57 research outputs found
Penyelesaian Tindak Pidana Perjudian yang Dilakukan oleh Anak Menurut UU No.11 Tahun 2012
The title of this legal writing is "The Completion of the Crime of Gambling Carried Out by minors based on the law Number 11 of 2012 on the Juvenile Justice system". This type of research is normative legal research. Normative legal research is a research conducted or focusing on norm of positive law in the form of legislation. Legal issues raised is whether the completion of the crime of gambling by children is in conformity with the law Number 11 of 2012 about the juvenile justice system. The purpose of this research is to determine and analyze the completion of the crime of gambling by children under the law of the juvenile justice system. The result showed that the efforts made to prevent criminal acts of a child is an attempt preventive and repressive efforts. Juvenile justice system is closely related to restorative justice. Regarding the obligation to make a diversion conducted by law enforcement officials, in particular under Article 7 and 96 of the law number 11 of 2012 on the Juvenile Justice System
Effect of microporous membrane properties and operating conditions on particle retention: Measurements and model studies
<p>Depth filtration with microporous membranes has been modelled by extending upon previous approaches of Polyakov<sup>[1–4]</sup> to incorporate pore size distribution, tortuosity, and cake buildup. The model-forecasts were benchmarked against filtration measurements performed with colloidal particles using three very different commercial membrane morphologies with the same nominal average pore size. The critical flux for each membrane was determined by a standard flux-stepping method. Particle retention and permeance were studied under constant flux or transmembrane pressure test conditions. Comparison of the forecast results with data shows reasonable qualitative agreement, but the results are very sensitive to the measurement uncertainties of the various properties.</p
Identification and Optimization of New Dual Inhibitors of B‑Raf and Epidermal Growth Factor Receptor Kinases for Overcoming Resistance against Vemurafenib
Epidermal growth factor receptor
(EGFR) amplification has been
demonstrated to be critical for the inherent and/or acquired resistance
against current B-Raf<sup>V600E</sup> inhibitor therapy for melanoma
and colorectal cancer patients. We describe the discovery and structure–activity
relationship study of a series of 1<i>H</i>-pyrazoloÂ[3,4-<i>b</i>]Âpyridine-5-carboxamide analogues as novel dual inhibitors
of EGFR and B-Raf<sup>V600E</sup> mutant. One of the most promising
compounds, <b>6a</b>, potently inhibited both of the kinases
with IC<sub>50</sub> values of 8.0 and 51 nM, respectively. The compound
also strongly suppressed the proliferation of a panel of intrinsic
and acquired resistant melanoma and/or colorectal cancer cells harboring
overexpressed EGFR with submicromolar IC<sub>50</sub> values. Further
mechanism investigation revealed that <b>6a</b> could sustainably
inhibit the activation of the MAPK path way in the resistant SK-MEL-28
PR30 melanoma cancer cells and WiDr colorectal cancer cells with EGFR
amplification. Our results support the hypothesis that the EGFR/B-Raf<sup>V600E</sup> dual inhibition might be a tractable strategy to overcome
the intrinsic and acquired resistance of melanoma and/or colorectal
cancers against the current B-Raf<sup>V600E</sup> inhibitor therapy
MOESM2 of Construction of energy-conserving sucrose utilization pathways for improving poly-ĂŽĹ‚-glutamic acid production in Bacillus amyloliquefaciens
Additional file 2: Table S2. Genes sequences used in this article
Design, Synthesis, and Biological Evaluation of 2‑Oxo-3,4-dihydropyrimido[4,5‑<i>d</i>]pyrimidinyl Derivatives as New Irreversible Epidermal Growth Factor Receptor Inhibitors with Improved Pharmacokinetic Properties
Structural
optimization of a series of 2-oxo-3,4-dihydropyrimidoÂ[4,5-<i>d</i>]Âpyrimidinyl compounds, potential new irreversible EGFR
