bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anterior segment parameters in normal dogs using the Pentacam®HR Scheimpflug system
Authors: Wolfel Allison E. , Pederson Samantha L. , Cleymaet Allison M. , Hess Ann M. , Freeman Kate S. 
Published: February 2019

AbstractObjectiveTo describe and compare normative anterior segment parameters between canine age groups using the Pentacam®HR Scheimpflug camera (Pentacam).Animals StudiedThirty‐six sedated dogs (60 eyes) of varying ages and breeds were imaged with the Pentacam; only nondiseased anterior segments were included.ProceduresDogs were divided into three age groups: Group 1 (1‐5 years), Group 2 (6‐10 years), and Group 3 (11‐15 years). Values assessed included central corneal thickness (CCT), anterior and posterior corneal elevation (ACE/PCE), anterior and posterior corneal curvature metrics, corneal volume (CV), anterior and posterior corneal astigmatism (AA/PA), anterior chamber depth (ACD), anterior chamber volume (ACV), and anterior chamber angle (ACA). Tukey‐adjusted pairwise comparisons were performed.ResultsOverall CCT (mean ± SD) was 631.07 ± 59.91 µm. Central corneal thickness was 608.60 ± 48.63 µm for Group 1, 648.57 ± 51.06 µm for Group 2, and 635.37 ± 73.71 µm for Group 3. Anterior corneal elevation (ACE) measured 9.08 ± 0.58 mm, PCE measured 8.04 ± 0.50 mm, and CV was 58.13 ± 5.39 mm3. Astigmatism values were 1.34 ± 0.94 D for AA and 0.46 ± 0.44 D for PA. Anterior chamber values were 3.76 ± 0.56 mm for ACD, 383.68 ± 66.24 mm3for ACV, and 23.62 ± 29.33˚ for ACA. Significant differences were found between Groups 1 and 2 for CV (55.08 ± 4.08 mm3and 60.32 ± 4.19 mm3, respectively), (P = 0.02).ConclusionsCorneal volume significantly increased between Group 1 and Group 2. Central corneal thickness increased from Group 1 to Group 3, but was not significant with the current sample size. There were no other differences between age groups.
A Refined JKR Model for Adhesion of a Rigid Sphere on a Soft Elastic Substrate
Authors: Zhang Lei , Ru C. Q. 
Published: February 2019

Abstract
Surface energy outside the contact zone, which is ignored in the classical Johnson–Kendall–Roberts (JKR) model, can play an essential role in adhesion mechanics of soft bodies. In this work, based on a simple elastic foundation model for a soft elastic half space with constant surface tension, an explicit expression for the change of surface energy outside the contact zone is proposed for a soft elastic substrate indented by a rigid sphere in terms of two JKR-type variables (δ, a), where a is the radius of the contact zone and δ is the indentation depth of the rigid sphere. The derived expression is added to the classical JKR model to achieve two explicit equations for the determination of the two JKR variables (δ, a). The results given by the present model are demonstrated with detailed comparison with known results reported in recent literature, which verified the validity and robust accuracy of the present method. In particular, the present model confirms that the change of surface energy of the substrate can play an essential role in micro/nanoscale contact of soft materials (defined by W/(E*R)≥0.1, where W is the adhesive energy, E* is the substrate elasticity, and R is the rigid sphere radius). The present model offers a simpler analytical method for adhesion mechanics of a rigid sphere on a soft elastic substrate when compared with several existing methods proposed in recent literature that request more substantial numerical calculations.
Coulomb Friction Crawling Model Yields Linear Force–Velocity Profile
Authors: Wu Ziyou , Zhao Dan , Revzen Shai 
Published: February 2019

Abstract
Conventional wisdom would have it that moving mechanical systems that dissipate energy by Coulomb friction have no relationship between force and average speed. One could argue that the work done by friction is constant per unit of distance travelled, and if propulsion forces exceed friction, the net work is positive, and the system accumulates kinetic energy without bound. We present a minimalistic model for legged propulsion with slipping under Coulomb friction, scaled to parameters representative of single kilogram robots and animals. Our model, amenable to exact solutions, exhibits nearly linear (R2 &gt; 0.96) relationships between actuator force and average speed over its entire range of parameters, and in both motion regimes, it supports. This suggests that the interactions inherent in multilegged locomotion may lead to governing equations more reminiscent of viscous friction than would be immediately obvious.
Displacement, deprivation and hard work among Syrian refugee children in Lebanon
Authors: Habib Rima R , Ziadee Micheline , Abi Younes Elio , Harastani Houda , Hamdar Layal , Jawad Mohammed , El Asmar Khalil 
Published: February 2019

