Related substances test and characterization of seratrodast in bulk drugs

A reversed-phase high-performance liquid chromatographic (RP-HPLC) method for related substances test of seratrodast in bulk drugs has been developed. The separation was achieved on a ZirChrom Kromasil C18 (200 mm×4.6 mm, 5 µm) column thermostated at 30 ºC using acetonitrile-0.05 M pH 3.0 potassium dihydrogen orthophosphate buffer (60:40, v/v) as a mobile phase. Wavelength was set at 267 nm. An external standard method using a dilution of the sample solution as reference was used for the purity test. The method was found to be simple, rapid, specific and sensitive with detection limit of 0.67 ng. A thorough study has been undertaken to identify and characterize an unknown impurity at a level over the identification threshold of 0.1 %, and its structure was elucidated as 7-(3,5,6-trimethyl-1,4-benzoquinone- 2-yl)-7-p-tolyl-heptanoic acid based on the data of MS, UV, IR and NMR spectra. Formation of the unknown impurity as well as the countermeasure was also discussedColegio de Farmacéuticos de la Provincia de Buenos Aire

Related substances test and characterization of seratrodast in bulk drugs

A reversed-phase high-performance liquid chromatographic (RP-HPLC) method for related substances test of seratrodast in bulk drugs has been developed. The separation was achieved on a ZirChrom Kromasil C18 (200 mm×4.6 mm, 5 µm) column thermostated at 30 ºC using acetonitrile-0.05 M pH 3.0 potassium dihydrogen orthophosphate buffer (60:40, v/v) as a mobile phase. Wavelength was set at 267 nm. An external standard method using a dilution of the sample solution as reference was used for the purity test. The method was found to be simple, rapid, specific and sensitive with detection limit of 0.67 ng. A thorough study has been undertaken to identify and characterize an unknown impurity at a level over the identification threshold of 0.1 %, and its structure was elucidated as 7-(3,5,6-trimethyl-1,4-benzoquinone- 2-yl)-7-p-tolyl-heptanoic acid based on the data of MS, UV, IR and NMR spectra. Formation of the unknown impurity as well as the countermeasure was also discussedColegio de Farmacéuticos de la Provincia de Buenos Aire

Mechanisms of increased risk of tumorigenesis in Atm and Brca1 double heterozygosity

<p>Abstract</p> <p>Background</p> <p>Both epidemiological and experimental studies suggest that heterozygosity for a single gene is linked with tumorigenesis and heterozygosity for two genes increases the risk of tumor incidence. Our previous work has demonstrated that <it>Atm/Brca1 </it>double heterozygosity leads to higher cell transformation rate than single heterozygosity. However, the underlying mechanisms have not been fully understood yet. In the present study, a series of pathways were investigated to clarify the possible mechanisms of increased risk of tumorigenesis in <it>Atm </it>and <it>Brca1 </it>heterozygosity.</p> <p>Methods</p> <p>Wild type cells, <it>Atm </it>or <it>Brca1 </it>single heterozygous cells, and <it>Atm</it>/<it>Brca1 </it>double heterozygous cells were used to investigate DNA damage and repair, cell cycle, micronuclei, and cell transformation after photon irradiation.</p> <p>Results</p> <p>Remarkable high transformation frequency was confirmed in <it>Atm</it>/<it>Brca1 </it>double heterozygous cells compared to wild type cells. It was observed that delayed DNA damage recognition, disturbed cell cycle checkpoint, incomplete DNA repair, and increased genomic instability were involved in the biological networks. Haploinsufficiency of either ATM or BRCA1 negatively impacts these pathways.</p> <p>Conclusions</p> <p>The quantity of critical proteins such as ATM and BRCA1 plays an important role in determination of the fate of cells exposed to ionizing radiation and double heterozygosity increases the risk of tumorigenesis. These findings also benefit understanding of the individual susceptibility to tumor initiation.</p

Simulation of thermal stress and fatigue life prediction of high speed steel work roll during hot rolling considering the initial residual stress

Considerable residual stress is produced during heat treatment. Compressive residual stress at the shell is conductive to improving the thermal fatigue life of a work roll, while tensile stress in the core could cause thermal breakage. In hot rolling, thermal stress occurs under the heating-cooling cycles over the roll surface due to the contact with the hot strip and water spray cooling. The combination of thermal stress and residual stress remarkably influences the life of a work roll. In this paper, finite element method (FEM) simulation of hot rolling is performed by treating the residual stress as the initial stress. Afterwards, the effects of the initial roll temperature and cooling conditions on thermal stress considering the initial residual stress are discussed. Lastly, the thermal fatigue life of a work roll is estimated based on the strain life model. The higher initial roll temperature causes a higher temperature but a lower compressive thermal stress at the roll surface. The surface temperature and compressive stress increase significantly in the insufficient cooling conditions, as well as the center tensile stress. The calculation of the fatigue life of a work roll based on the universal slopes model according to the 10% rule and 20% rule is reasonable compared with experimental results

Generation of integration-free neural progenitor cells from cells in human urine

Human neural stem cells hold great promise for research and therapy in neural disease. We describe the generation of integration-free and expandable human neural progenitor cells (NPCs). We combined an episomal system to deliver reprogramming factors with a chemically defined culture medium to reprogram epithelial-like cells from human urine into NPCs (hUiNPCs). These transgene-free hUiNPCs can self-renew and can differentiate into multiple functional neuronal subtypes and glial cells in vitro. Although functional in vivo analysis is still needed, we report that the cells survive and differentiate upon transplant into newborn rat brain.postprin

