bluuebunny/crossref_metadata_2025_split huggingface dataset:
p21 Ablation in Liver Enhances DNA Damage, Cholestasis, and Carcinogenesis
Authors: Ehedego Haksier , Boekschoten Mark V. , Hu Wei , Doler Carina , Haybaeck Johannes , Gaβler Nikolaus , Müller Michael , Liedtke Christian , Trautwein Christian 
Published: January 2015

Abstract
Genetic mouse studies suggest that the NF-κB pathway regulator NEMO (also known as IKKγ) controls chronic inflammation and carcinogenesis in the liver. However, the molecular mechanisms explaining the function of NEMO are not well defined. Here, we report that overexpression of the cell-cycle regulator p21 is a critical feature of liver inflammation and carcinogenesis caused by the loss of NEMO. NEMOΔhepa mice develop chronic hepatitis characterized by increased hepatocyte apoptosis and proliferation that causes the development of fibrosis and hepatocellular carcinoma (HCC), similar to the situation in human liver disease. Having identified p21 overexpression in this model, we evaluated its role in disease progression and LPS-mediated liver injury in double mutant NEMOΔhepa/p21−/− mice. Eight-week-old NEMOΔhepa/p21−/− animals displayed accelerated liver damage that was not associated with alterations in cell-cycle progression or the inflammatory response. However, livers from NEMOΔhepa/p21−/− mice displayed more severe DNA damage that was further characterized by LPS administration correlating with higher lethality of the animals. This phenotype was attenuated by genetic ablation of the TNF receptor TNF-R1 in NEMOΔhepa/p21−/− mice, demonstrating that DNA damage is induced via TNF. One-year-old NEMOΔhepa/p21−/− mice displayed greater numbers of HCC and severe cholestasis compared with NEMOΔhepa animals. Therefore, p21 overexpression in NEMOΔhepa animals protects against DNA damage, acceleration of hepatocarcinogenesis, and cholestasis. Taken together, our findings illustrate how loss of NEMO promotes chronic liver inflammation and carcinogenesis, and they identify a novel protective role for p21 against the generation of DNA damage. Cancer Res; 75(6); 1144–55. ©2015 AACR.
Integrating RAS Status into Prognostic Signatures for Adenocarcinomas of the Lung
Authors: Starmans Maud HW. , Pintilie Melania , Chan-Seng-Yue Michelle , Moon Nathalie C. , Haider Syed , Nguyen Francis , Lau Suzanne K. , Liu Ni , Kasprzyk Arek , Wouters Bradly G. , Der Sandy D. , Shepherd Frances A. , Jurisica Igor , Penn Linda Z. , Tsao Ming-Sound , Lambin Philippe , Boutros Paul C. 
Published: January 2015

AbstractPurpose: While the dysregulation of specific pathways in cancer influences both treatment response and outcome, few current prognostic markers explicitly consider differential pathway activation. Here we explore this concept, focusing on K-Ras mutations in lung adenocarcinoma (present in 25%–35% of patients).Experimental Design: The effect of K-Ras mutation status on prognostic accuracy of existing signatures was evaluated in 404 patients. Genes associated with K-Ras mutation status were identified and used to create a RAS pathway activation classifier to provide a more accurate measure of RAS pathway status. Next, 8 million random signatures were evaluated to assess differences in prognosing patients with or without RAS activation. Finally, a prognostic signature was created to target patients with RAS pathway activation.Results: We first show that K-Ras status influences the accuracy of existing prognostic signatures, which are effective in K-Ras-wild-type patients but fail in patients with K-Ras mutations. Next, we show that it is fundamentally more difficult to predict the outcome of patients with RAS activation (RASmt) than that of those without (RASwt). More importantly, we demonstrate that different signatures are prognostic in RASwt and RASmt. Finally, to exploit this discovery, we create separate prognostic signatures for RASwt and RASmt patients and show that combining them significantly improves predictions of patient outcome.Conclusions: We present a nested model for integrated genomic and transcriptomic data. This model is general and is not limited to lung adenocarcinomas but can be expanded to other tumor types and oncogenes. Clin Cancer Res; 21(6); 1477–86. ©2015 AACR.
Mechanism and functional impact of CD40 ligand-induced von Willebrand factor release from endothelial cells
Authors: Möller Kerstin , Adolph Oliver , Grünow Jennifer , Elrod Julia , Popa Miruna , Ghosh Subhajit , Schwarz Manuel , Schwale Chrysovalandis , Grässle Sandra , Huck Volker , Bruehl Claus , Wieland Thomas , Schneider Stefan W. , Nobiling Rainer , Wagner Andreas H. , Hecker Markus 
Published: January 2015

