31 research outputs found
Characterizing MRO in atomistic models of vitreous SiO generated using ab-initio molecular dynamics
Vitreous silica is the most versatile material for scientific and commercial
applications. Although large-scale atomistic models of vitreous-SiO
(v-SiO) having medium-range order (MRO) have been successfully developed by
melt-quench through classical molecular dynamics, the MRO is not well studied
for the smaller-scale models developed by melt-quench using ab-initio molecular
dynamics (AIMD). In this study, we obtain atomistic models of v-SiO by
performing melt-quench simulation using AIMD. The final structure is compared
with the experimental data and some recent atomistic models, on the basis of
the structural properties. Since AIMD allows for the estimation of electronic
structure, a detailed study of electronic properties is also done. It shows the
presence of defect states mainly due to dangling bonds in the band-gap region
of electronic density of states, whereas the edge-shared type of defective
structures in the glassy models are found to contribute mainly in the valence
band. In addition, Oxygen and Silicon vacancies as well as bridging Oxygen type
of defects were created and their contributions to the band-gap were studied.Comment: 28 pages, 12 figures, preprin
Peluang Imbuhan Pakan Herbal-Probiotik Komersial “Promix®” Sebagai Pengganti Antibiotic Growth Promoter (AGP) pada Ayam Pedaging yang Diberi Vaksin ND
With the prohibition of the use of Antibiotic growth promotors (AGP) used in animal feed, especially in broilers, the use of feed additives such as herbs, probiotics, prebiotics, synbiotics or mixtures of some of these ingredients is currently widely used as feed replacements for AGP substitutes. One of the commercial feed additives that contain combinations herbal and probiotics is Promix®. In broiler maintenance, one vaccine that must be given is Newcastle Disease (ND) vaccine. The purpose of this study was to determine the role of supplementation of commercial feed combination of herbs and probiotics in broilers given ND vaccines. A total of 42 broilers were divided into two, group A (vaccinated with ND) and B (not vaccinated ND), each with 21 heads. Group A is divided into groups A1, A2 and A3 each with 7 heads. The A1 group is given only basal feed; A2 basal feed and AGP; A3 basal feed and Promix®. Group B is divided by B1, B2 and B3 same as group A before. Broilers are maintained for 5 weeks and weighing each week. All data obtained were statistically analyzed using One Way ANOVA and continued with Duncan's post hoc test. The results of this study were that the group of chickens given the ND vaccine and given supplements of Promix® had greater weight gain (P˂0.05) compared to the AGP and basal groups in the fifth week while in the group of chickens that were not given the ND vaccine but given supplement Promix® feed had greater weight gain (P˂0.05) compared to the AGP and basal groups in the fourth week. In the fifth week there was no significant difference (P˂0.05) between all feed groups in the group not given the ND vaccine. The conclusion of this study that feed additives contain combinations herbal and probiotics can replace AGP as feed additive in broiler. By giving ND vaccine the weight gain of the feed group plus Promix® showed a significant increase in weight gain
Withaferin a-induced apoptosis in human breast cancer cells is mediated by reactive oxygen species
Withaferin A (WA), a promising anticancer constituent of Ayurvedic medicinal plant Withania somnifera, inhibits growth of MDA-MB-231 and MCF-7 human breast cancer cells in culture and MDA-MB-231 xenografts in vivo in association with apoptosis induction, but the mechanism of cell death is not fully understood. We now demonstrate, for the first time, that WA-induced apoptosis is mediated by reactive oxygen species (ROS) production due to inhibition of mitochondrial respiration. WA treatment caused ROS production in MDA-MB-231 and MCF-7 cells, but not in a normal human mammary epithelial cell line (HMEC). The HMEC was also resistant to WA-induced apoptosis. WA-mediated ROS production as well as apoptotic histone-associated DNA fragment release into the cytosol was significantly attenuated by ectopic expression of Cu,Zn-superoxide dismutase in both MDA-MB-231 and MCF-7 cells. ROS production resulting from WA exposure was accompanied by inhibition of oxidative phosphorylation and inhibition of complex III activity. Mitochondrial