In this study, the results of the calibration of the complex activated sludge model implemented in BioWin software for the
full-scale wastewater treatment plant are presented. Within the calibration of the model, sensitivity analysis of its parameters
and the fractions of carbonaceous substrate were performed. In the steady-state and dynamic calibrations, a successful agreement
between the measured and simulated values of the output variables was achieved. Sensitivity analysis revealed that upon the
calculations of normalized sensitivity coefficient (Si,j) 17 (steady-state) or 19 (dynamic conditions) kinetic and stoichiometric parameters are sensitive. Most of them are associated
with growth and decay of ordinary heterotrophic organisms and phosphorus accumulating organisms. The rankings of ten most
sensitive parameters established on the basis of the calculations of the mean square sensitivity measure (δjmsqr) indicate that irrespective of the fact, whether the steady-state or dynamic calibration was performed, there is an agreement
in the sensitivity of parameters. 相似文献
The evolutionary implications of recombination in HIV remain not fully understood. A plausible effect could be an enhancement of immune escape from cytotoxic T lymphocytes (CTLs). In order to test this hypothesis, we constructed a population dynamic model of immune escape in HIV and examined the viral-immune dynamics with and without recombination. Our model shows that recombination (i) increases the genetic diversity of the viral population, (ii) accelerates the emergence of escape mutations with and without compensatory mutations, and (iii) accelerates the acquisition of immune escape mutations in the early stage of viral infection. We see a particularly strong impact of recombination in systems with broad, non-immunodominant CTL responses. Overall, our study argues for the importance of recombination in HIV in allowing the virus to adapt to changing selective pressures as imposed by the immune system and shows that the effect of recombination depends on the immunodominance pattern of effector T cell responses. 相似文献
In past 5 years, the promise that came with genome sequencing has revolutionized the functional genomics research field at unprecedented manner. It would soon know what all known genes do, particularly genes involved in genetic improvement of animal health and increase food animal production. With the availability of full bovine genomic sequence, yet we still have a lot of daunting tasks on 'genotype-to-phenotype problem' particularly about the phenotypic variations and trying to predict what genes are likely to be involved, and improved integrated interactive database. This article outlined and discussed about the current status of bovine functional genomics, recent development in bovine genome databases particularly in annotation of bovine genome, bovine quantitative trait loci database and its potential impact to unveil the from genotype-to-phenotype problem. 相似文献
In many perceptual and cognitive decision-making problems, humans sample multiple noisy information sources serially, and integrate the sampled information to make an overall decision. We derive the optimal decision procedure for two-alternative choice tasks in which the different options are sampled one at a time, sources vary in the quality of the information they provide, and the available time is fixed. To maximize accuracy, the optimal observer allocates time to sampling different information sources in proportion to their noise levels. We tested human observers in a corresponding perceptual decision-making task. Observers compared the direction of two random dot motion patterns that were triggered only when fixated. Observers allocated more time to the noisier pattern, in a manner that correlated with their sensory uncertainty about the direction of the patterns. There were several differences between the optimal observer predictions and human behaviour. These differences point to a number of other factors, beyond the quality of the currently available sources of information, that influences the sampling strategy. 相似文献
Patients with chronic kidney disease (CKD) have an increased incidence of cancer. It is well known that long periods of hemodialysis
(HD) treatment are linked to DNA damage due to oxidative stress. In this study, we examined the effect of selenium (Se) supplementation
to CKD patients on HD on the prevention of oxidative DNA damage in white blood cells. Blood samples were drawn from 42 CKD
patients on HD (at the beginning of the study and after 1 and 3 months) and from 30 healthy controls. Twenty-two patients
were supplemented with 200 μg Se (as Se-rich yeast) per day and 20 with placebo (baker's yeast) for 3 months. Se concentration
in plasma and DNA damage in white blood cells expressed as the tail moment, including single-strand breaks (SSB) and oxidative
bases lesion in DNA, using formamidopyrimidine glycosylase (FPG), were measured. Se concentration in patients was significantly
lower than in healthy subjects (P < 0.0001) and increased significantly after 3 months of Se supplementation (P < 0.0001). Tail moment (SSB) in patients before the study was three times higher than in healthy subjects (P < 0.01). After 3 months of Se supplementation, it decreased significantly (P < 0.01) and was about 16% lower than in healthy subjects. The oxidative bases lesion in DNA (tail moment, FPG) of HD patients
at the beginning of the study was significantly higher (P < 0.01) compared with controls, and 3 months after Se supplementation it was 2.6 times lower than in controls (P < 0.01). No changes in tail moment was observed in the placebo group. In conclusion, our study shows that in CKD patients
on HD, DNA damage in white blood cells is higher than in healthy controls, and Se supplementation prevents the damage of DNA. 相似文献
Glioblastoma multiforme (GBM) is the most common and aggressive of the primary brain tumors. These tumors express multiple members of the epithelial sodium channel (ENaC)/degenerin (Deg) family and are associated with a basally active amiloride-sensitive cation current. We hypothesize that this glioma current is mediated by a hybrid channel composed of a mixture of ENaC and acid-sensing ion channel (ASIC) subunits. To test the hypothesis that ASIC1 interacts with αENaC and γENaC at the cellular level, we have used total internal reflection fluorescence microscopy (TIRFM) in live rat astrocytes transiently cotransfected with cDNAs for ASIC1-DsRed plus αENaC-yellow fluorescent protein (YFP) or ASIC1-DsRed plus γENaC-YFP. TIRFM images show colocalization of ASIC1 with both αENaC and γENaC. Furthermore, using TIRFM in stably transfected D54-MG cells, we also found that ASIC1 and αENaC both localize to a submembrane region following exposure to pH 6.0, similar to the acidic conditions found in the core of a glioblastoma lesion. Using high-resolution clear native gel electrophoresis, we found that ASIC1 forms a complex with ENaC subunits which migrates at ≈480 kDa in D54-MG glioma cells. These data suggest that different ENaC/Deg subunits interact and could combine to form a hybrid channel that likely underlies the amiloride-sensitive current seen in human glioma cells. 相似文献
Green fluorescent protein (GFP) was successfully used as a visual reporter at various stages of carrot (Daucus carota L.) transformation. GFP-fluorescence was non-invasively observed in protoplasts, callus and plants after the delivery of
mgfp5-er gene using two transformation methods: direct DNA transfer into polyethylene glycol (PEG) -treated protoplasts and inoculation
of root discs with Agrobacterium rhizogenes. Transient GFP-expression was detected in the treated protoplasts and monitored during the first week of the cell culture
until the stable level of expression was observed. It was useful for the comparison of protoplast susceptibility to DNA uptake
and the transgene expression as the fluorescence declined with various rates depending on the used carrot genotype and PEG-concentration.
