1,763 research outputs found

    Changes in neuronal CycD/Cdk4 activity affect aging, neurodegeneration, and oxidative stress.

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    Mitochondrial dysfunction has been implicated in human diseases, including cancer, and proposed to accelerate aging. The Drosophila Cyclin-dependent protein kinase complex cyclin D/cyclin-dependent kinase 4 (CycD/Cdk4) promotes cellular growth by stimulating mitochondrial biogenesis. Here, we examine the neurodegenerative and aging consequences of altering CycD/Cdk4 function in Drosophila. We show that pan-neuronal loss or gain of CycD/Cdk4 increases mitochondrial superoxide, oxidative stress markers, and neurodegeneration and decreases lifespan. We find that RNAi-mediated depletion of the mitochondrial transcription factor, Tfam, can abrogate CycD/Cdk4's detrimental effects on both lifespan and neurodegeneration. This indicates that CycD/Cdk4's pathological consequences are mediated through altered mitochondrial function and a concomitant increase in reactive oxygen species. In support of this, we demonstrate that CycD/Cdk4 activity levels in the brain affect the expression of a set of 'oxidative stress' genes. Our results indicate that the precise regulation of neuronal CycD/Cdk4 activity is important to limit mitochondrial reactive oxygen species production and prevent neurodegeneration

    Data-driven Spectroscopy of Cool Stars at High Spectral Resolution

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    The advent of large-scale spectroscopic surveys underscores the need to develop robust techniques for determining stellar properties ("labels," i.e., physical parameters and elemental abundances). However, traditional spectroscopic methods that utilize stellar models struggle to reproduce cool (< 4700 K) stellar atmospheres due to an abundance of unconstrained molecular transitions, making modeling via synthetic spectral libraries difficult. Because small, cool stars such as K and M dwarfs are both common and good targets for finding small, cool planets, establishing precise spectral modeling techniques for these stars is of high priority. To address this, we apply The Cannon, a data-driven method of determining stellar labels, to Keck High Resolution Echelle Spectrometer spectra of 141 cool (< 5200 K) stars from the California Planet Search. Our implementation is capable of predicting labels for small (< 1 R_⊙) stars of spectral types K and later with accuracies of 68 K in effective temperature (T_(eff)), 5% in stellar radius (R_*), and 0.08 dex in bulk metallicity ([Fe/H]), and maintains this performance at low spectral resolutions (R < 5000). As M dwarfs are the focus of many future planet-detection surveys, this work can aid efforts to better characterize the cool star population and uncover correlations between cool star abundances and planet occurrence for constraining planet formation theories

    Optimization of human mesenchymal stem cell manufacturing: the effects of animal/xeno-free media.

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    Due to their immunosuppressive properties, mesenchymal stem cells (MSC) have been evaluated for the treatment of immunological diseases. However, the animal-derived growth supplements utilized for MSC manufacturing may lead to clinical complications. Characterization of alternative media formulations is imperative for MSC therapeutic application. Human BMMSC and AdMSC were expanded in media supplemented with either human platelet lysates (HPL), serum-free media/xeno-free FDA-approved culture medium (SFM/XF), or fetal bovine serum (FBS) and the effects on their properties were investigated. The immunophenotype of resting and IFN-Îł primed BMMSC and AdMSC remained unaltered in all media. Both HPL and SFM/XF increased the proliferation of BMMSC and AdMSC. Expansion of BMMSC and AdMSC in HPL increased their differentiation, compared to SFM/XF and FBS. Resting BMMSC and AdMSC, expanded in FBS or SFM/XF, demonstrated potent immunosuppressive properties in both non-primed and IFN-Îł primed conditions, whereas HPL-expanded MSC exhibited diminished immunosuppressive properties. Finally, IFN-Îł primed BMMSC and AdMSC expanded in SFM/XF and HPL expressed attenuated levels of IDO-1 compared to FBS. Herein, we provide strong evidence supporting the use of the FDA-approved SFM/XF medium, in contrast to the HPL medium, for the expansion of MSC towards therapeutic applications

    901-97 Stroke and Long-term Anticoagulant Therapy in 3404 Post-Myocardial Infarction Patients

