32 research outputs found
Application of CFD for the analysis of medium-scale LHTS for district heating
No full textThe Finite Volume method has been used to analyse the behaviour of a medium-scale latent heat thermal storage system. The shell-and-tube storage system is filled with phase change material (RT100) in the shell and heat transfer fluid flows through the tube of the storage system. Normally, Organic PCM has low thermal conductivity. Numerous studies from the literature have been reviewed which discuss the enhancement of thermal conductivity of the PCM. The addition of graphite in the PCM is considered an effective way of improving the thermal conductivity of PCM. In this thesis, the major focus is to analyse the performance of the storage system with variation in the volumetric content of graphite in RT100. The four cases of a storage system having 0 %, 7,5 %, 15 %, and 30 % volumetric content of graphite in RT100 was investigated. The purpose of designing the graphite-paraffin-based LHTS was to transfer the heat from district heating to the building heating network. The solidification/melting fraction and variation of the temperature inside PCM and fluid at different time-period have been presented. The heat transfer rate and total heat extracted by fluid from the PCM have been calculated. The results show that the heat transfer rate becomes many folds of the pure PCM with increasing the amount of graphite in the PCM. The timewise variation of outlet heat transfer fluid has been shown for different Reynolds numbers and Stefan number
Temporal proteomic analysis of IGF-1R signalling in MCF-7 breast adenocarcinoma cells
No full textDysregulation of the insulin‐like growth factor 1 receptor signalling network is implicated in tumour growth and resistance to chemotherapy. We explored proteomic changes resulting from insulin‐like growth factor 1 stimulation of MCF‐7 adenocarcinoma cells as a function of time. Quantitative analysis using iTRAQ™ reagents and 2‐D LC‐MS/MS analysis of three biological replicates resulted in the identification of 899 proteins (p≤0.05) with an estimated mean false‐positive rate of 2.6%. Quantitative protein expression was obtained from 681 proteins. Further analysis by supervised k‐means clustering identified five temporal clusters, which were submitted to the FuncAssociate server to assign overrepresented gene ontology terms. Proteins associated with vesicle transport were significantly overrepresented. We further analyzed our data set for proteins showing temporal significance using the software, extraction and analysis of differential gene expression, resulting in 20 significantly and temporally changing proteins (p≤0.1). These significant proteins play roles in, among others, altered glucose metabolism (lactate dehydrogenase A and pyruvate kinase M1/M2) and cellular stress (nascent polypeptide‐associated complex subunit α and heat shock (HSC70) proteins). We used multiple reaction monitoring to validate these interesting proteins and have revealed several differences in relative peptide expression corresponding to protein isoforms and variants
Targeted proteomic analysis of glycolysis in cancer cells
No full textAltered expression of glycolysis proteins is an important yet poorly understood characteristic of cancer. To better understand the glycolytic changes during tumorigenesis, we designed a liquid chromatography multiple reaction monitoring (LC−MRM) assay targeting the “glycolysis proteome” in MCF-7 breast cancer cells, using isotope-coded dimethylation of peptides for relative quantification. In silico, dimethyl labeled tryptic peptides [M + 2H]2+ (of length n) and their yn-1 fragment ions were determined based on UniprotKB database sequence entries for glycolysis proteins, related branching pathways, and reference proteins. Using predicted transitions ([M + 2H]2+ → yn-1), MRM-initiated detection and sequencing (MIDAS) was performed on a dimethyl-labeled, tryptic digest from MCF-7 cells, using two-dimensional liquid chromatography mass spectrometry analysis. Three transitions for each peptide were selected from identified spectra and assessed using 1D-LC−MRM-MS. Collision energy (CE) and dwell times were optimized and matching transitions for “heavy” isotope-coded dimethylated peptides were calculated. Resulting LC−MRM transitions were then used to measure changes in the glycolytic proteome in insulin-like growth factor-1 (IGF-1)-stimulated MCF-7 cells and other breast cell lines. Increases in the expression of glycolysis proteins leading to lactic acid production were observed common to IGF-1-stimulated MCF-7 cells and the invasive MDA-MB-231 cell line. Preliminary analysis of lung tumors with varied states of differentiation demonstrated the clinical applicability of LC−MRM and showed decreased levels of PGK1 in poorly differentiated tumors
