bluuebunny/crossref_metadata_2025_split huggingface dataset:
Operation of a Two-Stroke, Spark-Ignition Engine on a Non-Conventional Lubricant
Authors: Ahles Jacob , Price Kyle , Eggart Brian , Miers Scott A. , Wiegand Andrew , Kowalski Darin , Biske Andrew 
Published: November 2017

Two-stroke engines are capable of providing very high power density levels in a cost effective, easy-to-maintain package. They are, however, typically susceptible to higher levels of hydrocarbon emissions, lower durability, and a shorter lifecycle when compared to four-stroke engines. These detriments are easily overlooked in some military applications where power density is paramount, but most commercial two-stroke engines require specialized consumable lubricant. Typical military applications strive to minimize their logistics “trails,” which includes minimizing the variety of fluids they require. As a result, there has been very limited success in fielding small two-stroke engines for military use.
As a preliminary study, MIL-PRF-2104K Single Common Powertrain Lubricant (SCPL, a four-stroke heavy diesel engine oil) was utilized as the consumable lubricant (in place of conventional two-stroke oil) in a liquid-cooled, semi-direct fuel injected, spark-ignition, two-stroke engine. Empirical data was collected to study the impact of the oil on deposit build-up, power, wear, combustion stability, and fuel conversion efficiency. Over 147 hours of operation were logged and analyzed.
The performance of the engine on SCPL was consistent with conventional two-stroke oil and showed no degradation over the test duration. Brake specific fuel consumption was not negatively impacted with SCPL. Increased deposit build-up in the exhaust ports and on the spark plugs were the primary negative impacts of the SCPL oil. Spark plugs with hotter classifications and modification of the oiling rate resulted in a reduction of soot accumulation and spark plug fouling.
Waste Heat Recovery for Heavy-Duty Diesel Engines: A Review of Mechanical Turbocompounding
Authors: Jääskeläinen Hannu , Majewski W. Addy 
Published: November 2017

Heat rejected with the exhaust gas, EGR, engine coolant and other engine components is a major source of efficiency loss in internal combustion engines. One important technology to recover some of this “wasted” heat is turbocompounding. The US Environmental Protection Agency (EPA) estimates that turbocompounding provides a 1.8% efficiency improvement, is already a commercial technology and a penetration rate of 10% is estimated by 2027. Line haul sleeper cab applications are the most likely to see the highest market penetration rates.
This paper presents an overview of mechanical turbocompounding for heavy-duty truck engines. For these applications, series turbocompounding is the most suitable configuration and a number of applications have used it since the early 1990s. Unlike other WHR technologies, turbocompounding interacts significantly with the engine through a higher exhaust backpressure. EGR makes it more challenging to realize an efficiency benefit from turbocompounding. It also makes emission control using aftertreatment technology more challenging due to a lower exhaust temperature.
Loss of cellular FLICE-inhibitory protein promotes acute cholestatic liver injury and inflammation from bile duct ligation
Authors: Gehrke Nadine , Nagel Michael , Straub Beate K. , Wörns Marcus A. , Schuchmann Marcus , Galle Peter R. , Schattenberg Jörn M. 
Published: November 2017

Cholestatic liver injury results from impaired bile flow or metabolism and promotes hepatic inflammation and fibrogenesis. Toxic bile acids that accumulate in cholestasis induce apoptosis and contribute to early cholestatic liver injury, which is amplified by accompanying inflammation. The aim of the current study was to evaluate the role of the antiapoptotic caspase 8-homolog cellular FLICE-inhibitory (cFLIP) protein during acute cholestatic liver injury. Transgenic mice exhibiting hepatocyte-specific deletion of cFLIP (cFLIP−/−) were used for in vivo and in vitro analysis of cholestatic liver injury using bile duct ligation (BDL) and the addition of bile acids ex vivo. Loss of cFLIP in hepatocytes promoted acute cholestatic liver injury early after BDL, which was characterized by a rapid release of proinflammatory and chemotactic cytokines (TNF, IL-6, IL-1β, CCL2, CXCL1, and CXCL2), an increased presence of CD68+ macrophages and an influx of neutrophils in the liver, and resulting apoptotic and necrotic hepatocyte cell death. Mechanistically, liver injury in cFLIP−/− mice was aggravated by reactive oxygen species, and sustained activation of the JNK signaling pathway. In parallel, cytoprotective NF-κB p65, A20, and the MAPK p38 were inhibited. Increased injury in cFLIP−/− mice was accompanied by activation of hepatic stellate cells and profibrogenic regulators. The antagonistic caspase 8-homolog cFLIP is a critical regulator of acute, cholestatic liver injury. NEW & NOTEWORTHY The current paper explores the role of a classical modulator of hepatocellular apoptosis in early, cholestatic liver injury. These include activation of NF-κB and MAPK signaling, production of inflammatory cytokines, and recruitment of neutrophils in response to cholestasis. Because these signaling pathways are currently exploited in clinical trials for the treatment of nonalcoholic steatohepatitis and cirrhosis, the current data will help in the development of novel pharmacological options in these indications.
β-PIX plays an important role in regulation of intestinal epithelial restitution by interacting with GIT1 and Rac1 after wounding
Authors: Rathor Navneeta , Chung Hee Kyoung , Wang Shelley R. , Qian Michael , Turner Douglas J. , Wang Jian-Ying , Rao Jaladanki N. 
Published: November 2017

