Miracle-dz/UniFAR-FTUs huggingface dataset:
EFFICIENT PARAMETERIZATION METHODS FOR GENERIC SHAPE OPTIMIZATION WITH ENGINEERING APPLICATIONS METODE UČINKOVITE PARAMETRIZACIJE ZA GENERIČKO OPTIMIRANJE OBLIKA S INŽENJERSKIM PRIMJENAMA DOCTORAL QUALIFYING EXAM DOKTORSKI KVALIFIKACIJSKI ISPIT

Engineering optimization very often includes complex and computationally expensive numerical simulations with time requirements ranging from few seconds to months per single simulation, depending on the simulated physics and available computational resources. Such optimization tasks should therefore contain no more than a small yet sufficient number of optimization variables. Additional difficulties arise when the underlying physics has nonlinear character modeled by nonlinear partial differential equations. The most common cases of engineering optimization involving computationally very expensive nonlinear simulation include problems in computational fluid dynamics. Furthermore, technical objects considered in fluid dynamics (ship hulls, wind-turbines or fan blades,.) are almost always complex three-dimensional shapes that cannot adequately be described with only a few shape variables. The most commonly used tools for generic shape representation are non-uniform rational basis spline (NURBS) curves and surfaces. NURBS surfaces can be used as mutually connected patches when the shape is too complex to be represented by a single NURBS surface. In recent years, a generalization of NURBS called T-splines is becoming increasingly more used. The objective of this doctoral qualifying exam is to review these and other currently available methods of generic shape parameterization and evaluate possibilities of integration with engineering optimization tasks related to computational fluid dynamic.
Circadian rhythms in rheumatoid arthritis: implications for pathophysiology and therapeutic management.

It is a well-known phenomenon that diseaserelated symptoms in patients with chronic inflammatory diseases exhibit circadian rhythms. This has been studied in, e.g., patients with rheumatoid arthritis (RA) (1–7). It is the clinical experience of rheumatologists that RA patients particularly experience joint pain, morning stiffness, and functional disability in the early morning hours. It is also remarkable that these diurnal variations demonstrate large amplitudes, with the patient’s condition being poor in the early morning and disease activity being mild or moderate in the early evening. This has been demonstrated using grip strength as a parameter; grip strength was, on average, 233 mmHg at 6:00 AM and 297 mm Hg at 6:00 PM, an increase of 27.5% (3). It has been further exemplified by overall pain reported using a 0–10-point visual analog scale, with an average pain score of 6.3 at 8:00 AM and 4.5 at 6:00 PM (decrease of 28.6%) (8). Results of assessment of symptoms in large clinical trials can vary markedly depending on the time of day that the visit takes place. The causal mechanisms underlying this pronounced diurnal cycle of changes in symptoms with a maximum in the morning are relevant to the pathophysiology of RA (9,10), to clinical patient care, and to optimization of treatment strategies (11). Since circadian rhythm is generated solely in the higher brain centers of the hypothalamus, learning from these experiments of nature can provide new clues to understanding neuroendocrine–immunologic pathways relevant to rheumatic diseases. This review briefly summarizes present knowledge on how circadian rhythm is generated in the central nervous system (CNS) and addresses studies demonstrating connections between the central oscillator and neuroendocrine pathways and the periphery (peripheral inflammation). Examples of circadian rhythms of hormones, specifically in relation to RA, are discussed, as is the circadian rhythm of pain, stiffness, and functional disability in health and disease. Circadian rhythms of RA-relevant immunologic parameters, including linkage between the diurnal variation of pain (and other RA symptoms and comorbidities) and the cycle of hormonal, neuronal, and immunologic parameters, are considered. Finally, important implications regarding therapy are derived, which in the future might lead to optimized treatment of RA and other chronic inflammatory diseases. A methodologic appendix (Appendix A) explains how several studies were mathematically analyzed and their data combined.
Inhibition of caspase‐3‐like activity prevents apoptosis while retaining functionality of human chondrocytes in vitro

