An HPLC-UV method for the measurement of permeability of marker drugs in the Caco-2 cell assay

The Caco-2 cell line has been used as a model to predict the in vitro permeability of the human intestinal barrier. The predictive potential of the assay relies on an appropriate in-house validation of the method. The objective of the present study was to develop a single HPLC-UV method for the identification and quantitation of marker drugs and to determine the suitability of the Caco-2 cell permeability assay. A simple chromatographic method was developed for the simultaneous determination of both passively (propranolol, carbamazepine, acyclovir, and hydrochlorothiazide) and actively transported drugs (vinblastine and verapamil). Separation was achieved on a C18 column with step-gradient elution (acetonitrile and aqueous solution of ammonium acetate, pH 3.0) at a flow rate of 1.0 mL/min and UV detection at 275 nm during the total run time of 35 min. The method was validated and found to be specific, linear, precise, and accurate. This chromatographic system can be readily used on a routine basis and its utilization can be extended to other permeability models. The results obtained in the Caco-2 bi-directional transport experiments confirmed the validity of the assay, given that high and low permeability profiles were identified, and P-glycoprotein functionality was established.

Dynamic expression of desmin, α-SMA and TGF-β1 during hepatic fibrogenesis induced by selective bile duct ligation in young rats

We previously described a selective bile duct ligation model to elucidate the process of hepatic fibrogenesis in children with biliary atresia or intrahepatic biliary stenosis. Using this model, we identified changes in the expression of alpha smooth muscle actin (α-SMA) both in the obstructed parenchyma and in the hepatic parenchyma adjacent to the obstruction. However, the expression profiles of desmin and TGF-β1, molecules known to be involved in hepatic fibrogenesis, were unchanged when analyzed by semiquantitative polymerase chain reaction (RT-PCR). Thus, the molecular mechanisms involved in the modulation of liver fibrosis in this experimental model are not fully understood. This study aimed to evaluate the molecular changes in an experimental model of selective bile duct ligation and to compare the gene expression changes observed in RT-PCR and in real-time quantitative PCR (qRT‐PCR). Twenty-eight Wistar rats of both sexes and weaning age (21-23 days old) were used. The rats were separated into groups that were assessed 7 or 60 days after selective biliary duct ligation. The expression of desmin, α-SMA and TGF-β1 was examined in tissue from hepatic parenchyma with biliary obstruction (BO) and in hepatic parenchyma without biliary obstruction (WBO), using RT-PCR and qRT‐PCR. The results obtained in this study using these two methods were significantly different. The BO parenchyma had a more severe fibrogenic reaction, with increased α-SMA and TGF-β1 expression after 7 days. The WBO parenchyma presented a later, fibrotic response, with increased desmin expression 7 days after surgery and increased α-SMA 60 days after surgery. The qRT‐PCR technique was more sensitive to expression changes than the semiquantitative method.

Tuotteistettu palvelu toimintolaskentajärjestelmän käyttöönottoon

Diplomityön tavoitteena oli kehittää tuotteistettu palvelu toimintolaskentajärjestelmän käyttöönottoon. Käyttöönotolla tarkoitettiin tässä työssä laskennan käyttöönottoa, eli laskentamallin rakentamista toimintolaskentajärjestelmään. Työ tehtiin Solenovo Oy:n toimeksiannosta ja tutkimusmenetelmänä käytettiin toimintatutkimusta. Työ koostuu teoreettisesta viitekehyksestä ja empiirisestä osuudesta. Työn teoreettinen viitekehys muodostuu kolmesta eri aihepiiriä käsittelevästä luvusta. Ensimmäinen käsittelee toimintolaskentaa ja erityisesti sen vahvuuksia, heikkouksia, käyttöönottoa, sekä eroja ja yhtäläisyyksiä verrattuna perinteiseen kustannuslaskentaan. Seuraavana käsitellään palveluita ja niiden kehittämistä. Palvelun kehittämismenetelmistä käsitellään tähän työhön valittu menetelmä service blueprint, sen rakenne ja kehittäminen. Kolmas teoreettisen viitekehyksen osa-alue on palveluiden tuotteistaminen, mikä tarkentui tässä työssä erityisesti asiantuntijapalveluiden tuotteistamiseen. Työn päätuloksena saavutettiin työn tärkein tavoite, eli kehitettiin tuotteistettu palvelu toimintolaskentajärjestelmän käyttöönottoon. Palvelu kehitettiin service blueprint-menetelmää hyödyntäen ja tuotteistettiin soveltuvilta osin. Koska kyseessä oli täysin uusi palvelu, tuotteistaminen painottui tuotteistamisen suunnitteluun ja sisäiseen tuotteistamiseen. Työn aikana määriteltiin palvelun vaatimukset ja sisältö modulointia hyödyntäen, ohjeistus palvelun toteutusta varten, arvioitiin palvelun eri vaiheisiin sisältyviä riskejä ja haasteita, sekä määriteltiin palvelun jatkokehitystarpeet.