DNA-deficient Rho-0 variants of MDA-MB-231 and MCF-7 cells were resistant to WA-induced ROS production, collapse of mitochondrial membrane potential, and apoptosis compared with respective wild-type cells. WA treatment resulted in activation of Bax and Bak in MDA-MB-231 and MCF-7 cells, and SV40 immortalized embryonic fibroblasts derived from Bax and Bak double knockout mouse were significantly more resistant to WA-induced apoptosis compared with fibroblasts derived from wild-type mouse. In conclusion, the present study provides novel insight into the molecular circuitry of WA-induced apoptosis involving ROS production and activation of Bax/Bak. © 2011 Hahm et al
Myogenic Differential Methylation: Diverse Associations with Chromatin Structure
Employing a new algorithm for identifying differentially methylated regions (DMRs) from reduced representation bisulfite sequencing profiles, we identified 1972 hypermethylated and 3250 hypomethylated myogenic DMRs in a comparison of myoblasts (Mb) and myotubes (Mt) with 16 types of nonmuscle cell cultures. DMRs co-localized with a variety of chromatin structures, as deduced from ENCODE whole-genome profiles. Myogenic hypomethylation was highly associated with both weak and strong enhancer-type chromatin, while hypermethylation was infrequently associated with enhancer-type chromatin. Both myogenic hypermethylation and hypomethylation often overlapped weak transcription-type chromatin and Polycomb-repressed-type chromatin. For representative genes, we illustrate relationships between DNA methylation, the local chromatin state, DNaseI hypersensitivity, and gene expression. For example, MARVELD2 exhibited myogenic hypermethylation in transcription-type chromatin that overlapped a silenced promoter in Mb and Mt while TEAD4 had myogenic hypomethylation in intronic subregions displaying enhancer-type or transcription-type chromatin in these cells. For LSP1, alternative promoter usage and active promoter-type chromatin were linked to highly specific myogenic or lymphogenic hypomethylated DMRs. Lastly, despite its myogenesis-associated expression, TBX15 had multiple hypermethylated myogenic DMRs framing its promoter region. This could help explain why TBX15 was previously reported to be underexpressed and, unexpectedly, its promoter undermethylated in placentas exhibiting vascular intrauterine growth restriction
Myogenic Differential Methylation: Diverse Associations with Chromatin Structure
Employing a new algorithm for identifying differentially methylated regions (DMRs) from reduced representation bisulfite sequencing profiles, we identified 1972 hypermethylated and 3250 hypomethylated myogenic DMRs in a comparison of myoblasts (Mb) and myotubes (Mt) with 16 types of nonmuscle cell cultures. DMRs co-localized with a variety of chromatin structures, as deduced from ENCODE whole-genome profiles. Myogenic hypomethylation was highly associated with both weak and strong enhancer-type chromatin, while hypermethylation was infrequently associated with enhancer-type chromatin. Both myogenic hypermethylation and hypomethylation often overlapped weak transcription-type chromatin and Polycomb-repressed-type chromatin. For representative genes, we illustrate relationships between DNA methylation, the local chromatin state, DNaseI hypersensitivity, and gene expression. For example, MARVELD2 exhibited myogenic hypermethylation in transcription-type chromatin that overlapped a silenced promoter in Mb and Mt while TEAD4 had myogenic hypomethylation in intronic subregions displaying enhancer-type or transcription-type chromatin in these cells. For LSP1, alternative promoter usage and active promoter-type chromatin were linked to highly specific myogenic or lymphogenic hypomethylated DMRs. Lastly, despite its myogenesis-associated expression, TBX15 had multiple hypermethylated myogenic DMRs framing its promoter region. This could help explain why TBX15 was previously reported to be underexpressed and, unexpectedly, its promoter undermethylated in placentas exhibiting vascular intrauterine growth restriction
The effect of aminophylline on urine output and fluid balance after a single dose in children admitted to the pediatric cardiac intensive care unit