BackgroundThe protracted Syrian war resulted in the largest refugee crisis of our time. The most vulnerable are children who face separation from parents, interruption of schooling and child labour. This study explores the living and working conditions of Syrian children in Lebanon.MethodsIn this cross-sectional study, we randomly selected 153 informal tented settlements and conducted interviewer-administered surveys among Syrian refugee working children in the Bekaa Valley in Lebanon. Those aged 8–18 completed a questionnaire on sociodemographic and occupational characteristics; those aged 4–8 years were surveyed through a household questionnaire.ResultsWe surveyed 1902 households, including 12 708 individuals and 4377 working children. Female-headed households were poorer and more food-insecure than male-headed households. Among working children (4–18 years), the average age of starting work was 10.9 years and 74.8% worked in agriculture. Compared with boys, girls earned less and were less likely to be enrolled in school. For 96.3% of working children aged 8–18 years, forced exodus to Lebanon was associated with a first child labour experience. Working conditions were harsh and worse for girls who compared to boys were less likely to receive their salary on time and take time off work. Girls worked longer in the sun and cold and were more likely to report having a health symptom at work, working under pressure and using sharp or heavy objects at work. Seventy-nine children reported knowing another child who died following a work accident.ConclusionChildren, as young as 4, are forced to work, and many are compelled to forgo educational opportunities in favour of harsh and harmful labour due to difficult economic conditions. State policies facilitating access to work for adult refugees will help families meet basic needs and decrease their dependence on child labour as a coping strategy.
TGR5-dependent hepatoprotection through the regulation of biliary epithelium barrier function
Authors: Merlen Grégory , Kahale Nicolas , Ursic-Bedoya Jose , Bidault-Jourdainne Valeska , Simerabet Hayat , Doignon Isabelle , Tanfin Zahra , Garcin Isabelle , Péan Noémie , Gautherot Julien , Davit-Spraul Anne , Guettier Catherine , Humbert Lydie , Rainteau Dominique , Ebnet Klaus , Ullmer Christoph , Cassio Doris , Tordjmann Thierry 
Published: February 2019

ObjectiveWe explored the hypothesis that TGR5, the bile acid (BA) G-protein-coupled receptor highly expressed in biliary epithelial cells, protects the liver against BA overload through the regulation of biliary epithelium permeability.DesignExperiments were performed under basal and TGR5 agonist treatment. In vitro transepithelial electric resistance (TER) and FITC-dextran diffusion were measured in different cell lines. In vivo FITC-dextran was injected in the gallbladder (GB) lumen and traced in plasma. Tight junction proteins and TGR5-induced signalling were investigated in vitro and in vivo (wild-type [WT] and TGR5-KO livers and GB). WT and TGR5-KO mice were submitted to bile duct ligation or alpha-naphtylisothiocyanate intoxication under vehicle or TGR5 agonist treatment, and liver injury was studied.ResultsIn vitro TGR5 stimulation increased TER and reduced paracellular permeability for dextran. In vivo dextran diffusion after GB injection was increased in TGR5-knock-out (KO) as compared with WT mice and decreased on TGR5 stimulation. In TGR5-KO bile ducts and GB, junctional adhesion molecule A (JAM-A) was hypophosphorylated and selectively downregulated among TJP analysed. TGR5 stimulation induced JAM-A phosphorylation and stabilisation both in vitro and in vivo, associated with protein kinase C-ζ activation. TGR5 agonist-induced TER increase as well as JAM-A protein stabilisation was dependent on JAM-A Ser285 phosphorylation. TGR5 agonist-treated mice were protected from cholestasis-induced liver injury, and this protection was significantly impaired in JAM-A-KO mice.ConclusionThe BA receptor TGR5 regulates biliary epithelial barrier function in vitro and in vivo through an impact on JAM-A expression and phosphorylation, thereby protecting liver parenchyma against bile leakage.
Himalayan earthquakes: a review of historical seismicity and early 21st century slip potential
Authors: Bilham Roger 
Published: February 2019

