130 research outputs found

    PENGARUH PERILAKU PEMERIKSA PAJAK DAN PROFESIONALISME PEMERIKSA PAJAK TERHADAP KINERJA PEMERIKSA PAJAK (Studi Pada KPP Pratama Bandung Karees )

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    ABSTRAK Penelitian ini bertujuan untuk mengetahui seberapa besar pengaruh perilaku pemeriksa pajak terhadap profesionalisme pemeriksa pajak dampaknya pada kinerja pemeriksa pajak dan untuk mengetahui seberapa besar pengaruh perilaku pemeriksa pajak dan profesionalisme pemeriksa pajak terhadap kinerja pemeriksa pajak . Metode penelitian yang digunakan adalah analisis deskriptif dan verifikatif. Populasi dari penelitian ini adalah pemeriksa pajak di KPP Pratama Bandung Karees yang berjumlah 30 responden. Te knik sampling yang digunakan adalah teknik sampling jenuh yaitu keseluruhan populasi dijadikan sampel penelitian. Analisis data dilakukan dengan menggunakan analisis path dan analisis regresi linier berganda. Hasil penelitian menunju k kan bahwa Perilaku Pemeriksa Pajak masuk ke dalam Kriteria cukup baik karena nilai rata - rata sebesar 33,77 berada pada interval 26,1 s/d 34. Secara parsial Perilaku Pemeriksa Pajak berpengaruh signifikan terhadap Kinerja Pemeriksa Pajak dengan kontribusi pengaruh sebesar 21, 6%. Profesionalisme Pemeriksa Pajak masuk ke dalam Kriteria cukup tinggi karena nilai rata - rata sebesar 47,8 berada pada interval 36,6 s/d 47,8 . Secara parsial Profesionalisme Pemeriksa Pajak berpengaruh signifikan terhadap Kinerja Pemeriksa Pajak dengan k ontribusi pengaruh sebesar 37,2%. Secara simultan Pengaruh Perilaku Pemeriksa Pajak dan Profesionalisme Pemeriksa Pajak terhadap Kinerja Pemeriksa Pajak adalah Perilaku Pemeriksa Pajak dan Profesionalisme Pemeriksa Pajak berpengaruh signifikan terhadap K inerja Pemeriksa Pajak dengan kontribusi pengaruh sebesar 59%. Pengaruh tidak langsung Perilaku Pemeriksa Pajak terhadap Kinerja Pemeriksa Pajak melalui Profesionalisme Pemeriksa Pajak sebesar 26,3%. Total pengaruh Perilaku Pemeriksa Pajak, Profesionalism e Pemeriksa Pajak terhadap Kinerja Pemeriksa Pajak sebesar 47,9%. Kata kunci : Perilaku Pemeriksa Pajak , Profesionalisme Pemeriksa Pajak dan Kinerja Pemeriksa Pajak

    Environmental controls on benthic food web functions and carbon resource use in subarctic lakes

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    Climate warming and consequent greening of subarctic landscapes increase the availability of organic carbon to the detrital food webs in aquatic ecosystems. This may cause important shifts in ecosystem functioning through the functional feeding patterns of benthic organisms that rely differently on climatically altered carbon resources. Twenty-five subarctic lakes in Finnish Lapland across a tree line ecotone were analysed for limnological and optical variables, carbon (delta C-13) and nitrogen (delta N-15) stable isotope (SI) composition of surface sediment organic matter (OM) and fossil Chironomidae (Diptera) remains to examine environmental controls behind chironomid functional feeding group (FFG) structure and their isotopic associations for assessing ecosystem functioning and carbon utilisation. We hypothesise that the chironomid SI signatures reflect increased allochthony with increasing allochthonous input, but the resource use may be altered by the functional characteristics of the assemblage. Multivariate analyses indicated that carbon geochemistry in the sediments (delta C-13, delta N-15, C/N), nutrients, indices of productivity (chlorophyll-a) and lake water optical properties, related to increasing presence of OM, played a key role in defining the chironomid FFG composition and isotopic signatures. Response modelling was used to examine how individual FFGs respond to environmental gradients. They showed divergent responses for OM quantity, dissolved organic carbon and nutrients between feeding strategies, suggesting that detritivores and filter feeders prefer contrasting carbon and nutrient conditions, and may thus hold paleoecological indicator potential to identify changes between different carbon fluxes. Benthic production was the primary carbon source for the chironomid assemblages according to a three-source SI mixing model, whereas pelagic and terrestrial components contributed less. Between-lake variability in source utilisation was high and controlled primarily by allochthonous OM inputs. Combination of biogeochemical modelling and functional classification is useful to widen our understanding of subarctic lake ecosystem functions and responses to climate-driven changes in limnology and catchment characteristics for long-term environmental change assessments and functional paleoecology.Peer reviewe

