Website Performance Evaluation and Estimation in an E-business Environment

This thesis introduces a new Predictus-model for performance evaluation and estimation in a multi-layer website environment. The model is based on soft computing ideas, i.e. simulation and statistical analysis. The aim is to improve energy consumption of the website's hardware and investment efficiency and to avoid loss of availability. The aim of optimised exploitation is reduced energy and maintenance costs on the one hand and increased end-user satisfaction due to robust and stable web services on the other. A method based on simulation of user requests is described. Instead of ordinary static parameter set, the dynamic extraction from previous log files is used. The distribution of existing requests is exploited to generate the actual based natural load. By loading the server system with valid and well-known requests, the behaviour of the server system is natural. The control back loop on the generation of work load assures the validity of the work load in the long-term. A method for identifying the actual performance of the website is described. Using the well-known load in simulation of usage by a large number of virtual users and observing the utilisation rate of server resources ensure the best information for the internal state of the system. The disturbance of the service website usage can be avoided using the mathematical extrapolation method to reach the saturation point on the single server resource

Behavior and diet of the Critically Endangered Eulemur cinereiceps in Manombo forest, southeast Madagascar

Manombo Special Reserve is a parcel of rainforest along the southeastern coast of Madagascar, containing eight lemur species, including the White-collared brown lemur (Eulemur cinereiceps [Eulemur albocollaris]). Following a drastic cyclone in the region in January of 1997, the population of E. cinereiceps at Manombo was reduced by half. Results indicate that individuals of this critically endangered species at Manombo consume a total of 54 plant species belonging to 24 families, with over two-thirds of the diet comprised of ripe and unripe fruits. White-collared brown lemurs also opportunistically feed on novel food items and invasive plants in their recovering habitat. We report the first record of E. cinereiceps consuming a shelf fungus species growing on invasive trees. During feeding, lemurs tore pieces of the fungus from the trees with their hands and mouth (chewing cycle duration mean 0.28 s; SD 0.01). White-collared brown lemurs also consumed spicy fruits of a non-native plant species (Aframomum angustifolium) growing in highly disturbed open areas. Feeding bouts typically began by stripping away the outer covering with the anterior dentition, with pulp and seeds then consumed (chewing cycle duration mean 0.22 s; SD 0.005). This is the first record of consumption of either of these resources for any lemur species at Manombo. Ability to feed on items like A. angustifolium may permit E. cinereiceps to avoid competition with other species in this highly degraded forest environment.RÉSUMÉ La Réserve Spéciale de Manombo est un fragment de forêt dense humide de basse altitude et située le long de la côte Sud-est de Madagascar. Cette partie de forêt abrite au total huit espèces de lémuriens, y compris le Lémur à collier blanc (Eulemur cinereiceps [Eulemur albocollaris]). Le passage dramatique du cyclone Gretelle dans la région en janvier 1997 a réduit de moitié la taille de la population d’E. cinereiceps dans sa zone de distribution. Les résultats des études effectuées sur les individus restants de cette espèce, qui est classée comme Gravement Menacée, permettent d’énumérer un total de 54 espèces de plantes appartenant à 24 familles qui sont consommées par l’espèce. D’autre part, deux tiers du régime alimentaire d’E. cinereiceps sont représentés par des fruits mûrs ou non. Le Lémur à collier blanc consomme occasionnellement une quantité assez importante de plantes envahissantes pour assurer ses besoins nutritifs, ce qui n’est pas habituel dans l’histoire naturelle de la vie des lémuriens. La présente étude constitue également la première observation de consommation d’une espèce inconnue de champignon par les représentants d’E. cinereiceps. Dans le présent cas, ledit champignon venait juste de pousser sur un pied mort de Cecropia peltata, une espèce allogène et envahissante de la région. Durant la prise de nourriture, l’animal a arraché des morceaux du champignon sur l’arbre mort avec la main et puis la bouche. La partie consommée a été mâchée par l’animal pendant une période de 0,28 s. Le Lémur à collier blanc consomme aussi des fruits épicés d’une espèce de plante allogène (Aframomum angustifolium) qui ne pousse que dans des zones ouvertes et extrêmement dégradées. La prise de nourriture sur cette espèce de plante commence par l’enlèvement de la partie dure du fruit, pour cela l’animal utilise ses dents antérieures très puissantes, puis il tire soigneusement en même temps avec ses dents et sa langue la partie charnue et les graines. Cette prise de nourriture s’effectue pendant une période d’environ 0,22 s. C’était la première fois dans l’histoire des lémuriens de Manombo que des observations ont été effectuées sur un animal en train de manger des espèces de plantes inhabituelles. L’aptitude de manger des espèces de plantes telle que A. angustifolium pourrait permettre à E. cinereiceps d’éviter la compétition avec les autres espèces de lémuriens vivant dans cet environnement dégradé

