Exhaled breath condensate as a matrix for combustion-based nanoparticle exposure and health effect evaluation

Health assessment and medical surveillance of workers exposed to combustion nanoparticles are challenging. The aim was to evaluate the feasibility of using exhaled breath condensate (EBC) from healthy volunteers for (1) assessing the lung deposited dose of combustion nanoparticles and (2) determining the resulting oxidative stress by measuring hydrogen peroxide (H2O2) and malondialdehyde (MDA). Methods: Fifteen healthy nonsmoker volunteers were exposed to three different levels of sidestream cigarette smoke under controlled conditions. EBC was repeatedly collected before, during, and 1 and 2 hr after exposure. Exposure variables were measured by direct reading instruments and by active sampling. The different EBC samples were analyzed for particle number concentration (light-scattering-based method) and for selected compounds considered oxidative stress markers. Results: Subjects were exposed to an average airborne concentration up to 4.3×10(5) particles/cm(3) (average geometric size ∼60-80 nm). Up to 10×10(8) particles/mL could be measured in the collected EBC with a broad size distribution (50(th) percentile ∼160 nm), but these biological concentrations were not related to the exposure level of cigarette smoke particles. Although H2O2 and MDA concentrations in EBC increased during exposure, only H2O2 showed a transient normalization 1 hr after exposure and increased afterward. In contrast, MDA levels stayed elevated during the 2 hr post exposure. Conclusions: The use of diffusion light scattering for particle counting proved to be sufficiently sensitive to detect objects in EBC, but lacked the specificity for carbonaceous tobacco smoke particles. Our results suggest two phases of oxidation markers in EBC: first, the initial deposition of particles and gases in the lung lining liquid, and later the start of oxidative stress with associated cell membrane damage. Future studies should extend the follow-up time and should remove gases or particles from the air to allow differentiation between the different sources of H2O2 and MDA.

Power quality improving with virtual flux-based voltage source line converter

Line converters have become an attractive AC/DC power conversion solution in industrial applications. Line converters are based on controllable semiconductor switches, typically insulated gate bipolar transistors. Compared to the traditional diode bridge-based power converters line converters have many advantageous characteristics, including bidirectional power flow, controllable de-link voltage and power factor and sinusoidal line current. This thesis considers the control of the lineconverter and its application to power quality improving. The line converter control system studied is based on the virtual flux linkage orientation and the direct torque control (DTC) principle. A new DTC-based current control scheme is introduced and analyzed. The overmodulation characteristics of the DTC converter are considered and an analytical equation for the maximum modulation index is derived. The integration of the active filtering features to the line converter isconsidered. Three different active filtering methods are implemented. A frequency-domain method, which is based on selective harmonic sequence elimination, anda time-domain method, which is effective in a wider frequency band, are used inharmonic current compensation. Also, a voltage feedback active filtering method, which mitigates harmonic sequences of the grid voltage, is implemented. The frequency-domain and the voltage feedback active filtering control systems are analyzed and controllers are designed. The designs are verified with practical measurements. The performance and the characteristics of the implemented active filtering methods are compared and the effect of the L- and the LCL-type line filteris discussed. The importance of the correct grid impedance estimate in the voltage feedback active filter control system is discussed and a new measurement-based method to obtain it is proposed. Also, a power conditioning system (PCS) application of the line converter is considered. A new method for correcting the voltage unbalance of the PCS-fed island network is proposed and experimentally validated.

Toimintojohtamisen soveltuminen päivittäistavarakaupan johtamiseen

Tutkimuksen tarkoituksena oli tutkia johdon näkökulmasta toimintojohtamisen soveltuvuutta Pirkanmaan Osuuskaupan päivittäistavarakaupan johtamiseen. Tavoitteena oli rakentaa esimerkkiyritykselle toimintolähtöinen organisaatiomalli ja tutkia organisaation muutoksen edellytyksiä sekä strategian vaikutusta organisaatiomallin valintaan. Tutkimuksessa käytetään konstruktiivista tutkimustapaa. Tutkimus on teoreettinen ja toiminta-analyyttinen case-tutkimus. Toimintojohtaminen, jonka tavoitteena on liiketoiminnan horisontaalinen ohjaus, ei sovellu päivittäistavarakaupan johtamiseen. Toimintojohtaminen ei lisää Pirkanmaan Osuuskaupan market-kaupan kilpailukykyä, koska sen resurssitarve on suuri ja näin ollen se on kustannustehokkuus-strategian vastainen. Organisaatiomuutos edellyttää erityisesti johdolta strategista ajattelua ja kykyä nähdä nykyisen toimintamallin uhat tulevaisuuden kilpailuympäristössä ja toisaalta nähdä tulevaisuuden menestystekijät, joita toteuttamalla yritys menestyy jatkossakin. Johdon tulee pystyä viestimään henkilöstölle muutoksen välttämättömyys ja kuva tulevaisuuden toimintamallista. Johdon rooli ja tuki organisaatiolle muutosprosessissa on keskeistä. Strategia on keino toteuttaa yrityksen visio, päämäärät ja tavoitteet. Toiminnan organisointi on keskeisin keino strategisten päämäärien ja tavoitteiden toteuttamiseksi.