Not any type of rice performs equally to improve lactose-induced diarrhea characteristics in rats: is amylose an antidiarrheal factor?

The effectiveness of different types of rice in relation to their ability to accelerate diarrhea recovering was evaluated in a rat model of osmotic diarrhea (OD). Animals (90-100 g) received protein free diet until reaching up to 20% weight loss, followed by lactose rich diet (LRD) to induce osmotic diarrhea. Rats presenting osmotic diarrhea were divided into 4 groups, which received lactose rich diet for 4 days from 8 am to 8 pm, and one of three experimental products containing 6% rice flour differing in amylose content during the night: high (HA), intermediate (IA), and low (LA). A group fed stock diet containing equivalent amount of lactose was taken as control and allowed to recover spontaneously. Amylose and viscosity (cp at 25 °C, 10 rpm) of final products were determined. Effectiveness was expressed as the ratio between percentages of normal vs. diarrheic stools during the treatment. Fecal characteristics in this rat model improved only as result of feeding high amylose content (HA) type of rice. In this experimental model of osmotic diarrhea in young rats, the antidiarrheal effects of rice were strongly dependent on the type of diet used and appear to be related to its amylose content.

Variational Ensemble Kalman Filtering in Hydrology

The current thesis manuscript studies the suitability of a recent data assimilation method, the Variational Ensemble Kalman Filter (VEnKF), to real-life fluid dynamic problems in hydrology. VEnKF combines a variational formulation of the data assimilation problem based on minimizing an energy functional with an Ensemble Kalman filter approximation to the Hessian matrix that also serves as an approximation to the inverse of the error covariance matrix. One of the significant features of VEnKF is the very frequent re-sampling of the ensemble: resampling is done at every observation step. This unusual feature is further exacerbated by observation interpolation that is seen beneficial for numerical stability. In this case the ensemble is resampled every time step of the numerical model. VEnKF is implemented in several configurations to data from a real laboratory-scale dam break problem modelled with the shallow water equations. It is also tried in a two-layer Quasi- Geostrophic atmospheric flow problem. In both cases VEnKF proves to be an efficient and accurate data assimilation method that renders the analysis more realistic than the numerical model alone. It also proves to be robust against filter instability by its adaptive nature.

Automated static image analysis as a novel tool in describing the physical properties of dietary fiber

Abstract The growing interest in the usage of dietary fiber in food has caused the need to provide precise tools for describing its physical properties. This research examined two dietary fibers from oats and beets, respectively, in variable particle sizes. The application of automated static image analysis for describing the hydration properties and particle size distribution of dietary fiber was analyzed. Conventional tests for water holding capacity (WHC) were conducted. The particles were measured at two points: dry and after water soaking. The most significant water holding capacity (7.00 g water/g solid) was achieved by the smaller sized oat fiber. Conversely, the water holding capacity was highest (4.20 g water/g solid) in larger sized beet fiber. There was evidence for water absorption increasing with a decrease in particle size in regards to the same fiber source. Very strong correlations were drawn between particle shape parameters, such as fiber length, straightness, width and hydration properties measured conventionally. The regression analysis provided the opportunity to estimate whether the automated static image analysis method could be an efficient tool in describing the hydration properties of dietary fiber. The application of the method was validated using mathematical model which was verified in comparison to conventional WHC measurement results.

New ways to do business plans in multicultural organizations

Business plans are made when establishing new company or when organizations launch new product or services. In this Master Thesis was examined the elements are included in the business plan and emphasized. Business plan is a wide document and can also contain company specific information, the literature review was restricted into three areas which were investigated from the relating literature and articles. The selected areas were Market Segmentation and Targeting, Competitive Environment, and Market Positioning and Strategy. The different business plan models were investigated by interviewing companies who operates in a different industry sectors from each other’s. The models were compared to each other and to the findings from literature. Based on interview results and literature findings, the business plan for fibre based packaging. The created business plan contains three selected areas. It was found that the selected business plan elements can be found from the interviewed companies’ business plans. The market segmentation was done by comparing the market share to known total market size. When analyzing the competitive environment, there was no one selected model in use. The tools to evaluate competitive environment was selected parts from both SWOT analysis and Porter’s five forces model in applicable part. Based on interview results, it can be state that the company or organization should find and built its own model for business plans. In order to receive the benefits for future planning, the company should use the same model for long time.

