334 research outputs found

    Rancang Bangun Lampu LED 12 Volt DC dengan Rangkaian Penggerak Berbasis Topologi Flyback

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    Driving circuit function as a source of voltage to drive an electronic circuit. Source of voltage (power supply) created using the switching mode with Flyback converter topology. Component used as the switch is Mosfet. Time to live (on) and off (off) controlled by the circuit mosfet Totempole to accelerate the process on or off of the switch with a frequency of 50 kHz generated by IC SG3524. Switching mode power supply with Flyback converter topology are made to produce a constant voltage of 87 volts. Input source that will be used is lead acid batteries 12 Volt supplies 78 pieces LED

    Perancangan Transformator Satu Fasa dan Tiga Fasa Menggunakan Perangkat Lunak Komputer

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    The transformer is widely used, both in the field of electricity and electronics. Use of the power system allows choosing the appropriate voltage and economical for each purposes. To obtain a good and satisfying design it is necessary to use computer software in design process. The design of single phase and three phase transformer with the help of computer software is intended to replace the conventional process which is done manually so as to improve the efficiency of time and energy. In this research, we use visual basic 6.0 as a program language and the golden ratio (1 : 1,618) is used as the ratio between the width and thickness of the iron cor

    Nuclear Nox4-derived reactive oxygen species in myelodysplastic syndromes

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    A role for intracellular ROS production has been recently implicated in the pathogenesis and progression of a wide variety of neoplasias. ROS sources, such as NAD(P)H oxidase (Nox) complexes, are frequently activated in AML (acute myeloid leukemia) blasts and strongly contribute to their proliferation, survival, and drug resistance. Myelodysplastic syndromes (MDS) comprise a heterogeneous group of disorders characterized by ineffective hematopoiesis, with an increased propensity to develop AML. The molecular basis for MDS progression is unknown, but a key element in MDS disease progression is the genomic instability. NADPH oxidases are now recognized to have specific subcellular localizations, this targeting to specific compartments for localized ROS production. Local Nox-dependent ROS production in the nucleus may contribute to the regulation of redox-dependent cell growth, differentiation, senescence, DNA damage, and apoptosis. We observed that Nox1, 2, and 4 isoforms and p22phox and Rac1 subunits are expressed in MDS/AML cell lines and MDS samples, also in the nuclear fractions. Interestingly, Nox4 interacts with ERK and Akt1 within nuclear speckle domain, suggesting that Nox4 could be involved in regulating gene expression and splicing factor activity. These data contribute to the elucidation of the molecular mechanisms used by nuclear ROS to drive MDS evolution to AML

    Level and course of FEV1 in relation to polymorphisms in NFE2L2 and KEAP1 in the general population

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    <p>Abstract</p> <p>Background</p> <p>The metabolism of xenobiotics plays an essential role in smoking related lung function loss and development of Chronic Obstructive Pulmonary Disease. Nuclear Factor Erythroid 2-Like 2 (NFE2L2 or NRF2) and its cytosolic repressor Kelch-like ECH-associated protein-1 (KEAP1) regulate transcription of enzymes involved in cellular detoxification processes and <it>Nfe2l2</it>-deficient mice develop tobacco-induced emphysema. We assessed the impact of Single Nucleotide Polymorphisms (SNPs) in both genes on the level and longitudinal course of Forced Expiratory Volume in 1 second (FEV<sub>1</sub>) in the general population.</p> <p>Methods</p> <p>Five <it>NFE2L2 </it>and three <it>KEAP1 </it>tagging SNPs were genotyped in the population-based Doetinchem cohort (n = 1,152) and the independent Vlagtwedde-Vlaardingen cohort (n = 1,390). On average 3 FEV<sub>1 </sub>measurements during 3 surveys, respectively 7 FEV<sub>1 </sub>measurements during 8 surveys were present. Linear Mixed Effect models were used to test cross-sectional and longitudinal genetic effects on repeated FEV<sub>1 </sub>measurements.</p> <p>Results</p> <p>In the Vlagtwedde-Vlaardingen cohort SNP rs11085735 in <it>KEAP1 </it>was associated with a higher FEV<sub>1 </sub>level (p = 0.02 for an additive effect), and SNP rs2364723 in <it>NFE2L2 </it>was associated with a lower FEV<sub>1 </sub>level (p = 0.06). The associations were even more significant in the pooled cohort analysis. No significant association of <it>KEAP1 </it>or <it>NFE2L2 </it>SNPs with FEV<sub>1 </sub>decline was observed.</p> <p>Conclusion</p> <p>This is the first genetic study on variations in key antioxidant transcriptional regulators <it>KEAP1 </it>and <it>NFE2L2 </it>and lung function in a general population. It identified 2 SNPs in <it>NFE2L2 </it>and <it>KEAP1 </it>which affect the level of FEV<sub>1 </sub>in the general population. It additionally shows that <it>NFE2L2 </it>and <it>KEAP1 </it>variations are unlikely to play a role in the longitudinal course of FEV<sub>1 </sub>in the general population.</p

    Panchromatic Observations of the Textbook GRB 110205A: Constraining Physical Mechanisms of Prompt Emission and Afterglow