Relative quantitative proteomic analysis reveals wound response proteins correlated with after-cooking darkening
No full textMany common potato tuber defects are difficult to elicidate because of the degree of genetic complexity involved, making systems biology approaches necessary. Interaction between chlorogenic acid and iron is responsible for the darkening of potato tuber tissues upon heating – termed after‐cooking darkening (ACD). To explore mechanisms of darkening severity in tuber tissues, we have employed relative quantitative proteomics to discover differentially expressed proteins involved in ACD. Tuber tissue samples were collected from a family of diploid clones which possess a highly segregated degree of the darkening. Exploiting this segregation, as well as the observation that darkening is more prevalent in the stem end of the tuber than the apical end, three sample groups were formed: (i) stem ends of three high‐ACD clones, (ii) stem ends of three low‐ACD clones, and (iii) apical ends of three low‐ACD clones. Protein samples were digested and differentially labeled using isotopic reductive methylation, allowing for an orthogonal two‐way comparison of protein profiles of the sample groups using 2‐D‐LC‐MS/MS. Using a cutoff fold change of 2 between the high‐ and the low‐ACD sample groups, 30 proteins showed a correlation with tissue darkening. Overall, we observed changes in relative protein abundance that showed an enhanced wound‐response program in high‐ACD tissues. Among these proteins, five proteins were further validated at the transcript level using qRT‐PCR. These proteins may be incorporated into design strategies to create potato cultivars with low levels of ACD
Cerebral atrophy in mild cognitive impairment and Alzheimer disease: rates and acceleration.
No full textOBJECTIVE: To quantify the regional and global cerebral atrophy rates and assess acceleration rates in healthy controls, subjects with mild cognitive impairment (MCI), and subjects with mild Alzheimer disease (AD). METHODS: Using 0-, 6-, 12-, 18-, 24-, and 36-month MRI scans of controls and subjects with MCI and AD from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, we calculated volume change of whole brain, hippocampus, and ventricles between all pairs of scans using the boundary shift integral. RESULTS: We found no evidence of acceleration in whole-brain atrophy rates in any group. There was evidence that hippocampal atrophy rates in MCI subjects accelerate by 0.22%/year2 on average (p = 0.037). There was evidence of acceleration in rates of ventricular enlargement in subjects with MCI (p = 0.001) and AD (p < 0.001), with rates estimated to increase by 0.27 mL/year2 (95% confidence interval 0.12, 0.43) and 0.88 mL/year2 (95% confidence interval 0.47, 1.29), respectively. A post hoc analysis suggested that the acceleration of hippocampal loss in MCI subjects was mainly driven by the MCI subjects that were observed to progress to clinical AD within 3 years of baseline, with this group showing hippocampal atrophy rate acceleration of 0.50%/year2 (p = 0.003). CONCLUSIONS: The small acceleration rates suggest a long period of transition to the pathologic losses seen in clinical AD. The acceleration in hippocampal atrophy rates in MCI subjects in the ADNI seems to be driven by those MCI subjects who concurrently progressed to a clinical diagnosis of AD
A qualitative proteome investigation of the sediment portion of human urine: Implications in the biomarker discovery process
No full textInherent to the biomarker discovery process is a comparative analysis of physiological states. It is therefore critical that the proteome detection protocol does not bias the analysis. With urine, the sediment portion, obtained upon thawing frozen urine, is routinely discarded prior to proteome analysis. However, our results demonstrate that such a practice inadvertently induces bias, having significant implications in the biomarker discovery process. We present the first proteome investigation of human urinary sediments, identifying 60 proteins in this phase by MS. Many sediment proteins were also detected in the urinary supernatant, indicating that several proteins partition between the two phases. This partitioning is dependant on the pH of the sample, as well as the degree of sample agitation. As a consequence of discarding the sediment portion of urine, the concentration of potential candidate biomarkers in the supernatant phase will be altered or, in other instances, may be completely removed from the sample. To minimize this, the pH of all samples should first be normalized, and the samples vigorously vortexed prior to discarding the sediments. For more comprehensive biomarker investigations, we suggest that urinary sediments be analyzed along with the supernatant proteins
Cell cycle stage-specific transcriptional activation of cyclins mediated by HAT2-dependent H4K10 acetylation of promoters in Leishmania donovani.
