Thyroxine and reserpine-induced changes in metabolic profiles of rat urine and the therapeutic effect of Liu Wei Di Huang Wan detected by UPLC-HDMS

The promise of metabonomics, a new "omics" technique, to validate Chinese medicines and the compatibility of Chinese formulas has been appreciated. The present study was undertaken to explore the excretion pattern of low molecular mass metabolites in the male Wistar-derived rat model of kidney yin deficiency induced with thyroxine and reserpine as well as the therapeutic effect of Liu Wei Di Huang Wan (LW) and its separated prescriptions, a classic traditional Chinese medicine formula for treating kidney yin deficiency in China. The study utilized ultra-performance liquid chromatography/electrospray ionization synapt high definition mass spectrometry (UPLC/ESI-SYNAPT-HDMS) in both negative and positive electrospray ionization (ESI). At the same time, blood biochemistry was examined to identify specific changes in the kidney yin deficiency. Distinct changes in the pattern of metabolites, as a result of daily administration of thyroxine and reserpine, were observed by UPLC-HDMS combined with a principal component analysis (PCA). The changes in metabolic profiling were restored to their baseline values after treatment with LW according to the PCA score plots. Altogether, the current metabonomic approach based on UPLC-HDMS and orthogonal projection to latent structures discriminate analysis (OPLS-DA) indicated 20 ions (14 in the negative mode, 8 in the positive mode, and 2 in both) as "differentiating metabolites".

The influence of fatty acid methyl ester profiles on inter-cycle variability in a heavy duty compression ignition engine

With the advent of alternative fuels, such as biodiesels and related blends, it is important to develop an understanding of their effects on inter-cycle variability which, in turn, influences engine performance as well as its emission. Using four methanol trans-esterified biomass fuels of differing carbon chain length and degree of unsaturation, this paper provides insight into the effect that alternative fuels have on inter-cycle variability. The experiments were conducted with a heavy-duty Cummins, turbo-charged, common-rail compression ignition engine. Combustion performance is reported in terms of the following key in-cylinder parameters: indicated mean effective pressure (IMEP), net heat release rate (NHRR), standard deviation of variability (StDev), coefficient of variation (CoV), peak pressure, peak pressure timing and maximum rate of pressure rise. A link is also established between the cyclic variability and oxygen ratio, which is a good indicator of stoichiometry. The results show that the fatty acid structures did not have a significant effect on injection timing, injection duration, injection pressure, StDev of IMEP, or the timing of peak motoring and combustion pressures. However, a significant effect was noted on the premixed and diffusion combustion proportions, combustion peak pressure and maximum rate of pressure rise. Additionally, the boost pressure, IMEP and combustion peak pressure were found to be directly correlated to the oxygen ratio. The emission of particles positively correlates with oxygen content in the fuel as well as in the air-fuel mixture resulting in a higher total number of particles per unit of mass.

Changes in health profiles of participants in an Australian police department’s Wellness program

Background: Little is known about the health effects of worksite wellness programs on police department staff. Objective: To examine 1-2 year changes in health profiles of participants in the Queensland Police Service’s wellness program. Methods: Participants underwent yearly physical assessments. Health profile data collected during assessments from 2008 to 2012 were included in the analysis. Data Analysis: Repeated-measures ANOVA was used for continuous outcome variables, related-samples Wilcoxon Signed Rank test for non-normally continuous variables, and McNemar’s test for binary variables. Results: Significant changes in physical measures included decreases in waist circumference and percent body fat, and increases in cardiorespiratory fitness and flexibility (p<0.01). Changes in serum cholesterol, haemoglobin, total cholesterol ratios, HDL, LDL and Triglyceride levels were also significant (p<0.01). Conclusion: Participants’ health profiles mostly improved between cycles although most changes were not clinically significant. As this evaluation used a single-group pre-test post-test design, it provides initial indications that wellness programs can benefit staff in police departments.

Endophenotype profiles of MTHFR and ACE gene polymorphisms in migraine susceptibility

Background Migraine is a debilitating neurological disorder affecting approximately 12% of the Caucasian population. There are two main sub-types of migraine, migraine without aura (MO) and migraine with aura (MA). Migraine exhibits varied phenotypic expression with sufferers experiencing a range of neurological and other symptoms. It is likely that multiple susceptibility genes play a role in this varied phenotypic expression, thus investigation of genotype-phenotype relationships may provide valuable insights into the role of susceptibility genes in this disorder. Methods This study investigated the links between migraine susceptibility genes, methylenetetrahydrofolate reductase (MTHFR) and angiotensin converting enzyme (ACE), and clinical manifestation through statistical analyses. Results The result showed that for the MTHFR genotypes, there was a statistically significant correlation with the TT homozygous genotype and visual disturbances, unilateral head pain and physical activity discomforts. It was also found that bilateral head pain was associated with the male gender. Conclusion From these study results, it is plausible to state that MTHFR genotypes affect the phenotypic expression of migraine disease manifestation.