GFP-monitoring in callus enabled the selection of stably expressing lines. It also allowed verification of the homogeneous
tissue composition with regard to the expression of the transgene. In plants, GFP-performance depended on the assayed tissue
and organ despite of the constitutive 35S promoter. The expression was visually detected in both vegetative and generative
parts, but particularly strong fluorescence was observed in leaf marginal meristems, petioles, stems, and styles. Those tissues
can be convenient for examination of the transgenic plants during their growth. The results encourage that GFP is a valuable
reporter and can be routinely used for optimization of transformation protocol, selection of transformants and monitoring
transgenic carrot. 相似文献
The relationship between the A-ring chair conformation of vitamin D compounds and their ability to bind the vitamin D receptor (VDR) has long attracted the attention of many researchers. It was established that in the crystalline complexes of hVDRmt with the natural hormone, 1alpha,25-dihydroxyvitamin D(3) (1), and its side-chain analogs the vitamins exist in beta-chair form with an equatorial orientation of 1alpha-OH. However, with all these ligands the interconversion between both A-ring forms would be possible in solution. In an attempt to verify the conformation of vitamin D compounds required for binding the VDR we prepared analog 4, characterized by the presence of an axial 1alpha-hydroxy group. Since the additional ring connecting 3beta-oxygen and C-2 prevents A-ring conformational flexibility, the synthesized vitamin 4 can exist exclusively in the alpha-chair form. The geometrical isomer 5 with a free 3beta-OH group was also obtained. The analog 5 binds very poorly to VDR, whereas the vitamin 4 is practically devoid of binding ability. Both compounds also show very low HL-60-differentiating activity. When tested in vivo in mice the analogs 4 and 5 exhibit significant calcemic responses with analog 4 showing more activity than analog 5. 相似文献
The action of selegiline, a selective and irreversible inhibitor of monoamine oxidase B, commonly applied in the therapy of Parkinson's disease, on glucose formation was investigated in isolated rabbit hepatocytes and kidney-cortex tubules, maintaining the whole body glucose homeostasis via gluconeogenic pathway activity. An intensive hepatic metabolism of selegiline resulted in formation of selegiline-N-oxide, desmethylselegiline, methamphetamine and amphetamine, whereas during slow degradation of the drug in freshly isolated renal tubules selegiline-N-oxide was mainly produced. At 100 μM concentration selegiline markedly diminished glucose synthesis in isolated renal tubules incubated with dihydroxyacetone or alanine + glycerol + octanoate (by about 60 and 30%, respectively), while at 5 μM concentration a similar degree of inhibition was achieved in renal tubules grown in primary culture under the same conditions (about 40 and 60%, respectively). Moreover, desmethylselegiline and selegiline-N-oxide considerably diminished glucose production in renal tubules whereas selegiline and its metabolites did not affect gluconeogenesis in hepatocytes. Contrary to control animals, following selegiline administration to alloxan-diabetic rabbits for 8 days (10 mg kg−1 body wt. daily) the blood glucose and serum creatinine levels were significantly diminished, suggesting a decrease in renal gluconeogenesis and improvement of kidney functions.
Since in renal tubules selegiline induced a decline in the intracellular levels of gluconeogenic intermediates and ATP content accompanied by a decrease in oxygen consumption in both kidney-cortex and hepatic mitochondria it seems possible that its inhibitory action on renal gluconeogenesis might result from an impairment of mitochondrial function, while an intensive selegiline metabolism in hepatocytes causes decrease of its concentration and in consequence no inhibition of gluconeogenesis. In view of these observations it is likely that an increased risk of selegiline-induced hypoglycemia might be expected particularly in patients exhibiting an impairment of liver function and following transdermal administration of this drug, i.e. under conditions of increased serum selegiline concentrations. 相似文献