Performance measurement model for projects from a strategic management perspective

This research studied the project performance measurement from the perspective of strategic management. The objective was to find a generic model for project performance measurement that emphasizes strategy and decision making. Research followed the guidelines of a constructive research methodology. As a result, the study suggests a model that measures projects with multiple meters during and after projects. Measurement after the project is suggested to be linked to the strategic performance measures of a company. The measurement should be conducted with centralized project portfolio management e.g. using the project management office in the organization. Metrics, after the project, measure the project’s actual benefit realization. During the project, the metrics are universal and they measure the accomplished objectives relation to costs, schedule and internal resource usage. Outcomes of these measures should be forecasted by using qualitative or stochastic methods. Solid theoretical background for the model was found from the literature that covers the subjects of performance measurement, projects and uncertainty. The study states that the model can be implemented in companies. This statement is supported by empirical evidence from a single case study. The gathering of empiric evidence about the actual usefulness of the model in companies is left to be done by the evaluative research in the future.

PERFORMANCE ANALYSIS OF A TACTICAL ASSET ALLOCATION – Evidence from the Black–Litterman model based fixed income portfolio

Over time the demand for quantitative portfolio management has increased among financial institutions but there is still a lack of practical tools. In 2008 EDHEC Risk and Asset Management Research Centre conducted a survey of European investment practices. It revealed that the majority of asset or fund management companies, pension funds and institutional investors do not use more sophisticated models to compensate the flaws of the Markowitz mean-variance portfolio optimization. Furthermore, tactical asset allocation managers employ a variety of methods to estimate return and risk of assets, but also need sophisticated portfolio management models to outperform their benchmarks. Recent development in portfolio management suggests that new innovations are slowly gaining ground, but still need to be studied carefully. This thesis tries to provide a practical tactical asset allocation (TAA) application to the Black–Litterman (B–L) approach and unbiased evaluation of B–L models’ qualities. Mean-variance framework, issues related to asset allocation decisions and return forecasting are examined carefully to uncover issues effecting active portfolio management. European fixed income data is employed in an empirical study that tries to reveal whether a B–L model based TAA portfolio is able outperform its strategic benchmark. The tactical asset allocation utilizes Vector Autoregressive (VAR) model to create return forecasts from lagged values of asset classes as well as economic variables. Sample data (31.12.1999–31.12.2012) is divided into two. In-sample data is used for calibrating a strategic portfolio and the out-of-sample period is for testing the tactical portfolio against the strategic benchmark. Results show that B–L model based tactical asset allocation outperforms the benchmark portfolio in terms of risk-adjusted return and mean excess return. The VAR-model is able to pick up the change in investor sentiment and the B–L model adjusts portfolio weights in a controlled manner. TAA portfolio shows promise especially in moderately shifting allocation to more risky assets while market is turning bullish, but without overweighting investments with high beta. Based on findings in thesis, Black–Litterman model offers a good platform for active asset managers to quantify their views on investments and implement their strategies. B–L model shows potential and offers interesting research avenues. However, success of tactical asset allocation is still highly dependent on the quality of input estimates.

From restrained golden age to creeping platinum age: A periodization of Latin American development in the Robinsonian tradition

ABSTRACTThis paper analyzes Joan Robinson's growth model, and then adapted in order to provide an exploratory taxonomy of Growth Eras. The Growth Eras or Ages were for Robinson a way to provide logical connections among output growth, capital accumulation, the degree of thriftiness, the real wage and illustrate a catalogue of growth possibilities. This modified taxonomy follows the spirit of Robinson's work, but it takes different theoretical approaches, which imply that some of her classifications do not fit perfectly the ones here suggested. Latin America has moved from a Golden Age in the 1950s and 1960s, to a Leaden Age in the 1980s, having two traverse periods, one in which the process of growth and industrialization accelerated in the late 1960s and early 1970s, which is here referred to as a Galloping Platinum Age, and one in which a process of deindustrialization, and reprimarization and maquilization of the productive structure took place, starting in the 1990s, which could be referred to as a Creeping Platinum Age.