Early gut mucosal restitution is a process by which intestinal epithelial cells (IECs) migrate over the wounded area, and its defective regulation occurs commonly in various critical pathological conditions. This rapid reepithelialization is mediated by different activating small GTP-binding proteins, but the exact mechanism underlying this process remains largely unknown. Recently, it has been reported that interaction between p21-activated kinase-interacting exchange factor (β-PIX) and G protein-coupled receptor kinase-interacting protein 1 (GIT1) activates small GTPases and plays an important role in the regulation of cell motility. Here, we show that induced association of β-PIX with GIT1 is essential for the stimulation of IEC migration after wounding by activating Rac1. Levels of β-PIX and GIT1 proteins and their association in differentiated IECs (line of IEC-Cdx2L1) were much higher than those observed in undifferentiated IECs (line of IEC-6), which was associated with an increase in IEC migration after wounding. Decreased levels of endogenous β-PIX by its gene-silencing destabilized β-PIX/GIT1 complexes, repressed Rac1 activity and inhibited cell migration over the wounded area. In contrast, ectopic overexpression of β-PIX increased the levels of β-PIX/GIT1 complexes, stimulated Rac1 activity, and enhanced intestinal epithelial restitution. Increased levels of cellular polyamines also stimulated β-PIX/GIT1 association, increased Rac1 activity, and promoted the epithelial restitution. Moreover, polyamine depletion decreased cellular abundances of β-PIX/GIT1 complex and repressed IEC migration after wounding, which was rescued by ectopic overexpression of β-PIX or GIT1. These results indicate that β-PIX/GIT1/Rac1 association is necessary for stimulation of IEC migration after wounding and that this signaling pathway is tightly regulated by cellular polyamines.NEW & NOTEWORTHY Our current study demonstrates that induced association of β-PIX with GIT1 is essential for the stimulation of intestinal epithelial restitution by activating Rac1, and this signaling pathway is tightly regulated by cellular polyamines.
Prior automatic posture and activity identification improves physical activity energy expenditure prediction from hip-worn triaxial accelerometry
Authors: Garnotel M. , Bastian T. , Romero-Ugalde H. M. , Maire A. , Dugas J. , Zahariev A. , Doron M. , Jallon P. , Charpentier G. , Franc S. , Blanc S. , Bonnet S. , Simon C. 
Published: November 2017

