Pengaruh Sosialisasi Perpajakan, Tarif Pajak, dan Pemahaman Perpajakan terhadap Kepatuhan Wajib Pajak (Studi pada UMKM yang Terdaftar sebagai Wajib Pajak di Kantor Pelayanan Pajak Pratama Batu)

This study is conducted to determine the effect of socialization of taxation, tax rates, and an understanding of taxation upon tax compliance. This study is included in the class explanatory research. SMEs are registered as a taxpayer in the Tax Office Pratama Batu is the population of this study. Samples are 96 respondents with purposive sampling method. The respondents criteria are taxpayer as SMEs sector with a turnover of not more than Rp 4.8 billion, - in a tax year. The results showed socialization taxation have a significant influence on tax compliance by 0.252, the tax rate has a significant influence on tax compliance of 0.413, and an understanding of taxation has a significant influence on tax compliance by 0.217. The dominant variable in this study is the tax rate. Advice to the DGT as the government agency that manages taxation state in Indonesia, one of the regulators in particular tax rates, is expected to consider carefully the tax rates that will be given to taxpayers, among which to conduct a survey or research in advance to the state tax payer especially SMEs with pay attention to several factors that tax compliance is increase

Mycobacterium tuberculosis Phosphoribosylpyrophosphate Synthetase: Biochemical Features of a Crucial Enzyme for Mycobacterial Cell Wall Biosynthesis

The selection and soaring spread of Mycobacterium tuberculosis multidrug-resistant (MDR-TB) and extensively drug-resistant strains (XDR-TB) is a severe public health problem. Currently, there is an urgent need for new drugs for tuberculosis treatment, with novel mechanisms of action and, moreover, the necessity to identify new drug targets. Mycobacterial phosphoribosylpyrophosphate synthetase (MtbPRPPase) is a crucial enzyme involved in the biosynthesis of decaprenylphosphoryl-arabinose, an essential precursor for the mycobacterial cell wall biosynthesis. Moreover, phosphoribosylpyrophosphate, which is the product of the PRPPase catalyzed reaction, is the precursor for the biosynthesis of nucleotides and of some amino acids such as histidine and tryptophan. In this context, the elucidation of the molecular and functional features of MtbPRPPase is mandatory. MtbPRPPase was obtained as a recombinant form, purified to homogeneity and characterized. According to its hexameric form, substrate specificity and requirement of phosphate for activity, the enzyme proved to belong to the class I of PRPPases. Although the sulfate mimicked the phosphate, it was less effective and required higher concentrations for the enzyme activation. MtbPRPPase showed hyperbolic response to ribose 5-phosphate, but sigmoidal behaviour towards Mg-ATP. The enzyme resulted to be allosterically activated by Mg2+ or Mn2+ and inhibited by Ca2+ and Cu2+ but, differently from other characterized PRPPases, it showed a better affinity for the Mn2+ and Cu2+ ions, indicating a different cation binding site geometry. Moreover, the enzyme from M. tuberculosis was allosterically inhibited by ADP, but less sensitive to inhibition by GDP. The characterization of M. tuberculosis PRPPase provides the starting point for the development of inhibitors for antitubercular drug design

Assessing Measurable Residual Disease in Chronic Myeloid Leukemia. BCR-ABL1 IS in the Avant-Garde of Molecular Hematology

Chronic myelogenous leukemia (CML) is a malignancy of the myeloid cell lineage characterized by a recurrent chromosomal abnormality: the Philadelphia chromosome, which results from the reciprocal translocation of the chromosomes 9 and 22. The Philadelphia chromosome contains a fusion gene called BCR-ABL1. The BCR-ABL1 codes for an aberrantly functioning tyrosine kinase that drives the malignant proliferation of the founding clone. The advent of tyrosine kinase inhibitors (TKI) represents a landmark in the treatment of CML, that has led to tremendous improvement in the remission and survival rates. Since the introduction of imatinib, the first TKI, several other TKI have been approved that further broadened the arsenal against CML. Patients treated with TKIs require sensitive monitoring of BCR-ABL1 transcripts with quantitative real-time polymerase chain reaction (qRT-PCT), which has become an essential part of managing patients with CML. In this review, we discuss the importance of the BCR-ABL1 assay, and we highlight the growing importance of BCR-ABL1 dynamics. We also introduce a mathematical correction for the BCR-ABL1 assay that could help homogenizing the use of the ABL1 as a control gene. Finally, we discuss the growing body of evidence concerning treatment-free remission. Along with the continuous improvement in the therapeutic arsenal against CML, the molecular monitoring of CML represents the avant-garde in the struggle to make CML a curable disease

Motion-corrected reconstruction of parametric images from dynamic PET data with the Synergistic Image Reconstruction Framework (SIRF)

Motion correction has been added to a PET-MR reconstruction tool, SIRF, by incorporating a registration package, NiftyReg. New functionality has been demonstrated in the context of estimating kinetic parameters in the left temporal lobe, comparing direct and indirect reconstructions and evaluating the impact of using motion correction.Principal component analysis was used to detect motion and to determine time frames, while STIR's parametric-OSEM was used to perform the motion-corrected direct parametric reconstruction.It was found that the variance in the left temporal lobe decreased when motion correction was performed, and the same was true of direct reconstructions compared to indirect.With SIRF, the entirety of the demonstrated functionality can be performed from a single Matlab or Python script

Assessment of three Resistance-Nodulation-Cell Division drug efflux transporters of Burkholderia cenocepacia in intrinsic antibiotic resistance