Abstract

This article summarizes recent advances in our knowledge of the past 1000 years of earthquakes in the Himalaya using geodetic, historical and seismological data, and identifies segments of the Himalaya that remain unruptured. The width of the Main Himalayan Thrust is quantified along the arc, together with estimates for the bounding coordinates of historical rupture zones, convergence rates, rupture propagation directions as constrained by felt intensities. The 2018 slip potential for fifteen segments of the Himalaya are evaluated and potential magnitudes assessed for future earthquakes should these segments fail in isolation or as contiguous ruptures. Ten of these fifteen segments are sufficiently mature currently to host a great earthquake (M
w
≥ 8). Fatal Himalayan earthquakes have in the past occurred mostly in the daylight hours. The death toll from a future nocturnal earthquake in the Himalaya could possibly exceed 100 000 due to increased populations and the vulnerability of present-day construction methods.
Climate change, water-related disasters, flood control and rainfall forecasting: a case study of the São Francisco River, Brazil
Authors: Kuwajima Julio Issao , Fan Fernando Mainardi , Schwanenberg Dirk , Assis Dos Reis Alberto , Niemann André , Mauad Frederico Fábio 
Published: February 2019

Abstract
Because of climate change, the frequency, intensity and/or duration of extreme weather events such as floods, droughts, storms and extreme temperatures is increasing. These events are often related to loss of property, money and life, especially in poor and developing countries where there is no or poor disaster management due to social and financial difficulties or due to a lack of synergy between the mitigation actions taken. Negative impacts can be reduced and losses can be better handled with proper water management techniques. However, these should not be handled solely with traditional management. The actual problem cannot be over simplified as merely a question of coping with resources availability and demand. Therefore, the present paper aims to summarize advances in weather forecasting and reservoir operation in the Upper São Francisco River, strategic to Brazil because it provides water to the semi-arid region and energy for economically thriving Brazilian regions. Moreover, it discusses challenges, opportunities and improvements needed to implement these advances in the current national integrated water resources management. This is mainly focused on water-related disaster mitigation.
Whole Genome–Derived Tiled Peptide Arrays Detect Prediagnostic Autoantibody Signatures in Non–Small-Cell Lung Cancer
Authors: Yan Yuanqing , Sun Nan , Wang Hong , Kobayashi Makoto , Ladd Jon J. , Long James P. , Lo Ken C. , Patel Jigar , Sullivan Eric , Albert Thomas , Goodman Gary E. , Do Kim-Anh , Hanash Samir M. 
Published: February 2019

Abstract

The majority of non–small-cell lung cancer (NSCLC) cases are diagnosed at advanced stages, primarily because earlier stages of the disease are either asymptomatic or may be attributed to other causes such as infection or long-term effects from smoking. Therefore, early detection of NSCLC would likely increase response and survival rates due to timely intervention. Here, we utilize a novel approach based on whole genome–derived tiled peptide arrays to identify epitopes associated with autoantibody reactivity in NSCLC as a potential means for early detection. Arrays consisted of 2,781,902 tiled peptides representing 20,193 proteins encoded in the human genome. Analysis of 86 prediagnostic samples and 86 matched normal controls from a high-risk cohort revealed 48 proteins with three or more reactive epitopes in NSCLC samples relative to controls. Independent mass spectrometry analysis identified 40 of the 48 proteins in prediagnostic sera from NSCLC samples, of which, 21 occurred in the immunoglobulin-bound fraction. In addition, 63 and 34 proteins encompassed three or more epitopes that were distinct for squamous cell lung cancer and lung adenocarcinoma, respectively. Collectively, these data show that tiled peptide arrays provide a means to delineate epitopes encoded across the genome that trigger an autoantibody response associated with tumor development.

Significance:
This study provides a modality for early diagnosis of NSCLC for precision oncology that can be applied to other cancer types.
Immuno-oncological Efficacy of RXDX-106, a Novel TAM (TYRO3, AXL, MER) Family Small-Molecule Kinase Inhibitor
Authors: Yokoyama Yumi , Lew Erin D. , Seelige Ruth , Tindall Elizabeth A. , Walsh Colin , Fagan Patrick C. , Lee Jack Y. , Nevarez Robin , Oh Joanne , Tucker Kathleen D. , Chen Marissa , Diliberto Amy , Vaaler Heather , Smith Kristen M. , Albert Amanda , Li Gary , Bui Jack D. 
Published: February 2019