Accelerometry is increasingly used to quantify physical activity (PA) and related energy expenditure (EE). Linear regression models designed to derive PAEE from accelerometry-counts have shown their limits, mostly due to the lack of consideration of the nature of activities performed. Here we tested whether a model coupling an automatic activity/posture recognition (AAR) algorithm with an activity-specific count-based model, developed in 61 subjects in laboratory conditions, improved PAEE and total EE (TEE) predictions from a hip-worn triaxial-accelerometer (ActigraphGT3X+) in free-living conditions. Data from two independent subject groups of varying body mass index and age were considered: 20 subjects engaged in a 3-h urban-circuit, with activity-by-activity reference PAEE from combined heart-rate and accelerometry monitoring (Actiheart); and 56 subjects involved in a 14-day trial, with PAEE and TEE measured using the doubly-labeled water method. PAEE was estimated from accelerometry using the activity-specific model coupled to the AAR algorithm (AAR model), a simple linear model (SLM), and equations provided by the companion-software of used activity-devices (Freedson and Actiheart models). AAR-model predictions were in closer agreement with selected references than those from other count-based models, both for PAEE during the urban-circuit (RMSE = 6.19 vs 7.90 for SLM and 9.62 kJ/min for Freedson) and for EE over the 14-day trial, reaching Actiheart performances in the latter (PAEE: RMSE = 0.93 vs. 1.53 for SLM, 1.43 for Freedson, 0.91 MJ/day for Actiheart; TEE: RMSE = 1.05 vs. 1.57 for SLM, 1.70 for Freedson, 0.95 MJ/day for Actiheart). Overall, the AAR model resulted in a 43% increase of daily PAEE variance explained by accelerometry predictions.NEW & NOTEWORTHY Although triaxial accelerometry is widely used in free-living conditions to assess the impact of physical activity energy expenditure (PAEE) on health, its precision and accuracy are often debated. Here we developed and validated an activity-specific model which, coupled with an automatic activity-recognition algorithm, improved the variance explained by the predictions from accelerometry counts by 43% of daily PAEE compared with models relying on a simple relationship between accelerometry counts and EE.
Peripheral Neuropathy Induced by Microtubule-Targeted Chemotherapies: Insights into Acute Injury and Long-term Recovery
Authors: Wozniak Krystyna M. , Vornov James J. , Wu Ying , Liu Ying , Carozzi Valentina A. , Rodriguez-Menendez Virginia , Ballarini Elisa , Alberti Paola , Pozzi Eleonora , Semperboni Sara , Cook Brett M. , Littlefield Bruce A. , Nomoto Kenichi , Condon Krista , Eckley Sean , DesJardins Christopher , Wilson Leslie , Jordan Mary A. , Feinstein Stuart C. , Cavaletti Guido , Polydefkis Michael , Slusher Barbara S. 
Published: November 2017

Abstract
Chemotherapy-induced peripheral neuropathy (CIPN) is a major cause of disability in cancer survivors. CIPN investigations in preclinical model systems have focused on either behaviors or acute changes in nerve conduction velocity (NCV) and amplitude, but greater understanding of the underlying nature of axonal injury and its long-term processes is needed as cancer patients live longer. In this study, we used multiple independent endpoints to systematically characterize CIPN recovery in mice exposed to the antitubulin cancer drugs eribulin, ixabepilone, paclitaxel, or vinorelbine at MTDs. All of the drugs ablated intraepidermal nerve fibers and produced axonopathy, with a secondary disruption in myelin structure within 2 weeks of drug administration. In addition, all of the drugs reduced sensory NCV and amplitude, with greater deficits after paclitaxel and lesser deficits after ixabepilone. These effects correlated with degeneration in dorsal root ganglia (DRG) and sciatic nerve and abundance of Schwann cells. Although most injuries were fully reversible after 3–6 months after administration of eribulin, vinorelbine, and ixabepilone, we observed delayed recovery after paclitaxel that produced a more severe, pervasive, and prolonged neurotoxicity. Compared with other agents, paclitaxel also displayed a unique prolonged exposure in sciatic nerve and DRG. The most sensitive indicator of toxicity was axonopathy and secondary myelin changes accompanied by a reduction in intraepidermal nerve fiber density. Taken together, our findings suggest that intraepidermal nerve fiber density and changes in NCV and amplitude might provide measures of axonal injury to guide clinical practice.
Significance: This detailed preclinical study of the long-term effects of widely used antitubulin cancer drugs on the peripheral nervous system may help guide clinical evaluations to improve personalized care in limiting neurotoxicity in cancer survivors. Cancer Res; 78(3); 817–29. ©2017 AACR.
Mutations in Homologous Recombination Genes and Outcomes in Ovarian Carcinoma Patients in GOG 218: An NRG Oncology/Gynecologic Oncology Group Study
Authors: Norquist Barbara M. , Brady Mark F. , Harrell Maria I. , Walsh Tom , Lee Ming K. , Gulsuner Suleyman , Bernards Sarah S. , Casadei Silvia , Burger Robert A. , Tewari Krishnansu S. , Backes Floor , Mannel Robert S. , Glaser Gretchen , Bailey Cheryl , Rubin Stephen , Soper John , Lankes Heather A. , Ramirez Nilsa C. , King Mary Claire , Birrer Michael J. , Swisher Elizabeth M. 
Published: November 2017