SummaryCo-stimulation via CD154 binding to CD40, pivotal for both innate and adaptive immunity, may also link haemostasis to vascular remodelling. Here we demonstrate that human platelet-bound or recombinant soluble CD154 (sCD154) elicit the release from and tethering of ultra-large (UL) von Willebrand factor (vWF) multimers to the surface of human cultured endothelial cells (ECs) exposed to shear stress. This CD40-mediated ULVWF multimer release from the Weibel-Palade bodies was triggered by consecutive activation of TRAF6, the tyrosine kinase c-Src and phospholipase Cγ1 followed by inositol-1,4,5 tris-phosphate-mediated calcium mobilisation. Subsequent exposure to human washed platelets caused ULVWF multimer-platelet string formation on the EC surface in a shear stress-dependent manner. Platelets tethered to these ULVWF multimers exhibited P-selectin on their surface and captured labelled monocytes from the superfusate. When exposed to shear stress and sCD154, native ECs from wild-type but not CD40 or vWF-deficient mice revealed a comparable release of ULVWF multimers to which murine washed platelets rapidly adhered, turning P-selectin-positive and subsequently capturing monocytes from the perfusate. This novel CD154-provoked ULVWF multimerplatelet string formation at normal to fast flow may contribute to vascular remodelling processes requiring the perivascular or intravascular accumulation of pro-inflammatory macrophages such as arteriogenesis or atherosclerosis.
Peroxisomes in cardiomyocytes and the peroxisome / peroxisome proliferator-activated receptor-loop
Authors: Colasante Claudia , Chen Jiangping , Ahlemeyer Barbara , Baumgart-Vogt Eveline 
Published: January 2015

SummaryIt is well established that the heart is strongly dependent on fatty acid metabolism. In cardiomyocytes there are two distinct sites for the β-oxidisation of fatty acids: the mitochondrion and the peroxisome. Although the metabolism of these two organelles is believed to be tightly coupled, the nature of this relationship has not been fully investigated. Recent research has established the significant contribution of mitochondrial function to cardiac ATP production under normal and pathological conditions. In contrast, limited information is available on peroxisomal function in the heart. This is despite these organelles harbouring metabolic pathways that are potentially cardioprotective, and findings that patients with peroxisomal diseases, such as adult Refsum’s disease, can develop heart failure. In this article, we provide a comprehensive overview on the current knowledge of peroxisomes and the regulation of lipid metabolism by PPARs in cardiomyocytes. We also present new experimental evidence on the differential expression of peroxisome-related genes in the heart chambers and demonstrate that even a mild peroxisomal biogenesis defect (Pex11α-/- ) can induce profound alterations in the cardiomyocyte’s peroxisomal compartment and related gene expression, including the concomitant deregulation of specific PPARs. The possible impact of peroxisomal dysfunction in the heart is discussed and a model for the modulation of myocardial metabolism via a peroxisome/PPAR-loop is proposed.
Predictors of thromboprophylaxis in hospitalised medical patients
Authors: Spirk David , Nendaz Mathieu , Aujesky Drahomir , Hayoz Daniel , Beer Jürg H. , Husmann Marc , Frauchiger Beat , Korte Wolfgang , Wuillemin Walter A. , Righini Marc , Bounameaux Henri , Kucher Nils 
Published: January 2015

summaryBoth, underuse and overuse of thromboprophylaxis in hospitalised medical patients is common. We aimed to explore clinical factors associated with the use of pharmacological or mechanical thromboprophylaxis in acutely ill medical patients at high (Geneva Risk Score ≥ 3 points) vs low (Geneva Risk Score < 3 points) risk of venous thromboembolism. Overall, 1,478 hospitalised medical patients from eight large Swiss hospitals were enrolled in the prospective Explicit ASsessment of Thromboembolic RIsk and Prophylaxis for Medical PATients in SwitzErland (ESTIMATE) cohort study. The study is registered on ClinicalTrials. gov, number NCT01277536. Thromboprophylaxis increased stepwise with increasing Geneva Risk Score (p< 0.001). Among the 962 high-risk patients, 366 (38 %) received no thromboprophylaxis; cancer-associated thrombocytopenia (OR 4.78, 95 % CI 2.75–8.31, p< 0.001), active bleeding on admission (OR 2.88, 95 % CI 1.69–4.92, p< 0.001), and thrombocytopenia without cancer (OR 2.54, 95 % CI 1.31–4.95, p=0.006) were independently associated with the absence of prophylaxis. The use of thromboprophylaxis declined with increasing severity of thrombocytopenia (p=0.001). Among the 516 low-risk patients, 245 (48 %) received thromboprophylaxis; none of the investigated clinical factors predicted its use. In conclusion, in acutely ill medical patients, bleeding and thrombocytopenia were the most important factors for the absence of thromboprophylaxis among highrisk patients. The use of thromboprophylaxis among low-risk patients was inconsistent, without clearly identifiable predictors, and should be addressed in further research.
Field Measurements of Surface and Near-Surface Turbulence in the Presence of Breaking Waves
Authors: Sutherland Peter , Melville W. Kendall 
Published: January 2015