Microalgal species selection for biodiesel production based on fuel properties derived from fatty acid profiles

Physical and chemical properties of biodiesel are influenced by structural features of the fatty acids, such as chain length, degree of unsaturation and branching of the carbon chain. This study investigated if microalgal fatty acid profiles are suitable for biodiesel characterization and species selection through Preference Ranking Organisation Method for Enrichment Evaluation (PROMETHEE) and Graphical Analysis for Interactive Assistance (GAIA) analysis. Fatty acid methyl ester (FAME) profiles were used to calculate the likely key chemical and physical properties of the biodiesel [cetane number (CN), iodine value (IV), cold filter plugging point, density, kinematic viscosity, higher heating value] of nine microalgal species (this study) and twelve species from the literature, selected for their suitability for cultivation in subtropical climates. An equal-parameter weighted (PROMETHEE-GAIA) ranked Nannochloropsis oculata, Extubocellulus sp. and Biddulphia sp. highest; the only species meeting the EN14214 and ASTM D6751-02 biodiesel standards, except for the double bond limit in the EN14214. Chlorella vulgaris outranked N. oculata when the twelve microalgae were included. Culture growth phase (stationary) and, to a lesser extent, nutrient provision affected CN and IV values of N. oculata due to lower eicosapentaenoic acid (EPA) contents. Application of a polyunsaturated fatty acid (PUFA) weighting to saturation led to a lower ranking of species exceeding the double bond EN14214 thresholds. In summary, CN, IV, C18:3 and double bond limits were the strongest drivers in equal biodiesel parameter-weighted PROMETHEE analysis.

A high-throughput panel for identifying clinically relevant mutation profiles in melanoma

Success with molecular-based targeted drugs in the treatment of cancer has ignited extensive research efforts within the field of personalized therapeutics. However, successful application of such therapies is dependent on the presence or absence of mutations within the patient's tumor that can confer clinical efficacy or drug resistance. Building on these findings, we developed a high-throughput mutation panel for the identification of frequently occurring and clinically relevant mutations in melanoma. An extensive literature search and interrogation of the Catalogue of Somatic Mutations in Cancer database identified more than 1,000 melanoma mutations. Applying a filtering strategy to focus on mutations amenable to the development of targeted drugs, we initially screened 120 known mutations in 271 samples using the Sequenom MassARRAY system. A total of 252 mutations were detected in 17 genes, the highest frequency occurred in BRAF (n = 154, 57%), NRAS (n = 55, 20%), CDK4 (n = 8, 3%), PTK2B (n = 7, 2.5%), and ERBB4 (n = 5, 2%). Based on this initial discovery screen, a total of 46 assays interrogating 39 mutations in 20 genes were designed to develop a melanoma-specific panel. These assays were distributed in multiplexes over 8 wells using strict assay design parameters optimized for sensitive mutation detection. The final melanoma-specific mutation panel is a cost effective, sensitive, high-throughput approach for identifying mutations of clinical relevance to molecular-based therapeutics for the treatment of melanoma. When used in a clinical research setting, the panel may rapidly and accurately identify potentially effective treatment strategies using novel or existing molecularly targeted drugs

Expression Profiles of Mitochondrial Genes in the Frontal Cortex and the Caudate Nucleus of Developing Humans and Mice Selectively Bred for High and Low Fear

A growing body of evidence suggests that mitochondrial function may be important in brain development and psychiatric disorders. However, detailed expression profiles of those genes in human brain development and fear-related behavior remain unclear. Using microarray data available from the public domain and the Gene Ontology analysis, we identified the genes and the functional categories associated with chronological age in the prefrontal cortex (PFC) and the caudate nucleus (CN) of psychiatrically normal humans ranging in age from birth to 50 years. Among those, we found that a substantial number of genes in the PFC (115) and the CN (117) are associated with the GO term: mitochondrion (FDR qv <0.05). A greater number of the genes in the PFC (91%) than the genes in the CN (62%) showed a linear increase in expression during postnatal development. Using quantitative PCR, we validated the developmental expression pattern of four genes including monoamine oxidase B (MAOB), NADH dehydrogenase flavoprotein (NDUFV1), mitochondrial uncoupling protein 5 (SLC25A14) and tubulin beta-3 chain (TUBB3). In mice, overall developmental expression pattern of MAOB, SLC25A14 and TUBB3 in the PFC were comparable to the pattern observed in humans (p<0.05). However, mice selectively bred for high fear did not exhibit normal developmental changes of MAOB and TUBB3. These findings suggest that the genes associated with mitochondrial function in the PFC play a significant role in brain development and fear-related behavior.

