324 research outputs found

    Body composition and cartilage biomarkers are affected by diet in growing large breed dogs

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    The purpose of this study was to describe cartilage and bone biochemical markers and body composition in growing large breed dogs and to determine if these masurements are affected by diets of similar caloric density but differing composition

    A 0535+26 in the August/September 2005 outburst observed by RXTE and INTEGRAL

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    In this Letter we present results from INTEGRAL and RXTE observations of the spectral and timing behavior of the High Mass X-ray Binary A 0535+26 during its August/September 2005 normal (type I) outburst with an average flux F(5-100keV)~400mCrab. The search for cyclotron resonance scattering features (fundamental and harmonic) is one major focus of the paper. Our analysis is based on data from INTEGRAL and RXTE Target of Opportunity Observations performed during the outburst. The pulse period is determined. X-ray pulse profiles in different energy ranges are analyzed. The broad band INTEGRAL and RXTE pulse phase averaged X-ray spectra are studied. The evolution of the fundamental cyclotron line at different luminosities is analyzed. The pulse period P is measured to be 103.39315(5)s at MJD 53614.5137. Two absorption features are detected in the phase averaged spectra at E_1~45keV and E_2~100keV. These can be interpreted as the fundamental cyclotron resonance scattering feature and its first harmonic and therefore the magnetic field can be estimated to be B~4x10^12G.Comment: 4 pages, 5 figures, accepted for publication in A&A Letter

    Calmodulin Interaction with hEAG1 Visualized by FRET Microscopy

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    BACKGROUND: Ca(2+)-mediated regulation of ion channels provides a link between intracellular signaling pathways and membrane electrical activity. Intracellular Ca(2+) inhibits the voltage-gated potassium channel EAG1 through the direct binding of calmodulin (CaM). Three CaM binding sites (BD-C1: 674-683, BD-C2: 711-721, BD-N: 151-165) have been identified in a peptide screen and were proposed to mediate binding. The participation of the three sites in CaM binding to the native channel, however, remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: Here we studied the binding of Ca(2+)/CaM to the EAG channel by visualizing the interaction between YFP-labeled CaM and Cerulean-labeled hEAG1 in mammalian cells by FRET. The results of our cellular approach substantiate that two CaM binding sites are predominantly involved; the high-affinity 1-8-14 based CaM binding domain in the N-terminus and the second C-terminal binding domain BD-C2. Mutations at these sites completely abolished CaM binding to hEAG1. CONCLUSIONS/SIGNIFICANCE: We demonstrated that the BD-N and BD-C2 binding domains are sufficient for CaM binding to the native channel, and, therefore, that BD-C1 is unable to bind CaM independently

    Transcriptomic analysis of cutaneous squamous cell carcinoma reveals a multi-gene prognostic signature associated with metastasis.

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    BackgroundMetastasis of cutaneous squamous cell carcinoma (cSCC) is uncommon. Current staging methods are reported to have sub-optimal performances in metastasis prediction. Accurate identification of patients with tumours at high risk of metastasis would have a significant impact on management.ObjectiveTo develop a robust and validated gene expression profile (GEP) signature for predicting primary cSCC metastatic risk using an unbiased whole transcriptome discovery-driven approach.MethodsArchival formalin-fixed paraffin-embedded primary cSCC with perilesional normal tissue from 237 immunocompetent patients (151 non-metastasising and 86 metastasising) were collected retrospectively from four centres. TempO-seq was used to probe the whole transcriptome and machine learning algorithms were applied to derive predictive signatures, with a 3:1 split for training and testing datasets.ResultsA 20-gene prognostic model was developed and validated, with an accuracy of 86.0%, sensitivity of 85.7%, specificity of 86.1%, and positive predictive value of 78.3% in the testing set, providing more stable, accurate prediction than pathological staging systems. A linear predictor was also developed, significantly correlating with metastatic risk.LimitationsThis was a retrospective 4-centre study and larger prospective multicentre studies are now required.ConclusionThe 20-gene signature prediction is accurate, with the potential to be incorporated into clinical workflows for cSCC

    Resonant Spin Excitation in an Overdoped High Temperature Superconductor

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    An inelastic neutron scattering study of overdoped Bi_2Sr_2CaCu_2O_{8+\delta} $ (T_c = 83 K) has revealed a resonant spin excitation in the superconducting state. The mode energy is E_res=38 meV, significantly lower than in optimally doped Bi_2Sr_2CaCu_2O_{8+\delta} (T_c = 91 K, E_ res =43 meV). This observation, which indicates a constant ratio E_res /k_B T_c \sim 5.4, helps resolve a long-standing controversy about the origin of the resonant spin excitation in high-temperature superconductors.Comment: final version: PRL 86, 1610 (2001

    Transcriptomic analysis of cutaneous squamous cell carcinoma reveals a multi-gene prognostic signature associated with metastasis.

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    BACKGROUND: Metastasis of cutaneous squamous cell carcinoma (cSCC) is uncommon. Current staging methods are reported to have sub-optimal performances in metastasis prediction. Accurate identification of patients with tumours at high risk of metastasis would have a significant impact on management. OBJECTIVE: To develop a robust and validated gene expression profile (GEP) signature for predicting primary cSCC metastatic risk using an unbiased whole transcriptome discovery-driven approach. METHODS: Archival formalin-fixed paraffin-embedded primary cSCC with perilesional normal tissue from 237 immunocompetent patients (151 non-metastasising and 86 metastasising) were collected retrospectively from four centres. TempO-seq was used to probe the whole transcriptome and machine learning algorithms were applied to derive predictive signatures, with a 3:1 split for training and testing datasets. RESULTS: A 20-gene prognostic model was developed and validated, with an accuracy of 86.0%, sensitivity of 85.7%, specificity of 86.1%, and positive predictive value of 78.3% in the testing set, providing more stable, accurate prediction than pathological staging systems. A linear predictor was also developed, significantly correlating with metastatic risk. LIMITATIONS: This was a retrospective 4-centre study and larger prospective multicentre studies are now required. CONCLUSION: The 20-gene signature prediction is accurate, with the potential to be incorporated into clinical workflows for cSCC
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