AbstractWave breaking removes energy from the surface wave field and injects it into the upper ocean, where it is dissipated by viscosity. This paper presents an investigation of turbulent kinetic energy (TKE) dissipation beneath breaking waves. Wind, wave, and turbulence data were collected in the North Pacific Ocean aboard R/P FLIP, during the ONR-sponsored High Resolution Air-Sea Interaction (HiRes) and Radiance in a Dynamic Ocean (RaDyO) experiments. A new method for measuring TKE dissipation at the sea surface was combined with subsurface measurements to allow estimation of TKE dissipation over the entire wave-affected surface layer. Near the surface, dissipation decayed with depth as z−1, and below approximately one significant wave height, it decayed more quickly, approaching z−2. High levels of TKE dissipation very near the sea surface were consistent with the large fraction of wave energy dissipation attributed to non-air-entraining microbreakers. Comparison of measured profiles with large-eddy simulation results in the literature suggests that dissipation is concentrated closer to the surface than previously expected, largely because the simulations did not resolve microbreaking. Total integrated dissipation in the water column agreed well with dissipation by breaking for young waves, (where cm is the mean wave frequency and is the atmospheric friction velocity), implying that breaking was the dominant source of turbulence in those conditions. The results of these extensive measurements of near-surface dissipation over three field experiments are discussed in the context of observations and ocean boundary layer modeling efforts by other groups.
Correcting for Position Errors in Variational Data Assimilation
Authors: Nehrkorn Thomas , Woods Bryan K. , Hoffman Ross N. , Auligné Thomas 
Published: January 2015

Abstract
The Feature Calibration and Alignment technique (FCA) has been developed to characterize errors that a human would ascribe to a change in the position or intensity of a coherent feature, such as a hurricane. Here the feature alignment part of FCA is implemented in the Weather Research and Forecasting Data Assimilation system (WRFDA) to correct position errors in background fields and tested in simulation for the case of Hurricane Katrina (2005). The displacement vectors determined by feature alignment can be used to explain part of the background error and make the residual background errors smaller and more Gaussian. Here a set of 2D displacement vectors to improve the alignment of features in the forecast and observations is determined by solving the usual variational data assimilation problem—simultaneously minimizing the misfit to observations and a constraint on the displacements. This latter constraint is currently implemented by hijacking the usual background term for the midlevel u- and υ-wind components. The full model fields are then aligned using a procedure that minimizes dynamical imbalances by displacing only conserved or quasi-conserved quantities. Simulation experiments show the effectiveness of these procedures in correcting gross position errors and improving short-term forecasts. Compared to earlier experiments, even this initial implementation of feature alignment produces improved short-term forecasts. Adding the calculation of displacements to WRFDA advances the key contribution of FCA toward mainstream implementation since all observations with a corresponding observation operator may be used and the existing methodology for estimating the background error covariances may be used to refine the displacement error covariances.
A novel mouse model of creatine transporter deficiency
Authors: Baroncelli Laura , Alessandrì Maria Grazia , Tola Jonida , Putignano Elena , Migliore Martina , Amendola Elena , Zonfrillo Francesca , Gross Cornelius , Leuzzi Vincenzo , Cioni Giovanni , Pizzorusso Tommaso 
Published: January 2015

Mutations in the creatine (Cr) transporter (CrT) gene lead to cerebral creatine deficiency syndrome-1 (CCDS1), an X-linked metabolic disorder characterized by cerebral Cr deficiency causing intellectual disability, seizures, movement and behavioral disturbances, language and speech impairment ( OMIM #300352).CCDS1 is still an untreatable pathology that can be very invalidating for patients and caregivers. Only two murine models of CCDS1, one of which is an ubiquitous knockout mouse, are currently available to study the possible mechanisms underlying the pathologic phenotype of CCDS1 and to develop therapeutic strategies. Given the importance of validating phenotypes and efficacy of promising treatments in more than one mouse model we have generated a new murine model of CCDS1 obtained by ubiquitous deletion of 5-7 exons in theSlc6a8gene. We showed a remarkable Cr depletion in the murine brain tissues and cognitive defects, thus resembling the key features of human CCDS1. These results confirm that CCDS1 can be well modeled in mice. This CrT−/ymurine model will provide a new tool for increasing the relevance of preclinical studies to the human disease.
Income Inequality and Health: Panel Data Evidence from Canada
Authors: Latif Ehsan 
Published: January 2015