Apoptosis was induced in a human chondrocyte cell line, T/C 28a4, by treatment with various stimuli, including camptothecin, tumor necrosis factor‐α, staurosporine, okadaic acid, and reduced serum conditions. All stimuli induced a cytosolic DEVDase activity, coincident with apoptosis. Caspase activities in the lysates were characterized and quantitated with peptide cleavage profiles. To confirm that the results were not related to the immortalized nature of the cell line, primary human chondrocytes also were shown to undergo apoptosis under similar conditions, which resulted in increased cytosolic DEVDase activity. There was little or no caspase‐1 (interleukin‐1β‐converting enzyme) or caspase‐8‐like activity in the apoptotic cells. In all cases, the irreversible nonselective caspase inhibitor, Z‐VAD‐FMK, and the caspase‐3‐selective inhibitor, Ac‐DMQD‐CHO, inhibited DEVDase activity and apoptosis, whereas the caspase‐1‐selective inhibitor, Ac‐YVAD‐CHO, had no effect. Human chondrocytes were stably and transiently transfected with a type‐II collagen gene (COL2A1) regulatory sequence driving a luciferase reporter as a specific marker of chondrocyte gene expression. Treatment of the cells with camptothecin or tumor necrosis factor‐α plus cycloheximide significantly inhibited COL2A1 transcriptional activity. Significantly, cotreatment with Z‐VAD‐FMK or Ac‐DMQD‐CHO maintained COL2A1‐reporter gene activity, indicating that the prevention of apoptosis by caspase‐3 inhibition was sufficient to maintain cell functionality as assessed by the retention of type‐II collagen promoter activity.
Gene expression profile analysis of Drosophila melanogaster selected for resistance to environmental stressors

Here, we report a detailed analysis of changes in gene expression in Drosophila melanogaster selected for ecologically relevant environmental stress resistance traits. We analysed females from seven replicated selection regimes and one control regime using whole genome gene expression arrays. When compared with gene expression profiles of control lines, we were able to detect consistent selection responses at the transcript level in each specific selection regime and also found a group of differentially expressed genes that were changed among all selected lines. Replicated selection lines showed similar changes in gene expression (compared with controls) and thus showed that 10 generations of artificial selection give a clear signal with respect to the resulting gene expression profile. The changes in gene expression in lines selected for increased longevity, desiccation and starvation resistance, respectively, showed high similarities. Cold resistance‐selected lines showed little differentiation from controls. Different methods of heat selection (heat survival, heat knock down and constant 30 °C) showed little similarity verifying that different mechanisms are involved in high temperature adaptation. For most individual selection regimes, and in the comparison of all selected lines and controls, the gene expression changes were exclusively in one direction, although the different selection regimes varied in the direction of response. The responses to selection restricted to individual selection regimes can be interpreted as stress specific, whereas the response shared among all selected lines can be considered as a general stress response. Here, we identified genes belonging to both types of responses to selection for stress resistance.
Peptidergic Regulation of Maturation of the Stimulus-Secretion Coupling in Fetal Islet &bgr; Cells