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    In a randomized, double-blind, placebo controlled trial (ASPECT) we studied 3404 post-myocardial infarction patients who suffered a stroke during long-term anticoagulant therapy. The duration of treatment ranged from 1 day to six years. Three years following randomization, 2% of the patients on anticoagulant therapy had a stroke compared to 4% in placebo.The incidence of stroke analyzed on “intention-to-treat” was 0.7 per 100 patient-years in the anticoagulant group and 1.2 per 100 patient-years in placebo, a hazard ratio (HR) of 0.60 with a 95% confidence interval (Cl) of 0.40 to 0.90, a 40% reduction in the risk of stroke in the anticoagulated group. A total of 19 intracranial bleeding was observed. The risk of hemorrhages was 8 times greater for anticoagulated patients compared to placebo. Eight of the 17 bleedings were fatal in the anticoagulant group and no fatal hemorrhages occurred in placebo. A total of 15 cerebral infarctions occurred in the anticoagulated group and 43 in placebo. Of the 14 hemorrhagic strokes, 6 were within INR 3.0–4.0 and 8 with an INR&gt;4.0, Of the 7 non-hemorrhagic strokes, 2 were at INR&lt;2, 3 within INR 3.0–4.0, 1 at INR&gt;4.0, and no measurement was available in one patient. The total number of patients who died or were severely disabled as a result of cerebral stroke amounted to 13 in the anticoagulated group, compared to 18 in placebo.ConclusionThe results of the ASPECT trial indicated that long-term anticoagulant therapy substantially reduced the risk of stroke in post-myocardial infarction patients. The increased risk of bleeding complications associated with anticoagulant therapy was offset by a marked reduction in ischemic events

    Field Theoretical Analysis of On-line Learning of Probability Distributions

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    On-line learning of probability distributions is analyzed from the field theoretical point of view. We can obtain an optimal on-line learning algorithm, since renormalization group enables us to control the number of degrees of freedom of a system according to the number of examples. We do not learn parameters of a model, but probability distributions themselves. Therefore, the algorithm requires no a priori knowledge of a model.Comment: 4 pages, 1 figure, RevTe

    Pelaksanaan Sentra Tari di Tk Bungoeng Melati Desa Cot Keumeneng Aceh Barat

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    Penelitian yang berjudul “Pelaksanaan Sentra Tari di TK Bungoeng Melati Desa Cot Keumeneng Aceh Barat” Mengangkat masalah bagaimanakah pembelajaran sentra tari Ranup lampuan di Taman Kanak-kanak Bungoeng Melati. Serta kendala apa saja yang dihadapi guru dalam pelaksanaan pembelajaran tari di Taman Kanak-kanak Bungoeng Melati Aceh Barat? Penelitian ini bertujuan untuk mendeskripsikan pembelajaran sentra tari yang diterapkan pada pembelajaran tari di Taman Kanak-kanak Bungoeng Melati Desa Cot Keumeneng Aceh Barat, dan mendeskripsikan kendala yang dihadapi guru dalam pelaksanaan pembelajaran tari ranup lampuan di Taman Kanak-kanak Bungoeng Melati Desa Cot Keumeneng Aceh Barat. Hasil penelitian menunjukkan bahwa kegiatan awal proses pembelajaran tari di Taman kanak-kanak bungoeng melati biasanya guru terlebih dulu aktif dalam memotivasi peserta didik agar mau mengikuti pembelajaran yang dilaksanakan. Hal ini bertujuan agar adanya hubungan keterikatan antara siswa dengan gurunya dalam mempelajari materi yang diajarkan serta dapat melihat sejauh mana peserta didik siap mengikuti proses belajar dengan baik. Langkah awal yang dilakukan guru dalam memotivasi peserta didik, biasanya guru terlebih dahulu memperlihatkan serta mempertontonkan beberapa jenis video/rekaman tari yang nantinya akan dipelajari. Kemudian guru menjelaskan/ menceritakan asal usul tari tersebut. Akan tetapi pembelajaran yang diterapkan memiliki pengaruh bagi anak-anak untuk dapat mengembangkan potensi yang ada pada dirinya sesuai dengan bakat dan minat ketika anak-anak tersebut beranjak remaja

    Analisis Kepuasan Penumpang Atas Kualitas Layanan Jasa CV. Indah Travel Terayek Tembilahan Pekanbaru

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    This study aims to find out the level of passenger satisfaction for the quality of service which includes tangible, reliability, responsiveness, assurance, andempathy on the CV. Indah Travel route of Tembilahan - Pekanbaru. This study uses Importance - Performance Analysis with Cartesian diagram. In this study, the populations were all passengers of CV. Indah Travel route of Tembilahan - Pekanbaru, which made 100 respondents who were sampled by Purposive Sampling Method that is taking samples to passengers with a minimum of 3 timeshave used the services of CV. Indah Travel. From the research and discussion of the analysis of satisfaction,then gained the value of variablefrom passenger satisfaction over the quality of the service -dimensional tangible / physical evidence amounted equal to 77.98 %, the dimensions of reliability of 66.41 %, dimensions responsiveness of 76.97 %, the dimension of assurance of 65 , 97 % and dimensions of empathy of 77.19 % . From the results of Importance and Performance Analysis (IPA), can be seen that the total average of all indicators of the five (5) service dimensions is 3.25 < 4.46 (P < E). It means the passengers are not satisfied with the service provided which is expectation exceed the performance.Keywords: Quality of Service and Passenger Satisfactio
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