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991.
Recent publication of a revised section for mycoplasma testing in the European Pharmacopoeia [1] has led to interest in validating a nucleic acid amplification technique (NAT) for use in detection of mycoplasma contaminants in biologics drugs. The replacement by or supplementation of the existing culture-based methods with a PCR-based method has several advantages for the biopharmaceutical industry, mainly with respect to reduced turnaround time for results, and potentially lowered cost. Replacement or substitution of existing methods by a PCR method requires the demonstration of equivalent assay limit of detection (LOD) and specificity. The experimental requirements for this comparability validation have been enumerated in detail in the EP section referenced above. In this publication, we describe the validation and comparability analysis of a PCR method performed exactly according to the EP guidance. Completion of this validation activity has resulted in the availability of an assay that meets or exceeds EP compliance requirements for a mycoplasma detection method. 相似文献
992.
Jaekwang Lee Suyeal Bae Seo-hee Lee Hojin Choi Young Hoon Kim Soo Jin Kim Gyu Tae Park Seung Kee Moon Dal-Hyun Kim Sungsook Lee Soon Kil Ahn Nam Song Choi Kyung Joo Lee 《Bioorganic & medicinal chemistry letters》2010,20(21):6327-6330
Prodrugs have proven to be very useful in enhancing aqueous solubility of sparingly water-soluble drugs, thereby increasing in vivo efficacy without a need of special excipients. In vitro and in vivo evaluations of a number of amino acid prodrugs of 1, a previously identified potent tubulin polymerization inhibitor and cytotoxic against various cancer cell lines led to the discovery of 3·HCl (l-valine attached) which is highly efficacious in mouse xenografts bearing human cancer. Pharmacokinetic analysis in rats revealed that compound 1 was released immediately upon administration of 3·HCl intravenously, with rapid clearance of 3·HCl indicating the effective cleavage of prodrug. Compound 3·HCl (CKD-516) has now been progressed to phase 1 clinical trial. 相似文献
993.
Media multitasking, or the concurrent consumption of multiple media forms, is increasingly prevalent in today’s society and has been associated with negative psychosocial and cognitive impacts. Individuals who engage in heavier media-multitasking are found to perform worse on cognitive control tasks and exhibit more socio-emotional difficulties. However, the neural processes associated with media multi-tasking remain unexplored. The present study investigated relationships between media multitasking activity and brain structure. Research has demonstrated that brain structure can be altered upon prolonged exposure to novel environments and experience. Thus, we expected differential engagements in media multitasking to correlate with brain structure variability. This was confirmed via Voxel-Based Morphometry (VBM) analyses: Individuals with higher Media Multitasking Index (MMI) scores had smaller gray matter density in the anterior cingulate cortex (ACC). Functional connectivity between this ACC region and the precuneus was negatively associated with MMI. Our findings suggest a possible structural correlate for the observed decreased cognitive control performance and socio-emotional regulation in heavy media-multitaskers. While the cross-sectional nature of our study does not allow us to specify the direction of causality, our results brought to light novel associations between individual media multitasking behaviors and ACC structure differences. 相似文献
994.
Su Mei Yew Chai Ling Chan Kok Wei Lee Shiang Ling Na Ruixin Tan Chee-Choong Hoh Wai-Yan Yee Yun Fong Ngeow Kee Peng Ng 《PloS one》2014,9(8)
Dematiaceous fungi (black fungi) are a heterogeneous group of fungi present in diverse environments worldwide. Many species in this group are known to cause allergic reactions and potentially fatal diseases in humans and animals, especially in tropical and subtropical climates. This study represents the first survey of dematiaceous fungi in Malaysia and provides observations on their diversity as well as in vitro response to antifungal drugs. Seventy-five strains isolated from various clinical specimens were identified by morphology as well as an internal transcribed spacer (ITS)-based phylogenetic analysis. The combined molecular and conventional approach enabled the identification of three classes of the Ascomycota phylum and 16 genera, the most common being Cladosporium, Cochliobolus and Neoscytalidium. Several of the species identified have not been associated before with human infections. Among 8 antifungal agents tested, the azoles posaconazole (96%), voriconazole (90.7%), ketoconazole (86.7%) and itraconazole (85.3%) showed in vitro activity (MIC ≤1 µg/mL) to the largest number of strains, followed by anidulafungin (89.3%), caspofungin (74.7%) and amphotericin B (70.7%). Fluconazole appeared to be the least effective with only 10.7% of isolates showing in vitro susceptibility. Overall, almost half (45.3%) of the isolates showed reduced susceptibility (MIC >1 µg/mL) to at least one antifungal agent, and three strains (one Pyrenochaeta unguis-hominis and two Nigrospora oryzae) showed potential multidrug resistance. 相似文献
995.