Analytical modelling of bacterial migration and accumulation with rate-limited sorption in discrete fractures

An analytical model for bacterial accumulation in a discrete fractllre has been developed. The transport and accumlllation processes incorporate into the model include advection, dispersion, rate-limited adsorption, rate-limited desorption, irreversible adsorption, attachment, detachment, growth and first order decay botl1 in sorbed and aqueous phases. An analytical solution in Laplace space is derived and nlln1erically inverted. The model is implemented in the code BIOFRAC vvhich is written in Fortran 99. The model is derived for two phases, Phase I, where adsorption-desorption are dominant, and Phase II, where attachment-detachment are dominant. Phase I ends yvhen enollgh bacteria to fully cover the substratllm have accllillulated. The model for Phase I vvas verified by comparing to the Ogata-Banks solution and the model for Phase II was verified by comparing to a nonHomogenous version of the Ogata-Banks solution. After verification, a sensitiv"ity analysis on the inpllt parameters was performed. The sensitivity analysis was condllcted by varying one inpllt parameter vvhile all others were fixed and observing the impact on the shape of the clirve describing bacterial concentration verSllS time. Increasing fracture apertllre allovvs more transport and thus more accllffilliation, "Vvhich diminishes the dllration of Phase I. The larger the bacteria size, the faster the sllbstratum will be covered. Increasing adsorption rate, was observed to increase the dllration of Phase I. Contrary to the aSSllmption ofllniform biofilm thickness, the accllffilliation starts frOll1 the inlet, and the bacterial concentration in aqlleous phase moving towards the olitiet declines, sloyving the accumulation at the outlet. Increasing the desorption rate, redllces the dliration of Phase I, speeding IIp the accllmlilation. It was also observed that Phase II is of longer duration than Phase I. Increasing the attachment rate lengthens the accliffililation period. High rates of detachment speeds up the transport. The grovvth and decay rates have no significant effect on transport, althollgh increases the concentrations in both aqueous and sorbed phases are observed. Irreversible adsorption can stop accllillulation completely if the vallIes are high.

Exploring the effects of change on nursing practice in acute ambulatory care settings : a qualitative study

As a result of the current changes taking place in the delivery of acute care services, the emergence of acute ambulatory care (AAC) settings is expanding. According to a literature review, the volume, acuity, and complexity of patient care in these settings is increasing while the time the patients spend under the care of nurses is decreasing. Two forces, hospital downsizing and advancing technology, are identified as the major contributors to the shift in acute care delivery. The effects that these changes are having on the clinical nursing practice of registered nurses working in AAC settings are not known. Given that AAC settings are rapidly expanding, it can be anticipated that the delivery of nursing care will continue to be compressed into a shorter time frame. Therefore, the following qualitative research question was formulated: What are the problems and issues related to clinical nursing practice in acute ambulatory settings? The purpose of this study was to explore the problems and issues associated with change and clinical nursing practice including the educational needs of nurses working in MC settings. Specific objectives of the study included the following: (a) to explore the problems and issues related to nursing practice in select AAC settings; (b) to explore the similarities and differences in perspectives related to role expectation between nurse managers, nurse educators, and staff nurses; and (c) to develop a conceptual framework that will guide the construction of an instrument needed for further research. This study used semistructured individual interviews and focus group sessions to collect data from the three categories of registered nurses. More specifically, data were collected from one nurse manager, two charge nurses, two nurse educators and fifteen staff nurses, working in three different MC settings of a major teaching hospital. Collected data were separately analyzed by the researcher and an external rater following grounded theory methodology. By using open and axial coding, the problems and issues identified by nurses were grouped into several major and minor themes. In final analysis, by using selective coding, the four core themes (intensification, moderation, frustration, and adaptation) were extracted. Each core theme was presented and discussed in relation to hospital downsizing and advancing technology. The relationships among the four core themes were discussed and depicted in a model termed the "Impact and Consequence Model on Nursing Practice in MC Settings." Implications for further research are discussed and research hypotheses, based on the research findings, are presented.

The influence on children of the purpose of experiencing reading vocabulary: encoding-retrieval interactions in word perception

This research looked at conditions which result in the development of integrated letter code information in the acquisition of reading vocabulary. Thirty grade three children of normal reading ability acquired new reading words in a Meaning Assigned task and a Letter Comparison task, and worked to increase skill for known reading words in a Copy task. The children were then assessed on their ability to identify the letters in these words. During the test each stimulus word for each child was exposed for 100 msec., after which each child reported as many of his or her letters as he or she could. Familiar words, new words, and a single letter identification task served as within subject controls. Following this, subjects were assessed for word meaning recall of the Meaning Assigned words and word reading times for words in all condi tions • The resul ts supported an episodic model of word recognition in which the overlap between the processing operations employed in encoding a word and those required when decoding it affected decoding performance. In particular, the Meaning Assigned and Copy tasks. appeared to facilitate letter code accessibility and integration in new and familiar words respectively. Performance in the Letter Comparison task, on the other hand, suggested that subjects can process the elements of a new word without integrating them into its lexical structure. It was concluded that these results favour an episodic model of word recognition.