Abstract
Using longitudinal data from the Canadian National Population Survey (1994–2006), this study examines the impact of income inequality on current health outcomes. The result suggests that once unobserved individual specific heterogeneity is controlled for, income inequality as measured by Gini Coefficient has no significant impact on current health status. This result holds true for contemporaneous income inequality as well as for lagged income inequalities. There are mixed results from the robustness check using various measures of income inequality. Decile Ratio (90P/10P) and Coefficient of Variation have no impacts on current health status. On the other hand, contemporaneous income inequality measured by Log Mean Deviation and Theil Index have significant negative effects on current health. All of the models suggest that absolute income has a significant positive effect on health status
Static Rheological Study of Ocimum basilicum Seed Gum
Authors: Salehi Fakhreddin , Kashaninejad Mahdi 
Published: January 2015

Abstract
A rotational viscometer was used to investigate the effect of different sugars (sucrose, glucose, fructose and lactose, 1–4% w/w) and salts (NaCl and CaCl2, 0.1–1% w/w), on rheological properties of Basil seed gum (BSG). The viscosity was dependent on type of sugar and salt addition. Interactions between BSG gum and sugars improved the viscosity of solutions, whereas the viscosity of the BSG solutions decreased in the presence of salts. Power law model well-described non-Newtonian shear thinning behavior of BSG. The consistency index was influenced by the sugars and salts content. Addition of sucrose, glucose, lactose and salts to BSG led to increases in flow behavior index (less shear thinning solutions), whereas fructose increased shear thinning of solutions. Flow behavior index values of the power law model vary as follows: 0.43–0.49, 0.53–0.64, 0.21–0.26, and 0.57–0.67 for sucrose, glucose, fructose and lactose, respectively. The consistency coefficient (k) of BSG was affected by sugars and salts. It decreased from 0.14 to 0.09 Pa.sn with increasing CaCl2 from 0 to 4% w/w (20°C, 0.2% w/w BSG). The consistency coefficient values vary as follows: 0.094–0.119, 0.075–0.098, 0.257–0.484, and 0.056–0.074 for sucrose, glucose, fructose and lactose, respectively.
Sorption processes of radiocesium in soil and bedrock
Authors: Lehto Jukka 
Published: January 2015

Abstract
Three recent studies on cesium sorption in soil and bedrock are reviewed. 137Cs, originating from fallouts of nuclear
weapons tests and the Chernobyl accident was found to decrease in an exponential manner in forest soil, and the highest fraction in
soil profiles was found in the organic layer. Also, the mineral layer below the organic layer contained a large fraction of cesium
inventory but at depths below 20 cm only a very small fraction was observed. In the bedrock of Olkiluoto, where the final
repository for spent nuclear fuel from the Finnish nuclear power plants will be constructed, mica mineral biotite plays the most
important role in cesium sorption. The selectivity of biotite decreases in the order Cs > K > Na > Ca and the overall selectivity
coefficient for Cs/Ca exchange was approximately five and seven orders of magnitude higher than those for Cs/Na and Cs/K exchange
reactions, respectively. Ion exchange isotherms for Cs/Na and Cs/K exchange were modelled by assuming three different ion exchange
sites: frayed edge sites (FES), basal plane sites and intermediate sites. The selectivity coefficients derived for these sites were
successfully used to predict cesium sorption in a mica gneiss rock. Sorption of cesium in mineral soil layers from the Olkiluoto
overburden were studied using three different approaches: model batch experiments, an in-situ method and calculations. All three
approaches gave the same trend but the distribution coefficient values varied in range of one order of magnitude.
Knochentumoren bei Echsen und Schlangen
Authors: Heckers K. O. , Pees M. , Aupperle H. , Dietz J. 
Published: January 2015

