Cyclin-dependent kinases 4 and 6 control tumor progression and direct glucose oxidation in the pentose cycle

Cyclin-dependent kinases CDK4 and CDK6 are essential for the control of the cell cycle through the G1 phase. Aberrant expression of CDK4 and CDK6 is a hall- mark of cancer, which would suggest that CDK4 and CDK6 are attractive targets for cancer therapy. Herein, we report that calcein AM is a potent specific inhibitor of CDK4 and CDK6 in HCT116 human colon adenocarcinoma cells, inhibiting retinoblastoma protein (pRb) phosphorylation and inducing cell cycle arrest in the G1 phase. The metabolic effects of calcein AM (the calcein acetoxymethyl-ester) on HCT116 cells were also evaluated and the flux between the oxidative and non-oxidative branches of the pentose phos-phate pathway was significantly altered. To elucidate whe-ther these metabolic changes were due to the inhibition of CDK4 and CDK6, we also characterized the metabolic profile of a CDK4, CDK6 and CDK2 triple knockout of mouse embryonic fibroblasts. The results show that the metabolic profile associated with the depletion of CDK4, CDK6 and CDK2 coincides with the metabolic changes induced by calcein AM on HCT116 cells, thus confirming that the inhibition of CDK4 and CDK6 disrupts the balance between the oxidative and non-oxidative branches of the pentose phosphate pathway. Taken together, these results indicate that low doses of calcein can halt cell division and kill tumor cells. Thus, selective inhibition of CDK4 and CDK6 may be of greater pharmacological interest, since inhibitors of these kinases affect both cell cycle progression and the robust metabolic profile of tumors.

Efeitos dos parâmetros operacionais na fotodegradação do azo corante direct red 23 na interface dióxido de titânio/água

The decolorization and degradation of direct red 23 azo dye have been investigated in aqueous suspension of titanium dioxide under artificial irradiation. The effects of some operational parameters such as azo dye concentration, catalyst loading, and solution pH were investigated at 30.0 ºC and optimized values were obtained. The first-order kinetic model was used to discuss the results. The UV-Vis spectra changes showed that the azo dye sample, collected after 6 h irradiation, was 98% decolorized while the residual total carbon was 97.9% degraded, indicating simultaneous photodecolorization and degradation.

Traducción técnica del capítulo III del libro Advanced Data Warehouse design: from conventional to spatial and temporal applications

The proposal to work on this final project came after several discussions held with Dr. Elzbieta Malinowski Gadja, who in 2008 published the book entitled Advanced Data Warehouse Design: From Conventional to Spatial and Temporal Applications (Data-Centric Systems and Applications). The project was carried out under the technical supervision of Dr. Malinowski and the direct beneficiary was the University of Costa Rica (UCR) where Dr. Malinowski is a professor at the Department of Computer Science and Informatics. The purpose of this project was twofold: First, to translate chapter III of said book with the intention of generating educational material for the use of the UCR and, second, to venture in the field of technical translation related to data warehouse. For the first component, the goal was to generate a final product that would eventually serve as an educational tool for the post-graduate courses of the UCR. For the second component, this project allowed me to acquire new skills and put into practice techniques that have helped me not only to perfom better in my current job as an Assistant Translator of the Inter-American BAnk (IDB), but also to use them in similar projects. The process was lenggthy and required torough research and constant communication with the author. The investigation focused on the search of terms and definitions to prepare the glossary, which was the basis to start the translation project. The translation process itself was carried out by phases, so that comments and corrections by the author could be taken into account in subsequent stages. Later, based on the glossary and the translated text, illustrations had been created in the Visio software were translated. In addition to the technical revision by the author, professor Carme Mangiron was in charge of revising the non-technical text. The result was a high-quality document that is currently used as reference and study material by the Department of Computer Science and Informatics of Costa Rica.

An easy and direct method for the synthesis of 1,2,4-triazole derivatives through carboxylic acids and hydrazinophthalazine

We have developed an easy method for the synthesis of thirteen compounds derived from 1,2,4-triazoles through a carboxylic acid and hydrazinophthalazine reaction, with a 75-85% yield mediated by the use of agents such as 1-ethyl-3-(3'-dimethylaminopropyl)-carbodiimide hydrochloride and 1-hydroxybenzotriazole. The operational simplicity of this method and the good yield of products make it valuable for the synthesis of new compounds with pharmacological activity.