Abstract

Expression of the TAM (TYRO3, AXL, MER) family of receptor tyrosine kinases (RTK) has been associated with cancer progression, metastasis, and drug resistance. In immune cells, TAM RTKs can dampen inflammation in favor of homeostatic wound-healing responses, thus potentially contributing to the evasion of cancer cells from immune surveillance. Here we characterize the small-molecule RXDX-106 as a selective and potent pan-TAM RTK inhibitor with slow dissociation kinetics and significant antitumor activity in multiple syngeneic tumor models. Expression of AXL and MER on both immune and tumor cells increased during tumor progression. Tumor growth inhibition (TGI) following treatment with RXDX-106 was observed in wild-type mice and was abrogated in immunodeficient mice, suggesting that the antitumor activity of RXDX-106 is, in part, due to the presence of immune cells. RXDX-106–mediated TGI was associated with increased tumor-infiltrating leukocytes, M1-polarized intratumoral macrophages, and activation of natural killer cells. RXDX-106 proportionally increased intratumoral CD8+ T cells and T-cell function as indicated by both IFNγ production and LCK phosphorylation (pY393). RXDX-106 exhibited its effects via direct actions on TAM RTKs expressed on intratumoral macrophages and dendritic cells, leading to indirect activation of other immune cells in the tumor. RXDX-106 also potentiated the effects of an immune checkpoint inhibitor, α-PD-1 Ab, resulting in enhanced antitumor efficacy and survival. Collectively, these results demonstrate the capacity of RXDX-106 to inhibit tumor growth and progression and suggest it may serve as an effective therapy against multiple tumor types.

Significance:
The pan-TAM small-molecule kinase inhibitor RXDX-106 activates both innate and adaptive immunity to inhibit tumor growth and progression, indicating its clinical potential to treat a wide variety of cancers.
Integrated Genomic and Functional microRNA Analysis Identifies miR-30-5p as a Tumor Suppressor and Potential Therapeutic Nanomedicine in Head and Neck Cancer
Authors: Saleh Anthony D. , Cheng Hui , Martin Scott E. , Si Han , Ormanoglu Pinar , Carlson Sophie , Clavijo Paul E. , Yang Xinping , Das Rita , Cornelius Shaleeka , Couper Jamie , Chepeha Douglas , Danilova Ludmila , Harris Thomas M. , Prystowsky Michael B. , Childs Geoffrey J. , Smith Richard V. , Robertson A. Gordon , Jones Steven J. M. , Cherniack Andrew D. , Kim Sang S. , Rait Antonina , Pirollo Kathleen F. , Chang Esther H. , Chen Zhong , Van Waes Carter 
Published: February 2019

Abstract

Purpose:
To identify deregulated and inhibitory miRNAs and generate novel mimics for replacement nanomedicine for head and neck squamous cell carcinomas (HNSCC).

Experimental Design:
We integrated miRNA and mRNA expression, copy number variation, and DNA methylation results from The Cancer Genome Atlas (TCGA), with a functional genome-wide screen.

Results:
We reveal that the miR-30 family is commonly repressed, and all 5 members sharing these seed sequence similarly inhibit HNSCC proliferation in vitro. We uncover a previously unrecognized inverse relationship with overexpression of a network of important predicted target mRNAs deregulated in HNSCC, that includes key molecules involved in proliferation (EGFR, MET, IGF1R, IRS1, E2F7), differentiation (WNT7B, FZD2), adhesion, and invasion (ITGA6, SERPINE1). Reexpression of the most differentially repressed family member, miR-30a-5p, suppressed this mRNA program, selected signaling proteins and pathways, and inhibited cell proliferation, migration, and invasion in vitro. Furthermore, a novel miR-30a-5p mimic formulated into a targeted nanomedicine significantly inhibited HNSCC xenograft tumor growth and target growth receptors EGFR and MET in vivo. Significantly decreased miR-30a/e family expression was related to DNA promoter hypermethylation and/or copy loss in TCGA data, and clinically with decreased disease-specific survival in a validation dataset. Strikingly, decreased miR-30e-5p distinguished oropharyngeal HNSCC with poor prognosis in TCGA (P = 0.002) and validation (P = 0.007) datasets, identifying a novel candidate biomarker and target for this HNSCC subset.