No full textChromatin modifications affect several processes. In investigating the Leishmania donovani histone acetyltransferase HAT2, using in vitro biochemical assays and HAT2-heterozygous genomic knockout we found the constitutively nuclear HAT2 acetylated histone H4K10 in vitro and in vivo. HAT2 was essential. HAT2-depleted cells displayed growth and cell cycle defects, and poor survival in host cells. Real time PCR and DNA microarray analyses, as well as rescue experiments, revealed that downregulation of cyclins CYC4 and CYC9 were responsible for S phase and G2/M defects of HAT2-depleted cells respectively. Leishmania genes are arranged in unidirectional clusters, and clustered genes are coordinately transcribed as long polycistronic units, typically from divergent strand switch regions (dSSRs) which initiate transcription bidirectionally on opposite strands. In investigating the mechanism by which CYC4 and CYC9 expression levels are reduced in HAT2-depleted cells without other genes in their polycistronic transcription units being coordinately downregulated, we found using reporter assays that CYC4 and CYC9 have their own specific promoters. Chromatin immunoprecipitation assays with H4acetylK10 antibodies and real time PCR analyses of RNA suggested these gene-specific promoters were activated in cell cycle-dependent manner. Nuclear run-on analyses confirmed that CYC4 and CYC9 were transcriptionally activated from their own promoters at specific cell cycle stages. Thus, there are two tiers of gene regulation. Transcription of polycistronic units primarily initiates at dSSRs, and this most likely occurs constitutively. A subset of genes have their own promoters, at least some of which are activated in a cell-cycle dependent manner. This second tier of regulation is more sensitive to H4K10 acetylation levels, resulting in downregulation of expression in HAT2-depleted cells. This report presents the first data pointing to cell cycle-specific activation of promoters in trypanosomatids, thus uncovering new facets of gene regulation in this parasite family
A new model for the analysis of laterally loaded piles
No full textThe current research intends to develop a model which is very simple and easy to obtain results for various kinds of foundation problems. A new approach is used here to develop the model. The finite difference method and Hermitian polynomials to develop the system equations in this model. Then the model is solved on a computer to obtain various data which can be used for load deflection prediction for a given kind of soil problem. One of the main features of this method is that it can very easily solve the case of a stratified soil. Most of the models developed by researchers earlier use empirical methods to consider the case of a stratified soil. However, this research does not intend to consider the case of material nonlinearity of the soil.
The results of the new variational model will be compared with those of the methods mentioned above, especially those of Poulos and a new axisymmetric finite element solution developed in this research. The finite element technique will be discussed later in this dissertation. This finite element program was developed by the author for the purpose of this research.
Also, one of the major contributions of the finite element method in this research is to develop a coefficient of soil resistance for the Winkler's model that will produce approximately a result equivalent to that of the finite element model. Here the soil is assumed to be homogeneous and semi-infinite with a value of Young's modulus of elasticity and Poisson's ratio. The results are presented using non-dimensional parameters, whereby knowing the values of £, v of the soil and Ep, Ip and I ofthe pile, the value of the k representing the modulus of subgrade reaction of the soil can be calculated. This technique will be discussed in a subsequent chapter in detail
