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)

Ubiquitin-specific protease 5 is required for the efficient repair of DNA double-strand breaks

During the DNA damage response (DDR), ubiquitination plays an important role in the recruitment and regulation of repair proteins. However, little is known about elimination of the ubiquitination signal after repair is completed. Here we show that the ubiquitin-specific protease 5 (USP5), a deubiquitinating enzyme, is involved in the elimination of the ubiquitin signal from damaged sites and is required for efficient DNA double-strand break (DSB) repair. Depletion of USP5 sensitizes cells to DNA damaging agents, produces DSBs, causes delayed disappearance of γH2AX foci after Bleocin treatment, and influences DSB repair efficiency in the homologous recombination pathway but not in the non-homologous end joining pathway. USP5 co-localizes to DSBs induced by laser micro-irradiation in a RAD18-dependent manner. Importantly, polyubiquitin chains at sites of DNA damage remained for longer periods in USP5-depleted cells. Our results show that disassembly of polyubiquitin chains by USP5 at sites of damage is important for efficient DSB repair. © 2014 Nakajima et al

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

The Ubiquitin E3/E4 Ligase UBE4A Adjusts Protein Ubiquitylation and Accumulation at Sites of DNA Damage, Facilitating Double-Strand Break Repair

Double-strand breaks (DSBs) are critical DNA lesions that robustly activate the elaborate DNA damage response (DDR) network. We identified a critical player in DDR fine-tuning: the E3/E4 ubiquitin ligase UBE4A. UBE4A's recruitment to sites of DNA damage is dependent on primary E3 ligases in the DDR and promotes enhancement and sustainment of K48- and K63-linked ubiquitin chains at these sites. This step is required for timely recruitment of the RAP80 and BRCA1 proteins and proper organization of RAP80- and BRCA1-associated protein complexes at DSB sites. This pathway is essential for optimal end resection at DSBs, and its abrogation leads to upregulation of the highly mutagenic alternative end-joining repair at the expense of error-free homologous recombination repair. Our data uncover a critical regulatory level in the DSB response and underscore the importance of fine-tuning the complex DDR network for accurate and balanced execution of DSB repair

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)