Metabolic profiling of fatty liver in young and middle-aged adults : Cross-sectional and prospective analyses of the Young Finns Study

Nonalcoholic fatty liver is associated with obesity-related metabolic disturbances, but little is known about the metabolic perturbations preceding fatty liver disease. We performed comprehensive metabolic profiling to assess how circulating metabolites, such as lipoprotein lipids, fatty acids, amino acids, and glycolysis-related metabolites, reflect the presence of and future risk for fatty liver in young adults. Sixty-eight lipids and metabolites were quantified by nuclear magnetic resonance metabolomics in the population-based Young Finns Study from serum collected in 2001 (n = 1,575), 2007 (n = 1,509), and 2011 (n = 2,002). Fatty liver was diagnosed by ultrasound in 2011 when participants were aged 34-49 years (19% prevalence). Cross-sectional associations as well as 4-year and 10-year risks for fatty liver were assessed by logistic regression. Metabolites across multiple pathways were strongly associated with the presence of fatty liver (P <0.0007 for 60 measures in age-adjusted and sex-adjusted cross-sectional analyses). The strongest direct associations were observed for extremely large very-low-density lipoprotein triglycerides (odds ratio [OR] = 4.86 per 1 standard deviation, 95% confidence interval 3.48-6.78), other very-low-density lipoprotein measures, and branched-chain amino acids (e.g., leucine OR = 2.94, 2.51-3.44). Strong inverse associations were observed for high-density lipoprotein measures, e.g., high-density lipoprotein size (OR = 0.36, 0.30-0.42) and several fatty acids including omega-6 (OR = 0.37, 0.32-0.42). The metabolic associations were attenuated but remained significant after adjusting for waist, physical activity, alcohol consumption, and smoking (P <0.0007). Similar aberrations in the metabolic profile were observed already 10 years before fatty liver diagnosis. Conclusion: Circulating lipids, fatty acids, and amino acids reflect fatty liver independently of routine metabolic risk factors; these metabolic aberrations appear to precede the development of fatty liver in young adults. (Hepatology 2017;65:491-500).Peer reviewe

DHCR24 exerts neuroprotection upon inflammation-induced neuronal death

Abstract Background DHCR24, involved in the de novo synthesis of cholesterol and protection of neuronal cells against different stress conditions, has been shown to be selectively downregulated in neurons of the affected brain areas in Alzheimer’s disease. Methods Here, we investigated whether the overexpression of DHCR24 protects neurons against inflammation-induced neuronal death using co-cultures of mouse embryonic primary cortical neurons and BV2 microglial cells upon acute neuroinflammation. Moreover, the effects of DHCR24 overexpression on dendritic spine density and morphology in cultured mature mouse hippocampal neurons and on the outcome measures of ischemia-induced brain damage in vivo in mice were assessed. Results Overexpression of DHCR24 reduced the loss of neurons under inflammation elicited by LPS and IFN-γ treatment in co-cultures of mouse neurons and BV2 microglial cells but did not affect the production of neuroinflammatory mediators, total cellular cholesterol levels, or the activity of proteins linked with neuroprotective signaling. Conversely, the levels of post-synaptic cell adhesion protein neuroligin-1 were significantly increased upon the overexpression of DHCR24 in basal growth conditions. Augmentation of DHCR24 also increased the total number of dendritic spines and the proportion of mushroom spines in mature mouse hippocampal neurons. In vivo, overexpression of DHCR24 in striatum reduced the lesion size measured by MRI in a mouse model of transient focal ischemia. Conclusions These results suggest that the augmentation of DHCR24 levels provides neuroprotection in acute stress conditions, which lead to neuronal loss in vitro and in vivo