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    We present a comprehensive analysis of a bright, long duration (T(sub 90) approx. 257 s) GRB 110205A at redshift z = 2.22. The optical prompt emission was detected by Swift/UVOT, ROTSE-IIIb and BOOTES telescopes when the GRB was still radiating in the gamma-ray band. Thanks to its long duration, nearly 200 s of observations were obtained simultaneously from optical, X-ray to gamma-ray (1 eV - 5 MeV), which makes it one of the exceptional cases to study the broadband spectral energy distribution across 6 orders of magnitude in energy during the prompt emission phase. In particular, by fitting the time resolved prompt spectra, we clearly identify, for the first time, an interesting two-break energy spectrum, roughly consistent with the standard GRB synchrotron emission model in the fast cooling regime. Although the prompt optical emission is brighter than the extrapolation of the best fit X/ -ray spectra, it traces the -ray light curve shape, suggesting a relation to the prompt high energy emission. The synchrotron + synchrotron self-Compton (SSC) scenario is disfavored by the data, but the models invoking a pair of internal shocks or having two emission regions can interpret the data well. Shortly after prompt emission (approx. 1100 s), a bright (R = 14.0) optical emission hump with very steep rise ( alpha approx. 5.5) was observed which we interpret as the emission from the reverse shock. It is the first time that the rising phase of a reverse shock component has been closely observed

    NF-κB Mediates Tumor Necrosis Factor α-Induced Expression of Optineurin, a Negative Regulator of NF-κB

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    Optineurin is a ubiquitously expressed multifunctional cytoplasmic protein encoded by OPTN gene. The expression of optineurin is induced by various cytokines. Here we have investigated the molecular mechanisms which regulate optineurin gene expression and the relationship between optineurin and nuclear factor κB (NF-κB). We cloned and characterized human optineurin promoter. Optineurin promoter was activated upon treatment of HeLa and A549 cells with tumor necrosis factor α (TNFα). Mutation of a putative NF-κB-binding site present in the core promoter resulted in loss of basal as well as TNFα-induced activity. Overexpression of p65 subunit of NF-κB activated this promoter through NF-κB site. Oligonucleotides corresponding to this putative NF-κB-binding site showed binding to NF-κB. TNFα-induced optineurin promoter activity was inhibited by expression of inhibitor of NF-κB (IκBα) super-repressor. Blocking of NF-κB activation resulted in inhibition of TNFα-induced optineurin gene expression. Overexpressed optineurin partly inhibited TNFα-induced NF-κB activation in Hela cells. Downregulation of optineurin by shRNA resulted in an increase in TNFα-induced as well as basal NF-κB activity. These results show that optineurin promoter activity and gene expression are regulated by NF-κB pathway in response to TNFα. In addition these results suggest that there is a negative feedback loop in which TNFα-induced NF-κB activity mediates expression of optineurin, which itself functions as a negative regulator of NF-κB

    Panchromatic observations of the textbook GRB 110205A: Constraining physical mechanisms of prompt emission and afterglow

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    We present a comprehensive analysis of a bright, long-duration (T 90 257 s) GRB 110205A at redshift z = 2.22. The optical prompt emission was detected by Swift/UVOT, ROTSE-IIIb, and BOOTES telescopes when the gamma-ray burst (GRB) was still radiating in the γ-ray band, with optical light curve showing correlation with γ-ray data. Nearly 200 s of observations were obtained simultaneously from optical, X-ray, to γ-ray (1 eV to 5MeV), which makes it one of the exceptional cases to study the broadband spectral energy distribution during the prompt emission phase. In particular, we clearly identify, for the first time, an interesting two-break energy spectrum, roughly consistent with the standard synchrotron emission model in the fast cooling regime. Shortly after prompt emission (1100s), a bright (R = 14.0) optical emission hump with very steep rise (α 5.5) was observed, which we interpret as the reverse shock (RS) emission. It is the first time that the rising phase of an RS component has been closely observed. The full optical and X-ray afterglow light curves can be interpreted within the standard reverse shock (RS) + forward shock (FS) model. In general, the high-quality prompt and afterglow data allow us to apply the standard fireball model to extract valuable information, including the radiation mechanism (synchrotron), radius of prompt emission (R GRB 3 × 1013cm), initial Lorentz factor of the outflow (Γ0 250), the composition of the ejecta (mildly magnetized), the collimation angle, and the total energy budget. © 2012. The American Astronomical Society. All rights reserved.

    Microneedle Array Design Determines the Induction of Protective Memory CD8+ T Cell Responses Induced by a Recombinant Live Malaria Vaccine in Mice

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    BACKGROUND: Vaccine delivery into the skin has received renewed interest due to ease of access to the immune system and microvasculature, however the stratum corneum (SC), must be breached for successful vaccination. This has been achieved by removing the SC by abrasion or scarification or by delivering the vaccine intradermally (ID) with traditional needle-and-syringes or with long microneedle devices. Microneedle patch-based transdermal vaccine studies have predominantly focused on antibody induction by inactivated or subunit vaccines. Here, our principal aim is to determine if the design of a microneedle patch affects the CD8(+) T cell responses to a malaria antigen induced by a live vaccine. METHODOLOGY AND FINDINGS: Recombinant modified vaccinia virus Ankara (MVA) expressing a malaria antigen was percutaneously administered to mice using a range of silicon microneedle patches, termed ImmuPatch, that differed in microneedle height, density, patch area and total pore volume. We demonstrate that microneedle arrays that have small total pore volumes induce a significantly greater proportion of central memory T cells that vigorously expand to secondary immunization. Microneedle-mediated vaccine priming induced significantly greater T cell immunity post-boost and equivalent protection against malaria challenge compared to ID vaccination. Notably, unlike ID administration, ImmuPatch-mediated vaccination did not induce inflammatory responses at the site of immunization or in draining lymph nodes. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that the design of microneedle patches significantly influences the magnitude and memory of vaccine-induced CD8(+) T cell responses and can be optimised for the induction of desired immune responses. Furthermore, ImmuPatch-mediated delivery may be of benefit to reducing unwanted vaccine reactogenicity. In addition to the advantages of low cost and lack of pain, the development of optimised microneedle array designs for the induction of T cell responses by live vaccines aids the development of solutions to current obstacles of immunization programmes
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