8,692 research outputs found

    Bandung Culinary Club

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    Makanan merupakan salah satu kebutuhan dasar manusia. Inilah mengapa industri makanan tidak pernah surut permintaan dari konsumen, dancenderung tetap kuat dan bertahan meskipun suatu negara sedang dilanda krisis. Industri food and beverage (F&B) di Indonesia khususnya jajanantelah tumbuh dengan pesat selama beberapa tahun terakhir, seiring dengan itu masyarakat pun semakin tertarik dengan karir sebagai wirausahawan dibidang kuliner. Namun, untuk menjadi wirausahawan tidak hanya membutuhkan produk yang bagus untuk dijual namun juga strategi penjualan.Setelah melalui studi literatur dan observasi, saat ini dibutuhkan fasilitas dan program yang diperuntukkan bagi orang yang memiliki gairah terhadapmakanan dan juga dunia wirausaha untuk menghasilkan bisnis F&B yang berhasil

    Colchicine therapy in acute coronary syndrome patients acts on caspase-1 to suppress NLRP3 inflammasome monocyte activation

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    Inflammasome activation, with subsequent release of pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18, has recently been implicated in atherosclerosis-associated inflammation. This study aims to assess in acute coronary syndrome (ACS) patients (1) inflammasome activation in circulating monocytes and (2) whether short-term oral colchicine, a recognized anti-inflammatory agent that has been shown to be cardio-protective in clinical studies, might acutely suppress inflammasome-dependent inflammation. ACS patients (n=21) were randomized to oral colchicine (1 mg followed by 0.5 mg 1 h later) or no treatment, and compared with untreated healthy controls (n=9). Peripheral venous blood was sampled pre- (day 1) and 24 h post- (day 2) treatment. Monocytes were cultured and stimulated with ATP. Analysis of key inflammasome markers was performed by ELISA. IL-1β secretion increased by 580.4% (P<0.01) in ACS patients compared with controls but only with ATP stimulation. Untreated ACS patients secreted significantly higher levels of IL-18 compared with healthy controls independent of ATP stimulation (P<0.05). Colchicine treatment in ACS patients markedly reduced intracellular and secreted levels of IL-1β compared with pre-treatment levels (P<0.05 for both), as well as significantly reducing pro-caspase-1 mRNA levels by 57.7% and secreted caspase-1 protein levels by 30.2% compared with untreated patients (P<0.05 for both). Monocytes from ACS patients are ‘primed’ to secrete inflammasome-related cytokines and short-term colchicine acutely and markedly suppresses monocyte caspase-1 activity, thereby reducing monocyte secretion of IL-1β

    A Sustained Dietary Change Increases Epigenetic Variation in Isogenic Mice

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    Epigenetic changes can be induced by adverse environmental exposures, such as nutritional imbalance, but little is known about the nature or extent of these changes. Here we have explored the epigenomic effects of a sustained nutritional change, excess dietary methyl donors, by assessing genomic CpG methylation patterns in isogenic mice exposed for one or six generations. We find stochastic variation in methylation levels at many loci; exposure to methyl donors increases the magnitude of this variation and the number of variable loci. Several gene ontology categories are significantly overrepresented in genes proximal to these methylation-variable loci, suggesting that certain pathways are susceptible to environmental influence on their epigenetic states. Long-term exposure to the diet (six generations) results in a larger number of loci exhibiting epigenetic variability, suggesting that some of the induced changes are heritable. This finding presents the possibility that epigenetic variation within populations can be induced by environmental change, providing a vehicle for disease predisposition and possibly a substrate for natural selection.This work was supported by the Australian Research Council (DP0771859) and the National Health and Medical Research Council (#459412, #635510)

    Guidance on Performing Focused Ethnographies with an Emphasis on Healthcare Research

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    Focused ethnographies can have meaningful and useful application in primary care, community, or hospital healthcare practice, and are often used to determine ways to improve care and care processes. They can be pragmatic and efficient ways to capture data on a specific topic of importance to individual clinicians or clinical specialties. While many examples of focused ethnographies are available in the literature, there is a limited availability of guidance documents for conducting this research. This paper defines focused ethnographies, locates them within the ethnographic genre, justifies their use in healthcare research, and outlines the methodological processes including those related to sampling, data collection and maintaining rigour. It also identifies and provides a summary of some recent focused ethnographies conducted in healthcare research. While the emphasis is placed on healthcare research, focused ethnographies can be applicable to any discipline whenever there is a desire to explore specific cultural perspectives held by sub - groups of people within a context - specific and problem - focused framework

    Pendidikan, Pengalaman Kerja dan Kompetensi Pengaruhnya terhadap Kinerja Karyawan pada PT. Pln (Persero) Wilayah Suluttenggo