Machine Learning and Clinical Text. Supporting Health Information Flow

Fluent health information flow is critical for clinical decision-making. However, a considerable part of this information is free-form text and inabilities to utilize it create risks to patient safety and cost-­effective hospital administration. Methods for automated processing of clinical text are emerging. The aim in this doctoral dissertation is to study machine learning and clinical text in order to support health information flow.First, by analyzing the content of authentic patient records, the aim is to specify clinical needs in order to guide the development of machine learning applications.The contributions are a model of the ideal information flow,a model of the problems and challenges in reality, and a road map for the technology development. Second, by developing applications for practical cases,the aim is to concretize ways to support health information flow. Altogether five machine learning applications for three practical cases are described: The first two applications are binary classification and regression related to the practical case of topic labeling and relevance ranking.The third and fourth application are supervised and unsupervised multi-class classification for the practical case of topic segmentation and labeling.These four applications are tested with Finnish intensive care patient records.The fifth application is multi-label classification for the practical task of diagnosis coding. It is tested with English radiology reports.The performance of all these applications is promising. Third, the aim is to study how the quality of machine learning applications can be reliably evaluated.The associations between performance evaluation measures and methods are addressed,and a new hold-out method is introduced.This method contributes not only to processing time but also to the evaluation diversity and quality. The main conclusion is that developing machine learning applications for text requires interdisciplinary, international collaboration. Practical cases are very different, and hence the development must begin from genuine user needs and domain expertise. The technological expertise must cover linguistics,machine learning, and information systems. Finally, the methods must be evaluated both statistically and through authentic user-feedback.

Concentrated Winding Multiphase Permanent Magnet Machine Design and Electromagnetic Properties – Case Axial Flux Machine

Concentrated winding permanent magnet machines and their electromagnetic properties are studied in this doctoral thesis. The thesis includes a number of main tasks related to the application of permanent magnets in concentrated winding open slot machines. Suitable analytical methods are required for the first design calculations of a new machine. Concentrated winding machines differ from conventional integral slot winding machines in such a way that adapted analytical calculation methods are needed. A simple analytical model for calculating the concentrated winding axial flux machines is provided. The next three main design tasks are discussed in more detail in the thesis. The magnetic length of the rotor surface magnet machines is studied, and it is shown that the traditional methods have to be modified also in this respect. An important topic in this study has been to evaluate and minimize the rotor permanent magnet Joule losses by using segmented magnets in the calculations and experiments. Determination of the magnetizing and leakage inductances for a concentrated winding machine and the torque production capability of concentrated winding machines with different pole pair numbers are studied, and the results are compared with the corresponding properties of integral slot winding machines. The thesis introduces a new practical permanent magnet motor type for industrial use. The special features of the machine are based on the option of using concentrated winding open slot constructions of permanent magnet synchronous machines in the normal speed ranges of industrial motors, for instance up to 3000 min-1, without excessive rotor losses. By applying the analytical equations and methods introduced in the thesis, a 37 kW 2400 min-1 12-slot 10-pole axial flux machine with rotor-surfacemounted magnets is designed. The performance of the designed motor is determined by experimental measurements and finite element calculations.

Computational and Experimental Investigation of the Grooved Roll in Paper Machine Environment