    Structure of S. aureus HPPK and the Discovery of a New Substrate Site Inhibitor

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    The first structural and biophysical data on the folate biosynthesis pathway enzyme and drug target, 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (SaHPPK), from the pathogen Staphylococcus aureus is presented. HPPK is the second essential enzyme in the pathway catalysing the pyrophosphoryl transfer from cofactor (ATP) to the substrate (6-hydroxymethyl-7,8-dihydropterin, HMDP). In-silico screening identified 8-mercaptoguanine which was shown to bind with an equilibrium dissociation constant, Kd, of ∼13 µM as measured by isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR). An IC50 of ∼41 µM was determined by means of a luminescent kinase assay. In contrast to the biological substrate, the inhibitor has no requirement for magnesium or the ATP cofactor for competitive binding to the substrate site. The 1.65 Å resolution crystal structure of the inhibited complex showed that it binds in the pterin site and shares many of the key intermolecular interactions of the substrate. Chemical shift and 15N heteronuclear NMR measurements reveal that the fast motion of the pterin-binding loop (L2) is partially dampened in the SaHPPK/HMDP/α,β-methylene adenosine 5′-triphosphate (AMPCPP) ternary complex, but the ATP loop (L3) remains mobile on the µs-ms timescale. In contrast, for the SaHPPK/8-mercaptoguanine/AMPCPP ternary complex, the loop L2 becomes rigid on the fast timescale and the L3 loop also becomes more ordered – an observation that correlates with the large entropic penalty associated with inhibitor binding as revealed by ITC. NMR data, including 15N-1H residual dipolar coupling measurements, indicate that the sulfur atom in the inhibitor is important for stabilizing and restricting important motions of the L2 and L3 catalytic loops in the inhibited ternary complex. This work describes a comprehensive analysis of a new HPPK inhibitor, and may provide a foundation for the development of novel antimicrobials targeting the folate biosynthetic pathway

    VPS29 Is Not an Active Metallo-Phosphatase but Is a Rigid Scaffold Required for Retromer Interaction with Accessory Proteins

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    VPS29 is a key component of the cargo-binding core complex of retromer, a protein assembly with diverse roles in transport of receptors within the endosomal system. VPS29 has a fold related to metal-binding phosphatases and mediates interactions between retromer and other regulatory proteins. In this study we examine the functional interactions of mammalian VPS29, using X-ray crystallography and NMR spectroscopy. We find that although VPS29 can coordinate metal ions Mn2+ and Zn2+ in both the putative active site and at other locations, the affinity for metals is low, and lack of activity in phosphatase assays using a putative peptide substrate support the conclusion that VPS29 is not a functional metalloenzyme. There is evidence that structural elements of VPS29 critical for binding the retromer subunit VPS35 may undergo both metal-dependent and independent conformational changes regulating complex formation, however studies using ITC and NMR residual dipolar coupling (RDC) measurements show that this is not the case. Finally, NMR chemical shift mapping indicates that VPS29 is able to associate with SNX1 via a conserved hydrophobic surface, but with a low affinity that suggests additional interactions will be required to stabilise the complex in vivo. Our conclusion is that VPS29 is a metal ion-independent, rigid scaffolding domain, which is essential but not sufficient for incorporation of retromer into functional endosomal transport assemblies

    ‘Orientalism is a partisan book’: applying Edward Said's insights to early modern travel writing

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    Since its publication in 1978, Edward Said's Orientalism has had a significant impact on postcolonial studies in a range of fields. This paper assesses his impact on the historiography of Anglophone travel writing concerning Ottoman Empire during the early modern period. Said's analysis of the relationship between representational power and colonial authority remains relevant to our understanding of early modern travel texts. Said's epistemology raises significant issues for historians of early modern intercultural encounters. This article summarises recent debates surrounding early modern travel narratives. It contrasts doctrinaire applications of Said's theory with more recent, particularistic studies. It provides a much-needed survey of travel writing historiography that considers the continuing impact of Said's postcolonial thought on the study of early modern travel narratives relating to the Ottoman Middle East. In so doing, it explores the lack of fit between early modern travel narratives and Said's methodology. I explore the methodological problems thrown up by conventional applications of Said's epistemology to precolonial travellers' texts. Based on a wide-ranging survey of Said's oeuvre, the article demonstrates that, more than 30 years on, Said's work remains relevant to the historiographical challenges presented by early modern English travel writing about Islam

    Aquatic therapy for children with Duchenne muscular dystrophy: a pilot feasibility randomised controlled trial and mixed-methods process evaluation.