Weight-preoccupation, personality and depression in university students : an interactionist perspective

The present research was designed to examine Beck's (1983; 1987) cognitive diathesis-stress model of depression in a new context. Specifically, this cross-sectional study investigated whether Beck's cognitive-personality traits of sociotropy and autonomy interacted with a specific daily hassle/stressor, weightpreoccupation, in the prediction of depressed mood in women and men. Weightpreoccupation was chosen as the particular daily stressor, because, according to Kanner, Coyne, Schaeffer, and Lazarus (1981). concern about weight and physical appearance were two of the most troublesome daily hassles among university students. ContraIy to current stereotypes, men also express concerns with weight and appearance (Cash, Winstead, &, landi, 1986), in both the direction of weight loss and weight/muscle gain (Drewnowski &, Yee, 1987). Thus, unique to this study was the examination of weight-preoccupation in men, not only in the direction of weight loss, but also in the direction of weight and muscle gain. Two hundred and fifty-one undergraduates were administered the revised SociotropyAutonomy Scale (SAS), the Beck Depression Inventory (BDij, the Hassles and Uplifts Scale, the Eating Disorders Inventory (EDI), and the Restraint Scale (RS). Through a process of model building, a final model was devised in which depression (ie., BDI total scores) was regressed on personality (Le., SAS Sociotropy) and weight-preoccupation (i.e., Drive for Thinness, Body Dissatisfaction, and the Restraint Scale). Separate hierarchical multiple regression analyses, with BDI as the dependent variable, were carried out for each of the 2 3 weight-preoccupation variables. Results revealed a specific congruent interaction between weight,..preoccupation and personality. Specifically, drive for thinness and body dissatisfaction interacted with sociotropy to predict depressed mood in both women and men, but the interaction between sociotropy and the Restraint Scale was marginal. Findings suggested that weight-preoccupied women and men experienced depressed mood to the extent that they were characterized as more highly sociotropic. As predicted, personality (i.e., sociotropy), moderated the relationship between daily stress (i.e., weight-preoccupation) and depression. Thus, results revealed that the proposed diathesis-stress model seemed to operate in the same manner for women and men. Moreover, the examination of weightpreoccupation among men (i.e., in the direction of both weight loss and weight/muscle gain) further revealed that, when curvilinearity was taken into account, highly sociotropic men, who had a low desire to gain weight and muscle mass (i.e., most likely those who desired to lose weight), experienced higher levels of depressed mood than those who had a "medium" desire for weight and muscle gain. However, the highest levels of depressed mood was experienced by highly sociotropic men who were highly weight-preoccupied in the direction of wanting to gain weight and muscle mass. In addition, possible reasons for the present fmdings, as wen as iimitations and impiicalions for future research are discussed.

Distribution of excitation energy in photosynthesis: a study of heat loss, photo chemical activity and fluorescence emission in intact calls of cyanobacterium.

Photosynthetic state transitions were investigated in the cyanobacterium Synechococcus sp. PCC 6301 by studying fluorescence emission, heat loss, and PS I activity in intact cells brought to state 1 and state 2. 77K fluorescence emission spectra were modelled with a sum of 6 components corresponding to PBS, PS II, and PS I emissions. The modelled data showed a large decrease in PS II fluorescence accompanied with a small increase in the PS I fluorescence upon transition to state 2 for excitation wavelengths absorbed by both PBS and ChI ll.. The fluorescence changes seen with ChI .a. excitations do not support the predictions of the mobile PBS model of state transition in PBS-containing organisms. Measurements of heat loss from intact cells in the two states were similar for both ChI it. and PBS excitations over three orders of magnitude of laser flash intensity. This suggests that the PBS does not become decoupled from PS II in state 2 as proposed by the PBS detachment model of state transition in PBS-containing organisms. PS I activity measurements done on intact cells showed no difference in the two states, in contrast with the predictions of all of the existing models of state transitions. Based on these results a model for state transition In PBScontaining organisms is proposed, with a PS II photoprotectory function.