Naresuan University Journal
Not a member yet
39887 research outputs found
Sort by
The Limits to Capital in Spain: The Roots of the 'New Normal'
No full textThis article contributes to a Marxist understanding of the roots of the contemporary predicament for many societies in which future economic growth is likely to be low and accompanied by mass ‘structural’ unemployment, increased inequality and further crises of social and political cohesion. It takes Spain as an exemplar of this ‘new normal’, and argues that the ‘irrational rationality’ of crisis in capitalism can be seen in successive cycles of crises that have resulted in the present catastrophe in that country, and also—by means of European economic and monetary union—in the delimiting of political opportunities to restore growth on any other basis than through the subordination of social reproduction to the power of money and (increasingly authoritarian) law. The article therefore supports value-theoretical, diachronic analyses of capitalist development that trace the prefiguration of contemporary forms of crisis in the formation and ‘resolution’ of preceding cycles of overaccumluation and devaluation
Protein quantification of human hepatic drug transporters and metabolizing enzymes: an inter-laboratory and methodological comparison
No full textPurpose: The use of mass spectrometry based techniques for quantifying expression levels of proteins has expanded lately. The quantification methods used are mainly based on targeted approaches with labeled standards or label free, global approaches. It is not clear to what extent the quantification of drug transporting proteins and metabolizing enzymes varies with different methodologies. We therefore distributed identical samples from human liver tissue to six laboratories using different methodologies and compared the expression of hepatic drug transporters and metabolic enzymes. Methods: Protein abundances of drug transporters and metabolizing enzymes were quantified in ten identical human liver samples in six laboratories using their respective in-house methods. A series of phase I-metabolizing enzymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, and CYP3A5), phase II-metabolizing enzymes (UGT1A1, UGT1A3, UGT2B7, and UGT2B15), uptake transporters (SLCO1A2, SLCO1B1, SLCO1B3, SCLO2B1, and SLC22A1), and efflux transporters (ABCB2, ABCC2, ABCC3, ABCG2, and SLC47A1) were included in the analysis. The quantifications were performed using five targeted proteomics methodologies. All five used stable isotope labeled peptide standards. The sixth laboratory used a global, label free approach. Three laboratories studied proteins in the whole cell lysate while the other three analyzed proteins in enriched membrane fractions. All samples were analyzed as technical duplicates at two independent occasions. Protein abundance levels obtained with the different techniques were compared. Enrichment factors were used to re-calculate abundance levels of proteins from membrane fractions to protein levels in whole cell. The inter-individual spread from the liver samples was analyzed as well. At the time of submission, data from five out of the six laboratories were been obtained and compared. Results: In general the mean values for the drug metabolizing enzymes were in good agreement between the different laboratories. The protein levels of the majority of the CYP-enzymes displayed a three-fold difference. The exception was the lower expressed CYP2B6 that showed more than ten-fold difference between the laboratories. The expression levels of UGT2B7 and UGT2B15 were in the same range as the majority of the CYP-enzymes and also differed three-fold. A higher variability in reported protein levels was displayed for the lower abundant UGT1A1 and UGT1A3. The mean values of both SLC- and ABC-transporting proteins were in the same range as the low abundant enzymes. In agreement to what was seen for the low abundant drug metabolizing enzymes, the variability of the drug transporting proteins was more than ten-fold between the laboratories. The protein levels obtained from the enriched membrane fractions (n=2) differed more compared to the protein levels analyzed in whole cell lysates (n=3). The technical repeats correlated better for the targeted approaches compared to the global approach. Conclusion: Despite large differences in methodologies, the highly abundant proteins were in good agreement. A higher variability was seen for the lower abundant proteins. Protein levels varied significantly between the different membrane enrichment methods. A higher variability between the technical duplicates was seen in the results from the label free, global approach. Further analysis investigating the impact of enrichment procedures, peptide quality and sensitivity of quantification will provide additional information on the causes of the variability
A new algorithm to diagnose atrial ectopic origin from multi lead ECG systems - insights from 3D virtual human atria and torso
No full textRapid atrial arrhythmias such as atrial fibrillation (AF) predispose to ventricular arrhythmias, sudden cardiac death and stroke. Identifying the origin of atrial ectopic activity from the electrocardiogram (ECG) can help to diagnose the early onset of AF in a cost-effective manner. The complex and rapid atrial electrical activity during AF makes it difficult to obtain detailed information on atrial activation using the standard 12-lead ECG alone. Compared to conventional 12-lead ECG, more detailed ECG lead configurations may provide further information about spatio-temporal dynamics of the body surface potential (BSP) during atrial excitation. We apply a recently developed 3D human atrial model to simulate electrical activity during normal sinus rhythm and ectopic pacing. The atrial model is placed into a newly developed torso model which considers the presence of the lungs, liver and spinal cord. A boundary element method is used to compute the BSP resulting from atrial excitation. Elements of the torso mesh corresponding to the locations of the placement of the electrodes in the standard 12-lead and a more detailed 64-lead ECG configuration were selected. The ectopic focal activity was simulated at various origins across all the different regions of the atria. Simulated BSP maps during normal atrial excitation (i.e. sinoatrial node excitation) were compared to those observed experimentally (obtained from the 64-lead ECG system), showing a strong agreement between the evolution in time of the simulated and experimental data in the P-wave morphology of the ECG and dipole evolution. An algorithm to obtain the location of the stimulus from a 64-lead ECG system was developed. The algorithm presented had a success rate of 93%, meaning that it correctly identified the origin of atrial focus in 75/80 simulations, and involved a general approach relevant to any multi-lead ECG system. This represents a significant improvement over previously developed algorithms
A longitudinal study of cortical grey matter lesion subtypes in relapse-onset multiple sclerosis.