Production planning development in global manufacturing company

Larox Corporation is a provider of full service filtration in solid and liquid separation. Larox develops, designs, manufactures and supplies industrial filters. By Larox’s continuous development principle, a project for more efficient production was started. At the same time production planning was taken under review. Aim for this Master’s thesis was to find software designed for production planning purposes replacement for old Microsoft Excel based method. In this Master’s thesis current way of production planning was thoroughly analyzed and improvement targets were specified and also requirements for new software were assigned. Primary requirements for new software were possibility to production scheduling, planning, follow-up and also for long-time capacity planning and tracking. Also one demand was that new software should have data link to Larox’s current ERP-system. Result of this Master’s thesis was to start using Larox’s ERP-system also for production planning purposes. New mode of operation fulfils all requirements which were placed to new system. By using new method of production planning, production planners can get more easier and reliable data than from current system.

Adaptation of TRIZ Method for Problem Solving in Process Engineering

TRIZ is one of the well-known tools, based on analytical methods for creative problem solving. This thesis suggests adapted version of contradiction matrix, a powerful tool of TRIZ and few principles based on concept of original TRIZ. It is believed that the proposed version would aid in problem solving, especially those encountered in chemical process industries with unit operations. In addition, this thesis would help fresh process engineers to recognize importance of various available methods for creative problem solving and learn TRIZ method of creative problem solving. This thesis work mainly provides idea on how to modify TRIZ based method according to ones requirements to fit in particular niche area and solve problems efficiently in creative way. Here in this case, the contradiction matrix developed is based on review of common problems encountered in chemical process industry, particularly in unit operations and resolutions are based on approaches used in past to handle those issues.

Development of molecular-based techniques for the detection, identification and quantification of food-borne pathogens

