3,201 research outputs found

    Analisis Perhitungan Harga Pokok Produksi Dengan Penerapan Metode Full Costing Pada UMKM Kota Banda Aceh

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    Calculation and acquisition cost of production is strongly Influenced by the application of the method right, so the cost of production is obtained to indicate the actual value occurs. This study conducted on Banda Aceh micro, small and medium enterprises, especially processing businesses of tofu. The purpose of this study is to analyze the production cost price calculation and allocation of costs applied by Banda Aceh micro, small and medium enterprises with the calculation the cost of production using the full costing method. The type of data used in this study is qualitative data which presented in a descriptive or shape description, and quantitative data is presented in the numbers. Sources of data derived from primary data results of interviews conducted with business owners tofu in Banda Aceh, and secondary data obtained from the literature review and other literature that supports the writing of this study. The results indicate that the acquisition cost of production using the full costing method is better in analyzing production costs, its caused the calculation cost of production using the full costing method has included all overhead costs, both fixed and variable during the production process.Keywords— Cost of Production, Full Costing, Process Cos

    Development and Validation of a New RP-HPLC Method for the Determination of Aprepitant in Solid Dosage Forms

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    Purpose: To develop and validate a new, simple, sensitive, rapid, cost-effective and accurate reverse phase-high performance liquid chromatography (RP-HPLC) method for the determination of aprepitant (APT) in capsule dosage form.Methods: The method developed for the determination of APT in capsule formulation involved using RP-HPLC which incorporated a C18 column 250 x 2.5 mm i.d, 5 μm particle size, in isocratic mode, with mobile phase comprising of methanol: water in the ratio of 90:10 (v/v). The flow rate was 1 mL/min and the detection was monitored at 220 nm. The total run time was 10 min and the column was maintained at ambient temperature.Results: APT was eluted in the given mobile phase with a retention time (tr) of 4.473 min. The linearity for the quantification of APT was 0.1 - 10 μg/mL (R2 =0.989, Y= 33032x + 71501) with coefficients of variation (based on mean peak area for six replicate injections) in the range 0.04 to 0.132. The limits of detection and of quantification were 0.028 and 0.094 μg/mL, respectively. Recovery of the method was 99.56 - 100.5 % while the relative standard deviation (RSD) of intra-day and inter-day precision was 0.85 and 1.05, respectively. System precision and method precision were 0.013 and 1.400 %, respectively. The specificity data of the proposed method indicated that excipients in the capsules did not interfere with the drug peak. Furthermore, the well-shaped peaks buttressed the specificity of the method.Conclusion: The proposed RP-HPLC method is simple, sensitive, rapid, cost-effective and accurate for the determination of APT in both bulk materials and pharmaceutical dosage forms.Keywords: Aprepitant, RP-HPLC, Isocratic, Pharmaceutical dosage forms, Analysis, Validatio

    The fundamental problem of command : plan and compliance in a partially centralised economy

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    When a principal gives an order to an agent and advances resources for its implementation, the temptations for the agent to shirk or steal from the principal rather than comply constitute the fundamental problem of command. Historically, partially centralised command economies enforced compliance in various ways, assisted by nesting the fundamental problem of exchange within that of command. The Soviet economy provides some relevant data. The Soviet command system combined several enforcement mechanisms in an equilibrium that shifted as agents learned and each mechanism's comparative costs and benefits changed. When the conditions for an equilibrium disappeared, the system collapsed.Comparative Economic Studies (2005) 47, 296–314. doi:10.1057/palgrave.ces.810011

    A Genetic Screen for Dihydropyridine (DHP)-Resistant Worms Reveals New Residues Required for DHP-Blockage of Mammalian Calcium Channels

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    Dihydropyridines (DHPs) are L-type calcium channel (Cav1) blockers prescribed to treat several diseases including hypertension. Cav1 channels normally exist in three states: a resting closed state, an open state that is triggered by membrane depolarization, followed by a non-conducting inactivated state that is triggered by the influx of calcium ions, and a rapid change in voltage. DHP binding is thought to alter the conformation of the channel, possibly by engaging a mechanism similar to voltage dependent inactivation, and locking a calcium ion in the pore, thereby blocking channel conductance. As a Cav1 channel crystal structure is lacking, the current model of DHP action has largely been achieved by investigating the role of candidate Cav1 residues in mediating DHP-sensitivity. To better understand DHP-block and identify additional Cav1 residues important for DHP-sensitivity, we screened 440,000 randomly mutated Caenorhabditis elegans genomes for worms resistant to DHP-induced growth defects. We identified 30 missense mutations in the worm Cav1 pore-forming (α1) subunit, including eleven in conserved residues known to be necessary for DHP-binding. The remaining polymorphisms are in eight conserved residues not previously associated with DHP-sensitivity. Intriguingly, all of the worm mutants that we analyzed phenotypically exhibited increased channel activity. We also created orthologous mutations in the rat α1C subunit and examined the DHP-block of current through the mutant channels in culture. Six of the seven mutant channels examined either decreased the DHP-sensitivity of the channel and/or exhibited significant residual current at DHP concentrations sufficient to block wild-type channels. Our results further support the idea that DHP-block is intimately associated with voltage dependent inactivation and underscores the utility of C. elegans as a screening tool to identify residues important for DHP interaction with mammalian Cav1 channels

    On Polynomial Stability of Coupled Partial Differential Equations in 1D

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    We study the well-posedness and asymptotic behaviour of selected PDE-PDE and PDE-ODE systems on one-dimensional spatial domains, namely a boundary coupled wave-heat system and a wave equation with a dynamic boundary condition. We prove well-posedness of the models and derive rational decay rates for the energy using an approach where the coupled systems are formulated as feedback interconnections of impedance passive regular linear systems.Comment: 12 pages, 1 figure, accepted for publication in the Proceedings of "Semigroups of Operators: Theory and Applications", Kazimierz Dolny, Poland, October 201