No full textBACKGROUND: Cortical grey matter (GM) lesions are common in multiple sclerosis (MS), but little is known about their temporal evolution. We investigated this in people with relapsing-remitting (RR) and secondary progressive (SP) MS. METHODS: 27 people with RRMS, and 22 with SPMS were included in this study. Phase-sensitive inversion recovery scans were acquired on 2 occasions. Cortical GM lesions were classified as intracortical (IC, only involving GM) and leucocortical (LC, mixed GM-white matter (WM)); WM lesions touching the cortex as juxtacortical (JC). On follow-up scans, new IC, LC and JC lesions were identified, and any change in classification of lesions previously observed was noted. WM lesion counts in the whole brain were assessed on PD/T2-weighted scans. RESULTS: Over a mean (SD) of 21.0 (5.8) months, the number of new IC lesions per person per year was greater in SPMS (1.6 (1.9)) than RRMS (0.8 (1.9)) (Mann-Whitney p=0.039). All new LC lesions arose from previously seen IC lesions (SPMS 1.4 (1.8) per person per year, and RRMS 1.1 (1.0)), and none arose de novo, or from previously seen JC lesions. Changes in cortical GM (either new IC or IC converting to LC) lesion counts did not correlate with the changes in WM lesion counts. CONCLUSIONS: New cortical GM lesions rarely arise from the WM and the rate of new IC lesion formation is not closely linked with WM lesion accrual. IC lesion formation appears to be more common in SPMS than RRMS
Chromosomal integration vectors allowing flexible expression of foreign genes in Campylobacter jejuni
No full textBACKGROUND: Campylobacter jejuni is a major cause of human gastroenteritis yet there is limited knowledge of how disease is caused. Molecular genetic approaches are vital for research into the virulence mechanisms of this important pathogen. Vectors that allow expression of genes in C. jejuni via recombination onto the chromosome are particularly useful for genetic complementation of insertional knockout mutants and more generally for expression of genes in particular C. jejuni host backgrounds. METHODS: A series of three vectors that allow integration of genes onto the C. jejuni chromosome were constructed by standard cloning techniques with expression driven from three different strong promoters. Following integration onto the C. jejuni chromosome expression levels were quantified by fluorescence measurements and cells visualized by fluorescence microscopy. RESULTS: We have created plasmid, pCJC1, designed for recombination-mediated delivery of genes onto the C. jejuni chromosome. This plasmid contains a chloramphenicol resistance cassette (cat) with upstream and downstream restriction sites, flanked by regions of the C. jejuni pseudogene Cj0223. Cloning of genes immediately upstream or downstream of the cat gene allows their subsequent introduction onto the C. jejuni chromosome within the pseudogene. Gene expression can be driven from the native gene promoter if included, or alternatively from the cat promoter if the gene is cloned downstream of, and in the same transcriptional orientation as cat. To provide increased and variable expression of genes from the C. jejuni chromosome we modified pCJC1 through incorporation of three relatively strong promoters from the porA, ureI and flaA genes of C. jejuni, Helicobacter pylori and Helicobacter pullorum respectively. These promoters along with their associated ribosome binding sites were cloned upstream of the cat gene on pCJC1 to create plasmids pCJC2, pCJC3 and pCJC4. To test their effectiveness, a green fluorescent protein (gfp) reporter gene was inserted downstream of each of the three promoters and following integration of promoter-gene fusions onto the C. jejuni host chromosome, expression levels were quantified. Expression from the porA promoter produced the highest fluorescence, from flaA intermediate levels and from ureI the lowest. Expression of gfp from the porA promoter enabled visualization by fluorescent microscopy of intracellular C. jejuni cells following invasion of HeLa cells. CONCLUSIONS: The plasmids constructed allow stable chromosomal expression of genes in C. jejuni and, depending on the promoter used, different expression levels were obtained making these plasmids useful tools for genetic complementation and high level expression
Incentives or Standards: What Determines Accounting Quality Changes around IFRS Adoption?
No full textElectron transfer kinetics on natural crystals of MoS2 and graphite
No full textHere, we evaluate the electrochemical performance of sparsely studied natural crystals of molybdenite and graphite, which have increasingly been used for fabrication of next generation monolayer molybdenum disulphide and graphene energy storage devices. Heterogeneous electron transfer kinetics of several redox mediators, including Fe(CN)(6)(3-/4-), Ru(NH3)(6)(3+/2+) and IrCl62-/3- are determined using voltammetry in a micro-droplet cell. The kinetics on both materials are studied as a function of surface defectiveness, surface ageing, applied potential and illumination. We find that the basal planes of both natural MoS2 and graphite show significant electroactivity, but a large decrease in electron transfer kinetics is observed on atmosphere-aged surfaces in comparison to in situ freshly cleaved surfaces of both materials. This is attributed to surface oxidation and adsorption of airborne contaminants at the surface exposed to an ambient environment. In contrast to semimetallic graphite, the electrode kinetics on semiconducting MoS2 are strongly dependent on the surface illumination and applied potential. Furthermore, while visibly present defects/cracks do not significantly affect the response of graphite, the kinetics on MoS2 systematically accelerate with small increase in disorder. These findings have direct implications for use of MoS2 and graphene/graphite as electrode materials in electrochemistry-related applications