<p>Abstract</p> <p>Background</p> <p><it>Burkholderia cenocepacia </it>are opportunistic Gram-negative bacteria that can cause chronic pulmonary infections in patients with cystic fibrosis. These bacteria demonstrate a high-level of intrinsic antibiotic resistance to most clinically useful antibiotics complicating treatment. We previously identified 14 genes encoding putative Resistance-Nodulation-Cell Division (RND) efflux pumps in the genome of <it>B. cenocepacia </it>J2315, but the contribution of these pumps to the intrinsic drug resistance of this bacterium remains unclear.</p> <p>Results</p> <p>To investigate the contribution of efflux pumps to intrinsic drug resistance of <it>B. cenocepacia </it>J2315, we deleted 3 operons encoding the putative RND transporters RND-1, RND-3, and RND-4 containing the genes <it>BCAS0591</it>-<it>BCAS0593</it>, <it>BCAL1674</it>-<it>BCAL1676</it>, and <it>BCAL2822</it>-<it>BCAL2820</it>. Each deletion included the genes encoding the RND transporter itself and those encoding predicted periplasmic proteins and outer membrane pores. In addition, the deletion of <it>rnd-3 </it>also included <it>BCAL1672</it>, encoding a putative TetR regulator. The <it>B. cenocepacia rnd-3 </it>and <it>rnd-4 </it>mutants demonstrated increased sensitivity to inhibitory compounds, suggesting an involvement of these proteins in drug resistance. Moreover, the <it>rnd-3 </it>and <it>rnd-4 </it>mutants demonstrated reduced accumulation of N-acyl homoserine lactones in the growth medium. In contrast, deletion of the <it>rnd-1 </it>operon had no detectable phenotypes under the conditions assayed.</p> <p>Conclusion</p> <p>Two of the three inactivated RND efflux pumps in <it>B. cenocepacia </it>J2315 contribute to the high level of intrinsic resistance of this strain to some antibiotics and other inhibitory compounds. Furthermore, these efflux systems also mediate accumulation in the growth medium of quorum sensing molecules that have been shown to contribute to infection. A systematic study of RND efflux systems in <it>B. cenocepacia </it>is required to provide a full picture of intrinsic antibiotic resistance in this opportunistic bacterium.</p

Impact of the inversion time on regional brain perfusion estimation with clinical arterial spin labeling protocols

Objective: Evaluating the impact of the Inversion Time (TI) on regional perfusion estimation in a pediatric cohort using Arterial Spin Labeling (ASL). Materials and methods: Pulsed ASL (PASL) was acquired at 3 T both at TI 1500 ms and 2020 ms from twelve MRI-negative patients (age range 9–17 years). A volume of interest (VOIs) and a voxel-wise approach were employed to evaluate subject-specific TI-dependent Cerebral Blood Flow (CBF) differences, and grey matter CBF Z-score differences. A visual evaluation was also performed. Results: CBF was higher for TI 1500 ms in the proximal territories of the arteries (PTAs) (e.g. insular cortex and basal ganglia — P < 0.01 and P < 0.05 from the VOI analysis, respectively), and for TI 2020 ms in the distal territories of the arteries (DTAs), including the watershed areas (e.g. posterior parietal and occipital cortex — P < 0.001 and P < 0.01 from the VOI analysis, respectively). Similar differences were also evident when analyzing patient-specific CBF Z-scores and at a visual inspection. Conclusions: TI influences ASL perfusion estimates with a region-dependent effect. The presence of intraluminal arterial signal in PTAs and the longer arterial transit time in the DTAs (including watershed areas) may account for the TI-dependent differences. Watershed areas exhibiting a lower perfusion signal at short TIs (~ 1500 ms) should not be misinterpreted as focal hypoperfused areas

Vibration issues in timber structures: A state-of-the-art review

The increasing use of timber structures worldwide has brought attention to the challenges posed by their lightweight nature, making them more prone to vibrations than more massive structures. Consequently, significant research efforts have been dedicated to understanding and mitigating vibrations in timber structures, while scientific committees strive to establish suitable design regulations. This study aims to classify and identify the main research themes related to timber structure vibrations and highlight future research needs and directions. A bibliometricbased selection process briefly introduces each research topic, presenting the latest findings and proposals for vibration design in timber structures. The paper emphasizes the key outcomes and significant contributions to understanding and addressing vibration issues in timber structures. These findings serve as valuable guidance for researchers, designers, and regulatory bodies involved in designing and assessing timber structures subjected to vibrations

Mutant p53R270H drives altered metabolism and increased invasion in pancreatic ductal adenocarcinoma

Pancreatic cancer is characterized by nearly universal activating mutations in KRAS. Among other somatic mutations, TP53 is mutated in more than 75% of human pancreatic tumors. Genetically engineered mice have proven instrumental in studies of the contribution of individual genes to carcinogenesis. Oncogenic Kras mutations occur early during pancreatic carcinogenesis and are considered an initiating event. In contrast, mutations in p53 occur later during tumor progression. In our model, we recapitulated the order of mutations of the human disease, with p53 mutation following expression of oncogenic Kras. Further, using an inducible and reversible expression allele for mutant p53, we inactivated its expression at different stages of carcinogenesis. Notably, the function of mutant p53 changes at different stages of carcinogenesis. Our work establishes a requirement for mutant p53 for the formation and maintenance of pancreatic cancer precursor lesions. In tumors, mutant p53 becomes dispensable for growth. However, it maintains the altered metabolism that characterizes pancreatic cancer and mediates its malignant potential. Further, mutant p53 promotes epithelial-mesenchymal transition (EMT) and cancer cell invasion. This work generates new mouse models that mimic human pancreatic cancer and expands our understanding of the role of p53 mutation, common in the majority of human malignancies