    Deleted in Liver Cancer 1 (DLC1) Utilizes a Novel Binding Site for Tensin2 PTB Domain Interaction and Is Required for Tumor-Suppressive Function

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    Background: Deleted in liver cancer 1 (DLC1) is a Rho GTPase-activating protein (RhoGAP) frequently deleted and underexpressed in hepatocellular carcinoma (HCC) as well as in other cancers. Recent independent studies have shown interaction of DLC1 with members of the tensin focal adhesion protein family in a Src Homology 2 (SH2) domain-dependent mechanism. DLC1 and tensins interact and co-localize to punctate structures at focal adhesions. However, the mechanisms underlying the interaction between DLC1 and various tensins remain controversial. Methodology/Principal Findings: We used a co-immunoprecipitation assay to identify a previously undocumented binding site at 375-385 of DLC1 that predominantly interacted with the phosphotyrosine binding (PTB) domain of tensin2. DLC1-tensin2 interaction is completely abolished in a DLC1 mutant lacking this novel PTB binding site (DLC1ΔPTB). However, as demonstrated by immunofluorescence and co-immunoprecipitation, neither the focal adhesion localization nor the interaction with tensin1 and C-terminal tensin-like (cten) were affected. Interestingly, the functional significance of this novel site was exhibited by the partial reduction of the RhoGAP activity, which, in turn, attenuated the growth-suppressive activity of DLC1 upon its removal from DLC1. Conclusions/Significance: This study has provided new evidence that DLC1 also interacts with tensin2 in a PTB domain-dependent manner. In addition to properly localizing focal adhesions and preserving RhoGAP activity, DLC1 interaction with tensin2 through this novel focal adhesion binding site contributes to the growth-suppressive activity of DLC1. © 2009 Chan et al.published_or_final_versio

    Deleted in Liver Cancer 1 (DLC1) Negatively Regulates Rho/ROCK/MLC Pathway in Hepatocellular Carcinoma

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    Aims: Deleted in liver cancer 1 (DLC1), a member of RhoGTPase activating protein (GAP) family, is known to have suppressive activities in tumorigenicity and cancer metastasis. However, the underlying molecular mechanisms of how DLC1 suppresses cell motility have not been fully elucidated. Rho-kinase (ROCK) is an immediate down-stream effector of RhoA in mediating cellular cytoskeletal events and cell motility. In the present study, we aimed to investigate the effects of DLC1 on Rho/ROCK signaling pathway in hepatocellular carcinoma (HCC). Methodology/Principal Findings: We demonstrated that DLC1 negatively regulated ROCK-dependent actomyosin contractility. From immumofluorescence study, we found that ectopic expression of DLC1 abrogated Rho/ROCK-mediated cytoskeletal reorganization including formation of stress fibers and focal adhesions. It also downregulated cortical phosphorylation of myosin light chain 2 (MLC2). These inhibitory events by DLC1 were RhoGAP-dependent, as RhoGAP-deficient mutant of DLC1 (DLC1 K714E) abolished these inhibitory events. In addition, from western study, DLC1 inhibited ROCK-related myosin light chain phosphatase targeting unit 1 (MYPT1) phosphorylation at Threonine 853. By examining cell morphology under microscope, we found that ectopic expression of dominant-active ROCK released cells from DLC1-induced cytoskeletal collapse and cell shrinkage. Conclusion: Our data suggest that DLC1 negatively regulates Rho/ROCK/ MLC2. This implicates a ROCK-mediated pathway of DLC1 in suppressing metastasis of HCC cells and enriches our understanding in the molecular mechanisms involved in the progression of hepatocellular carcinoma. © 2008 Wong et al.published_or_final_versio

    Disposition of Federally Owned Surpluses

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    PDZ domains are scaffolding modules in protein-protein interactions that mediate numerous physiological functions by interacting canonically with the C-terminus or non-canonically with an internal motif of protein ligands. A conserved carboxylate-binding site in the PDZ domain facilitates binding via backbone hydrogen bonds; however, little is known about the role of these hydrogen bonds due to experimental challenges with backbone mutations. Here we address this interaction by generating semisynthetic PDZ domains containing backbone amide-to-ester mutations and evaluating the importance of individual hydrogen bonds for ligand binding. We observe substantial and differential effects upon amide-to-ester mutation in PDZ2 of postsynaptic density protein 95 and other PDZ domains, suggesting that hydrogen bonding at the carboxylate-binding site contributes to both affinity and selectivity. In particular, the hydrogen-bonding pattern is surprisingly different between the non-canonical and canonical interaction. Our data provide a detailed understanding of the role of hydrogen bonds in protein-protein interactions

    On staying grounded and avoiding Quixotic dead ends

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    The 15 articles in this special issue on The Representation of Concepts illustrate the rich variety of theoretical positions and supporting research that characterize the area. Although much agreement exists among contributors, much disagreement exists as well, especially about the roles of grounding and abstraction in conceptual processing. I first review theoretical approaches raised in these articles that I believe are Quixotic dead ends, namely, approaches that are principled and inspired but likely to fail. In the process, I review various theories of amodal symbols, their distortions of grounded theories, and fallacies in the evidence used to support them. Incorporating further contributions across articles, I then sketch a theoretical approach that I believe is likely to be successful, which includes grounding, abstraction, flexibility, explaining classic conceptual phenomena, and making contact with real-world situations. This account further proposes that (1) a key element of grounding is neural reuse, (2) abstraction takes the forms of multimodal compression, distilled abstraction, and distributed linguistic representation (but not amodal symbols), and (3) flexible context-dependent representations are a hallmark of conceptual processing
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