A semiempirical dynamic model of reversible open circuit voltage drop in a PEM fuel cell

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149313/1/er4127_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149313/2/er4127.pd

Effect of land use and environmental variables on phytoplankton community structure in high-elevation river, upper Yangtze river, China

The Qinghai-Tibet Plateau is an ecologically fragile region. The changes in physicochemical parameters of water quality [PPOWQ] and land use types [LUT] in different regions will affect the phytoplankton community in rivers, thus threatening the ecosystem. Taking the phytoplankton community as an indicator variable, it is of great significance to study the relative influence of symbiotic factors on regulating human activities and river ecological protection. The results showed that the proportions of Bacillariophyta, Cyanophyta, and Chlorophyta were >84% in the phytoplankton community of taxa composition. The abundance of the phytoplankton community varied from 1.47 × 105 to 7.58 × 105 cells/L. Bacillariophyta had the highest average abundance (>82%). The results of the variance partitioning analysis showed that PPOWQ was the main variable affecting the changes in the phytoplankton community. Redundancy analysis showed that local factors (total nitrogen, salinity, water temperature) and regional factors (forestland, grassland, unused land) (p < 0.05) were the main factors causing the changes in community structure and abundance of dominant algae. The analysis of structural equation models showed that LUT had the least direct impact on the abundance of the phytoplankton community, mainly through changing nutrients and physical parameters. Water temperature and nutrients are still the main factors affecting phytoplankton community abundance. Farmland and forestland are the main sources of total nitrogen in rivers. In general, in the ecologically vulnerable area, it is of guiding significance for the ecological monitoring and management of plateau rivers. In addition to considering water quality, it is also necessary to reasonably plan the LUT around rivers

Expression of Twist 1 in bone marrow and extramedullary lesions of patients with myeloma and its prognostic significance

In patients with multiple myeloma (MM) extramedullary (EM) lesions could be a possible indicator of poor prognosis. Twist 1, an EMT related transcription factor, is known to play an important role in embryonic development and also in the process of tumor cell proliferation, apoptosis, metastasis etc. The Twist 1 protein expression hence has prognostic significance in MM. This study investigates expression of Twist-1 in MM patients with extramedullary lesions and its relationship with clinicopathological data and prognosis, so as to elucidate the clinical significance of Twist-1 expression. Patients with MM complicated with EM lesions were selected retrospectively, including 35 cases in the bone marrow group (MM complicated with extramedullary lesions) and 80 cases in the extramedullary group (MM combined with extramedullary lesions). The expression of Twist 1 protein was detected by immunohistochemistry. The relationship between Twist 1 protein expression and general clinicopathological data was analyzed by statistics. The relationship between Twist 1 protein expression and prognosis was analyzed by COX single factor and multivariate regression analysis. Immunohistochemical staining showed that the expression level of Twist-1 protein in the nucleus of myeloma cells in the extramedullary group was significantly higher than that of the bone marrow group. However, in the cytoplasm of myeloma cells, there was no significant difference in the expression level of Twist-1 protein between the extramedullary group and the bone marrow group. The expression level of Twist-1 protein in extramedullary tissue was not related to sex, age, D-S stage, ISS stage, immunoglobulin type, creatinine and hemoglobin. The expression level of β2-microglobulin in Twist-1 high expression group was significantly higher than that of Twist-1 low expression group. Follow-up findings discovered that overall survival (OS) of Twist 1 high expression group was significantly lower than that of Twist 1 low expression group. COX multivariate analysis showed that Twist 1 protein and International Staging System (ISS) stage were independent risk factors affecting OS for 3 years. The high expression rate of Twist 1 protein in extramedullary lesions of MM patients with extramedullary lesions is significantly higher than that in bone marrow tissues of patients with extramedullary lesions. The results suggest that high expression of Twist 1 protein is an independent risk factor affecting the prognosis of MM patients with extramedullary lesions

Expression of Twist 1 in bone marrow and extramedullary lesions of patients with myeloma and its prognostic significance

