Kebijakan Reformulasi Ancaman Pidana Mati Tindak Pidana Korupsi dalam Peraturan Perundang-undangan

Corruption in Indonesia systematically in all sectors of public life, has threatened the efforts of sustainable development and the achievement of social welfare in Indonesia. Society demanded that the death sentence meted out to the criminals, so that corruption can be prevented and eradicated systematically. However, until now there has been no single criminals sentenced to death. This happens because of the legal weaknesses in the formulation death sentence for corruption. Some disadvantages juridical include: the death penalty only for offenses threatened enrich themselves / others / corporate corruption, death penalty only for corruption perpetrated under certain circumstances, the law does not formulate terms / limitations repetition acts criminal (recidive) for corruption, crime repeated terms and repetition period in terms of providing capital punishment for repeat offenses (recidive) for corruption. Reformulation of capital punishment for corruption should be threatened by the principal alternative to other types of criminal offense-specific corruption offenses considered very disgraceful and extremely harmful and damaging the wider society (nation / state). In addition, given the threat of the death penalty is a last resort in combating corruption should also formulated an alternative capital punishment or other forms of death penalty mitigation

Ni and Ni Silicides Ohmic Contacts on N-type 6H-SiC with Medium and Low Doping Level

Ni silicides contacts, which are expected to be advantageous contact materials on SiC, were tested in this work. Prepared contact structures were ohmic with low contact resistivity approximately 8×10-4 Ω cm2 after annealing at 960°C as far as the SiC substrate with a medium doping level was concerned, no matter whether Ni or Ni silicides were used. At lower annealing temperatures, only Schottky behavior was observed by means of I-V characteristics measurements. In the case of SiC substrate with a low doping level, the behavior differed. It was necessary to anneal the structures at 1070°C to see ohmic behavior appearing with resistivities reaching 8×10-3 Ω cm2 and this was valid only for Ni and Ni2Si. Raman spectroscopy measurements confirmed formation of single Ni silicides as expected. It was found that Ni silicides can keep as good resistivity as Ni contacts while they interact with SiC in limited way and their undesirable drop-like morphology is expected to be overcome for example with a covering layer

Kebijakan Reformasi Maqâshid Al-Syarîah dan Kontribusinya dalam Formulasi Alternatif Keringanan Pidana Penjara

Criminal law is often built on the paradigm of giving suffering to perpetrators of crime. This paradigm is no longer in accordance with the concept of modern punishment which focuses on efforts to foster criminals so that they would no longer repeat their actions. The changes in the paradigm of punishment, to some extent, have been accommodated by Article 73 of the Criminal Code Bill which contains alternative provisions/criminal sanctions.in jail. With this provision, a prisoner with one year or under punishment is able to repay his sentence as long as there are certain emergency conditions leading to a precarious situation/worry to him if he has to undergo consecutive penalties. This study tries to examine the new provision, using a normative juridical approach from the perspective of Islamic law. This study concludes that the paradigmatic change in punishment as shown in article 73 of the Criminal Code Bill has conformity with the perspective of maqâshid al-syarî'ah which put forward the 5 (five) main objectives in the law, namely maintaining and nurturing religion (al-dîn), soul (al-nafs), descent (al-nasl), wealth (al-mâl), and mind (al-aql)

Development of SYK NanoBRET cellular target engagement assays for gain–of–function variants

Spleen tyrosine kinase (SYK) is a non-receptor tyrosine kinase that is activated by phosphorylation events downstream of FcR, B-cell and T-cell receptors, integrins, and C-type lectin receptors. When the tandem Src homology 2 (SH2) domains of SYK bind to phosphorylated immunoreceptor tyrosine-based activation motifs (pITAMs) contained within these immunoreceptors, or when SYK is phosphorylated in interdomain regions A and B, SYK is activated. SYK gain-of-function (GoF) variants were previously identified in six patients that had higher levels of phosphorylated SYK and phosphorylated downstream proteins JNK and ERK. Furthermore, the increased SYK activation resulted in the clinical manifestation of immune dysregulation, organ inflammation, and a predisposition for lymphoma. The knowledge that the SYK GoF variants have enhanced activity was leveraged to develop a SYK NanoBRET cellular target engagement assay in intact live cells with constructs for the SYK GoF variants. Herein, we developed a potent SYK-targeted NanoBRET tracer using a SYK donated chemical probe, MRL-SYKi, that enabled a NanoBRET cellular target engagement assay for SYK GoF variants, SYK(S550Y), SYK(S550F), and SYK(P342T). We determined that ATP-competitive SYK inhibitors bind potently to these SYK variants in intact live cells. Additionally, we demonstrated that MRL-SYKi can effectively reduce the catalytic activity of SYK variants, and the phosphorylation levels of SYK(S550Y) in an epithelial cell line (SW480) stably expressing SYK(S550Y)

Efficacy and safety of ascending doses of praziquantel against Schistosoma haematobium infection in preschool-aged and school-aged children : a single-blind randomised controlled trial