In the paper machine, it is not a desired feature for the boundary layer flows in the fabric and the roll surfaces to travel into the closing nips, creating overpressure. In this thesis, the aerodynamic behavior of the grooved roll and smooth rolls is compared in order to understand the nip flow phenomena, which is the main reason why vacuum and grooved roll constructions are designed. A common method to remove the boundary layer flow from the closing nip is to use the vacuum roll construction. The downside of the use of vacuum rolls is high operational costs due to pressure losses in the vacuum roll shell. The deep grooved roll has the same goal, to create a pressure difference over the paper web and keep the paper attached to the roll or fabric surface in the drying pocket of the paper machine. A literature review revealed that the aerodynamic functionality of the grooved roll is not very well known. In this thesis, the aerodynamic functionality of the grooved roll in interaction with a permeable or impermeable wall is studied by varying the groove properties. Computational fluid dynamics simulations are utilized as the research tool. The simulations have been performed with commercial fluid dynamics software, ANSYS Fluent. Simulation results made with 3- and 2-dimensional fluid dynamics models are compared to laboratory scale measurements. The measurements have been made with a grooved roll simulator designed for the research. The variables in the comparison are the paper or fabric wrap angle, surface velocities, groove geometry and wall permeability. Present-day computational and modeling resources limit grooved roll fluid dynamics simulations in the paper machine scale. Based on the analysis of the aerodynamic functionality of the grooved roll, a grooved roll simulation tool is proposed. The smooth roll simulations show that the closing nip pressure does not depend on the length of boundary layer development. The surface velocity increase affects the pressure distribution in the closing and opening nips. The 3D grooved roll model reveals the aerodynamic functionality of the grooved roll. With the optimal groove size it is possible to avoid closing nip overpressure and keep the web attached to the fabric surface in the area of the wrap angle. The groove flow friction and minor losses play a different role when the wrap angle is changed. The proposed 2D grooved roll simulation tool is able to replicate the grooved aerodynamic behavior with reasonable accuracy. A small wrap angle predicts the pressure distribution correctly with the chosen approach for calculating the groove friction losses. With a large wrap angle, the groove friction loss shows too large pressure gradients, and the way of calculating the air flow friction losses in the groove has to be reconsidered. The aerodynamic functionality of the grooved roll is based on minor and viscous losses in the closing and opening nips as well as in the grooves. The proposed 2D grooved roll model is a simplification in order to reduce computational and modeling efforts. The simulation tool makes it possible to simulate complex paper machine constructions in the paper machine scale. In order to use the grooved roll as a replacement for the vacuum roll, the grooved roll properties have to be considered on the basis of the web handling application.

Effects of Surface Properties and Wood Modification into Direct Printing on Wood

Building industry is a high volume branch which could provide prominent markets for wood based interior decoration solutions. Competition in interior decoration markets requires versatility in appearance. Versatility in wood appearance and added value could be achieved by printing grain patterns of different species or images directly onto wood. The problem when planning wood printing’s implementing into durable applications is basically how to transfer a high quality image or print sustainably onto wood, which is porous, heterogeneous, dimensionally unstable, non-white and rough. Wood preservation or treating, and modification can provide durability against degradation but also effect to the surface properties of wood which will effect on printability. Optimal adhesion is essential into print quality, as too high ink absorbance can cause spreading and too low ink absorbance cause pale prints. Different printing techniques have different requirements on materials and production. The direct printing on wood means, that intermedias are not used. Printing techniques with flexible printing plates or in fact non-impact techniques provide the best basis for wood printing. Inkjet printing of wood with different mechanical or chemical surface treatments, and wood plastic composite material gave good results that encourage further studies of the subject. Sanding the wood surface anti-parallel to the grain gave the best overall printing quality. Spreading parallel to the grain could not be avoided totally, except in cases where wood was treated hydrophobic so adhesion of the ink was not sufficient. Grain pattern of the underlying wood stays clearly visible in the printed images. Further studies should be made to fine tune the methods that already gave good results. Also effects of moisture content of wood, different inks, and long-term exposure to UV-radiation should be tested.

A comparison of electrodeposited Ti/β-PbO2 and Ti-Pt/β-PbO2 anodes in the electrochemical degradation of the direct yellow 86 dye

The electrochemical performance of electrodeposited Ti/β-PbO2 and Ti-Pt/β-PbO2 anodes was galvanostatically evaluated (batch mode, 50 mA cm-2) to degrade the Direct Yellow 86 dye (100 or 200 mg L-1 in 0.1 mol L-1 Na2SO4 + 1.5 g L-1 NaCl), investigating the effect of pH and temperature. Similar results were obtained for both electrodes and the best conditions for removal of color and chemical oxygen demand are pH 7 and 40 °C, when 90% decolorization is attained by passing a charge of only ~0.13 A h L-1 and total mineralization is achieved with expenditure of ~5 kW h m-3.

