Program Perhitungan Efektivitas Waktu Dan Biaya Pemakaian Tower Crane

Pada pelaksanaan proyek gedung bertingkat, Tower Crane (TC) merupakan alat untuk mengangkat material baik arah vertikal maupun horisontal. Untuk efisiensi biaya proyek, perkiraan jadwal dan waktu penggunaan TC perlu direncanakan sebelum pelaksanaan konstruksi.TC umumnya digunakan pada banyak pekerjaan dengan karakteristik berbeda seperti pekerjaan pengangkatan tulangan, bekisting, pengecoran, dan lain-lain, sehingga perlu diperhatikan waktu penggunaan TC yang berkaitan dengan schedule proyek, dimana keterlambatan waktu pekerjaan di lapangan dapat mengakibatkan durasi yang lebih untuk TC dan akan mempengaruhi pertambahan biaya yang dikeluarkan pada proyek. Oleh sebab itu, diperlukan program yang dapat menghitung efektivitas waktu dan biaya pemakaian TC. Dengan mempelajari karakteristik dan spesifikasi TC serta observasi lapangan pada proyek Educity Residence, Surabaya, maka dibuatlah program perhitungan efektivitas waktu dan biaya pemakaian TC. Perkiraan waktu mencakup gerakan horisontal (Trolley), vertikal (hoist), dan rotasi (swing) yang dihitung secara matematis untuk setiap jenis pekerjaan dengan memperhatikan kondisi manajemen dan kondisi pekerjaan. Hasil dari program ini diharapkan dapat membantu kontraktor dalam mengatur pemakaian TC di lapangan

Isolasi Andrografolid dari Andrographis Paniculata (Burm. F.) Ness Menggunakan Metode Purifikasi dan Kristalisasi

Sambiloto (Andrographis paniculata (Burm. f.) Ness) merupakan tanaman yang banyak dimanfaatkan dalam pengobatan. Zat aktif utama dalam sambiloto adalah andrografolid yang merupakan zat pahit pada tanaman tersebut. Isolat andrografolid telah tebukti memiliki berbagai macam aktivitas farmakologi seperti antihiperglikemia menghambat platelet-activating factor), anti virus herpes simplex tipe 1, menghambat viabilitas TD-47 sel kanker payudara, dan menurunkan kadar kolesterol. Penelitian terbaru menunjukkan bahwa andrografolid menunjukkan aktivitas sebagai anti inflamasi dalam kasus rheumatoid arthritis. Beberapa macam tahapan isolasi telah dilakukan untuk memperoleh andrografolid dari Andrographis paniculata (Burm. f.) Ness pada penelitian-penelitian sebelumnya. Pada penelitian ini dilakukan isolasi terhadap andrografolid dari Andrographis paniculata (Burm. f.) Ness menggunakan metode purifikasi dan kristalisasi yang bertujuan untuk mendapatkan isolat andrografolid murni dengan lebih efisien. Hasil penelitian menunjukkan bahwa isolat yang diperoleh menggunakan metoda purifikasi dan kristalisasi mendapatkan rendemen sebesar 0,48%

Default Pathway of var2csa Switching and Translational Repression in Plasmodium falciparum

Antigenic variation is a subtle process of fundamental importance to the survival of a microbial pathogen. In Plasmodium falciparum malaria, PfEMP1 is the major variable antigen and adhesin expressed at the surface of the infected erythrocyte, which is encoded for by members of a family of 60 var-genes. Peri-nuclear repositioning and epigenetic mechanisms control their mono-allelic expression. The switching of PfEMP1 depends in part on variable transition rates and short-lived immune responses to shared minor epitopes. Here we show var-genes to switch to a common gene that is highly transcribed, but sparsely translated into PfEMP1 and not expressed at the erythrocyte surface. Highly clonal and adhesive P. falciparum, which expressed distinct var-genes and the corresponding PfEMP1s at onset, were propagated without enrichment or panning. The parasites successively and spontaneously switched to transcribe a shared var-gene (var2csa) matched by the loss of PfEMP1 surface expression and host cell-binding. The var2csa gene repositioned in the peri-nuclear area upon activation, away from the telomeric clusters and heterochromatin to transcribe spliced, full-length RNA. Despite abundant transcripts, the level of intracellular PfEMP1 was low suggesting post-transcriptional mechanisms to partake in protein expression. In vivo, off-switching and translational repression may constitute one pathway, among others, coordinating PfEMP1 expression

Expression of P. falciparum var Genes Involves Exchange of the Histone Variant H2A.Z at the Promoter