722-726In patients with multiple myeloma (MM) extramedullary (EM) lesions could be a possible indicator of poor prognosis. Twist 1, an EMT related transcription factor, is known to play an important role in embryonic development and also in the process of tumor cell proliferation, apoptosis, metastasis etc. The Twist 1 protein expression hence has prognostic significance in MM. This study investigates expression of Twist-1 in MM patients with extramedullary lesions and its relationship with clinicopathological data and prognosis, so as to elucidate the clinical significance of Twist-1 expression. Patients with MM complicated with EM lesions were selected retrospectively, including 35 cases in the bone marrow group (MM complicated with extramedullary lesions) and 80 cases in the extramedullary group (MM combined with extramedullary lesions). The expression of Twist 1 protein was detected by immunohistochemistry. The relationship between Twist 1 protein expression and general clinicopathological data was analyzed by statistics. The relationship between Twist 1 protein expression and prognosis was analyzed by COX single factor and multivariate regression analysis. Immunohistochemical staining showed that the expression level of Twist-1 protein in the nucleus of myeloma cells in the extramedullary group was significantly higher than that of the bone marrow group. However, in the cytoplasm of myeloma cells, there was no significant difference in the expression level of Twist-1 protein between the extramedullary group and the bone marrow group. The expression level of Twist-1 protein in extramedullary tissue was not related to sex, age, D-S stage, ISS stage, immunoglobulin type, creatinine and hemoglobin. The expression level of β2-microglobulin in Twist-1 high expression group was significantly higher than that of Twist-1 low expression group. Follow-up findings discovered that overall survival (OS) of Twist 1 high expression group was significantly lower than that of Twist 1 low expression group. COX multivariate analysis showed that Twist 1 protein and International Staging System (ISS) stage were independent risk factors affecting OS for 3 years. The high expression rate of Twist 1 protein in extramedullary lesions of MM patients with extramedullary lesions is significantly higher than that in bone marrow tissues of patients with extramedullary lesions. The results suggest that high expression of Twist 1 protein is an independent risk factor affecting the prognosis of MM patients with extramedullary lesions

Restriction landmark genomic scanning (RLGS) spot identification by second generation virtual RLGS in multiple genomes with multiple enzyme combinations.

BackgroundRestriction landmark genomic scanning (RLGS) is one of the most successfully applied methods for the identification of aberrant CpG island hypermethylation in cancer, as well as the identification of tissue specific methylation of CpG islands. However, a limitation to the utility of this method has been the ability to assign specific genomic sequences to RLGS spots, a process commonly referred to as "RLGS spot cloning."ResultsWe report the development of a virtual RLGS method (vRLGS) that allows for RLGS spot identification in any sequenced genome and with any enzyme combination. We report significant improvements in predicting DNA fragment migration patterns by incorporating sequence information into the migration models, and demonstrate a median Euclidian distance between actual and predicted spot migration of 0.18 centimeters for the most complex human RLGS pattern. We report the confirmed identification of 795 human and 530 mouse RLGS spots for the most commonly used enzyme combinations. We also developed a method to filter the virtual spots to reduce the number of extra spots seen on a virtual profile for both the mouse and human genomes. We demonstrate use of this filter to simplify spot cloning and to assist in the identification of spots exhibiting tissue-specific methylation.ConclusionThe new vRLGS system reported here is highly robust for the identification of novel RLGS spots. The migration models developed are not specific to the genome being studied or the enzyme combination being used, making this tool broadly applicable. The identification of hundreds of mouse and human RLGS spot loci confirms the strong bias of RLGS studies to focus on CpG islands and provides a valuable resource to rapidly study their methylation

Global methylation profiling of lung cancer identifies novel methylated genes

Epigenetic changes, including DNA methylation, are a common finding in cancer. In lung cancers methylation of cytosine residues may affect tumor initiation and progression in several ways, including the silencing of tumor suppressor genes through promoter methylation and by providing the targets for adduct formation of polycyclic aromatic hydrocarbons present in combustion products of cigarette smoke. Although the importance of aberrant DNA methylation is well established, the extent of DNA methylation in lung cancers has never been determined. Restriction landmark genomic scanning (RLGS) is a highly reproducible two-dimensional gel electrophoresis that allows the determination of the methylation status of up to 2000 promoter sequences in a single gel. We selected 1184 CpG islands for RLGS analysis and determined their methylation status in 16 primary non-small cell lung cancers. Some tumors did not show methylation whereas others showed up to 5.3% methylation in all CpG islands of the profile. Cloning of 21 methylated loci identified 11 genes and 6 ESTs. We demonstrate that methylation is part of the silencing process of BMP3B in primary tumors and lung cancer cell lines