Despite decades of experience with praziquantel treatment in school-aged children (SAC) and adults, we still face considerable knowledge gaps relevant to the successful treatment of preschool-aged children (PSAC). This study aimed to assess the efficacy and safety of escalating praziquantel dosages in PSAC infected with Schistosoma haematobium.; We conducted a randomised, dose-finding trial in PSAC (2-5 years) and as comparator a cohort of SAC (6-15 years) infected with S. haematobium in Côte d'Ivoire. A total of 186 PSAC and 195 SAC were randomly assigned to 20, 40 or 60 mg/kg praziquantel or placebo. The nature of the dose-response relationship in terms of cure rate (CR) was the primary objective. Egg reduction rate (ERR) and tolerability were secondary outcomes. CRs and ERRs were assessed using triplicate urine filtration over 3 consecutive days. Available-case analysis was performed including all participants with primary endpoint data.; A total of 170 PSAC and 174 SAC received treatment. Almost 90% of PSAC and three quarters of SAC were lightly infected with S. haematobium. Follow-up data were available for 157 PSAC and 166 SAC. In PSAC, CRs of praziquantel were 85.7% (30/35), 78.0% (32/41) and 68.3% (28/41) at 20, 40 and 60 mg/kg and 47.5% (19/40) for placebo. In SAC, CRs were 10.8% for placebo (4/37), 55.6% for 20 mg/kg (25/45), 68.3% for 40 mg/kg (28/41) and 60.5% for 60 mg/kg (26/43). ERRs based on geometric means ranged between 96.5% (60 mg/kg) and 98.3% (20 mg/kg) in PSAC and between 97.6% (20 mg/kg and 60 mg/kg) and 98.6% (40 mg/kg) in SAC. Adverse events were mild and transient.; Praziquantel revealed dose-independent efficacy against light infections of S. haematobium. Over the dose range tested, praziquantel displayed a ceiling effect with the highest response for 20 mg/kg in PSAC. In SAC maximum efficacy was obtained with 40 mg/kg praziquantel. Further investigations are required in children with moderate to heavy infections.; This trial is registered with International Standard Randomised Controlled Trial Number ISRCTN15280205

Effects of Intracellular Calcium and Actin Cytoskeleton on TCR Mobility Measured by Fluorescence Recovery

Background: The activation of T lymphocytes by specific antigen is accompanied by the formation of a specialized signaling region termed the immunological synapse, characterized by the clustering and segregation of surface molecules and, in particular, by T cell receptor (TCR) clustering. Methodology/Principal Findings: To better understand TCR motion during cellular activation, we used confocal microscopy and photo-bleaching recovery techniques to investigate the lateral mobility of TCR on the surface of human T lymphocytes under various pharmacological treatments. Using drugs that cause an increase in intracellular calcium, we observed a decrease in TCR mobility that was dependent on a functional actin cytoskeleton. In parallel experiments measurement of filamentous actin by FACS analysis showed that raising intracellular calcium also causes increased polymerization of the actin cytoskeleton. These in vitro results were analyzed using a mathematical model that revealed effective binding parameters between TCR and the actin cytoskeleton. Conclusion/Significance: We propose, based on our results, that increase in intracellular calcium levels leads to actin polymerization and increases TCR/cytoskeleton interactions that reduce the overall mobility of the TCR. In a physiological setting, this may contribute to TCR re-positioning at the immunological synapse

The global response to the COVID-19 pandemic: how have immunology societies contributed?

The COVID-19 pandemic is shining a spotlight on the field of immunology like never before. To appreciate the diverse ways in which immunologists have contributed,Nature Reviews Immunologyinvited the president of the International Union of Immunological Societies and the presidents of 15 other national immunology societies to discuss how they and their members responded following the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).For this Viewpoint,Nature Reviews Immunologyasked the presidents of 16 immunology societies from around the world to discuss how their society and its members responded to the COVID-19 pandemic. Their answers highlight the incredible contributions that immunologists around the globe have made following the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

HIV-1 Nef Employs Two Distinct Mechanisms to Modulate Lck Subcellular Localization and TCR Induced Actin Remodeling

The Nef protein acts as critical factor during HIV pathogenesis by increasing HIV replication in vivo via the modulation of host cell vesicle transport and signal transduction processes. Recent studies suggested that Nef alters formation and function of immunological synapses (IS), thereby modulating exogenous T-cell receptor (TCR) stimulation to balance between partial T cell activation required for HIV-1 spread and prevention of activation induced cell death. Alterations of IS function by Nef include interference with cell spreading and actin polymerization upon TCR engagement, a pronounced intracellular accumulation of the Src kinase Lck and its reduced IS recruitment. Here we use a combination of Nef mutagenesis and pharmacological inhibition to analyze the relative contribution of these effects to Nef mediated alterations of IS organization and function on TCR stimulatory surfaces. Inhibition of actin polymerization and IS recruitment of Lck were governed by identical Nef determinants and correlated well with Nef's association with Pak2 kinase activity. In contrast, Nef mediated Lck endosomal accumulation was separable from these effects, occurred independently of Pak2, required integrity of the microtubule rather than the actin filament system and thus represents a distinct Nef activity. Finally, reduction of TCR signal transmission by Nef was linked to altered actin remodeling and Lck IS recruitment but did not require endosomal Lck rerouting. Thus, Nef affects IS function via multiple independent mechanisms to optimize virus replication in the infected host