Power profiles of multifocal contact lenses and their interpretation

Purpose Many contact lens (CL) manufacturers produce simultaneous-image lenses in which power varies either smoothly or discontinuously with zonal radius. We present in vitro measurements of some recent CLs and discuss how power profiles might be approximated in terms of nominal distance corrections, near additions, and on-eye visual performance. Methods Fully hydrated soft, simultaneous-image CLs from four manufacturers (Air Optix AQUA, Alcon; PureVision multifocal, Bausch & Lomb; Acuvue OASYS for Presbyopia, Vistakon; Biofinity multifocal- ‘‘D’’ design, Cooper Vision) were measured with a Phase focus Lens Profiler (Phase Focus Ltd., Sheffield,UK) in a wet cell and powerswere corrected to powers in air. All lenses had zero labeled power for distance. Results Sagittal power profiles revealed that the ‘‘low’’ add PureVision and Air Optix lenses exhibit smooth (parabolic) profiles, corresponding to negative spherical aberration. The ‘‘mid’’ and ‘‘high’’ add PureVision and Air Optix lenses have biaspheric designs, leading to different rates of power change for the central and peripheral portions. All OASYS lenses display a series of concentric zones, separated by abrupt discontinuities; individual profiles can be constrained between two parabolically decreasing curves, each giving a valid description of the power changes over alternate annular zones. Biofinity lenses have constant power over the central circular region of radius 1.5 mm, followed by an annular zone where the power increases approximately linearly, the gradient increasing with the add power, and finally an outer zone showing a slow, linear increase in power with a gradient being almost independent of the add power. Conclusions The variation in power across the simultaneous-image lenses produces enhanced depth of focus. The throughfocusnature of the image, which influences the ‘‘best focus’’ (distance correction) and the reading addition, will vary with several factors, including lens centration, the wearer’s pupil diameter, and ocular aberrations, particularly spherical aberration; visual performance with some designs may show greater sensitivity to these factors.

T helper cell cytokine profiles following endurance exercise

Endurance exercise can cause immunosuppression and increase the risk of upper respiratory illness. The present study examined changes in the secretion of T helper (Th) cell cytokines after endurance exercise. Ten highly trained road cyclists [mean±SEM: age 24.2±1.7 years; height 1.82±0.02 m; body mass 73.8±2.0 kg; peak oxygen uptake 65.9±2.3 mL/(kg•min)] performed 2 h of cycling exercise at 90% of the second ventilatory threshold. Peripheral blood mononuclear cells were isolated and stimulated with phytohemagglutinin. Plasma cortisol concentrations and the concentration of Th1/Th2/Th17 cell cytokines were examined. Data were analyzed using both traditional statistics and magnitude-based inferences. Results revealed a significant decrease in plasma cortisol at 4–24 h postexercise compared with pre-exercise values. Qualitative analysis revealed postexercise changes in concentrations of plasma cortisol, IL-2, TNF, IL-4, IL-6, IL-10, and IL-17A compared with pre-exercise values. A Th1/Th2 shift was evident immediately postexercise. Furthermore, for multiple cytokines, including IL-2 and TNF (Th1), IL-6 and IL-10 (Th2), and IL-17 (Th17), no meaningful change in concentration occurred until more than 4 h postexercise, highlighting the duration of exercise-induced changes in immune function. These results demonstrate the importance of considering “clinically” significant versus statistically significant changes in immune cell function after exercise.