La presencia de microorganismos patógenos en alimentos es uno de los problemas esenciales en salud pública, y las enfermedades producidas por los mismos es una de las causas más importantes de enfermedad. Por tanto, la aplicación de controles microbiológicos dentro de los programas de aseguramiento de la calidad es una premisa para minimizar el riesgo de infección de los consumidores. Los métodos microbiológicos clásicos requieren, en general, el uso de pre-enriquecimientos no-selectivos, enriquecimientos selectivos, aislamiento en medios selectivos y la confirmación posterior usando pruebas basadas en la morfología, bioquímica y serología propias de cada uno de los microorganismos objeto de estudio. Por lo tanto, estos métodos son laboriosos, requieren un largo proceso para obtener resultados definitivos y, además, no siempre pueden realizarse. Para solucionar estos inconvenientes se han desarrollado diversas metodologías alternativas para la detección identificación y cuantificación de microorganismos patógenos de origen alimentario, entre las que destacan los métodos inmunológicos y moleculares. En esta última categoría, la técnica basada en la reacción en cadena de la polimerasa (PCR) se ha convertido en la técnica diagnóstica más popular en microbiología, y recientemente, la introducción de una mejora de ésta, la PCR a tiempo real, ha producido una segunda revolución en la metodología diagnóstica molecular, como pude observarse por el número creciente de publicaciones científicas y la aparición continua de nuevos kits comerciales. La PCR a tiempo real es una técnica altamente sensible -detección de hasta una molécula- que permite la cuantificación exacta de secuencias de ADN específicas de microorganismos patógenos de origen alimentario. Además, otras ventajas que favorecen su implantación potencial en laboratorios de análisis de alimentos son su rapidez, sencillez y el formato en tubo cerrado que puede evitar contaminaciones post-PCR y favorece la automatización y un alto rendimiento. En este trabajo se han desarrollado técnicas moleculares (PCR y NASBA) sensibles y fiables para la detección, identificación y cuantificación de bacterias patogénicas de origen alimentario (Listeria spp., Mycobacterium avium subsp. paratuberculosis y Salmonella spp.). En concreto, se han diseñado y optimizado métodos basados en la técnica de PCR a tiempo real para cada uno de estos agentes: L. monocytogenes, L. innocua, Listeria spp. M. avium subsp. paratuberculosis, y también se ha optimizado y evaluado en diferentes centros un método previamente desarrollado para Salmonella spp. Además, se ha diseñado y optimizado un método basado en la técnica NASBA para la detección específica de M. avium subsp. paratuberculosis. También se evaluó la aplicación potencial de la técnica NASBA para la detección específica de formas viables de este microorganismo. Todos los métodos presentaron una especificidad del 100 % con una sensibilidad adecuada para su aplicación potencial a muestras reales de alimentos. Además, se han desarrollado y evaluado procedimientos de preparación de las muestras en productos cárnicos, productos pesqueros, leche y agua. De esta manera se han desarrollado métodos basados en la PCR a tiempo real totalmente específicos y altamente sensibles para la determinación cuantitativa de L. monocytogenes en productos cárnicos y en salmón y productos derivados como el salmón ahumado y de M. avium subsp. paratuberculosis en muestras de agua y leche. Además este último método ha sido también aplicado para evaluar la presencia de este microorganismo en el intestino de pacientes con la enfermedad de Crohn's, a partir de biopsias obtenidas de colonoscopia de voluntarios afectados. En conclusión, este estudio presenta ensayos moleculares selectivos y sensibles para la detección de patógenos en alimentos (Listeria spp., Mycobacterium avium subsp. paratuberculosis) y para una rápida e inambigua identificación de Salmonella spp. La exactitud relativa de los ensayos ha sido excelente, si se comparan con los métodos microbiológicos de referencia y pueden serusados para la cuantificación de tanto ADN genómico como de suspensiones celulares. Por otro lado, la combinación con tratamientos de preamplificación ha resultado ser de gran eficiencia para el análisis de las bacterias objeto de estudio. Por tanto, pueden constituir una estrategia útil para la detección rápida y sensible de patógenos en alimentos y deberían ser una herramienta adicional al rango de herramientas diagnósticas disponibles para el estudio de patógenos de origen alimentario.

Adjoint goal-based error norms for adaptive mesh ocean modelling

Flow in the world's oceans occurs at a wide range of spatial scales, from a fraction of a metre up to many thousands of kilometers. In particular, regions of intense flow are often highly localised, for example, western boundary currents, equatorial jets, overflows and convective plumes. Conventional numerical ocean models generally use static meshes. The use of dynamically-adaptive meshes has many potential advantages but needs to be guided by an error measure reflecting the underlying physics. A method of defining an error measure to guide an adaptive meshing algorithm for unstructured tetrahedral finite elements, utilizing an adjoint or goal-based method, is described here. This method is based upon a functional, encompassing important features of the flow structure. The sensitivity of this functional, with respect to the solution variables, is used as the basis from which an error measure is derived. This error measure acts to predict those areas of the domain where resolution should be changed. A barotropic wind driven gyre problem is used to demonstrate the capabilities of the method. The overall objective of this work is to develop robust error measures for use in an oceanographic context which will ensure areas of fine mesh resolution are used only where and when they are required. (c) 2006 Elsevier Ltd. All rights reserved.

Family-based association analysis with ordered categorical phenotypes, covariates and interactions

Genetic association analyses of family-based studies with ordered categorical phenotypes are often conducted using methods either for quantitative or for binary traits, which can lead to suboptimal analyses. Here we present an alternative likelihood-based method of analysis for single nucleotide polymorphism (SNP) genotypes and ordered categorical phenotypes in nuclear families of any size. Our approach, which extends our previous work for binary phenotypes, permits straightforward inclusion of covariate, gene-gene and gene-covariate interaction terms in the likelihood, incorporates a simple model for ascertainment and allows for family-specific effects in the hypothesis test. Additionally, our method produces interpretable parameter estimates and valid confidence intervals. We assess the proposed method using simulated data, and apply it to a polymorphism in the c-reactive protein (CRP) gene typed in families collected to investigate human systemic lupus erythematosus. By including sex interactions in the analysis, we show that the polymorphism is associated with anti-nuclear autoantibody (ANA) production in females, while there appears to be no effect in males.