Abstract
Purpose: We hypothesized that mutations in homologous recombination repair (HRR) genes beyond BRCA1 and BRCA2 improve outcomes for ovarian carcinoma patients treated with platinum therapy and would impact the relative benefit of adding prolonged bevacizumab.
Experimental Design: We sequenced DNA from blood and/or neoplasm from 1,195 women enrolled in GOG-0218, a randomized phase III trial in advanced ovarian carcinoma of bevacizumab added to carboplatin and paclitaxel. Defects in HRR were defined as damaging mutations in 16 genes. Proportional hazards models were used to estimate relative hazards for progression-free survival (PFS) and overall survival (OS).
Results: Of 1,195 women with ovarian carcinoma, HRR mutations were identified in 307 (25.7%). Adjusted hazards for progression and death compared with those without mutations were lower for women with non-BRCA HRR mutations [HR = 0.73; 95% confidence interval (CI), 0.57–0.94; P = 0.01 for PFS; HR = 0.67; 95% CI, 0.50–0.90; P = 0.007 for OS] and BRCA1 mutations (HR = 0.80; 95% CI, 0.66–0.97; P = 0.02 for PFS; HR = 0.74; 95% CI, 0.59–0.94; P = 0.01 for OS) and were lowest for BRCA2 mutations (HR = 0.52; 95% CI, 0.40–0.67; P &lt; 0.0001 for PFS; HR = 0.36; 95% CI, 0.25–0.53; P &lt; 0.0001 for OS). A test of interaction showed no difference in the effect of bevacizumab on PFS between cases with and without mutations.
Conclusions: HRR mutations, including non-BRCA genes, significantly prolong PFS and OS in ovarian carcinoma and should be stratified for in clinical trials. The benefit of adding bevacizumab was not significantly modified by mutation status. Clin Cancer Res; 24(4); 777–83. ©2017 AACR.
Whole-Exome Sequencing of Cell-Free DNA Reveals Temporo-spatial Heterogeneity and Identifies Treatment-Resistant Clones in Neuroblastoma
Authors: Chicard Mathieu , Colmet-Daage Leo , Clement Nathalie , Danzon Adrien , Bohec Mylène , Bernard Virginie , Baulande Sylvain , Bellini Angela , Deveau Paul , Pierron Gaëlle , Lapouble Eve , Janoueix-Lerosey Isabelle , Peuchmaur Michel , Corradini Nadège , Defachelles Anne Sophie , Valteau-Couanet Dominique , Michon Jean , Combaret Valérie , Delattre Olivier , Schleiermacher Gudrun 
Published: November 2017

AbstractPurpose: Neuroblastoma displays important clinical and genetic heterogeneity, with emergence of new mutations at tumor progression.Experimental Design: To study clonal evolution during treatment and follow-up, an innovative method based on circulating cell-free DNA (cfDNA) analysis by whole-exome sequencing (WES) paired with target sequencing was realized in sequential liquid biopsy samples of 19 neuroblastoma patients.Results: WES of the primary tumor and cfDNA at diagnosis showed overlap of single-nucleotide variants (SNV) and copy number alterations, with 41% and 93% of all detected alterations common to the primary neuroblastoma and cfDNA. CfDNA WES at a second time point indicated a mean of 22 new SNVs for patients with progressive disease. Relapse-specific alterations included genes of the MAPK pathway and targeted the protein kinase A signaling pathway. Deep coverage target sequencing of intermediate time points during treatment and follow-up identified distinct subclones. For 17 seemingly relapse-specific SNVs detected by cfDNA WES at relapse but not tumor or cfDNA WES at diagnosis, deep coverage target sequencing detected these alterations in minor subclones, with relapse-emerging SNVs targeting genes of neuritogenesis and cell cycle. Furthermore a persisting, resistant clone with concomitant disappearance of other clones was identified by a mutation in the ubiquitin protein ligase HERC2.Conclusions: Modelization of mutated allele fractions in cfDNA indicated distinct patterns of clonal evolution, with either a minor, treatment-resistant clone expanding to a major clone at relapse, or minor clones collaborating toward tumor progression. Identification of treatment-resistant clones will enable development of more efficient treatment strategies. Clin Cancer Res; 24(4); 939–49. ©2017 AACR.
Surviving Ovarian Cancer: An Affair between Defective DNA Repair and RB1
Authors: Peng Guang , Mills Gordon B. 
Published: November 2017

Abstract
Detailed clinical and molecular evaluation of large cohorts of exceptional survivors provides an unprecedented opportunity to identify mechanisms underlying long-term survival that can drive future therapeutic approaches and biomarker development. Exceptional survivors of high-grade serous ovarian cancer demonstrate concurrent disruption of homologous recombination DNA repair and retinoblastoma protein. Clin Cancer Res; 24(3); 508–10. ©2017 AACR.
See related article by Garsed et al., p. 569
Gender-Related Differences and Short-Term Outcome of Stroke: Results from a Hospital-Based Registry in Sub-Saharan Africa
Authors: Mapoure Yacouba Njankouo , Eyambe Ngowo Lydia , Dzudie Anastase Tamdja , Ayeah Chia Mark , Ba Hamadou , Hentchoya Romuald , Luma Henry Namme 
Published: November 2017