Conclusions:
We identify the miR-30 family as an important regulator of signal networks and tumor suppressor in a subset of HNSCC patients, which may benefit from miRNA replacement nanomedicine therapy.
Role of Krüppel-like Factor 4-p21CIP1 Axis in Breast Cancer Stem-like Cell Inhibition by Benzyl Isothiocyanate
Authors: Kim Su-Hyeong , Singh Shivendra V. 
Published: February 2019

Abstract
Cancer chemoprevention by benzyl isothiocyanate (BITC), which is derived from cruciferous vegetables like garden cress, in a transgenic mouse model of breast cancer is associated with inhibition of breast cancer stem-like cells (bCSC), but the molecular regulators of this effect remain elusive. This study demonstrates a protective effect of Krüppel-like factor 4 (KLF4)-p21CIP1 axis in bCSC inhibition by BITC. Exposure of human breast cancer cells (MCF-7, MDA-MB-231, and SUM159) to plasma-achievable concentrations of BITC resulted in a robust induction of KLF4 mRNA and its protein expression as determined by qRT-PCR and Western blotting or confocal microscopy. BITC-mediated suppression of bCSC markers, including aldehyde dehydrogenase 1 activity and mammosphere frequency, was significantly augmented by transient or stable knockdown of KLF4. Western blotting and IHC revealed relatively higher levels of KLF4 protein in mammary tumor sections from BITC-treated mice in comparison with controls, but the difference was insignificant. Analysis of the breast cancer RNA-Seq data from The Cancer Genome Atlas indicated significant positive correlation between expression of KLF4 and that of p21CIP1 (CDKN1A) but not β-Catenin (CTNNB1). Knockdown of p21CIP1 protein also amplified BITC-mediated suppression of bCSC. Finally, KLF4 was recruited to the promoter of p21CIP1 as indicated by chromatin immunoprecipitation assay. These results indicate that induction of KLF4–p21CIP1 axis attenuates inhibitory effect of BITC on bCSC self-renewal. Translational implication of these findings is that breast cancer chemoprevention by BITC may be augmented with a combination regimen involving BITC and an inhibitor of KLF4.
John Dewey no cinema
Authors: Accorsi Fernanda Amorim , Teruya Teresa Kazuko 
Published: February 2019

Este artigo problematiza o filme americano Além da sala de aula (Beyond the blackboard, EUA), de 2011, cuja história retrata a escola de um abrigo temporário em que estudam os filhos de pessoas que não têm onde morar. O filme evidencia o papel da professora Stacey Bess, interpretada pela atriz canadense Emily VanCamp. Nosso eixo de análise tem como base os princípios educativos discutidos no livro Vida e educação, de John Dewey. Objetivamos verificar, em especial, a prática docente, o comportamento dos alunos e os conceitos de educação e escola exibidos no filme e compará-los com os apresentados no livro de Dewey. Constatamos que, embora o filme não anuncie as premissas educativas do autor, a prática pedagógica apresentada se assemelha àquela defendida por ele, bem como os conceitos de aluno, escola e educação apresentados também têm relação com as discussões realizadas por Dewey.
Can CMIP5 Earth System Models Reproduce the Interannual Variability of Air–Sea CO2 Fluxes over the Tropical Pacific Ocean?
Authors: Jin Chenxi , Zhou Tianjun , Chen Xiaolong 
Published: February 2019

Abstract
Interannual variability of air–sea CO2 exchange is an important metric that represents the interaction between the carbon cycle and climate change. Although previous studies report a large bias in the CO2 flux interannual variability in many Earth system models (ESMs), the reason for this bias remains unclear. In this study, the performance of ESMs in phase 5 of the Coupled Model Intercomparison Project (CMIP5) is assessed in the context of the variability of air–sea CO2 flux over the tropical Pacific related to El Niño–Southern Oscillation (ENSO) using an emission-driven historical experiment. Using empirical orthogonal function (EOF) analysis, the first principal component of air–sea CO2 flux shows a significant relationship with the Niño-3.4 index in both the observation-based product and models. In the observation-based product, the spatial pattern of EOF1 shows negative anomalies in the central Pacific, which is, however, in contrast to those in several ESMs, and even opposite in sign to those in HadGEM2-ES and MPI-ESM-LR. The unrealistic response of the air–sea CO2 flux to ENSO mainly originates from the biases in the anomalous surface-water CO2 partial pressure (). A linear Taylor expansion by decomposing the anomalous into contributions from salinity, sea surface temperature, dissolved inorganic carbon (DIC), and alkalinity is applied to diagnose the biases. The results show that decreased during El Niño results from reduced upwelling of high-concentration DIC from deeper layers that overwhelms the increasing caused by warmer sea surface temperature. Overly weak reduction of vertical motion during El Niño and weak vertical gradients of climatological DIC concentration are the main reasons for biases in the negative surface DIC anomalies and eventually the anomalies. This study highlights the importance of both physical ocean responses to El Niño and climatological distributions of carbon-related tracers in the simulation of the interannual variability of air–sea CO2 fluxes.