725 research outputs found

    Evaluation of annual resolution coral geochemical records as climate proxies in the Great Barrier Reef of Australia

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    Sampling of annually banded massive coral skeletons at annual (or higher) resolutions is increasingly being used to obtain replicate long-term time series of changing seawater conditions. However, few of these studies have compared and calibrated the lower annual resolution records based on coral geochemical tracers with the corresponding instrumental climate records, although some studies have inferred the climatic significance of annual coral series derived from averages of monthly or sub-annual records. Here, we present annual resolution analysis of coral records of elemental and stable isotopic composition that are approximately 70\ua0years long. These records were preserved in two coexisting colonies of Porites sp. from Arlington Reef, on the Great Barrier Reef in Australia, and are used to evaluate the climatic significance of annually resolved coral geochemical proxies. The geochemical records of coral sample “10AR2,” with its faster and relatively constant annual growth rate, appear to have been independent of skeletal growth rate and other vital effects. The annual resolution of Sr/Ca and ΔδO time series was shown to be a good proxy for annual sea surface temperature (SST; r\ua0=\ua0−0.67, n\ua0=\ua073, p\ua

    Remotely acting SMCHD1 gene regulatory elements: in silico prediction and identification of potential regulatory variants in patients with FSHD

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    Background: Facioscapulohumeral dystrophy (FSHD) is commonly associated with contraction of the D4Z4 macro-satellite repeat on chromosome 4q35 (FSHD1) or mutations in the SMCHD1 gene (FSHD2). Recent studies have shown that the clinical manifestation of FSHD1 can be modified by mutations in the SMCHD1 gene within a given family. The absence of either D4Z4 contraction or SMCHD1 mutations in a small cohort of patients suggests that the disease could also be due to disruption of gene regulation. In this study, we postulated that mutations responsible for exerting a modifier effect on FSHD might reside within remotely acting regulatory elements that have the potential to interact at a distance with their cognate gene promoter via chromatin looping. To explore this postulate, genome-wide Hi-C data were used to identify genomic fragments displaying the strongest interaction with the SMCHD1 gene. These fragments were then narrowed down to shorter regions using ENCODE and FANTOM data on transcription factor binding sites and epigenetic marks characteristic of promoters, enhancers and silencers

    Pseudospin symmetry and its approximation in real nuclei

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    The origin of pseudospin symmetry and its broken in real nuclei are discussed in the relativistic mean field theory. In the exact pseudospin symmetry, even the usual intruder orbits have degenerate partners. In real nuclei, pseudospin symmetry is approximate, and the partners of the usual intruder orbits will disappear. The difference is mainly due to the pseudo spin-orbit potential and the transition between them is discussed in details. The contribution of pseudospin-orbit potential for intruder orbits is quite large, compared with that for pseudospin doublets. The disappearance of the pseudospin partner for the intruder orbit can be understood from the properties of its wave function.Comment: 10 pages, 3 figure

    Personalized Drug Dosage – Closing the Loop

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    A brief account is given of various approaches to the individualization of drug dosage, including the use of pharmacodynamic markers, therapeutic monitoring of plasma drug concentrations, genotyping, computer-guided dosage using ‘dashboards’, and automatic closed-loop control of pharmacological action. The potential for linking the real patient to his or her ‘virtual twin’ through the application of physiologically-based pharmacokinetic modeling is also discussed

    No clear benefit or drawback to the use of closed drainage after primary total knee arthroplasty: a systematic review and meta-analysis

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    BACKGROUND: Closed drainage after primary total knee arthroplasty (TKA) has been used routinely for many decades, but controversies have arisen in recent years. The purposes of this study were to compare the clinical outcomes of closed drainage with nondrainage after primary TKA; and to assess the benefit and drawback of closed drainage. METHODS: Electronic databases (PubMed/Medline, CENTRAL, Embase and Web of Science) were systematically searched for randomised controlled trials (RCTs) that investigated the efficacy and risks of closed drainage after primary TKA. Two investigators independently reviewed studies for eligibility, assessed the risk of bias and extracted the data. A meta-analysis was then performed using Review Manager Software. RESULTS: Twelve RCTs totalling 889 TKAs were identified. No significant differences in infection rate or blood loss were found between the closed drainage and nondrainage TKAs, and there was also no significant difference in haematoma formation, deep venous thrombosis, postoperative VAS score or range of motion between the two groups. CONCLUSIONS: There appears to be no clear benefit or drawback to the use of closed drainage after primary TKA. Improving the use of closed drainage might provide better outcomes

    Timp1 interacts with beta-1 integrin and CD63 along melanoma genesis and confers anoikis resistance by activating PI3-K signaling pathway independently of Akt phosphorylation