<b><i>Background:</i></b> Studies suggest that sex differences have an impact on patients with stroke, but existing data in Africa remain inconclusive about this inference. <b><i>Objectives:</i></b> To study sex differences in terms of the clinical profile and short-term outcome of stroke in the Douala General Hospital, Cameroon. <b><i>Methods:</i></b> A hospital-based prospective cohort study was carried out in a tertiary care hospital over an 8-year period, which included all patients admitted for confirmed acute stroke. Information about the history of stroke with emphasis on clinical profile and outcome was collected. Descriptive statistics, <i>t</i> test, and chi square test were used for comparisons, while the Kaplan-Meier curve was used for survival rate analysis. <b><i>Results:</i></b> Of the 818 patients included, 455 (55.6%) were male patients. When compared to males, female patients are more likely to experience a stroke at an older age (mean age 62.3 ± 14.1 vs. 58.4 ± 12.9 years, <i>p</i> &#x3c; 0.001), to be unmarried, to remain unemployed, and to have higher rates of cardio-embolic stroke (<i>p</i> = 0.049), body mass index (<i>p</i> = 0.031), altered levels of consciousness at presentation (<i>p</i> = 0.005), higher mean HDL cholesterol levels (<i>p</i> = 0.001), and in-hospital complications (<i>p</i> = 0.011), especially urinary tract infections (<i>p</i> = 0.018). Males were more likely to have health insurance, to smoke, to consume alcohol (<i>p</i> &#x3c; 0.001), and to have higher rates of dysarthria (<i>p</i> = 0.004), higher mean uric acid (<i>p</i> = 0.013), and creatinine (<i>p</i> &#x3c; 0.001) concentrations. Ischemic and hemorrhagic strokes were more prevalent in men (<i>p</i> = 0.003). There are no sex differences in terms of stroke severity, length-of-hospital stay, case fatality, and functional outcome on admission. <b><i>Conclusions:</i></b> Sex differences exist in the clinical profile of stroke but not in the outcome. Knowledge of these differences could help influence stroke prevention, thereby improving stroke burden in Africa.
Critérios de delimitação de áreas de influência em Estudos de Impacto Ambiental de rodovias: abordagem de processos de dinâmica superficial
Authors: Menin Fernanda Asseff , Reis Fábio Augusto Gomes Vieira , Giordano Lucilia do Carmo , Amaral Ana Maria Carrascosa do , Gabelini Beatriz Marques , Cerri Rodrigo Irineu 
Published: November 2017

O objetivo deste artigo foi avaliar os critérios de delimitação de áreas de estudo e de influência em Estudos de Impacto Ambiental (EIAs) de rodovias, com foco em componentes do meio físico associados aos processos de dinâmica superficial. Foram analisados os quatro processos de licenciamento ambiental da Rodovia dos Tamoios, localizada no litoral norte do estado de São Paulo. Os resultados demonstraram que o desmembramento e o licenciamento de um mesmo empreendimento em diferentes EIAs e Relatórios de Impacto Ambiental (Rima) em processos distintos em períodos de tempo curtos dificultam a avaliação integrada da viabilidade ambiental do empreendimento, inclusive a própria delimitação das áreas de estudo e de influência. Pode-se concluir, ainda, que não houve discussão sobre os critérios usados para estabelecer essas áreas nos EIAs analisados, inclusive nos próprios Termos de Referência, impossibilitando compreender como se chegou aos limites propostos, especialmente quando se trata de faixas fixas ao longo do traçado do empreendimento; verificou-se que essas porções não foram definidas de acordo com os diferentes componentes dos meios físico, biótico e socioeconômico. Como proposta, recomenda-se que os processos de dinâmica superficial sejam usados como os critérios básicos para delimitação das áreas de influência, principalmente da Área Diretamente Afetada (ADA), para os componentes de Geomorfologia, Geologia, Pedologia e Geotecnia. E que em estudos de empreendimentos lineares em ambientes os diferentes relevos e as bacias hidrográficas sejam as unidades de gerenciamento territorial usadas para desenvolvimento dos estudos, pelo menos no que se refere à Área de Influência Indireta (AII) e à Área de Influência Direta (AID). Outro ponto importante é que a discussão sobre os limites das áreas de estudo e de influência dos empreendimentos se inicie durante a elaboração dos estudos e dos projetos anteriores ao licenciamento ambiental.