27 research outputs found

    Pengaruh Ukuran Dan Fraksi Organik Terhadap Kuantitas Dan Kualitas Timbulan Lindi

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    Timbunan sampah pada landfill (TPA) akan mengalami degradasi dan akan menghasilkan cairan (lindi) baik kuantitas maupun kualitasnya. Kuantitas dan kualitas timbulan lindi dari sampah perkotaan akan dipengaruhi oleh beberapa faktor seperti: komposisi dan karakteristik sampah, kadar air, umur sampah dan kondisi cuaca (iklim). Pada kegiatan studi ini bertujuan untuk mengetahui pengaruh komposisi sampah (jumlah fraksi organik) dan karakteristik sampah (ukuran butiran) terhadap karakteristik timbulan lindi.Dalam rangka untuk mendapatkan tujuan studi, maka metode yang diterapkan adalah melakukan percobaan laboratorium menggunakan reaktor biodegradasi volume 1500 mL. Dalam percobaan ini digunakan dua kelompok reaktor yaitu; kelompok pertama, digunakan untuk pengujian pengaruh persentase fraksi organik, sedangkan kelompok kedua dimaksudkan untuk pengujian pengaruh ukuran butiran sampah terhadap karakteristik lindi.Sebagai parameter kualitas lindi ditentukan TSS, BOD, dan COD, sedangkan parameter kuantitas lindi adalah volume cairan yang keluar dari reaktor. Berdasarkan hasil percobaan diketahui bahwa jumlah (persentase) fraksi organik dan ukuran butiran sampah dapat berpengaruh terhadap karakteristik timbulan lindi. Secara keseluruhan konsentrasi TSS, BOD, dan COD semakin besar sejalan dengan bertambahnya persentase fraksi organik. Hal yang sama terjadi untuk ukuran butiran samaph semakin kecil, maka TSS, BOD, dan COD semakin besar. Adapun volume timbulan lind

    Strategi Penurunan Pencemaran Limbah Domestik Di Sungai Code DIY

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    Kualitas air sungai terutama yang terletak di kawasan urban saat ini kondisinya semakin memprihatinkan. Upaya mengatasi permasalahan pencemaran air yang paling efektif adalah mencegah masuknya bahan pencemaran ke dalam badan air. Penelitian ini bertujuan untuk menganalisis tingkat pencemaran limbah dometik, menganalisis potensi pencemar air yang masuk ke Sungai Code, serta menganalisis strategi pengelolaan Sungai Code untuk menurunkan beban pencemaran yang masuk dari sumber domestik. Pengambilan sampel air limbah untuk uji laboratorium dari sumber pencemar domestik untuk 12 IPAL komunal. Parameter yang dianalisis antara lain COD, TSS, dan NH 3 . Penentuan responden didasarkan pada pendekatan penentuan sampel secara acak pada wilayah tertentu (area random sampling). Analisis Data terdiri dari analisa pencemaran limbah domestik, analisis potensi sumber pencemar, serta analisis strategi penurunan bebab pencemaran. Hasil penelitian menunjukkan kondisi yang baik, dimana konsentrasi outlet lebih rendah daripada inlet antara lain untuk COD di titik 2,3,4, dan 8, TSS di titik 2,3,4,5,6,11, dan 12 serta untuk NH 3 di titik 2,3,4,8, dan 9. Artinya, IPAL pada titik selain itu perlu dicek kembali optimalisasi fungsinya. Strategi sosial penurunan pencemaran limbah domestik antara lain dengan pemberdayaan masyarakat, penguatan komunitas lokal, serta optimalisasi kelembagaan formal

    Dysregulation of Mesenchymal Cell Survival Pathways in Severe Fibrotic Lung Disease: The Effect of Nintedanib Therapy