Using narrow beam profiles to quantify focal spot size, for accurate Monte Carlo simulations of SRS/SRT systems

This study investigates the variation of photon field penumbra shape with initial electron beam diameter, for very narrow beams. A Varian Millenium MLC (Varian Medical Systems, Palo Alto, USA) and a Brainlab m3 microMLC (Brainlab AB. Feldkirchen, Germany) were used, with one Varian iX linear accelerator, to produce fields that were (nominally) 0.20 cm across. Dose profiles for these fields were measured using radiochromic film and compared with the results of simulations completed using BEAMnrc and DOSXYZnrc, where the initial electron beam was set to FWHM = 0.02, 0.10, 0.12, 0.15, 0.20 and 0.50 cm. Increasing the electron-beam FWHM produced increasing occlusion of the photon source by the closely spaced collimator leaves and resulted in blurring of the simulated profile widths from 0.26 to 0.64 cm, for the MLC, from 0.12 to 0.43 cm, for the microMLC. Comparison with measurement data suggested that the electron spot size in the clinical linear accelerator was between FWHM = 0.10 and 0.15 cm, encompassing the result of our previous output-factor based work, which identified a FWHM of 0.12. Investigation of narrow-beam penumbra variation has been found to be a useful procedure, with results varying noticeably with linear accelerator spot size and allowing FWHM estimates obtained using other methods to be verified.

An algebraic approach for determination of DG parameters to support voltage profiles in radial distribution networks

Rapidly increasing electricity demands and capacity shortage of transmission and distribution facilities are the main driving forces for the growth of Distributed Generation (DG) integration in power grids. One of the reasons for choosing a DG is its ability to support voltage in a distribution system. Selection of effective DG characteristics and DG parameters is a significant concern of distribution system planners to obtain maximum potential benefits from the DG unit. This paper addresses the issue of improving the network voltage profile in distribution systems by installing a DG of the most suitable size, at a suitable location. An analytical approach is developed based on algebraic equations for uniformly distributed loads to determine the optimal operation, size and location of the DG in order to achieve required levels of network voltage. The developed method is simple to use for conceptual design and analysis of distribution system expansion with a DG and suitable for a quick estimation of DG parameters (such as optimal operating angle, size and location of a DG system) in a radial network. A practical network is used to verify the proposed technique and test results are presented.

Process compliance measurement based on behavioural profiles

Process compliance measurement is getting increasing attention in companies due to stricter legal requirements and market pressure for operational excellence. On the other hand, the metrics to quantify process compliance have only been defined recently. A major criticism points to the fact that existing measures appear to be unintuitive. In this paper, we trace back this problem to a more foundational question: which notion of behavioural equivalence is appropriate for discussing compliance? We present a quantification approach based on behavioural profiles, which is a process abstraction mechanism. Behavioural profiles can be regarded as weaker than existing equivalence notions like trace equivalence, and they can be calculated efficiently. As a validation, we present a respective implementation that measures compliance of logs against a normative process model. This implementation is being evaluated in a case study with an international service provider.

Process compliance analysis based on behavioural profiles

Process compliance measurement is getting increasing attention in companies due to stricter legal requirements and market pressure for operational excellence. In order to judge on compliance of the business processing, the degree of behavioural deviation of a case, i.e., an observed execution sequence, is quantified with respect to a process model (referred to as fitness, or recall). Recently, different compliance measures have been proposed. Still, nearly all of them are grounded on state-based techniques and the trace equivalence criterion, in particular. As a consequence, these approaches have to deal with the state explosion problem. In this paper, we argue that a behavioural abstraction may be leveraged to measure the compliance of a process log – a collection of cases. To this end, we utilise causal behavioural profiles that capture the behavioural characteristics of process models and cases, and can be computed efficiently. We propose different compliance measures based on these profiles, discuss the impact of noise in process logs on our measures, and show how diagnostic information on non-compliance is derived. As a validation, we report on findings of applying our approach in a case study with an international service provider.

Causal behavioural profiles : efficient computation, applications, and evaluation

Analysis of behavioural consistency is an important aspect of software engineering. In process and service management, consistency verification of behavioural models has manifold applications. For instance, a business process model used as system specification and a corresponding workflow model used as implementation have to be consistent. Another example would be the analysis to what degree a process log of executed business operations is consistent with the corresponding normative process model. Typically, existing notions of behaviour equivalence, such as bisimulation and trace equivalence, are applied as consistency notions. Still, these notions are exponential in computation and yield a Boolean result. In many cases, however, a quantification of behavioural deviation is needed along with concepts to isolate the source of deviation. In this article, we propose causal behavioural profiles as the basis for a consistency notion. These profiles capture essential behavioural information, such as order, exclusiveness, and causality between pairs of activities of a process model. Consistency based on these profiles is weaker than trace equivalence, but can be computed efficiently for a broad class of models. In this article, we introduce techniques for the computation of causal behavioural profiles using structural decomposition techniques for sound free-choice workflow systems if unstructured net fragments are acyclic or can be traced back to S- or T-nets. We also elaborate on the findings of applying our technique to three industry model collections.