inhibitors, was performed to improve pharmacokinetic properties of
the compounds. This led to compound <b>2v</b> with improved
aqueous solubility and good pharmacokinetic properties which at the
nanomolar level potently inhibits gefitinib-resistant EGFR<sup>L858R/T790M</sup> kinase and displays strong antiproliferative activity against H1975
nonsmall cell lung cancer cells. The new inhibitor also shows promising
antitumor efficacy in a murine EGFR<sup>L858R/T790M</sup>-driven H1975
xenograft model without effect on body weight. These studies provide
new lead compounds for further development of drugs for treatment
of gefitinib-resistant nonsmall cell lung cancer patients
Discovery and Optimization of 3‑(2-(Pyrazolo[1,5‑<i>a</i>]pyrimidin-6-yl)ethynyl)benzamides as Novel Selective and Orally Bioavailable Discoidin Domain Receptor 1 (DDR1) Inhibitors
Discoidin
domain receptor 1 (DDR1) is an emerging potential molecular target
for new anticancer drug discovery. We have discovered a series of
3-(2-(pyrazoloÂ[1,5-<i>a</i>]Âpyrimidin-6-yl) ethynyl)Âbenzamides
that are selective and orally bioavailable DDR1 inhibitors. The two
most promising compounds (<b>7rh</b> and <b>7rj</b>) inhibited
the enzymatic activity of DDR1, with IC<sub>50</sub> values of 6.8
and 7.0 nM, respectively, but were significantly less potent in suppressing
the kinase activities of DDR2, Bcr-Abl, and c-Kit. Further study revealed
that <b>7rh</b> bound with DDR1 with a <i>K</i><sub>d</sub> value of 0.6 nM, while it was significantly less potent to
the other 455 kinases tested. The S(35) and S(10) selectivity scores
of <b>7rh</b> were 0.035 and 0.008, respectively. The compounds
also potently inhibited the proliferation of cancer cells expressing
high levels of DDR1 and strongly suppressed cancer cell invasion,
adhesion, and tumorigenicity. Preliminary pharmacokinetic studies
suggested that they possessed good PK profiles, with oral bioavailabilities
of 67.4% and 56.2%, respectively
Design, Synthesis, and Biological Evaluation of Pyrazolo[1,5‑<i>a</i>]pyridine-3-carboxamides as Novel Antitubercular Agents
A series of pyrazoloÂ[1,5-<i>a</i>]Âpyridine-3-carboxamide
derivatives were designed and synthesized as new anti-<i>Mycobacterium
tuberculosis</i> (Mtb) agents. The compounds exhibit promising <i>in vitro</i> potency with nanomolar MIC values against the drug
susceptive H37Rv strain and a panel of clinically isolated multidrug-resistant
Mtb (MDR-TB) strains. One of the representative compounds (<b>5k</b>) significantly reduces the bacterial burden in an autoluminescent
H37Ra infected mouse model, suggesting its promising potential to
be a lead compound for future antitubercular drug discovery
MOESM1 of Enhancing poly-ĂŽĹ‚-glutamic acid production in Bacillus amyloliquefaciens by introducing the glutamate synthesis features from Corynebacterium glutamicum
Additional file 1: Table S1. Primers used in this work
MOESM1 of Enhancing poly-ĂŽĹ‚-glutamic acid production in Bacillus amyloliquefaciens by introducing the glutamate synthesis features from Corynebacterium glutamicum
Additional file 1: Table S1. Primers used in this work
The distribution and new functions of PKs.
(A) The distribution of PKs across the tree of life, as referenced in Jillian F. Banfield’s study [38]. The blue color in pie chart represents species with PKs present in all genome sequenced species. (B) The catalytic activity of PKs from different species on different substrates. The displayed 7 PKs not only exhibited activity on F6P or Xu5P, but also demonstrated the ability to convert short-chain ketoses into AcP. The corresponding table on the right represents the catalytic activity of these 7 candidate PKs on 6 classes of ketose or ketose phosphate. Each color represents to a specific enzyme activity (U/mg). Detailed catalytic activity data are shown in S1 Table. The raw data was listed in S1 Data. AcP, acetyl-phosphate; F6P, fructose-6-phosphate; PK, phosphoketolase; Xu5P, xylulose-5-phosphate.</p
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