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    Impaired apoptotic clearance of myofibroblasts can result in the continuous expansion of scar tissue during the persistent injury in the lung. However, the molecular and cellular mechanisms underlying the apoptotic clearance of multiple mesenchymal cells including fibrocytes, fibroblasts and myofibroblasts in severe fibrotic lung diseases such as idiopathic pulmonary fibrosis (IPF) remain largely unknown. We analyzed the apoptotic pathways activated in mesenchymal cells of IPF and in a mouse model of TGFα-induced pulmonary fibrosis. We found that fibrocytes and myofibroblasts in fibrotic lung lesions have acquired resistance to Fas-induced apoptosis, and an FDA-approved anti-fibrotic agent, nintedanib, effectively induced apoptotic cell death in both. In support, comparative gene expression analyses suggest that apoptosis-linked gene networks similarly dysregulated in both IPF and a mouse model of TGFα-induced pulmonary fibrosis. TGFα mice treated with nintedanib show increased active caspase 3-positive cells in fibrotic lesions and reduced fibroproliferation and collagen production. Further, the long-term nintedanib therapy attenuated fibrocyte accumulation, collagen deposition, and lung function decline during TGFα-induced pulmonary fibrosis. These results highlight the importance of inhibiting survival pathways and other pro-fibrotic processes in the various types of mesenchymal cells and suggest that the TGFα mouse model is relevant for testing of anti-fibrotic drugs either alone or in combination with nintedanib

    Structural Studies of BaTiO3 Ferroelectric Material Prepared by Green Chemistry (Sol-gel) Method

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    Nano particle Barium Titanate (BT) is the first ferroelectric ceramics and a good nominee for a variety of applications from large family of Perovskite. In this study BaTiO3 was synthesised by using Sol-gel (green chemistry) method. It is environmental friendly method and has a significant influence on the structure and properties of BT. XRD patterns were indexed on the basis of tetragonal-BaTiO3 phase. The microstructure of the samples was investigated by using Scanning electron microscope (SEM). The grain size range was 90 nm for the dried gel powder for the powder calcined at . 1150°C. Infrared (IR) spectrum was recorded at room temperature. The absorption peak observed at 545 cm-1 found to be BT characterization peak

    WISDOM-II: Screening against multiple targets implicated in malaria using computational grid infrastructures

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    <p>Abstract</p> <p>Background</p> <p>Despite continuous efforts of the international community to reduce the impact of malaria on developing countries, no significant progress has been made in the recent years and the discovery of new drugs is more than ever needed. Out of the many proteins involved in the metabolic activities of the <it>Plasmodium </it>parasite, some are promising targets to carry out rational drug discovery.</p> <p>Motivation</p> <p>Recent years have witnessed the emergence of grids, which are highly distributed computing infrastructures particularly well fitted for embarrassingly parallel computations like docking. In 2005, a first attempt at using grids for large-scale virtual screening focused on plasmepsins and ended up in the identification of previously unknown scaffolds, which were confirmed in vitro to be active plasmepsin inhibitors. Following this success, a second deployment took place in the fall of 2006 focussing on one well known target, dihydrofolate reductase (DHFR), and on a new promising one, glutathione-S-transferase.</p> <p>Methods</p> <p>In silico drug design, especially vHTS is a widely and well-accepted technology in lead identification and lead optimization. This approach, therefore builds, upon the progress made in computational chemistry to achieve more accurate <it>in silico </it>docking and in information technology to design and operate large scale grid infrastructures.</p> <p>Results</p> <p>On the computational side, a sustained infrastructure has been developed: docking at large scale, using different strategies in result analysis, storing of the results on the fly into MySQL databases and application of molecular dynamics refinement are MM-PBSA and MM-GBSA rescoring. The modeling results obtained are very promising. Based on the modeling results, <it>In vitro </it>results are underway for all the targets against which screening is performed.</p> <p>Conclusion</p> <p>The current paper describes the rational drug discovery activity at large scale, especially molecular docking using FlexX software on computational grids in finding hits against three different targets (PfGST, PfDHFR, PvDHFR (wild type and mutant forms) implicated in malaria. Grid-enabled virtual screening approach is proposed to produce focus compound libraries for other biological targets relevant to fight the infectious diseases of the developing world.</p