Environmental justice for the governance of aquatic environments

Environmental justice sheds light on the distributive and procedural aspects of planning and decision-making. We examined the challenges arising from the perspective of environmental justice on multi-level and participatory environmental governance by exploring the governance of aquatic environments in the Helsinki Metropolitan Area. We found three main challenges and potential responses to them. First, even though most of Helsinki’s shoreline is free and/or accessible by road and accordingly used actively by people for recreational purposes, many parts of the shoreline are perceived as inaccessible, reflecting a need to combine factual and perceived accessibility of aquatic environments in detail during the planning processes and to discuss reasons for possible discrepancies between these two. Second, there was a remarkable seasonal variation in the use of aquatic environments, so more attention should be paid to social-demographic factors explaining the distribution of the use of urban nature. Third, it seems to be difficult to capture the variety of perceptions of people and to integrate them into planning and decision-making processes even on a local scale, and this challenge is likely even more pronounced on higher levels of planning and governance. Thus, better integration of regional and local-scale planning procedures should be encouraged. Building on these observations, we conclude that integration of procedural and distributive environmental justice into the practices of the governance of aquatic environments could remarkably decrease unwanted trade-offs and potential conflicts in their use and management.Peer reviewe

Impaired HDL2-mediated cholesterol efflux is associated with metabolic syndrome in families with early onset coronary heart disease and low HDL-cholesterol level

<div><p>Objective</p><p>The potential of high-density lipoproteins (HDL) to facilitate cholesterol removal from arterial foam cells is a key function of HDL. We studied whether cholesterol efflux to serum and HDL subfractions is impaired in subjects with early coronary heart disease (CHD) or metabolic syndrome (MetS) in families where a low HDL-cholesterol level (HDL-C) predisposes to early CHD.</p><p>Methods</p><p>HDL subfractions were isolated from plasma by sequential ultracentrifugation. THP-1 macrophages loaded with acetyl-LDL were used in the assay of cholesterol efflux to total HDL, HDL2, HDL3 or serum.</p><p>Results</p><p>While cholesterol efflux to serum, total HDL and HDL3 was unchanged, the efflux to HDL2 was 14% lower in subjects with MetS than in subjects without MetS (p<0.001). The efflux to HDL2 was associated with components of MetS such as plasma HDL-C (r = 0.76 in men and r = 0.56 in women, p<0.001 for both). The efflux to HDL2 was reduced in men with early CHD (p<0.01) only in conjunction with their low HDL-C. The phospholipid content of HDL2 particles was a major correlate with the efflux to HDL2 (r = 0.70, p<0.001). A low ratio of HDL2 to total HDL was associated with MetS (p<0.001).</p><p>Conclusion</p><p>Our results indicate that impaired efflux to HDL2 is a functional feature of the low HDL-C state and MetS in families where these risk factors predispose to early CHD. The efflux to HDL2 related to the phospholipid content of HDL2 particles but the phospholipid content did not account for the impaired efflux in cardiometabolic disease, where a combination of low level and poor quality of HDL2 was observed.</p></div

