Role of trabectedin in the treatment of soft tissue sarcoma.

Interest in marine natural products has allowed the discovery of new drugs and trabectedin (ET-743, Yondelis), derived from the marine tunicate Ecteinascidia turbinata, was approved for clinical use in 2007. It binds to the DNA minor groove leading to interferences with the intracellular transcription pathways and DNA-repair proteins. In vitro antitumor activity was demonstrated against various cancer cell lines and soft tissue sarcoma cell lines. In phase I studies tumor responses were observed also in osteosarcomas and different soft tissue sarcoma subtypes. The most common toxicities were myelosuppression and transient elevation of liver function tests, which could be reduced by dexamethasone premedication. The efficacy of trabectedin was established in three phase II studies where it was administered at 1.5 mg/m2 as a 24 h intravenous infusion repeated every three weeks, in previously treated patients. The objective response rate was 3.7%-8.3% and the tumor control rate (which included complete response, partial response and stable disease) was obtained in half of patients for a median overall survival reaching 12 months. In nonpretreated patients the overall response rate was 17%. Twenty-four percent of patients were without progression at six months. The median overall survival was almost 16 months with 72% surviving at one year. Predictive factors of response are being explored to identify patients who are most likely to respond to trabectedin. Combination with other agents are currently studied with promising results. In summary trabectedin is an active new chemotherapeutic agents that has demonstrated its role in the armamentarium of treatments for patients with sarcomas.

Direct mapping of 19F in 19FDG-6P in brain tissue at subcellular resolution using soft X-ray fluorescence

Low energy x-ray fluorescence (LEXRF) detection was optimized for imaging cerebral glucose metabolism by mapping the fluorine LEXRF signal of 19 F in 19 FDG, trapped as intracellular 19 F-deoxyglucose-6-phosphate ( 19 FDG-6P) at 1μm spatial resolution from 3μm thick brain slices. 19 FDG metabolism was evaluated in brain structures closely resembling the general cerebral cytoarchitecture following formalin fixation of brain slices and their inclusion in an epon matrix. 2-dimensional distribution maps of 19 FDG-6P were placed in a cytoarchitectural and morphological context by simultaneous LEXRF mapping of N and O, and scanning transmission x-ray (STXM) imaging. A disproportionately high uptake and metabolism of glucose was found in neuropil relative to intracellular domains of the cell body of hypothalamic neurons, showing directly that neurons, like glial cells, also metabolize glucose. As 19 F-deoxyglucose-6P is structurally identical to 18 F-deoxyglucose-6P, LEXRF of subcellular 19 F provides a link to in vivo 18 FDG PET, forming a novel basis for understanding the physiological mechanisms underlying the 18 FDG PET image, and the contribution of neurons and glia to the PET signal.

Network governance and the domestic adoption of soft rules

European regulatory networks (ERNs) are in charge of producing and disseminating non-bindings standards, guidelines and recommendations in a number of important domains, such as banking and finance, electricity and gas, telecommunications, and competition regulation. The goal of these soft rules is to promote 'best practices', achieve co-ordination among regulatory authorities and ensure the consistent application of harmonized pro-competition rules across Europe. This contribution examines the domestic adoption of the soft rules developed within the four main ERNs. Different factors are expected to influence the process of domestic adoption: the resources of regulators; the existence of a review panel; and the interdependence of the issues at stake. The empirical analysis supports hypotheses about the relevance of network-level factors: monitoring and public reporting procedures increase the final level of adoption, while soft rules concerning highly interdependent policy areas are adopted earlier.

Epithelioid soft tissue tumors.

Epithelioid neoplasms are generally carcinomas. As confirmation that every rule is meant to be broken, some sarcomas demonstrate epithelioid morphology, and can even express cytokeratins. These sarcomas have unique behavior, for example, a much higher rate of lymph node metastasis than other sarcomas. This group of sarcomas also presents diagnostic and therapeutic challenges to those clinicians who help patients contend with these difficult tumors. In this review, some of the major categories of epithelioid soft tissue tumors are described, with clinical data reported as available. Some of these tumors provide excellent opportunities to examine newer protein-targeted agents in investigational settings.

