Analisis Faktor-Faktor yang Memengaruhi Tingkat Kepatuhan Wajib Pajak Orang Pribadi di Lingkungan Kantor Pelayanan Pajak Pratama, Tigaraksa Tangerang

Tax collection is not an easy matter. Active participation from the tax authorities also requires the willingness of the taxpayer. A public reaction can be seen from the taxpayer\u27s willingness to pay taxes. Willingness and awareness to pay taxes represent a value contributed by someone (which has been determined by regulation). Tax is used to finance public expenditures without any direct benefit. Taxpayer\u27s awareness about taxation functions as state funding is needed to improve tax compliance and to determine the level of tax compliance in implementing their tax obligations. Limitation of the scope of this study is the effect of the level of awareness of paying taxes, taxpayer\u27s understanding about tax benefits, tax penalties, and understanding of service quality to the tax authorities of individual taxpayer compliance in the fulfillment of tax obligations, as well as restricted to data obtained through questionnaires received and filled by the individual taxpayer of Tigaraksa Pratama Tax Office area. Data were obtained through questionnaire and processed and analyzed using parametric statistical tests and multiple linear regression with 4 independent variables and one dependent variable resulted in the conclusion that the factors that most influence taxpayer compliance in carrying out its tax liability is the use of sanctions against taxpayers who do not carry out its obligations under applicable legislation

Dimethyl Fumarate Ameliorates Lewis Rat Experimental Autoimmune Neuritis and Mediates Axonal Protection

<div><p>Background</p><p>Dimethyl fumarate is an immunomodulatory and neuroprotective drug, approved recently for the treatment of relapsing-remitting multiple sclerosis. In view of the limited therapeutic options for human acute and chronic polyneuritis, we used the animal model of experimental autoimmune neuritis in the Lewis rat to study the effects of dimethyl fumarate on autoimmune inflammation and neuroprotection in the peripheral nervous system.</p><p>Methods and Findings</p><p>Experimental autoimmune neuritis was induced by immunization with the neuritogenic peptide (amino acids 53–78) of P2 myelin protein. Preventive treatment with dimethyl fumarate given at 45 mg/kg twice daily by oral gavage significantly ameliorated clinical neuritis by reducing demyelination and axonal degeneration in the nerve conduction studies. Histology revealed a significantly lower degree of inflammatory infiltrates in the sciatic nerves. In addition, we detected a reduction of early signs of axonal degeneration through a reduction of amyloid precursor protein expressed in axons of the peripheral nerves. This reduction correlated with an increase of nuclear factor (erythroid derived 2)-related factor 2 positive axons, supporting the neuroprotective potential of dimethyl fumarate. Furthermore, nuclear factor (erythroid derived 2)-related factor 2 expression in Schwann cells was only rarely detected and there was no increase of Schwann cells death during EAN.</p><p>Conclusions</p><p>We conclude that immunmodulatory and neuroprotective dimethyl fumarate may represent an innovative therapeutic option in human autoimmune neuropathies.</p></div

Clinical EAN course under dimethyl fumarate treatment.

<p>EAN was induced in Lewis rats by immunisation on day 0 with P2 peptide 53–78 plus CFA. Rats received DMF diluted in 0,08% methylcellulose in tap water at doses of 15 mg/kg, 30mg/kg and 45mg/kg twice daily from day 0 to day 23-post immunisation by oral gavage. Control rats received 0,08% methylcellulose in tap water only. Mean values and SEM are depicted, ROC Area under curve (AUC) 45mg/kg vs. methylcellulose, n = 8 * p<0,05. The experiment was repeated 2 times with similar results.</p

Dimethyl fumarate improved proximal and distal nerve conduction.

<p>(A) Representative CMAP (compound motor action potentials) traces during EAN course at days −1 and 16 p.i. showing a conduction block for methylcellulose-treated rats at day 16 p.i. whereas for 45 mg/kg DMF-treated rats no conduction block was recorded. (B) Representative F-wave traces after distal stimulation showing prolonged F-waves latencies only for the methylcellulose-treated group at day 16 p.i. in comparison to day -1. Rats treated with 45mg/kg did not show any significant differences in the F-wave latencies between day -1 and 16 p.i. The black vertical line defines the motor (M) response and the F (F-wave) response latency. On the left of the red vertical line applies the M response regarding distance (horizontally, ms) and vertically (mV) and on the right of the red vertical line applies the F response data (ms, mV), (M: M response, F: F response, D: distance of one side of the dotted lined squares). (C) After proximal and distal stimulation of the sciatic nerve the conduction velocity was calculated. A statistical significant reduction of the MNCV (motor nerve conduction velocity) appeared for the control group and the 15mg/kg group (p<0,0001 ***, n = 10), but no difference in the MNCV was seen for the 45mg/kg DMF treated group indicating a protective role of DMF against demyelination. Mean values and SEM are depicted.</p

Dimethyl fumarate reduced inflammatory infiltrates of T cells and macrophages in sciatic nerves of EAN rats.