Improving Cross Direction Basis Weight Profile in a Fourdrinier Paper Machine

The purpose of this study was to improve PM7’s basis weight CD profile in Stora Enso’s Berghuizer mill and to search mechanical defects which affect to the formation of the basis weight CD profile. In the theoretical part PM7’s structure was presented and the formation of the basis weight and caliper CD profiles was examined as well as disturbances which are affecting to the formation. The function of the control system was scrutinised for the side of CD profiles as well as the formation of the measured CD profiles. Tuning of the control system was examined through the response model and filtering. Specification of the response model and filtering was explained and how to determine 2sigma statistical number. In the end of the theoretical part ATPA hardware and a new profile browser were introduced. In the experimental part focus was in the beginning to search and remove mechanical defects which are affecting to CD profiles. The next step was to verify the reliability of the online measurements, to study the stability of the basis weight CD profile and to find out so called fingerprint, a basis weight CD profile which is unique for each paper machine. New response model and filtering value for basis weight CD profile was determined by bump tests. After a follow up period the affect of the new response model and filtering was analysed.

Influence of chloride-mediated oxidation on the electrochemical degradation of the direct black 22 dye using boron-doped diamond and β-PbO2 anodes

The Direct Black 22 dye was electrooxidized at 30 mA cm-2 in a flow cell using a BDD or β-PbO2 anode, varying pH (3, 7, 11), temperature (10, 25, 45 °C), and [NaCl] (0 or 1.5 g L-1). In the presence of NaCl, decolorization rates were similar for all conditions investigated, but much higher than predicted through a theoretical model assuming mass-transport control; similar behavior was observed for COD removal (at pH 7, 25 °C), independently of the anode. With no NaCl, COD removals were also higher than predicted with a theoretical model, which suggests the existence of distinct dye degradation pathways.

DIRECT INFUSION ESI-MS APPLIED IN THE DETECTION OF BYPRODUCTS DUE TO REDUCTIVE DEGRADATION OF ACETAMIPRID BY ZERO-VALENT IRON

This study investigated the reductive degradation of acetamiprid (5 mg L-1) in aqueous medium (at pH 2.0) induced by zero-valent iron (50 mg). The process was monitored using high-performance liquid chromatography (HPLC) to determine the degradation rate as a function of reaction time, and direct infusion electrospray ionization mass spectrometry (DI-ESI-MS) to search for (and potentially characterize) any possible byproducts formed during degradation. The results obtained via HPLC showed that after 60 min, the degradation of the substrate reached nearly 100% in an acidic medium, whereas the mineralization rate (as determined by total organic carbon measurements) was as low as 3%. Data obtained by DI-ESI-MS showed that byproducts were formed mainly by insertions of hydrogen atoms into the nitrile, imine, and pyridine ring moieties, in addition to the observation of chlorine substitution by hydrogen replacement (hydrodechlorination) reactions.

Simulating the performance of paper machine control

The topic of this thesis is the simulation of a combination of several control and data assimilation methods, meant to be used for controlling the quality of paper in a paper machine. Paper making is a very complex process and the information obtained from the web is sparse. A paper web scanner can only measure a zig zag path on the web. An assimilation method is needed to process estimates for Machine Direction (MD) and Cross Direction (CD) profiles of the web. Quality control is based on these measurements. There is an increasing need for intelligent methods to assist in data assimilation. The target of this thesis is to study how such intelligent assimilation methods are affecting paper web quality. This work is based on a paper web simulator, which has been developed in the TEKES funded MASI NoTes project. The simulator is a valuable tool in comparing different assimilation methods. The thesis contains the comparison of four different assimilation methods. These data assimilation methods are a first order Bayesian model estimator, an ARMA model based on a higher order Bayesian estimator, a Fourier transform based Kalman filter estimator and a simple block estimator. The last one can be considered to be close to current operational methods. From these methods Bayesian, ARMA and Kalman all seem to have advantages over the commercial one. The Kalman and ARMA estimators seems to be best in overall performance.