ZusammenfassungGegenstand und Ziel: Beschreibung der pathologischen Befunde von 13 Tumoren des Knochen-und Knorpelgewebes bei Echsen (n = 8) und Schlangen (n = 5) im klinischen Kontext. Material und Methoden: In einem 12-jährigen Zeitraum (2001–2013) ergab die histopathologische Untersuchung von 358 zur Routinediagnostik eingesandten Tumoren von Reptilien in 13 Fällen (acht Exzisate, zwei Amputate, zwei Bioptate und vier Tierkörper) die Diagnose eines Knochentumors. Makroskopisch wiesen die Tumorproben im Anschnitt einen hellen Farbton und eine feste bis harte Konsistenz auf. Zur histologischen Beurteilung wurden repräsentative Lokalisationen gegebenenfalls entkalkt, in Paraffin eingebettet und mit Hämatoxylin und Eosin angefärbt. Die Diagnosestellung erfolgte anhand der WHO-Klassifikationen der Veterinär-und Humanmedizin. Ergebnisse: Bei verschiedenen Echsenarten fanden sich benige Knochenzubildungen (ossifizierendes Fibrom [n = 2], fibröse Dysplasie [n = 1]) sowie maligne Knorpel(Chondrosarkom [n = 2]) und Knochenneoplasien (fibroblastisches Osteosarkom [n = 2], kleinzelliges Osteosarkom [n = 1]) im Kopf-(n = 5) und Gliedmaßenskelett (n = 3). Schlangen wiesen ausschließlich maligne Knorpelneoplasien (Chondrosarkom [n = 2], dedifferenziertes Chondrosarkom [n = 3]) der Wirbelsäule auf. Das histologische Erscheinungsbild der malignen Neoplasien reichte von niedrigbis zu hochmalignen differenzierten Tumorzellverbänden, die in unterschiedlicher Menge Osteoid oder eine hyaline Matrix produzierten. Eine Heilung ließ sich bei einem ossifizierenden Fibrom durch vollständige chirurgische Exzision und bei zwei Chondrosarkomen durch eine Amputation erreichen. Bei vier postmortal untersuchten Tierkörpern mit malignen Tumoren waren keine Metastasen nachweisbar. Schlussfolgerung und klinische Relevanz: Primäre Neoplasien des Knochens sind seltene Tumoren bei Reptilien. Unter Berücksichtigung der Informationen zum therapeutischen Vorgehen und weiteren Verlauf erweist sich bei Echsen die vollständige chirurgische Entfernung der Neoplasie durch Exzision oder Amputation als Therapie der Wahl. Entsprechend kann bei Schlangen eine tumorreduktive Gewebeentnahme die Überlebenszeit möglicherweise deutlich verlängern.
Los cuatro aspectos esenciales por investigar
Authors: París José Antonio 
Published: January 2015

El marketing tradicional angloamericano ofrece una metodología de investigación de mercados simple, aunque no esencial. El costo de asumir esta metodología ha dejado un lamentable saldo de 85 % de probabilidad de fracasos de los planes de marketing lanzados en los mercados de la actualidad. Es de esperarse que esta situación sea inadmisible para las empresas de los mercados latinoamericanos, ya que por su estrecha magnitud de sus mercados y la poca inserción internacional están obligadas a mejorar notablemente su performance investigativa e ir a las cuestiones de fondo, para sentar los cimientos sobre los que se debe apoyar su plan de marketing. En este artículo, se presentan los nueve niveles de investigación y se promueven técnicas de investigación alternativas que están cambiando los resultados de los planes de marketing que hemos denominado esencial.
Lorenza Panero
Authors: Cobo Borda Juan Gustavo 
Published: January 2015

En esta edición de Poliantea, Juan Gustavo Cobo Borda presenta una aproximación a la obra de Lorenza Panero. El escritor encuentra en las coloridas luminografías de la artista un discurso simbólico sobre el lenguaje de la naturaleza y la percepción.
Resultados de la revisión ambiental inicial em la Institución Universitaria Politécnico Grancolombiano.
Authors: Avendaño Espitia Hernando , Camacho Delgado Clemencia , Castro Pedro Pablo 
Published: January 2015

Diagnóstico Ambiental en la Institución Universitaria Politécnico Grancolombiano siguiendo las Normas ISO 14001 , hace parte, junto con la Evaluación de la Flora y Suelos del Politécnico Grancolombia- no y el Diseño de un Plan de Mejoramiento Ambiental , de una pri- mera etapa de análisis de la situación ambiental de la institución desde las perspectivas de los impactos generados por ella y del cumplimiento de la legislación ambiental vigente. Como fruto de estos trabajos, siguiendo la misma línea, se desarro- lla actualmente el proyecto Análisis Estructural y Diseño de un Sis- tema de Gestión Ambiental , orientado por los normas de ISO 14001. En este estudio se hará una valoración comparativa de los Sistemas de Gestión Ambiental (SGA), en diferentes universidades y empre- sas, para establecer, finalmente, un Plan de Manejo Ambiental Ins- titucional ajustado a la naturaleza de la organización como institu- ción de formación académica.