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    Background: Anoikis resistance is one of the abilities acquired along tumor progression. This characteristic is associated with metastasis development, since tumorigenic cells must survive independently of cell-matrix interactions in this process. in our laboratory, it was developed a murine melanocyte malignant transformation model associated with a sustained stressful condition. After subjecting melan-a melanocytes to 1, 2, 3 and 4 cycles of anchorage impediment, anoikis resistant cells were established and named 1C, 2C, 3C and 4C, respectively. These cells showed altered morphology and PMA independent cell growth, but were not tumorigenic, corresponding to pre-malignant cells. After limiting dilution of 4C pre-malignant cells, melanoma cell lines with different characteristics were obtained. Previous data from our group showed that increased Timp1 expression correlated with anoikis-resistant phenotype. Timp1 was shown to confer anchorage-independent growth capability to melan-a melanocytes and render melanoma cells more aggressive when injected into mice. However, the mechanisms involved in anoikis regulation by Timp1 in tumorigenic cells are not clear yet.Methods: the beta 1-integrin and Timp1 expression were evaluated by Western blotting and CD63 protein expression by flow cytometry using specific antibodies. To analyze the interaction among Timp1, CD63 and beta 1-integrin, immunoprecipitation assays were performed, anoikis resistance capability was evaluated in the presence or not of the PI3-K inhibitors, Wortmannin and LY294002. Relative expression of TIMP1 and CD63 in human metastatic melanoma cells was analyzed by real time PCR.Results: Differential association among Timp1, CD63 and beta 1-integrins was observed in melan-a melanocytes, 4C pre-malignant melanocytes and 4C11- and 4C11+ melanoma cells. Timp1 present in conditioned medium of melanoma cells rendered melan-a melanocytes anoikis-resistant through PI3-K signaling pathway independently of Akt activation. in human melanoma cell lines, in which TIMP1 and beta-1 integrin were also found to be interacting, TIMP1 and CD63 levels together was shown to correlate significantly with colony formation capacity.Conclusions: Our results show that Timp1 is assembled in a supramolecular complex containing CD63 and beta 1-integrins along melanoma genesis and confers anoikis resistance by activating PI3-K signaling pathway, independently of Akt phosphorylation. in addition, our data point TIMP1, mainly together with CD63, as a potential biomarker of melanoma.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, Dept Pharmacol, São Paulo, BrazilUniversidade Federal de São Paulo, Microbiol Immunol & Parasitol Dept, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biochem, São Paulo, BrazilLudwig Inst Canc Res, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pharmacol, São Paulo, BrazilUniversidade Federal de São Paulo, Microbiol Immunol & Parasitol Dept, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biochem, São Paulo, BrazilFAPESP: 2011/12306-1FAPESP: 2010/18715-8CAPES: 2867/10Web of Scienc

    Search for Anomalous Production of Events with Two Photons and Additional Energetic Objects at CDF

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    submitted to Phys. Rev. DWe present results of a search for anomalous production of two photons together with an electron, muon, τ\tau lepton, missing transverse energy, or jets using ppˉp\bar{p} collision data from 1.1-2.0 fb1^{-1} of integrated luminosity collected by the Collider Detector at Fermilab (CDF). The event yields and kinematic distributions are examined for signs of new physics without favoring a specific model of new physics. The results are consistent with the standard model expectations. The search employs several new analysis techniques that significantly reduce instrumental backgrounds in channels with an electron and missing transverse energy.We present results of a search for anomalous production of two photons together with an electron, muon, τ lepton, missing transverse energy, or jets using pp̅ collision data from 1.1–2.0  fb-1 of integrated luminosity collected by the Collider Detector at Fermilab (CDF). The event yields and kinematic distributions are examined for signs of new physics without favoring a specific model of new physics. The results are consistent with the standard model expectations. The search employs several new analysis techniques that significantly reduce instrumental backgrounds in channels with an electron and missing transverse energy.Peer reviewe

    Wet and cold climate conditions recorded by coral geochemical proxies during the beginning of the first millennium CE in the northern South China Sea

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    The past two millennia include some distinct climate intervals, such as the Medieval Warm Period (MWP) and the Little Ice Age (LIA), which were caused by natural forcing factors, as well as the Current Warm Period (CWP) that has been linked to anthropogenic factors. Therefore, this period has been of great interest to climate change researchers. However, most studies are based on terrestrial proxy records, historical documentary data, and simulation results, and the ocean and the tropical record are very limited. The Eastern Han, Three Kingdoms, and Western Jin periods (25–316 CE) cover the beginning first millennium CE in China, and were characterized by a cold climate and frequent wars and regime changes. This study used paired Sr/Ca and δO series recovered from a fossil coral to reconstruct the sea surface water conditions during the late Eastern Han to Western Jin periods (167–309 CE) at Wenchang, eastern Hainan Island in the northern South China Sea (SCS), to investigate climate change at this time. The long-term sea surface temperature (SST) during the study interval was 25.1 °C, which is about 1.5 °C lower than that of the CWP (26.6 °C). Compared with the average value of 0.40‰ during the CWP, the long-term average seawater δO (−0.06‰) was more negative. These results indicate that the climate conditions during the study period were cold and wet and comparable with those of the LIA. This colder climate may have been associated with the weaker summer solar irradiance. The wet conditions were caused by the reduced northward shift of the intertropical convergence zone/monsoon rainbelt associated with the retreat of the East Asian summer monsoon. Interannual and interdecadal climate variability may also have contributed to the variations in SST and seawater δO recorded over the study period
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