The stimulus-secretion coupling of the insulin-producing pancreatic islet &bgr; cell is subject to functional maturation during fetal life. We studied the maturation of a glucose-responsive insulin release from fetal rat islets and specifically investigated the impact of peptidergic regulation. To this end, islets were isolated from 21-day-old fetal rats and maintained for 7 days in tissue culture at 3.3 or 11.1 m M glucose and various supplements. In islets cultured in low glucose, acutely raising the ambient glucose concentration to 16.7 m M evoked a modest stimulation of short-term insulin release that was more pronounced in islets maintained in high glucose. Moreover, the insulin content was much higher in islets cultured in high than in low glucose. Culture with growth hormone (GH) markedly amplified both basal and stimulated short-term insulin secretion from islets maintained in either low or high glucose. Additionally, GH significantly elevated the insulin content in islets maintained in low glucose. Transforming growth factor &agr; (TGF-&agr;) increased basal, but not glucose-stimulated, insulin release and insulin content in islets cultured in low glucose. Gastrin, expressed in islets during fetal life, did not affect basal or glucose-stimulated insulin release, or insulin content, in islets maintained in either low or high glucose. The addition of gastrin to TGF-&agr; did not affect the results obtained with the latter peptide. Gastrin-releasing peptide failed to influence basal or glucose-responsive insulin secretory rates, and insulin content, at either glucose concentration during culture. The somatostatin analog Sandostatin (octreotide acetate) neither influenced basal nor stimulated short-term insulin release at any glucose concentration present during culture, whereas the hormone significantly decreased the insulin content of islets cultured in high glucose. Pancreastatin, produced by porcine islet &bgr; and &dgr; cells, failed to influence basal or glucose-responsive insulin secretory rates, and islet insulin content, at either glucose concentration during culture. Culture with gastric inhibitory peptide (GIP) or glucagon-like peptide I (GLP-1), two proposed incretins, did not affect short-term insulin secretion in response to 3.3 or 16.7 m M glucose irrespective of the ambient glucose concentration during culture. To the contrary, GLP-1, but not GIP, increased the content of insulin in islets cultured in low glucose. We conclude that islet &bgr;-cell differentiation and functional maturation of the stimulus-secretion coupling can be modulated in vitro in fetal rat pancreatic tissue by peptidergic regulation and glycemic stimulation. We suggest that GH and TGF-&agr; stimulate, while somatostatin, through paracrine interaction, may inhibit, these processes. These effectors may be of regulatory significance in the in vivo development of glucose-sensitive &bgr; cells, and defects in these mechanisms may result in glucose intolerance in adult subjects.
Effect of ALDH2 and CYP2E1 gene polymorphisms on drinking behavior and alcoholic liver disease in Japanese male workers.

AIMS We examined the relationships of ALDH2 and CYP2E1 genotypes on drinking behavior and the incidence of alcoholic liver disease in Japanese male workers. METHODS Two hundred and eighty-seven Japanese men were selected from one metal company to adjust for similar economic and social backgrounds. Drinking behavior was assessed from a self-assessment questionnaire. Genotypes of ALDH2 and CYP2E1 were analyzed with the polymerase chain reaction-single strand conformation polymorphism and with the polymerase chain reaction-restriction fragment length polymorphism, respectively. RESULTS The frequency of the ALDH2 genotype was 55% for typical homozygotes, 42% for heterozygotes, and 4% for atypical homozygotes. The frequency of the CYP2E1 genotype was 62% for c1 homozygotes, 35% for heterozygotes, and 3% for c2 homozygotes. The ALDH2 genotype closely influenced drinking habits, but not the CYP2E1 genotype. Among habitual drinkers, ALDH2 typical homozygotes consumed significantly larger amounts of ethanol than ALDH2 heterozygotes, whereas CYP2E1 genotypes did not influence daily alcohol consumption. Sixteen men (5.6%) were diagnosed with alcoholic liver disease. In terms of ALDH2 genotypes, 12 cases (7.6%) were typical homozygotes and 4 (3.4%) were heterozygotes, whereas the incidence of alcoholic liver disease was not different between c1/c1 homozygotes and c1/c2 heterozygotes. When the interactive contribution of the ALDH2 and CYP2E1 genotypes on drinking behavior and the incidence of alcoholic liver disease were examined, there were no significant differences in the CYP2E1 genotype among the subjects with the same ALDH2 genotype. CONCLUSION The ALDH2 genotype is strongly associated with individual alcohol drinking behavior and the development of alcoholic liver disease in Japanese male workers, but the CYP2E1 genotype is not.
Marked basophilia in acute promyelocytic leukaemia treated with all‐trans retinoic acid: molecular analysis of the cell origin of the basophils