A three-shot improvement scheme for hard-decision based linear decorrelating detector in DS/CDMA

This paper proposes a three-shot improvement scheme for the hard-decision based method (HDM), an implementation solution for linear decorrelating detector (LDD) in asynchronous DS/CDMA systems. By taking advantage of the preceding (already reconstructed) bit and the matched filter output for the following two bits, the coupling between temporally adjacent bits (TABs), which always exists for asynchronous systems, is greatly suppressed and the performance of the original HDM is substantially improved. This new scheme requires no signaling overhead yet offers nearly the same performance as those more complicated methods. Also, it can easily accommodate the change in the number of active users in the channel, as no symbol/bit grouping is involved. Finally, the influence of synchronisation errors is investigated.

The evaluation of CloudSat and CALIPSO ice microphysical products using ground-based cloud radar and lidar observations

In this paper, the statistical properties of tropical ice clouds (ice water content, visible extinction, effective radius, and total number concentration) derived from 3 yr of ground-based radar–lidar retrievals from the U.S. Department of Energy Atmospheric Radiation Measurement Climate Research Facility in Darwin, Australia, are compared with the same properties derived using the official CloudSat microphysical retrieval methods and from a simpler statistical method using radar reflectivity and air temperature. It is shown that the two official CloudSat microphysical products (2B-CWC-RO and 2B-CWC-RVOD) are statistically virtually identical. The comparison with the ground-based radar–lidar retrievals shows that all satellite methods produce ice water contents and extinctions in a much narrower range than the ground-based method and overestimate the mean vertical profiles of microphysical parameters below 10-km height by over a factor of 2. Better agreements are obtained above 10-km height. Ways to improve these estimates are suggested in this study. Effective radii retrievals from the standard CloudSat algorithms are characterized by a large positive bias of 8–12 μm. A sensitivity test shows that in response to such a bias the cloud longwave forcing is increased from 44.6 to 46.9 W m−2 (implying an error of about 5%), whereas the negative cloud shortwave forcing is increased from −81.6 to −82.8 W m−2. Further analysis reveals that these modest effects (although not insignificant) can be much larger for optically thick clouds. The statistical method using CloudSat reflectivities and air temperature was found to produce inaccurate mean vertical profiles and probability distribution functions of effective radius. This study also shows that the retrieval of the total number concentration needs to be improved in the official CloudSat microphysical methods prior to a quantitative use for the characterization of tropical ice clouds. Finally, the statistical relationship used to produce ice water content from extinction and air temperature obtained by the Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) satellite is evaluated for tropical ice clouds. It is suggested that the CALIPSO ice water content retrieval is robust for tropical ice clouds, but that the temperature dependence of the statistical relationship used should be slightly refined to better reproduce the radar–lidar retrievals.

A spatio-temporal structure-based approach to drought characterisation

Drought characterisation is an intrinsically spatio-temporal problem. A limitation of previous approaches to characterisation is that they discard much of the spatio-temporal information by reducing events to a lower-order subspace. To address this, an explicit 3-dimensional (longitude, latitude, time) structure-based method is described in which drought events are defined by a spatially and temporarily coherent set of points displaying standardised precipitation below a given threshold. Geometric methods can then be used to measure similarity between individual drought structures. Groupings of these similarities provide an alternative to traditional methods for extracting recurrent space-time signals from geophysical data. The explicit consideration of structure encourages the construction of summary statistics which relate to the event geometry. Example measures considered are the event volume, centroid, and aspect ratio. The utility of a 3-dimensional approach is demonstrated by application to the analysis of European droughts (15 °W to 35°E, and 35 °N to 70°N) for the period 1901–2006. Large-scale structure is found to be abundant with 75 events identified lasting for more than 3 months and spanning at least 0.5 × 106 km2. Near-complete dissimilarity is seen between the individual drought structures, and little or no regularity is found in the time evolution of even the most spatially similar drought events. The spatial distribution of the event centroids and the time evolution of the geographic cross-sectional areas strongly suggest that large area, sustained droughts result from the combination of multiple small area (∼106 km2) short duration (∼3 months) events. The small events are not found to occur independently in space. This leads to the hypothesis that local water feedbacks play an important role in the aggregation process.