Error en el consentimiento: swaps y preferentes

La problemàtica jurídica-social que ha sorgit aquests darrers anys amb les permutes financeres i les participacions preferents ha fet plantejar si s'ha produït un error en el consentiment contractual amb aquest tipus de productes financers. A partir del contingut del Codi Civil espanyol i la doctrina, s'han analitzat els elements essencials del contracte, així com, la legislació aplicable als instruments financers. Amb l’ ajuda de la jurisprudència s'ha pogut comprovar que en la majoria de casos portats als tribunals en relació a aquests contractes, en els quals, es demana l'anul·labilitat contractual, el fonament principal es basa en la vulneració de les entitats de crèdit dels seus deures legals . En el present treball queda palesa la importància d'enllaçar l'element contractual del consentiment amb l'obligació que tenen les entitats de crèdit d'informar els seus clients. Així, la incorrecta formació sobre la realitat contractual que els clients manifesten amb el consentiment, passa sense cap dubte per la necessitat d'obtenir tota la informació rellevant del contracte. L’obligació d’informació està estretament lligada al deure de classificar als clients, totes dues són un compromís legal que tenen les entitats en la seva funció de lleialtat empresària. Les entitats financeres deuen per tant classificar els seus clients i proporcionals la informació, amb més rigor si cap , en el cas de clients minoristes. Per tot això, veiem que en aquells casos de clients minoristes en els quals no s'ha pogut demostrar per part de les entitats de crèdit que es va proporcionar tota la informació necessària, s'ha produït un error en el consentiment. Els clients no coneixien l’autèntic abast de la vinculació ni els costos als quals s'havia obligat , no hi ha dubte que en molts dels casos d'haver conegut la realitat, no haguessin contractat.

Error en el posicionamiento indoor en dispositivos mo¿viles

Location information is becoming increasingly necessary as every new smartphone incorporates a GPS (Global Positioning System) which allows the development of various applications based on it. However, it is not possible to properly receive the GPS signal in indoor environments. For this reason, new indoor positioning systems are being developed.As indoors is a very challenging scenario, it is necessary to study the precision of the obtained location information in order to determine if these new positioning techniques are suitable for indoor positioning.

Minimum error contrast enhancement

Contrast enhancement is an image processing technique where the objective is to preprocess the image so that relevant information can be either seen or further processed more reliably. These techniques are typically applied when the image itself or the device used for image reproduction provides poor visibility and distinguishability of different regions of interest inthe image. In most studies, the emphasis is on the visualization of image data,but this human observer biased goal often results to images which are not optimal for automated processing. The main contribution of this study is to express the contrast enhancement as a mapping from N-channel image data to 1-channel gray-level image, and to devise a projection method which results to an image with minimal error to the correct contrast image. The projection, the minimum-error contrast image, possess the optimal contrast between the regions of interest in the image. The method is based on estimation of the probability density distributions of the region values, and it employs Bayesian inference to establish the minimum error projection.

Origins of production errors and significance of employee empowerment in reducing production error amount in sheet metal fabricating industry

The market place of the twenty-first century will demand that manufacturing assumes a crucial role in a new competitive field. Two potential resources in the area of manufacturing are advanced manufacturing technology (AMT) and empowered employees. Surveys in Finland have shown the need to invest in the new AMT in the Finnish sheet metal industry in the 1990's. In this run the focus has been on hard technology and less attention is paid to the utilization of human resources. In manymanufacturing companies an appreciable portion of the profit within reach is wasted due to poor quality of planning and workmanship. The production flow production error distribution of the sheet metal part based constructions is inspectedin this thesis. The objective of the thesis is to analyze the origins of production errors in the production flow of sheet metal based constructions. Also the employee empowerment is investigated in theory and the meaning of the employee empowerment in reducing the overall production error amount is discussed in this thesis. This study is most relevant to the sheet metal part fabricating industrywhich produces sheet metal part based constructions for electronics and telecommunication industry. This study concentrates on the manufacturing function of a company and is based on a field study carried out in five Finnish case factories. In each studied case factory the most delicate work phases for production errors were detected. It can be assumed that most of the production errors are caused in manually operated work phases and in mass production work phases. However, no common theme in collected production error data for production error distribution in the production flow can be found. Most important finding was still that most of the production errors in each case factory studied belong to the 'human activity based errors-category'. This result indicates that most of the problemsin the production flow are related to employees or work organization. Development activities must therefore be focused to the development of employee skills orto the development of work organization. Employee empowerment gives the right tools and methods to achieve this.