Summary. We report a patient with acute promyelocytic leukaemia who developed marked basophilia during all‐trans retinoic acid treatment. We studied genomic DNA and RNA extracted from the patient's peripheral leucocytes in order to determine the origin of the basophils. The RARα rearranged band in the Southern blot analysis and a chimaeric product of PML‐RARα by polymerase chain reaction were strongly visible before ATRA treatment, but at the time of maximal basophilia both of them were markedly diminished. These findings suggest that the basophils which appeared during the ATRA treatment are reactive in nature rather than a leukaemic clone.
Protective Effect of Cinnamon Aqueous Extract on Cypermethrin-Induced Hepatotoxicity in Albino Rats

Cypermethrin is a synthetic pyrethroid with potent insecticidal property. Cinnamon is one of the oldest medicinal plants used in traditional medicine.The present work was carried out to evaluate the effect of cinnamon aqueous extract on liver injury induced by the cypermethrin in albino rats. Animals were divided into 4 groups. Group 1: control, Group 2: given cinnamon (200mg/kg b.w.), Group 3: given cypermethrin at a dose level 1/10 LD50 for 6 weeks, Group 4: given cypermethrin and cinnamon. Liver were obtained from these groups for histological, histochemical and immunohistochemical preparations. Liver tissues of cypermethrintreated animals showed leucocytic infiltrations, rupture of sinusoids with hemorrhages, congested blood vessels, cytoplasmic vacuolation of the hepatocytes and fatty infiltration. Histochemical results revealed depletion of carbohydrates and protein. Expression of PCNA was increased in the liver of treated rats. Biochemical results showed that cypermethrin caused elevation in ALT and AST. Treating animals with cypermethrin and cinnamon revealed an improvement in the histological, histochemical and biochemical changes with decrease in expression of PCNA. In conclusion, the administration of cinnamon aqueous extract provided significant protection against cypermethrin-induced hepatotoxicity in albino rats by its antioxidant effects.
Four years of experimental climate change modifies the microbial drivers of N2O fluxes in an upland grassland ecosystem

Emissions of the trace gas nitrous oxide (N2O) play an important role for the greenhouse effect and stratospheric ozone depletion, but the impacts of climate change on N2O fluxes and the underlying microbial drivers remain unclear. The aim of this study was to determine the effects of sustained climate change on field N2O fluxes and associated microbial enzymatic activities, microbial population abundance and community diversity in an extensively managed, upland grassland. We recorded N2O fluxes, nitrification and denitrification, microbial population size involved in these processes and community structure of nitrite reducers (nirK) in a grassland exposed for 4 years to elevated atmospheric CO2 (+200 ppm), elevated temperature (+3.5 °C) and reduction of summer precipitations (−20%) as part of a long‐term, multifactor climate change experiment. Our results showed that both warming and simultaneous application of warming, summer drought and elevated CO2 had a positive effect on N2O fluxes, nitrification, N2O release by denitrification and the population size of N2O reducers and NH4 oxidizers. In situ N2O fluxes showed a stronger correlation with microbial population size under warmed conditions compared with the control site. Specific lineages of nirK denitrifier communities responded significantly to temperature. In addition, nirK community composition showed significant changes in response to drought. Path analysis explained more than 85% of in situ N2O fluxes variance by soil temperature, denitrification activity and specific denitrifying lineages. Overall, our study underlines that climate‐induced changes in grassland N2O emissions reflect climate‐induced changes in microbial community structure, which in turn modify microbial processes.
The impact of pain in the immature brain

Abstract Clinical and laboratory investigations of neonatal pain suggest that preterm neonates are more vulnerable to stress and painful procedures and have heightened responses to successive stimuli. Preterm infants receiving intensive care are subjected to frequent invasive and stressful procedures as well as more chronic environmental influences. Acute episodic pain may cause early neurologic injury. Repeated and prolonged exposure to pain may alter subsequent psychokinetic development, as well as affect long-term neurodevelopmental, behavioral and social-emotional outcome. Several pain measures exist to assess pain in full-term and preterm neonates, including behavioral indicators and physiological indicators of pain. Therapeutic interventions can provide comfort and analgesia in preterm neonates. Guidelines for preventing or treating neonatal pain and its adverse consequences include recognition of the sources of pain and routine assessments of neonatal pain, avoidance of recurrent painful stimuli and the use of specific non-pharmacological and pharmacological interventions.
Correlation of functional and ultrastructural abnormalities of mitochondria in mouse heart carrying a pathogenic mutant mtDNA with a 4696-bp deletion.