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    BACKGROUND: Duchenne muscular dystrophy (DMD) is a rare disease that causes the progressive loss of motor abilities such as walking. Standard treatment includes physiotherapy. No trial has evaluated whether or not adding aquatic therapy (AT) to land-based therapy (LBT) exercises helps to keep muscles strong and children independent. OBJECTIVES: To assess the feasibility of recruiting boys with DMD to a randomised trial evaluating AT (primary objective) and to collect data from them; to assess how, and how well, the intervention and trial procedures work. DESIGN: Parallel-group, single-blind, randomised pilot trial with nested qualitative research. SETTING: Six paediatric neuromuscular units. PARTICIPANTS: Children with DMD aged 7-16 years, established on corticosteroids, with a North Star Ambulatory Assessment (NSAA) score of 8-34 and able to complete a 10-m walk without aids/assistance. Exclusions: > 20% variation between baseline screens 4 weeks apart and contraindications. INTERVENTIONS: Participants were allocated on a 1 : 1 ratio to (1) optimised, manualised LBT (prescribed by specialist neuromuscular physiotherapists) or (2) the same plus manualised AT (30 minutes, twice weekly for 6 months: active assisted and/or passive stretching regime; simulated or real functional activities; submaximal exercise). Semistructured interviews with participants, parents (n = 8) and professionals (n = 8) were analysed using Framework analysis. An independent rater reviewed patient records to determine the extent to which treatment was optimised. A cost-impact analysis was performed. Quantitative and qualitative data were mixed using a triangulation exercise. MAIN OUTCOME MEASURES: Feasibility of recruiting 40 participants in 6 months, participant and therapist views on the acceptability of the intervention and research protocols, clinical outcomes including NSAA, independent assessment of treatment optimisation and intervention costs. RESULTS: Over 6 months, 348 children were screened - most lived too far from centres or were enrolled in other trials. Twelve (30% of target) were randomised to AT (n = 8) or control (n = 4). People in the AT (n = 8) and control (n = 2: attrition because of parental report) arms contributed outcome data. The mean change in NSAA score at 6 months was -5.5 [standard deviation (SD) 7.8] for LBT and -2.8 (SD 4.1) in the AT arm. One boy suffered pain and fatigue after AT, which resolved the same day. Physiotherapists and parents valued AT and believed that it should be delivered in community settings. The independent rater considered AT optimised for three out of eight children, with other children given programmes that were too extensive and insufficiently focused. The estimated NHS costs of 6-month service were between £1970 and £2734 per patient. LIMITATIONS: The focus on delivery in hospitals limits generalisability. CONCLUSIONS: Neither a full-scale frequentist randomised controlled trial (RCT) recruiting in the UK alone nor a twice-weekly open-ended AT course delivered at tertiary centres is feasible. Further intervention development research is needed to identify how community-based pools can be accessed, and how families can link with each other and community physiotherapists to access tailored AT programmes guided by highly specialised physiotherapists. Bayesian RCTs may be feasible; otherwise, time series designs are recommended. TRIAL REGISTRATION: Current Controlled Trials ISRCTN41002956. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 27. See the NIHR Journals Library website for further project information

    Crowdsourcing hypothesis tests: Making transparent how design choices shape research results

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    To what extent are research results influenced by subjective decisions that scientists make as they design studies? Fifteen research teams independently designed studies to answer fiveoriginal research questions related to moral judgments, negotiations, and implicit cognition. Participants from two separate large samples (total N > 15,000) were then randomly assigned to complete one version of each study. Effect sizes varied dramatically across different sets of materials designed to test the same hypothesis: materials from different teams renderedstatistically significant effects in opposite directions for four out of five hypotheses, with the narrowest range in estimates being d = -0.37 to +0.26. Meta-analysis and a Bayesian perspective on the results revealed overall support for two hypotheses, and a lack of support for three hypotheses. Overall, practically none of the variability in effect sizes was attributable to the skill of the research team in designing materials, while considerable variability was attributable to the hypothesis being tested. In a forecasting survey, predictions of other scientists were significantly correlated with study results, both across and within hypotheses. Crowdsourced testing of research hypotheses helps reveal the true consistency of empirical support for a scientific claim.</div

    SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

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    Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types
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