The purpose of this retrospective study was to investigate the effects of a single dose of aminophylline on urine output and fluid balance in children admitted to the cardiac intensive care unit. A retrospective study was performed to compare variables of interest before and 24 hours after aminophylline administration in children under the age of 18 years who were admitted to the cardiac intensive care unit at our institution from January 2011 onwards. Variables of interest included age, weight, aminophylline dose, concurrently administered diuretics, specific hemodynamic parameters, and blood urea nitrogen and creatinine levels. Variables such as urine output and fluid balance were measured through a binary endpoint. Data were compared in a paired fashion and continuous variables were compared through paired t-tests. Analyses were conducted using SPSS Version 23.0. A total of 14 patients were included in the study. There was no significant change in hemodynamic parameters or creatinine levels before and after intravenous aminophylline administration of 5 mg/kg. There was a significant difference in urine output, fluid balance, and blood urea nitrogen levels from the baseline value. Concurrent usage of diuretics did not show significant association with a difference in urine output or fluid balance from baseline. No significant adverse reactions were noted 24 hours after administration of aminophylline. Use of aminophylline dosed at 5 mg/kg is safe and leads to improvement in urine output and fluid balance without negatively impacting systemic oxygen delivery or renal filtration function
Novel siRNA formulation to effectively knockdown mutant p53 in osteosarcoma
<div><p>Objectives</p><p>The tumor suppressor p53 plays a crucial role in the development of osteosarcoma. The primary objective of this study is to develop and optimize lipid based nanoparticle formulations that can carry siRNA and effectively silence mutant p53 in 318–1, a murine osteosarcoma cell line.</p><p>Methods</p><p>The nanoparticles were composed of a mixture of two lipids (cholesterol and DOTAP) and either PLGA or PLGA-PEG and prepared by using an EmulsiFlex-B3 high pressure homogenizer. A series of studies that include using different nanoparticles, different amount of siRNAs, cell numbers, incubation time, transfection media volume, and storage temperature was performed to optimize the gene silencing efficiency.</p><p>Key findings</p><p>Replacement of lipids by PLGA or PLGA-PEG decreased the particle size and overall cytotoxicity. Among all lipid-polymer nanoformulations, nanoparticles with 10% PLGA showed highest mutant p53 knockdown efficiency while maintaining higher cell viability when a nanoparticle to siRNA ratio equal to 6.8:0.66 and 75 nM siRNA was used. With long term storage the mutant p53 knockdown efficiency decreased to a greater extent.</p><p>Conclusions</p><p>This study warrants a future evaluation of this formulation for gene silencing efficiency of mutant p53 in tissue culture and animal models for the treatment of osteosarcoma.</p></div
Improvement in the dissolution rate and tableting properties of cefuroxime axetil by melt-granulated dispersion and surface adsorption
AbstractA combination of melt-granulated dispersion and surface adsorption techniques was used to enhance the dissolution and tableting properties of cefuroxime axetil (CA). Gelucire 50/13 was used as the melt-dispersion carrier and Sylysia 350 was used to adsorb the melt dispersion. Solubility studies showed an 8-fold increase in solubility at a ratio of 1:1.5 for CA:Gelucire 50/13. The minimum quantity of Sylysia 350 required to achieve the desired flowability and compressibility was 0.5 parts of Sylysia 350 per unit of Gelucire 50/13. Phase solubility studies showed negative ΔGtr0 values for Gelucire 50/13 at various concentrations (2–10%, w/v), indicating the spontaneous nature of solubilization. FT-IR and DSC spectra exhibited drug-excipient compatibility. Molecular modeling by a computational method employing energy minimization revealed entrapment of CA in Gelucire 50/13. The total potential energy of CA (70.562kcal/mol) was reduced to 33.578kcal/mol after solid dispersion with Gelucire 50/13. P-XRD studies indicated that the presence of Sylysia 350 is less likely to promote the reversion of the amorphous CA to a crystalline state. In vitro dissolution studies demonstrated an improved dissolution rate, and drug release at 15min (Q15min) exhibited a 15-fold improvement. The rapidly dissolving CA tablets showed improved dissolution with improved tableting properties
The toxicity and p53 knockdown efficiency of different hybrid nanoparticles.
<p>The toxicity and p53 knockdown efficiency of different hybrid nanoparticles.</p