We examined the correlation of functional and structural abnormalities of cardiac mitochondria created by pathogenic mutant mtDNAs using mito-mice with hearts carrying 88% mutant DeltamtDNA4696 with a 4696 deletion. COX histochemistry, quantitative PCR analysis, and electronmicrographs showed that accumulation of 91.6% DeltamtDNA4696 in single cardiac muscle fibers induced progressive reduction of COX activity to form COX-negative fibers. Moreover, hearts carrying 88% DeltamtDNA4696 consisted of three types of cardiac muscle fibers with different functional properties, COX-positive, -negative, and -intermediate fibers, which corresponded respectively to three types of fibers with different structural properties; type A fibers containing mitochondria with only lamellar cristae, type B containing mitochondria with only tubular cristae, and type C possessing mitochondria with both lamellar and tubular cristae. These observations suggest that lamellar cristae with COX activity transform into tubular cristae without COX activity along with the accumulation of DeltamtDNA4696, which would be responsible for insufficient supply of mtDNA products required to keep the normal structure and function of mitochondrial cristae. The correlation of these structural and functional abnormalities of cristae should provide important insight into diagnosis of cardiomyopathies caused by accumulation of pathogenic mutant mtDNAs.
Distributed Synchronization Control to Trajectory Tracking of Multiple Robot Manipulators

This paper investigates the issue of designing decentralized control laws to cooperatively command a team of general fully actuated manipulators. The purpose is to synchronize their movements while tracking a common desired trajectory. Based on the well-known consensus algorithm, the control strategy consists in synchronizing the joint position and the velocity of each robot in the network with respect to neighboring robots' joints and velocities. Modeled by an undirected graph, the cooperative robot network requires just local neighbor-to-neighbor information exchange between manipulators. So, it does not assume the existence of an explicit leader in the team. Based above all on combination of Lyapunov direct method and cross-coupling strategy, the proposed decentralized control law is extended to an adaptive synchronization control taking into account parameter uncertainties. To address the time delay problems in the network communication channels, the suggested synchronization control law robustly synchronizes robots to track a given trajectory. To this end, Krasovskii functional method has been used to deal with the delay-dependent stability problem. A real-time software simulator is developed to visualize the robot manipulators coordination.
Smoking in Adults in Sri Lanka: Prevalence and Attitudes

A questionnaire was administered to 1565 adults to identify the prevalence of smoking and to assess respondents' attitudes toward smoking. Of men 41% were yearly smokers, 27.8% were monthly smokers and 21% were daily smokers. The corresponding figures for women were 3.4%, 2% and 0.6% respectively. Higher prevalence rates were observed among less educated, middle-aged men who were from underprivileged families. About 23% of men and 0.9% of women were monthly alcohol users. Alcohol use seems to be positively associated with smoking. A considerable portion of both smokers and non-smokers expressed a favorable attitude towards smoking habits of adult males (40.1% of smokers and 12.8% of non-smokers) and towards the tobacco industry (25.1% of smokers and 13.1 of non-smokers). Since the majority of people in Sri Lanka are non-smokers, attitudinal support given by them in promoting smoking in the society needs to be addressed effectively in smoking control interventions. Asia Pac J Public Health 2005: 17(1): 40-45.
Perceived economic benefits of telecom access at the Bottom of the Pyramid in emerging Asia

Many in the ‘ICT for development’ movement highlight the benefits that telecommunication, the Internet and other information and communication technologies (broadly put, ICTs) can bring to the table in the fight against poverty. A number of studies have attempted to demonstrate the impacts of access on income at the macro-level. However supporting evidence for these arguments at the household level is limited at best.