Objectives
The aim of this study was to identify psychosocial factors related to the onset of bipolar I disorder (BD). To do so, the Bipolar Disorder Etiology Scale (BDES), based on psychological behaviorism, was developed and validated. Using the BDES, common factors related to both major depressive disorder (MDD) and BD and specific factors related only to BD were investigated.Method
The BDES, which measures 17 factors based on psychological behaviorism hypotheses, was developed and validated. This scale was administered to 113 non-clinical control subjects, 30 subjects with MDD, and 32 people with BD. ANOVA and post hoc analyses were conducted. Subscales on which MDD and BD groups scored higher than controls were classified as common factors, while those on which the BD group scored higher than MDD and control groups were classified as specific factors.Results
The BDES has acceptable reliability and validity. Twelve common factors influence both MDD and BD and one specific factor influences only BD. Common factors include the following: learning grandiose self-labeling, learning dangerous behavior, reinforcing impulsive behavior, exposure to irritability, punishment of negative emotional expression, lack of support, sleep problems, antidepressant problems, positive arousal to threat, lack of social skills, and pursuit of short-term pleasure. The specific factor is manic emotional response.Conclusions
Manic emotional response was identified as a specific factor related to the onset of BD, while parents’ grandiose labeling is a candidate for a specific factor. Many factors are related to the onset of both MDD and BD. 相似文献996.
Hai-Yan Xu Xiuju Fu Lionel Kim Hock Lee Stefan Ma Kee Tai Goh Jiancheng Wong Mohamed Salahuddin Habibullah Gary Kee Khoon Lee Tian Kuay Lim Paul Anantharajah Tambyah Chin Leong Lim Lee Ching Ng 《PLoS neglected tropical diseases》2014,8(5)
Weather factors are widely studied for their effects on indicating dengue incidence trends. However, these studies have been limited due to the complex epidemiology of dengue, which involves dynamic interplay of multiple factors such as herd immunity within a population, distinct serotypes of the virus, environmental factors and intervention programs. In this study, we investigate the impact of weather factors on dengue in Singapore, considering the disease epidemiology and profile of virus serotypes. A Poisson regression combined with Distributed Lag Non-linear Model (DLNM) was used to evaluate and compare the impact of weekly Absolute Humidity (AH) and other weather factors (mean temperature, minimum temperature, maximum temperature, rainfall, relative humidity and wind speed) on dengue incidence from 2001 to 2009. The same analysis was also performed on three sub-periods, defined by predominant circulating serotypes. The performance of DLNM regression models were then evaluated through the Akaike''s Information Criterion. From the correlation and DLNM regression modeling analyses of the studied period, AH was found to be a better predictor for modeling dengue incidence than the other unique weather variables. Whilst mean temperature (MeanT) also showed significant correlation with dengue incidence, the relationship between AH or MeanT and dengue incidence, however, varied in the three sub-periods. Our results showed that AH had a more stable impact on dengue incidence than temperature when virological factors were taken into consideration. AH appeared to be the most consistent factor in modeling dengue incidence in Singapore. Considering the changes in dominant serotypes, the improvements in vector control programs and the inconsistent weather patterns observed in the sub-periods, the impact of weather on dengue is modulated by these other factors. Future studies on the impact of climate change on dengue need to take all the other contributing factors into consideration in order to make meaningful public policy recommendations. 相似文献
997.
Three new species of the mycophagous aleocharine genus Gyrophaena Mannerheim are described in Korea. The types and paratypes of the new species are designated. Illustrations of the diagnostic characters and habitus photographs of new species are provided with a key to Korean species of Gyrophaena. 相似文献
998.