Flavopiridol Pharmacogenetics: Clinical and Functional Evidence for the Role of SLCO1B1/OATP1B1 in Flavopiridol Disposition

Flavopiridol is a cyclin-dependent kinase inhibitor in phase II clinical development for treatment of various forms of cancer. When administered with a pharmacokinetically (PK)-directed dosing schedule, flavopiridol exhibited striking activity in patients with refractory chronic lymphocytic leukemia. This study aimed to evaluate pharmacogenetic factors associated with inter-individual variability in pharmacokinetics and outcomes associated with flavopiridol therapy.Thirty-five patients who received single-agent flavopiridol via the PK-directed schedule were genotyped for 189 polymorphisms in genes encoding 56 drug metabolizing enzymes and transporters. Genotypes were evaluated in univariate and multivariate analyses as covariates in a population PK model. Transport of flavopiridol and its glucuronide metabolite was evaluated in uptake assays in HEK-293 and MDCK-II cells transiently transfected with SLCO1B1. Polymorphisms in ABCC2, ABCG2, UGT1A1, UGT1A9, and SLCO1B1 were found to significantly correlate with flavopiridol PK in univariate analysis. Transport assay results indicated both flavopiridol and flavopiridol-glucuronide are substrates of the SLCO1B1/OATP1B1 transporter. Covariates incorporated into the final population PK model included bilirubin, SLCO1B1 rs11045819 and ABCC2 rs8187710. Associations were also observed between genotype and response. To validate these findings, a second set of data with 51 patients was evaluated, and overall trends for associations between PK and PGx were found to be consistent.Polymorphisms in transport genes were found to be associated with flavopiridol disposition and outcomes. Observed clinical associations with SLCO1B1 were functionally validated indicating for the first time its relevance as a transporter of flavopiridol and its glucuronide metabolite. A second 51-patient dataset indicated similar trends between genotype in the SLCO1B1 and other candidate genes, thus providing support for these findings. Further study in larger patient populations will be necessary to fully characterize and validate the clinical impact of polymorphisms in SLCO1B1 and other transporter and metabolizing enzyme genes on outcomes from flavopiridol therapy

Effects of nonantibiotic growth promoter combinations on growth performance, nutrient utilization, digestive enzymes, intestinal morphology, and cecal microflora of broilers.

Given the ban on antibiotic growth promoters, the effects of nonantibiotic alternative growth promoter combinations (NAGPCs) on the growth performance, nutrient utilization, digestive enzyme activity, intestinal morphology, and cecal microflora of broilers were evaluated. All birds were fed pellets of two basal diets-starter (0-21 d) and grower (22-42 d)-with either enramycin (ENR) or NAGPC supplemented. 1) control + ENR; 2) control diet (CON, basal diet); 3) control + mannose oligosaccharide (MOS) + mannanase (MAN) + sodium butyrate (SB) (MMS); 4) control + MOS + MAN + Bacillus subtilis (BS) (MMB); 5) control + MOS + fruit oligosaccharide (FOS) + SB (MFS); 6) control + FOS + BS (MFB); 7) control + MOS + FOS + MAN (MFM); 8) control + MOS + BS + phytase (PT) (MBP). ENR, MOS, FOS, SB, MAN, PT, and BS were added at 100, 2,000, 9,000, 1,500, 300, 37, and 500 mg/kg, respectively. The experiment used a completely random block design with six replicates per group: 2400 Ross 308 broilers in the starter phase and 768 in the grower phase. All NAGPCs significantly improved body weight gain (P < 0.01), utilization of dry matter, organic matter, and crude protein (P < 0.05), villus height and villus height/crypt depth in the jejunum and ileum (P < 0.01), and decreased the feed conversion ratio (P < 0.01) at d 21 and 42. MMS, MMB, MFB, and MFM duodenum trypsin, lipase, and amylase activities increased significantly (P < 0.05) at d 21 and 42. On d 21 and 42, MMS, MMB, and MBP increased the abundance of Firmicutes and Bacteroides whereas MMB, MFB, and MBP decreased the abundance of Proteobacteria, compared to ENR and CON. Overall, the NAGPCs were found to have some beneficial effects and may be used as effective antibiotic replacements in broilers