Plasmodium falciparum employs antigenic variation to evade the human immune response by switching the expression of different variant surface antigens encoded by the var gene family. Epigenetic mechanisms including histone modifications and sub-nuclear compartmentalization contribute to transcriptional regulation in the malaria parasite, in particular to control antigenic variation. Another mechanism of epigenetic control is the exchange of canonical histones with alternative variants to generate functionally specialized chromatin domains. Here we demonstrate that the alternative histone PfH2A.Z is associated with the epigenetic regulation of var genes. In many eukaryotic organisms the histone variant H2A.Z mediates an open chromatin structure at promoters and facilitates diverse levels of regulation, including transcriptional activation. Throughout the asexual, intraerythrocytic lifecycle of P. falciparum we found that the P. falciparum ortholog of H2A.Z (PfH2A.Z) colocalizes with histone modifications that are characteristic of transcriptionally-permissive euchromatin, but not with markers of heterochromatin. Consistent with this finding, antibodies to PfH2A.Z co-precipitate the permissive modification H3K4me3. By chromatin-immunoprecipitation we show that PfH2A.Z is enriched in nucleosomes around the transcription start site (TSS) in both transcriptionally active and silent stage-specific genes. In var genes, however, PfH2A.Z is enriched at the TSS only during active transcription in ring stage parasites. Thus, in contrast to other genes, temporal var gene regulation involves histone variant exchange at promoter nucleosomes. Sir2 histone deacetylases are important for var gene silencing and their yeast ortholog antagonises H2A.Z function in subtelomeric yeast genes. In immature P. falciparum parasites lacking Sir2A or Sir2B high var transcription levels correlate with enrichment of PfH2A.Z at the TSS. As Sir2A knock out parasites mature the var genes are silenced, but PfH2A.Z remains enriched at the TSS of var genes; in contrast, PfH2A.Z is lost from the TSS of de-repressed var genes in mature Sir2B knock out parasites. This result indicates that PfH2A.Z occupancy at the active var promoter is antagonized by PfSir2A during the intraerythrocytic life cycle. We conclude that PfH2A.Z contributes to the nucleosome architecture at promoters and is regulated dynamically in active var genes

A tetraoxane-based antimalarial drug candidate that overcomes PfK13-C580Y dependent artemisinin resistance.

K13 gene mutations are a primary marker of artemisinin resistance in Plasmodium falciparum malaria that threatens the long-term clinical utility of artemisinin-based combination therapies, the cornerstone of modern day malaria treatment. Here we describe a multinational drug discovery programme that has delivered a synthetic tetraoxane-based molecule, E209, which meets key requirements of the Medicines for Malaria Venture drug candidate profiles. E209 has potent nanomolar inhibitory activity against multiple strains of P. falciparum and P. vivax in vitro, is efficacious against P. falciparum in in vivo rodent models, produces parasite reduction ratios equivalent to dihydroartemisinin and has pharmacokinetic and pharmacodynamic characteristics compatible with a single-dose cure. In vitro studies with transgenic parasites expressing variant forms of K13 show no cross-resistance with the C580Y mutation, the primary variant observed in Southeast Asia. E209 is a superior next generation endoperoxide with combined pharmacokinetic and pharmacodynamic features that overcome the liabilities of artemisinin derivatives

CD36 selection of 3D7 Plasmodium falciparum associated with severe childhood malaria results in reduced VAR4 expression

<p>Abstract</p> <p>Background</p> <p>A subset of the <it>Plasmodium falciparum </it>erythrocyte membrane protein 1 (PfEMP1_SM) is involved in the cytoadherence of <it>P. falciparum</it>-infected red blood cells (iRBC) contributing to the pathogenesis of severe disease among young children in malaria endemic areas. The PfEMP1_SMare encoded by group A <it>var </it>genes that are composed of a more constrained range of amino acid sequences than groups B and C <it>var </it>genes encoding PfEMP1_UMassociated with uncomplicated malaria. Also, unlike <it>var </it>genes from groups B and C, those from group A do not have sequences consistent with CD36 binding – a major cytoadhesion phenotype of <it>P. falciparum </it>isolates.</p> <p>Methods</p> <p>A 3D7 PfEMP1_SMsub-line (3D7_SM) expressing VAR4 (PFD1235w/MAL8P1.207) was selected for binding to CD36. The protein expression of this parasite line was monitored by surface staining of iRBC using VAR4-specific antibodies. The serological phenotype of the 3D7_SMparasites was determined by flow cytometry using malaria semi-immune and immune plasma and transcription of the 59 <it>var </it>genes in 3D7 were analysed by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) using <it>var</it>-specific primers.</p> <p>Results</p> <p>A selection-induced increased adhesion of 3D7_SMiRBC to CD36 resulted in a reduced <it>var4 </it>transcription and VAR4 surface expression.</p> <p>Conclusion</p> <p>VAR4 is not involved in CD36 adhesion. The current findings are consistent with the notion that CD36 adhesion is not associated with particular virulent parasite phenotypes, such as those believed to be exhibited by VAR4 expressing parasites.</p

Quantifying primaquine effectiveness and improving adherence: a round table discussion of the APMEN Vivax Working Group.

The goal to eliminate malaria from the Asia-Pacific by 2030 will require the safe and widespread delivery of effective radical cure of malaria. In October 2017, the Asia Pacific Malaria Elimination Network Vivax Working Group met to discuss the impediments to primaquine (PQ) radical cure, how these can be overcome and the methodological difficulties in assessing clinical effectiveness of radical cure. The salient discussions of this meeting which involved 110 representatives from 18 partner countries and 21 institutional partner organizations are reported. Context specific strategies to improve adherence are needed to increase understanding and awareness of PQ within affected communities; these must include education and health promotion programs. Lessons learned from other disease programs highlight that a package of approaches has the greatest potential to change patient and prescriber habits, however optimizing the components of this approach and quantifying their effectiveness is challenging. In a trial setting, the reactivity of participants results in patients altering their behaviour and creates inherent bias. Although bias can be reduced by integrating data collection into the routine health care and surveillance systems, this comes at a cost of decreasing the detection of clinical outcomes. Measuring adherence and the factors that relate to it, also requires an in-depth understanding of the context and the underlying sociocultural logic that supports it. Reaching the elimination goal will require innovative approaches to improve radical cure for vivax malaria, as well as the methods to evaluate its effectiveness