<p>(A) Rats were daily force fed with DMF or tap water and 16 days p.i. (at expected disease maximum), sciatic nerves were isolated and stained for CD3⁺ cells (a, b, c) and CD68⁺ cells (macrophages) (d, e, f). Representative photos of sciatic nerves in transverse sections of methylcellulose-treated animals (a and d), 15 mg/kg DMF-treated animals (b and e) and 45mg/kg DMF treated animals (c and f). Scale bars indicate 100μm. (B) Mean numbers of T cells per mm² sciatic nerve sections and B. Mean numbers of macrophages (CD68⁺) per mm² sciatic nerve sections as calculated by immunohistochemistry on day 16 p.i. from EAN rats (n = 6/group) receiving orally DMF at different doses (15mg/kg, 45mg/kg/day) and methylcellulose-treated rats. Mean values and SEM are depicted (** p<0,005, ***p<0,0001). The experiment was repeated 2 times with similar results.</p

The Relation of the Ne peak-to-peak amplitude at Fz and CAG-index.

<p>This figure shows a linear relation of the Ne peak-to-peak amplitude at electrode Fz with the CAG-index, derived via (CAG_n – 35.5) × “age of the patient” <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000086#pone.0000086-Paulsen1" target="_blank">[see: 2]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000086#pone.0000086-SanchezPernaute1" target="_blank">30]</a>.</p

Dimethyl fumarate did not induce Nrf2 in Schwann cells at the peak of EAN course.

<p>Representative photos of double (merge) Nrf2 positive Schwann cells (S100 positive) staining for sciatic nerve transverse sections of rats (n = 6/group) treated with DMF 15mg/kg, 45mg/kg and methylcellulose. No statistical significant increase between Nrf2 positive Schwann cells for DMF-treated vs. methylcellulose-treated rats on day 16 p.i. was detected (insets depict details of staining). Scale bars indicate 50μm.</p

Event-related potentials of the Ne/ERN and CRN.

<div><p>The Ne/ERN (false responses) and CRN (correct responses) for HD and controls at electrode FCz (top) and at Fz (bottom).</p> <p>The x-axis denotes time in milliseconds (ms).</p> <p>The y-axis denotes voltage in µV.</p> <p>The bar plots denote significant differences in the peak-to-peak amplitude of the Ne/ERN between the groups for the electrodes FCz (left) and Fz (right).</p></div

Dimethyl fumarate induced Nrf2 at the peak of EAN course.

<p>(A) Representative photos of Nrf2 staining for sciatic nerve transverse sections of rats (n = 6/group) treated with DMF 15mg/kg (d-f), 45mg/kg (g-i) and methylcellulose-treated animals (a-c), showing an increase of Nrf2 positive cells for 45mg/kg DMF-treated rats. Pictures a, d and g show nuclear stain (DAPI), pictures b, e and h Nrf2 stain and pictures c, f and i indicate double staining. Scale bars indicate 100μm. (B) Percentage of Nrf2 positive staining per sciatic nerve section measured by immunofluorescent staining on day 16 p.i. from EAN rats (n = 6/group) receiving DMF at different doses (15mg/kg, 45mg/kg/day) and methylcellulose-treated rats. Mean values and SEM are depicted (*p<0,05).</p

Dimethyl fumarate reduced early axonal damage at the peak of EAN course.

<p>(A) Representative photos of APP (amyloid precursor protein) staining for sciatic nerve transverse sections of rats (n = 6/group) treated with DMF 15mg/kg (b, e), 45mg/kg (c, f) and methylcellulose-treated animals (a, d), showing an reduction of APP positive cells for DMF-treated rats. Scale bars indicate 100μm for a-c and 50μm for d-f. (B) Mean numbers of APP positive cells per mm² sciatic nerve sections as calculated by immunohistochemistry on day 16 p.i. from EAN rats (n = 6/group) receiving orally DMF at different doses (15mg/kg, 45mg/kg/day) and methylcellulose-treated rats. Mean values and SEM are depicted (*p<0,05). The experiment was repeated 2 times with similar results.</p