Metabolic profiling of pregnancy : cross-sectional and longitudinal evidence

Background: Pregnancy triggers well-known alterations in maternal glucose and lipid balance but its overall effects on systemic metabolism remain incompletely understood. Methods: Detailed molecular profiles (87 metabolic measures and 37 cytokines) were measured for up to 4260 women (24-49 years, 322 pregnant) from three population-based cohorts in Finland. Circulating molecular concentrations in pregnant women were compared to those in non-pregnant women. Metabolic profiles were also reassessed for 583 women 6 years later to uncover the longitudinal metabolic changes in response to change in the pregnancy status. Results: Compared to non-pregnant women, all lipoprotein subclasses and lipids were markedly increased in pregnant women. The most pronounced differences were observed for the intermediate-density, low-density and high-density lipoprotein triglyceride concentrations. Large differences were also seen for many fatty acids and amino acids. Pregnant women also had higher concentrations of low-grade inflammatory marker glycoprotein acetyls, higher concentrations of interleukin-18 and lower concentrations of interleukin-12p70. The changes in metabolic concentrations for women who were not pregnant at baseline but pregnant 6 years later (or vice versa) matched (or were mirror-images of) the cross-sectional association pattern. Cross-sectional results were consistent across the three cohorts and similar longitudinal changes were seen for 653 women in 4-year and 497 women in 10-year follow-up. For multiple metabolic measures, the changes increased in magnitude across the three trimesters. Conclusions: Pregnancy initiates substantial metabolic and inflammatory changes in the mothers. Comprehensive characterisation of normal pregnancy is important for gaining understanding of the key nutrients for fetal growth and development. These findings also provide a valuable molecular reference in relation to studies of adverse pregnancy outcomes.Peer reviewe

New Insights into Alzheimer's Disease Progression: A Combined TMS and Structural MRI Study

BACKGROUND: Combination of structural and functional data of the human brain can provide detailed information of neurodegenerative diseases and the influence of the disease on various local cortical areas. METHODOLOGY AND PRINCIPAL FINDINGS: To examine the relationship between structure and function of the brain the cortical thickness based on structural magnetic resonance images and motor cortex excitability assessed with transcranial magnetic stimulation were correlated in Alzheimer's disease (AD) and mild cognitive impairment (MCI) patients as well as in age-matched healthy controls. Motor cortex excitability correlated negatively with cortical thickness on the sensorimotor cortex, the precuneus and the cuneus but the strength of the correlation varied between the study groups. On the sensorimotor cortex the correlation was significant only in MCI subjects. On the precuneus and cuneus the correlation was significant both in AD and MCI subjects. In healthy controls the motor cortex excitability did not correlate with the cortical thickness. CONCLUSIONS: In healthy subjects the motor cortex excitability is not dependent on the cortical thickness, whereas in neurodegenerative diseases the cortical thinning is related to weaker cortical excitability, especially on the precuneus and cuneus. However, in AD subjects there seems to be a protective mechanism of hyperexcitability on the sensorimotor cortex counteracting the prominent loss of cortical volume since the motor cortex excitability did not correlate with the cortical thickness. Such protective mechanism was not found on the precuneus or cuneus nor in the MCI subjects. Therefore, our results indicate that the progression of the disease proceeds with different dynamics in the structure and function of neuronal circuits from normal conditions via MCI to AD

Semaphorin 4D promotes bone invasion in head and neck squamous cell carcinoma

Head and neck squamous cell carcinomas (HNSCCs) frequently invade the bones of the facial skeleton. Semaphorin 4D (Sema4D) is an axon guidance molecule produced by oligodendrocytes. Sema4D was also identified in the bone microenvironment and many cancer tissues including HNSCC. To date, however, the role of Sema4D in cancer-associated bone disease is still unknown. This is the first study to demonstrate the role of Sema4D in bone invasion of cancer. In the clinical tissue samples of bone lesion of HNSCC, Sema4D was detected at high levels, and its expression was correlated with insulin-like growth factor-I (IGF-I) expression. In vitro experiments showed that IGF-I regulates Sema4D expression and Sema4D increased proliferation, migration and invasion in HNSCC cells. Sema4D also regulated the expression of receptor activator of nuclear factor κβ ligand (RANKL) in osteoblasts, and this stimulated osteoclastgenesis. Furthermore, knockdown of Sema4D in HNSCC cells inhibited tumor growth and decreased the number of osteoclasts in a mouse xenograft model. Taken together, IGF-I-driven production of Sema4D in HNSCCs promotes osteoclastogenesis and bone invasion

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms