary and of differing material properties inside and outside the transformed inclusion are also given. The analytical results indicate that non-negative dissipation typically limits the transformation strain to being a constant of order unity times the critical stress at transformation divided by a relevant elastic modulus.
The Onset of Instabilities in Mixed Convection Boundary Layer Flow Over a Heated Horizontal Circular Cylinder
Authors: Mouloud Smail , Nait-Bouda Faïçal , Sadaoui Djamel , Mendil Fatsah 
Published: February 2019

AbstractThe purpose of this study is to examine the instabilities of a two-dimensional mixed convection boundary layer flow induced by an impinging ascending flow on a heated horizontal cylinder. A significant amount of works is done in recent years on this problem because of its wide range of applications. However, they did not check the stability of the flow in the face of small disturbances that occur in reality. For this, we adopt the linear stability theory by first solving the steady basic flow and then solving the linear perturbed problem. Thus, the governing equations of the basic flow are reduced to two coupled partial differential equations and solved numerically with the Keller-Box method. The corresponding steady solution is obtained, by varying the position along the cylinder’s surface, for different values of Richardson number (λ) and Prandtl number (Pr), up to, respectively, 3000 and 20. To examine the onset of thermal instabilities, the linear stability analysis is done using the normal mode decomposition with small harmonic disturbances. The Richardson number λ is chosen as the control parameter of these instabilities. The resulting eigenvalue problem is solved numerically by the use of the pseudospectral method based on the Laguerre polynomials. The computed results for neutral and temporal growth curves are depicted and discussed in detail through graphs for various parametric conditions. The critical conditions are illustrated graphically to show from which thermodynamic state, the flow begins to become unstable. As a main result, from ξ = 0 to ξ ≈ π/3, we found that forced and mixed convection flow cases are linearly stable in this region. However, in free convection case (λ &gt; 100), it appears that the stagnation zone is the most unstable one and then the instability decreases along the cylinder’s surface up to the limit of its first third, thus giving the most stable zone of the cylinder. Beyond ξ ≈ 1.2, strong instabilities are noted also for low values of Richardson number, and the flow tends to an unstable state even in the absence of thermal effect, i.e., hydrodynamically unstable Ri = 0, probably due to the occurring of the boundary layer separation.
Examining intervention mechanisms of action using mediation analysis within a randomised trial of a whole-school health intervention
Authors: Bonell Chris , Allen Elizabeth , Opondo Charles , Warren Emily , Elbourne Diana Ruth , Sturgess Joanna , Bevilacqua Leonardo , McGowan Jennifer , Mathiot Anne , Viner Russell M 
Published: February 2019

BackgroundInterventions to modify school environments are effective in promoting young people’s health across outcomes, but mechanisms are poorly understood. We assessed mediation in a trial of the Learning Together intervention, building on the recent publication of results of effectiveness for reducing bullying and benefits across secondary outcomes and generally good implementation fidelity.MethodsWithin a cluster-randomised trial involving 40 English schools, we examined student-reported and staff-reported school climate and student-reported involvement with delinquent peers at 24-month and 36-month follow-up, assessing the reliability of measures and whether these mediated health outcomes at a final follow-up.ResultsResponse rates and reliability were good for student-reported but not staff-reported measures. The intervention increased student-reported but not staff-reported-positive school climate but, like effects on student health outcomes, these manifested only at a final follow-up. The intervention reduced student-reported contact with delinquent peers at an interim follow-up. Student-reported potential mediators measured at the interim follow-up were associated with most health outcomes at the final follow-up. Adjustment for student-reported school climate and contact with delinquent peers at the interim follow-up did not reduce the associations between trial arm and our health outcomes.ConclusionDespite being constrained by imperfect measures and by the late manifestation of impacts on student-reported school climate undermining ability to assess mediation, our study for the first time provides tentative evidence that mediation of intervention effects via improved climate and disengagement from delinquent peers is plausible. Our study provides the first evidence from a trial that whole-school interventions may work by modifying school environments and student relationships.Trial registration numberISRCTN10751359.
Declines in anogenital warts diagnoses since the change in 2012 to use the quadrivalent HPV vaccine in England: data to end 2017
Authors: Checchi Marta , Mesher David , Mohammed Hamish , Soldan Kate 
Published: February 2019

ObjectivesIn 2008, a national human papillomavirus (HPV) vaccination programme for females was introduced in England using the bivalent vaccine (HPV16 and 18 only). In 2012, the programme changed to offer the quadrivalent vaccine that includes protection against the two HPV types that cause the majority of anogenital warts (AGW; HPV6 and 11). We present data reporting AGW diagnoses in sexual health clinics (SHCs) in England to the end of 2017, including diagnoses among birth cohorts offered the quadrivalent vaccine.MethodsUsing data from all SHCs across England, we performed ecological analyses to consider rates of AGW diagnoses by age, gender and sexual orientation. We tested for trends over time of diagnoses of AGW in young females, heterosexual males, and men who have sex with men (MSM) between the ages of 15 and 24 years during both bivalent (2009 to 2013) and quadrivalent (2014 to 2017) vaccine time periods using Poisson regression.ResultsBetween 2014 and 2017, there was strong evidence for a decreasing trend in the rate of AGW diagnoses at SHC among females aged 15–17 years from 257.5 to 45.7 per 100 000 population (82.3% decline) and same aged heterosexual males from 59.1 to 19.1 per 100 000 population (67.7% decline). The reductions in the incidence of AGW diagnoses in MSM aged 15–17 years were less clear (decreased by 13.6% between 2014 and 2017, from 129.9 to 112.2 per 100 000 population).ConclusionsThe moderate, unexpected declines in AGW seen since the introduction of a high-coverage HPV vaccination programme using the bivalent vaccine are being followed, as expected, by much larger declines among females offered the quadrivalent vaccine and same-aged heterosexual males. Surveillance plans are in place to continue to monitor AGW diagnoses to evaluate the impact of both female and targeted MSM HPV vaccination on early disease outcomes.
Trabectedin Inhibits EWS-FLI1 and Evicts SWI/SNF from Chromatin in a Schedule-dependent Manner
Authors: Harlow Matt L. , Chasse Maggie H. , Boguslawski Elissa A. , Sorensen Katie M. , Gedminas Jenna M. , Kitchen-Goosen Susan M. , Rothbart Scott B. , Taslim Cenny , Lessnick Stephen L. , Peck Anderson S. , Madaj Zachary B. , Bowman Megan J. , Grohar Patrick J. 
Published: February 2019

AbstractPurpose:The successful clinical translation of compounds that target specific oncogenic transcription factors will require an understanding of the mechanism of target suppression to optimize the dose and schedule of administration. We have previously shown trabectedin reverses the gene signature of the EWS-FLI1 transcription factor. In this report, we establish the mechanism of suppression and use it to justify the reevaluation of this drug in the clinic in patients with Ewing sarcoma.Experimental Design: We demonstrate a novel epigenetic mechanism of trabectedin using biochemical fractionation and chromatin immunoprecipitation sequencing. We link the effect to drug schedule and EWS-FLI1 downstream target expression using confocal microscopy, qPCR, Western blot analysis, and cell viability assays. Finally, we quantitate target suppression within the three-dimensional architecture of the tumor in vivo using 18F-FLT imaging.Results:Trabectedin evicts the SWI/SNF chromatin-remodeling complex from chromatin and redistributes EWS-FLI1 in the nucleus leading to a marked increase in H3K27me3 and H3K9me3 at EWS-FLI1 target genes. These effects only occur at high concentrations of trabectedin leading to suppression of EWS-FLI1 target genes and a loss of cell viability. In vivo, low-dose irinotecan is required to improve the magnitude, penetrance, and duration of target suppression in the three-dimensional architecture of the tumor leading to differentiation of the Ewing sarcoma xenograft into benign mesenchymal tissue.Conclusions:These data provide the justification to evaluate trabectedin in the clinic on a short infusion schedule in combination with low-dose irinotecan with 18F-FLT PET imaging in patients with Ewing sarcoma.
Targeting the Tumor Microenvironment in Radiation Oncology: Proceedings from the 2018 ASTRO–AACR Research Workshop
Authors: McGee Heather M. , Jiang Dadi , Soto-Pantoja David R. , Nevler Avinoam , Giaccia Amato J. , Woodward Wendy A. 
Published: February 2019

Abstract
The development of cancer and their response to radiation are intricately linked to the tumor microenvironment (TME) in which they reside. Tumor cells, immune cells, and stromal cells interact with each other and are influenced by the microbiome and metabolic state of the host, and these interactions are constantly evolving. Stromal cells not only secrete extracellular matrix and participate in wound contraction, but they also secrete fibroblast growth factors(FGF) molecules, which mediate macrophage differentiation. Tumor-associated macrophages migrate to hypoxic areas and secrete vascular endothelial growth factor (VEGF) to promote angiogenesis. The microbiome and its byproducts alter the metabolic milieu by shifting the balance between glucose utilization and fatty acid oxidation, and these changes subsequently influence the immune response in the TME. Not only does radiation exert cell-autonomous effects on tumor cells, but it influences both the tumor-promoting and tumor-suppressive components in the TME. To gain a deeper understanding of how the TME influences the response to radiation, the American Society for Radiation Oncology and the American Association of Cancer Research organized a scientific workshop on July 26–27, 2018, to discuss how the microbiome, the immune response, the metabolome, and the stroma all shift the balance between radiosensitivity and radioresistance. The proceedings from this workshop are discussed here and highlight recent discoveries in the field, as well as the most important areas for future research.
O processo de fruição do modificador-player no modelo de design audiovisual
Authors: Azevedo Amanda , Becker Valdecir 
Published: February 2019