Kyoung Song In-Soo Yoon Nam Ah Kim Dong-Hwan Kim Jongmin Lee Hee Jung Lee Saehyung Lee Sunghyun Choi Min-Koo Choi Ha Hyung Kim Seong Hoon Jeong Woo Sung Son Dae-Duk Kim Young Kee Shin 《PloS one》2014,9(5)
The purpose of this study was to develop a biobetter version of recombinant human interferon-β 1a (rhIFN-β 1a) to improve its biophysical properties, such as aggregation, production and stability, and pharmacokinetic properties without jeopardizing its activity. To achieve this, we introduced additional glycosylation into rhIFN-β 1a via site-directed mutagenesis. Glycoengineering of rhIFN-β 1a resulted in a new molecular entity, termed R27T, which was defined as a rhIFN-β mutein with two N-glycosylation sites at 80th (original site) and at an additional 25th amino acid due to a mutation of Thr for Arg at position 27th of rhIFN-β 1a. Glycoengineering had no effect on rhIFN-β ligand-receptor binding, as no loss of specific activity was observed. R27T showed improved stability and had a reduced propensity for aggregation and an increased half-life. Therefore, hyperglycosylated rhIFN-β could be a biobetter version of rhIFN-β 1a with a potential for use as a drug against multiple sclerosis. 相似文献
999.
Todd M. Pitts Timothy P. Newton Erica L. Bradshaw-Pierce Rebecca Addison John J. Arcaroli Peter J. Klauck Stacey M. Bagby Stephanie L. Hyatt Alicia Purkey John J. Tentler Aik Choon Tan Wells A. Messersmith S. Gail Eckhardt Stephen Leong 《PloS one》2014,9(11)
Background
The activation of the MAPK and PI3K/AKT/mTOR pathways is implicated in the majority of cancers. Activating mutations in both of these pathways has been described in colorectal cancer (CRC), thus indicating their potential as therapeutic targets. This study evaluated the combination of a PI3K/mTOR inhibitor (PF-04691502/PF-502) in combination with a MEK inhibitor (PD-0325901/PD-901) in CRC cell lines and patient-derived CRC tumor xenograft models (PDTX).Materials and Methods
The anti-proliferative effects of PF-502 and PD-901 were assessed as single agents and in combination against a panel of CRC cell lines with various molecular backgrounds. Synergy was evaluated using the Bliss Additivity method. In selected cell lines, we investigated the combination effects on downstream effectors by immunoblotting. The combination was then evaluated in several fully genetically annotated CRC PDTX models.Results
The in vitro experiments demonstrated a wide range of IC50 values for both agents against a cell line panel. The combination of PF-502 and PD-901 demonstrated synergistic anti-proliferative activity with Bliss values in the additive range. As expected, p-AKT and p-ERK were downregulated by PF-502 and PD-901, respectively. In PDTX models, following a 30-day exposure to PF-502, PD-901 or the combination, the combination demonstrated enhanced reduction in tumor growth as compared to either single agent regardless of KRAS or PI3K mutational status.Conclusions
The combination of a PI3K/mTOR and a MEK inhibitor demonstrated enhanced anti-proliferative effects against CRC cell lines and PDTX models. 相似文献1000.
Simrinder Singh Sodhi Mrinmoy Ghosh Ki Duk Song Neelesh Sharma Jeong Hyun Kim Nam Eun Kim Sung Jin Lee Chul Woong Kang Sung Jong Oh Dong Kee Jeong 《PloS one》2014,9(7)
The novel liver protein acetyl-CoA acetyltransferase-2 (ACAT2) is involved in the beta-oxidation and lipid metabolism. Its comprehensive relative expression, in silico non-synonymous single nucleotide polymorphism (nsSNP) analysis, as well as its annotation in terms of metabolic process with another protein from the same family, namely, acetyl-CoA acyltransferase-2 (ACAA2) was performed in Sus scrofa. This investigation was conducted to understand the most important nsSNPs of ACAT2 in terms of their effects on metabolic activities and protein conformation. The two most deleterious mutations at residues 122 (I to V) and 281 (R to H) were found in ACAT2. Validation of expression of genes in the laboratory also supported the idea of differential expression of ACAT2 and ACAA2 conceived through the in silico analysis. Analysis of the relative expression of ACAT2 and ACAA2 in the liver tissue of Jeju native pig showed that the former expressed significantly higher (P<0.05). Overall, the computational prediction supported by wet laboratory analysis suggests that ACAT2 might contribute more to metabolic processes than ACAA2 in swine. Further associations of SNPs in ACAT2 with production traits might guide efforts to improve growth performance in Jeju native pigs. 相似文献