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    Keberhasilan suatu Perusahaan tergantung dari kualitas sumber daya manusia yang berada didalamnya.Oleh karena itu, Perusahaan berusaha meningkatkan kinerja karyawannya agar lebih terampil dan berkompetensi tinggi dalam bidangnya, agar Perusahaan dapat memberikan pelayanan terbaik kepada konsumen dan dapat memberikan kinerja yang optimal. Tujuan penelitian ini adalah untuk mengetahui apakah Pendidikan, Pengalaman Kerja, dan Kompetensi berpengaruh terhadap Kinerja Karyawan PT. PLN (Persero) wilayah Suluttengo. Metode yang digunakan asosiatif dengan teknik analisis regresi linear berganda. Populasi penelitian sebanyak 168 dan sampel yang digunakan 70 responden. Hasil penelitian menunjukkan Pendidikan, Pengalaman Kerja, dan Kompetensi berpengaruh baik secara simultan maupun parsial terhadap Kinerja Karyawan. Sebaiknya pimpinan PT. PLN (Persero) Suluttenggo memperhatikan pendidikan, pengalaman kerja dan kompetensi karyawan karena memiliki pengaruh terhadap kinerjanya serta untuk mencapai tujuan Perusahaannya. Kata kunci: pendidikan, pengalaman kerja, kompetensi, kinerj

    Agouti C57BL/6N embryonic stem cells for mouse genetic resources.

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    We report the characterization of a highly germline competent C57BL/6N mouse embryonic stem cell line, JM8. To simplify breeding schemes, the dominant agouti coat color gene was restored in JM8 cells by targeted repair of the C57BL/6 nonagouti mutation. These cells provide a robust foundation for large-scale mouse knockout programs that aim to provide a public resource of targeted mutations in the C57BL/6 genetic background

    CemOrange2 fusions facilitate multifluorophore subcellular imaging in C. elegans

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    Due to its ease of genetic manipulation and transparency, Caenorhabditis elegans (C. elegans) has become a preferred model system to study gene function by microscopy. The use of Aequorea victoria green fluorescent protein (GFP) fused to proteins or targeting sequences of interest, further expanded upon the utility of C. elegans by labeling subcellular structures, which enables following their disposition during development or in the presence of genetic mutations. Fluorescent proteins with excitation and emission spectra different from that of GFP accelerated the use of multifluorophore imaging in real time. We have expanded the repertoire of fluorescent proteins for use in C. elegans by developing a codon-optimized version of Orange2 (CemOrange2). Proteins or targeting motifs fused to CemOrange2 were distinguishable from the more common fluorophores used in the nematode; such as GFP, YFP, and mKate2. We generated a panel of CemOrange2 fusion constructs, and confirmed they were targeted to their correct subcellular addresses by colocalization with independent markers. To demonstrate the potential usefulness of this new panel of fluorescent protein markers, we showed that CemOrange2 fusion proteins could be used to: 1) monitor biological pathways, 2) multiplex with other fluorescent proteins to determine colocalization and 3) gain phenotypic knowledge of a human ABCA3 orthologue, ABT-4, trafficking variant in the C. elegans model organism

    A preexisting rare PIK3CA e545k subpopulation confers clinical resistance to MEK plus CDK4/6 inhibition in NRAS melanoma and is dependent on S6K1 signaling

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    Combined MEK and CDK4/6 inhibition (MEKi + CDK4i) has shown promising clinical outcomes in patients with NRAS- mutant melanoma. Here, we interrogated longitudinal biopsies from a patient who initially responded to MEKi + CDK4i therapy but subsequently developed resistance. Whole-exome sequencing and functional validation identified an acquired PIK3CA E545K mutation as conferring drug resistance. We demonstrate that PIK3CA E545K preexisted in a rare subpopulation that was missed by both clinical and research testing, but was revealed upon multiregion sampling due to PIK3CA E545K being nonuniformly distributed. This resistant population rapidly expanded after the initiation of MEKi + CDK4i therapy and persisted in all successive samples even after immune checkpoint therapy and distant metastasis. Functional studies identified activated S6K1 as both a key marker and specific therapeutic vulnerability downstream of PIK3CA E545K -induced resistance. These results demonstrate that difficult-to-detect preexisting resistance mutations may exist more often than previously appreciated and also posit S6K1 as a common downstream therapeutic nexus for the MAPK, CDK4/6, and PI3K pathways. SIGNIFICANCE: We report the first characterization of clinical acquired resistance to MEKi + CDK4i, identifying a rare preexisting PIK3CA E545K subpopulation that expands upon therapy and exhibits drug resistance. We suggest that single-region pretreatment biopsy is insufficient to detect rare, spatially segregated drug-resistant subclones. Inhibition of S6K1 is able to resensitize PIK3CA E545K -expressing NRAS-mutant melanoma cells to MEKi + CDK4i. © 2018 AAC
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