    Discovery of potent, novel, non-toxic anti-malarial compounds via quantum modelling, virtual screening and in vitro experimental validation

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    <p>Abstract</p> <p>Background</p> <p>Developing resistance towards existing anti-malarial therapies emphasize the urgent need for new therapeutic options. Additionally, many malaria drugs in use today have high toxicity and low therapeutic indices. Gradient Biomodeling, LLC has developed a quantum-model search technology that uses quantum similarity and does not depend explicitly on chemical structure, as molecules are rigorously described in fundamental quantum attributes related to individual pharmacological properties. Therapeutic activity, as well as toxicity and other essential properties can be analysed and optimized simultaneously, independently of one another. Such methodology is suitable for a search of novel, non-toxic, active anti-malarial compounds.</p> <p>Methods</p> <p>A set of innovative algorithms is used for the fast calculation and interpretation of electron-density attributes of molecular structures at the quantum level for rapid discovery of prospective pharmaceuticals. Potency and efficacy, as well as additional physicochemical, metabolic, pharmacokinetic, safety, permeability and other properties were characterized by the procedure. Once quantum models are developed and experimentally validated, the methodology provides a straightforward implementation for lead discovery, compound optimizzation and <it>de novo </it>molecular design.</p> <p>Results</p> <p>Starting with a diverse training set of 26 well-known anti-malarial agents combined with 1730 moderately active and inactive molecules, novel compounds that have strong anti-malarial activity, low cytotoxicity and structural dissimilarity from the training set were discovered and experimentally validated. Twelve compounds were identified <it>in silico </it>and tested <it>in vitro</it>; eight of them showed anti-malarial activity (IC50 ≤ 10 μM), with six being very effective (IC50 ≤ 1 μM), and four exhibiting low nanomolar potency. The most active compounds were also tested for mammalian cytotoxicity and found to be non-toxic, with a therapeutic index of more than 6,900 for the most active compound.</p> <p>Conclusions</p> <p>Gradient's metric modelling approach and electron-density molecular representations can be powerful tools in the discovery and design of novel anti-malarial compounds. Since the quantum models are agnostic of the particular biological target, the technology can account for different mechanisms of action and be used for <it>de novo </it>design of small molecules with activity against not only the asexual phase of the malaria parasite, but also against the liver stage of the parasite development, which may lead to true causal prophylaxis.</p

    Low potency toxins reveal dense interaction networks in metabolism

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    Background The chemicals of metabolism are constructed of a small set of atoms and bonds. This may be because chemical structures outside the chemical space in which life operates are incompatible with biochemistry, or because mechanisms to make or utilize such excluded structures has not evolved. In this paper I address the extent to which biochemistry is restricted to a small fraction of the chemical space of possible chemicals, a restricted subset that I call Biochemical Space. I explore evidence that this restriction is at least in part due to selection again specific structures, and suggest a mechanism by which this occurs. Results Chemicals that contain structures that our outside Biochemical Space (UnBiological groups) are more likely to be toxic to a wide range of organisms, even though they have no specifically toxic groups and no obvious mechanism of toxicity. This correlation of UnBiological with toxicity is stronger for low potency (millimolar) toxins. I relate this to the observation that most chemicals interact with many biological structures at low millimolar toxicity. I hypothesise that life has to select its components not only to have a specific set of functions but also to avoid interactions with all the other components of life that might degrade their function. Conclusions The chemistry of life has to form a dense, self-consistent network of chemical structures, and cannot easily be arbitrarily extended. The toxicity of arbitrary chemicals is a reflection of the disruption to that network occasioned by trying to insert a chemical into it without also selecting all the other components to tolerate that chemical. This suggests new ways to test for the toxicity of chemicals, and that engineering organisms to make high concentrations of materials such as chemical precursors or fuels may require more substantial engineering than just of the synthetic pathways involved

    Why medical students do not like to join rural health service? An exploratory study in India