Este artigo analisa a transformação da fruição de conteúdos audiovisuais, que está impactando sua produção e modificando sua recepção. A propagação de conteúdos audiovisuais tem se intensificado nos últimos anos devido à disseminação de softwares de produção, modificação e distribuição, com interfaces simples e eficientes. A partir de bases fornecidas pelas áreas de interação humano-computador e estudos da audiência, este artigo usa o modelo do design audiovisual como proposta metodológica para compreender a fruição das audiências, as novas relações mediadas por softwares e, por fim, a definição sobre o papel do modificador-player nesse modelo. Os resultados apontam para o desenvolvimento de competências e habilidades dos indivíduos como fatores relevantes para a fruição de conteúdos audiovisuais.
Robust CTCF-Based Chromatin Architecture Underpins Epigenetic Changes in the Heart Failure Stress–Gene Response
Authors: Lee Dominic Paul , Tan Wilson Lek Wen , Anene-Nzelu Chukwuemeka George , Lee Chang Jie Mick , Li Peter Yiqing , Luu Tuan Danh Anh , Chan Cheryl Xueli , Tiang Zenia , Ng Shi Ling , Huang Xingfan , Efthymios Motakis , Autio Matias I. , Jiang Jianming , Fullwood Melissa Jane , Prabhakar Shyam , Lieberman Aiden Erez , Foo Roger Sik-Yin 
Published: February 2019

Background:

The human genome folds in 3 dimensions to form thousands of chromatin loops inside the nucleus, encasing genes and
cis
-regulatory elements for accurate gene expression control. Physical tethers of loops are anchored by the DNA-binding protein CTCF and the cohesin ring complex. Because heart failure is characterized by hallmark gene expression changes, it was recently reported that substantial CTCF-related chromatin reorganization underpins the myocardial stress–gene response, paralleled by chromatin domain boundary changes observed in CTCF knockout.

Methods:

We undertook an independent and orthogonal analysis of chromatin organization with mouse pressure-overload model of myocardial stress (transverse aortic constriction) and cardiomyocyte-specific knockout of
Ctcf
. We also downloaded published data sets of similar cardiac mouse models and subjected them to independent reanalysis.

Results:

We found that the cardiomyocyte chromatin architecture remains broadly stable in transverse aortic constriction hearts, whereas
Ctcf
knockout resulted in ≈99% abolition of global chromatin loops. Disease gene expression changes correlated instead with differential histone H3K27-acetylation enrichment at their respective proximal and distal interacting genomic enhancers confined within these static chromatin structures. Moreover, coregulated genes were mapped out as interconnected gene sets on the basis of their multigene 3D interactions.

Conclusions:
This work reveals a more stable genome-wide chromatin framework than previously described. Myocardial stress–gene transcription responds instead through H3K27-acetylation enhancer enrichment dynamics and gene networks of coregulation. Robust and intact CTCF looping is required for the induction of a rapid and accurate stress response.
The Effects of Enhanced Sea Ice Export from the Ross Sea on Recent Cooling and Freshening of the Southeast Pacific
Authors: Cerovečki Ivana , Meijers Andrew J. S. , Mazloff Matthew R. , Gille Sarah T. , Tamsitt Veronica M. , Holland Paul R. 
Published: February 2019

Abstract
The top 2000 m of the Southern Ocean has freshened and warmed over recent decades. However, the high-latitude (south of 50°S) southeast Pacific was observed to be cooler and fresher in the years 2008–10 compared to 2005–07 over a wide depth range including surface, mode, and intermediate waters. The causes and impacts of this event are analyzed using the ocean–sea ice data-assimilating Southern Ocean State Estimate (SOSE) and observationally based products. In 2008–10, a strong positive southern annular mode coincided with a negative El Niño–Southern Oscillation and a deep Amundsen Sea low. Enhanced meridional winds drove strong sea ice export from the eastern Ross Sea, bringing large amounts of ice to the Amundsen Sea ice edge. In 2008, together with increased precipitation, this introduced a strong freshwater anomaly that was advected eastward by the Antarctic Circumpolar Current (ACC), mixing along the way. This anomaly entered the ocean interior not only as Antarctic Intermediate Water, but also as lighter Southeast Pacific Subantarctic Mode Water (SEPSAMW). A numerical particle release experiment carried out in SOSE showed that the Ross Sea sector was the dominant source of particles reaching the SEPSAMW formation region. This suggests that large-scale climate fluctuations can induce strong interannual variability of volume and properties of SEPSAMW. These fluctuations act at different time scales: instantaneously via direct forcing and also lagged over advective time scales of several years from upstream regions.