SalK/SalR, a Two-Component Signal Transduction System, Is Essential for Full Virulence of Highly Invasive Streptococcus suis Serotype 2

BACKGROUND: Streptococcus suis serotype 2 (S. suis 2, SS2) has evolved into a highly infectious entity, which caused the two recent large-scale outbreaks of human SS2 epidemic in China, and is characterized by a toxic shock-like syndrome. However, the molecular pathogenesis of this new emerging pathogen is still poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: 89K is a newly predicted pathogenicity island (PAI) which is specific to Chinese epidemic strains isolated from these two SS2 outbreaks. Further bioinformatics analysis revealed a unique two-component signal transduction system (TCSTS) located in the candidate 89K PAI, which is orthologous to the SalK/SalR regulatory system of Streptococcus salivarius. Knockout of salKR eliminated the lethality of SS2 in experimental infection of piglets. Functional complementation of salKR into the isogenic mutant DeltasalKR restored its soaring pathogenicity. Colonization experiments showed that the DeltasalKR mutant could not colonize any susceptible tissue of piglets when administered alone. Bactericidal assays demonstrated that resistance of the mutant to polymorphonuclear leukocyte (PMN)-mediated killing was greatly decreased. Expression microarray analysis exhibited a transcription profile alteration of 26 various genes down-regulated in the DeltasalKR mutant. CONCLUSIONS/SIGNIFICANCE: These findings suggest that SalK/SalR is requisite for the full virulence of ethnic Chinese isolates of highly pathogenic SS2, thus providing experimental evidence for the validity of this bioinformatically predicted PAI

Spatiotemporal Variation and Circulation Characteristics of Extreme Maximum Temperature Events in East China (1961&ndash;2020)

This study analyzed the spatiotemporal variation characteristics of extreme maximum temperature events (EMTEs) in East China in the last 60 years and investigated the relationship between EMTEs and atmospheric circulation. The arithmetic mean, linear trend, and the Mann&ndash;Kendall test were applied to daily maximum temperature (DMT) data (1961&ndash;2020) from 345 meteorological observation stations with complete observation records in East China to compile four characteristic indexes of EMTEs: intensity, consecutive days, first days, and last days. The analysis of these indexes revealed the following: (1) The annual number of days with a DMT &ge; 35 &deg;C increased at the rate of 1.45 d/decade (p &le; 0.05); the mutation occurred in 2009 with a growth rate before and after the mutation of 0.4 and 2.8 d/10a, respectively. Most of the region showed an increasing trend, with the most significant increase to the east of the Yangtze River Delta, in coastal areas of Zhejiang and Fujian, and south of Jiangxi. (2) The EMTE intensity rose at the rate of 0.15 &deg;C/decade (p &le; 0.05). Most areas showed a significant upward trend, and the historical extreme values of EMTEs mostly appeared in the 21st century. (3) The annual mean growth rate of consecutive EMTE days was 0.24 d/10a, which increased significantly after 2003. In comparison with 1961&ndash;2002, consecutive EMTE days increased by 35% during 2003&ndash;2020. The rate of increase was significant (p &le; 0.05) for most areas east of the Yangtze River Delta, coastal areas of Zhejiang and Fujian, and areas south of Jiangxi. The mean mutation time was 2003, and the growth rate before and after the mutation was 0.4 and 1.4 d/10a, respectively. (4) The mean first EMTE day advanced and the mean last EMTE day became delayed, especially in the 21st century. Over the study period, the mean first EMTE day advanced by 12 days and the mean last EMTE day became delayed by 7 days. (5) The analysis of National Centers for Environmental Prediction/National Center for Atmospheric Research reanalysis data indicated that an increasing number of EMTEs have occurred in East China. The reason is that this region experiences atmospheric subsidence resulting from the intensification and westward extension of the subtropical high coupled with the weakening and northward displacement of the mid-latitude westerly trough

A Smart Exhibition Platform of Power Measurement Vehicle based on the GIS and GPS Techniques

A kind of embedded, GIS and GPS centered, smart exhibition platform of power system engineering vehicle were developed in this paper. The system was composed by three parts, which is the vehicle terminal, the server software platform and the monitoring center. The Windows NT Server, Oracle software and VB.NET were used as the developing tools. Together with the GIS and GPS technologies, the N-tier Architecture and the reusable component technology were used to display the real time information of engineering vehicle. The trial operation in the Chongqing Power Electrical Corp. indicated that, with the special structure, the application program development has no connection with the software platform, the heterogeneous database interaction is very convenient, and the system is open, safety and efficient. This smart exhibition system enhanced the dispatching management on the power measurement engineering vehicle, improved the reaction ability on the sudden accident of power equipment and power measurement equipment, and played an important role in the safety maintenance of power grid as well as the loss decrease caused by the measurement errors of power measurement equipment

A Sparse Recovery Algorithm Based on Arithmetic Optimization

At present, the sparse recovery problem is mainly solved by convx optimization algorithm and greedy tracking method. However, the former has defects in recovery efficiency and the latter in recovery ability, and neither of them can obtain effective recovery under large sparsity or small observation degree. In this paper, we propose a new sparse recovery algorithm based on arithmetic optimization algorithm and combine the ideas of greedy tracking method. The proposed algorithm uses arithmetic optimization algorithm to solve the sparse coefficient of the signal in the transform domain, so as to reconstruct the original signal. At the same time, the greedy tracking technique is combined to design the initial position of the operator before solving, so that it can be searched better. Experiments show that compared with other methods, the proposed algorithm can not only obtain more effective recovery, but also run faster under general conditions of observation number. At the same time, It can also recover the signal better in the presence of noise