Method for exploratory cluster analysis and visualisation of single-trial ERP ensembles

Background: The validity of ensemble averaging on event-related potential (ERP) data has been questioned, due to its assumption that the ERP is identical across trials. Thus, there is a need for preliminary testing for cluster structure in the data. New method: We propose a complete pipeline for the cluster analysis of ERP data. To increase the signalto-noise (SNR) ratio of the raw single-trials, we used a denoising method based on Empirical Mode Decomposition (EMD). Next, we used a bootstrap-based method to determine the number of clusters, through a measure called the Stability Index (SI). We then used a clustering algorithm based on a Genetic Algorithm (GA)to define initial cluster centroids for subsequent k-means clustering. Finally, we visualised the clustering results through a scheme based on Principal Component Analysis (PCA). Results: After validating the pipeline on simulated data, we tested it on data from two experiments – a P300 speller paradigm on a single subject and a language processing study on 25 subjects. Results revealed evidence for the existence of 6 clusters in one experimental condition from the language processing study. Further, a two-way chi-square test revealed an influence of subject on cluster membership.

A new method for the characterisation and verification of local spatial predictability for convective scale ensembles

The use of kilometre-scale ensembles in operational forecasting provides new challenges for forecast interpretation and evaluation to account for uncertainty on the convective scale. A new neighbourhood based method is presented for evaluating and characterising the local predictability variations from convective scale ensembles. Spatial scales over which ensemble forecasts agree (agreement scales, S^A) are calculated at each grid point ij, providing a map of the spatial agreement between forecasts. By comparing the average agreement scale obtained from ensemble member pairs (S^A(mm)_ij), with that between members and radar observations (S^A(mo)_ij), this approach allows the location-dependent spatial spread-skill relationship of the ensemble to be assessed. The properties of the agreement scales are demonstrated using an idealised experiment. To demonstrate the methods in an operational context the S^A(mm)_ij and S^A(mo)_ij are calculated for six convective cases run with the Met Office UK Ensemble Prediction System. The S^A(mm)_ij highlight predictability differences between cases, which can be linked to physical processes. Maps of S^A(mm)_ij are found to summarise the spatial predictability in a compact and physically meaningful manner that is useful for forecasting and for model interpretation. Comparison of S^A(mm)_ij and S^A(mo)_ij demonstrates the case-by-case and temporal variability of the spatial spread-skill, which can again be linked to physical processes.

Fragment-Based QSAR and Molecular Modeling Studies on a Series of Discodermolide Analogs as Microtubule-Stabilizing Anticancer Agents

Inhibition of microtubule function is an attractive rational approach to anticancer therapy. Although taxanes are the most prominent among the microtubule-stabilizers, their clinical toxicity, poor pharmacokinetic properties, and resistance have stimulated the search for new antitumor agents having the same mechanism of action. Discodermolide is an example of nontaxane natural product that has the same mechanism of action, demonstrating superior antitumor efficacy and therapeutic index. The extraordinary chemical and biological properties have qualified discodermolide as a lead structure for the design of novel anticancer agents with optimized therapeutic properties. In the present work, we have employed a specialized fragment-based method to develop robust quantitative structure - activity relationship models for a series of synthetic discodermolide analogs. The generated molecular recognition patterns were combined with three-dimensional molecular modeling studies as a fundamental step on the path to understanding the molecular basis of drug-receptor interactions within this important series of potent antitumoral agents.

Integration of Ligand- and Target-Based Virtual Screening for the Discovery of Cruzain Inhibitors

A myriad of methods are available for virtual screening of small organic compound databases. In this study we have successfully applied a quantitative model of consensus measurements, using a combination of 3D similarity searches (ROCS and EON), Hologram Quantitative Structure Activity Relationships (HQSAR) and docking (FRED, FlexX, Glide and AutoDock Vina), to retrieve cruzain inhibitors from collected databases. All methods were assessed individually and then combined in a Ligand-Based Virtual Screening (LBVS) and Target-Based Virtual Screening (TBVS) consensus scoring, using Receiving Operating Characteristic (ROC) curves to evaluate their performance. Three consensus strategies were used: scaled-rank-by-number, rank-by-rank and rank-by-vote, with the most thriving the scaled-rank-by-number strategy, considering that the stiff ROC curve appeared to be satisfactory in every way to indicate a higher enrichment power at early retrieval of active compounds from the database. The ligand-based method provided access to a robust and predictive HQSAR model that was developed to show superior discrimination between active and inactive compounds, which was also better than ROCS and EON procedures. Overall, the integration of fast computational techniques based on ligand and target structures resulted in a more efficient retrieval of cruzain inhibitors with desired pharmacological profiles that may be useful to advance the discovery of new trypanocidal agents.