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    Introduction: Inadequate, inequitable distribution of the medical workforce remains a challenge across the globe, and India is no exception. Odisha, a state in India faces a major shortage of doctors particularly in rural and remote areas. In order to address this challenge, it is essential to understand medical students′ career plans, specialization preferences, choices of job location and sector, and views on working in rural and remote areas. This study explored the immediate and long-term career plans of final year medical students, their intended practice locations and underlying reasons for the choices. Methodology: A cross-sectional survey was conducted in all the medical colleges (three government and three private) in the state of Odisha. Through the systematic sampling method, data were gathered from 390 final year students. A semi-structured questionnaire was administered to the students and data were analyzed using SPSS version 20. Results: Of the 390 students, 290 (74.35%) were from a government college. The most preferred immediate career goal was postgraduation studies (45.9% of students in government medical schools and 54% in private). About 17% of government students and 9% of private students showed willingness to work in rural areas, in the long run. Nearly 44.5% mentioned opportunities for career growth, followed by the possibilities for higher education (26.8%) as major the factors for preferring an urban posting. Similarly, higher pay scales, better working conditions were major factors for preferring the private sector. Most of the students maintained that good housing, better salaries, and adequate facilities at the workplace would attract more students toward rural service. Conclusion: Since public funded medical students are not motivated to serve in rural settings, increasing the number of places or establishing new medical institutions may not be an effective solution to the issue. Approaches such as extended clinical apprenticeship in rural health facilities, long-term community engagement during medical studentship could be considered

    Inhibition of Aurora Kinase B attenuates fibroblast activation and pulmonary fibrosis

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    Fibroblast activation including proliferation, survival, and ECM production is central to initiation and maintenance of fibrotic lesions in idiopathic pulmonary fibrosis (IPF). However, druggable molecules that target fibroblast activation remain limited. In this study, we show that multiple pro‐fibrotic growth factors, including TGFα, CTGF, and IGF1, increase aurora kinase B (AURKB) expression and activity in fibroblasts. Mechanistically, we demonstrate that Wilms tumor 1 (WT1) is a key transcription factor that mediates TGFα‐driven AURKB upregulation in fibroblasts. Importantly, we found that inhibition of AURKB expression or activity is sufficient to attenuate fibroblast activation. We show that fibrosis induced by TGFα is highly dependent on AURKB expression and treating TGFα mice with barasertib, an AURKB inhibitor, reverses fibroblast activation, and pulmonary fibrosis. Barasertib similarly attenuated fibrosis in the bleomycin model of pulmonary fibrosis. Together, our preclinical studies provide important proof‐of‐concept that demonstrate barasertib as a possible intervention therapy for IPF.SynopsisFibroblast activation is central for the initiation and maintenance of fibrotic lesions in idiopathic pulmonary fibrosis. Our preclinical study describes the pathological role for AURKB in fibroblast activation and presents a potential therapy for the treatment of pulmonary fibrosis using barasertib.AURKB is upregulated in the lungs of IPF patients and mouse models of pulmonary fibrosis.WT1 binds directly to the promoter of AURKB to upregulates its expression.AURKB functions as a positive regulator of fibroproliferation, myofibroblast survival, and ECM production.In vivo barasertib therapy attenuates TGFα‐and bleomycin‐induced pulmonary fibrosis.Fibroblast activation is central for the initiation and maintenance of fibrotic lesions in idiopathic pulmonary fibrosis. Our preclinical study describes the pathological role for AURKB in fibroblast activation and presents a potential therapy for the treatment of pulmonary fibrosis using barasertib.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162746/7/emmm202012131-sup-0003-SDataFig1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162746/6/emmm202012131-sup-0002-EVFigs.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162746/5/emmm202012131-sup-0006-SDataFig6.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162746/4/emmm202012131.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162746/3/emmm202012131-sup-0005-SDataFig4.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162746/2/emmm202012131-sup-0001-Appendix.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162746/1/emmm202012131_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162746/9/emmm202012131.reviewer_comments.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162746/8/emmm202012131-sup-0004-SDataFig2.pd
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