Error en el posicionamiento indoor en dispositivos móviles

Location information is becoming increasingly necessary as every new smartphone incorporates a GPS (Global Positioning System) which allows the development of various applications based on it. However, it is not possible to properly receive the GPS signal in indoor environments. For this reason, new indoor positioning systems are being developed. As indoors is a very challenging scenario, it is necessary to study the precision of the obtained location information in order to determine if these new positioning techniques are suitable for indoor positioning.

Functional error modeling for uncertainty quantification in hydrogeology

Approximate models (proxies) can be employed to reduce the computational costs of estimating uncertainty. The price to pay is that the approximations introduced by the proxy model can lead to a biased estimation. To avoid this problem and ensure a reliable uncertainty quantification, we propose to combine functional data analysis and machine learning to build error models that allow us to obtain an accurate prediction of the exact response without solving the exact model for all realizations. We build the relationship between proxy and exact model on a learning set of geostatistical realizations for which both exact and approximate solvers are run. Functional principal components analysis (FPCA) is used to investigate the variability in the two sets of curves and reduce the dimensionality of the problem while maximizing the retained information. Once obtained, the error model can be used to predict the exact response of any realization on the basis of the sole proxy response. This methodology is purpose-oriented as the error model is constructed directly for the quantity of interest, rather than for the state of the system. Also, the dimensionality reduction performed by FPCA allows a diagnostic of the quality of the error model to assess the informativeness of the learning set and the fidelity of the proxy to the exact model. The possibility of obtaining a prediction of the exact response for any newly generated realization suggests that the methodology can be effectively used beyond the context of uncertainty quantification, in particular for Bayesian inference and optimization.

THE IMPACT OF ARCHITECTURAL DESIGN ON SOFTWARE DEVELOPMENT

Tässä työssä tutkitaan ohjelmistoarkkitehtuurisuunnitteluominaisuuksien vaikutusta erään client-server –arkkitehtuuriin perustuvan mobiilipalvelusovelluksen suunnittelu- ja toteutusaikaan. Kyseinen tutkimus perustuu reaalielämän projektiin, jonka kvalitatiivinen analyysi paljasti arkkitehtuurikompponenttien välisten kytkentöjen merkittävästi vaikuttavan projektin työmäärään. Työn päätavoite oli kvantitatiivisesti tutkia yllä mainitun havainnon oikeellisuus. Tavoitteen saavuttamiseksi suunniteltiin ohjelmistoarkkitehtuurisuunnittelun mittaristo kuvaamaan kyseisen järjestelmän alijärjestelmien arkkitehtuuria ja luotiin kaksi suunniteltua mittaristoa käyttävää, työmäärää (komponentin suunnittelu-, toteutus- ja testausaikojen summa) arvioivaa mallia, joista toinen on lineaarinen ja toinen epälineaarinen. Näiden mallien kertoimet sovitettiin optimoimalla niiden arvot epälineaarista gloobaalioptimointimenetelmää, differentiaalievoluutioalgoritmia, käyttäen, niin että mallien antamat arvot vastasivat parhaiten mitattua työmäärää sekä kaikilla ominaisuuksilla eli attribuuteilla että vain osalla niistä (yksi jätettiin vuorotellen pois). Kun arkkitehtuurikompenttien väliset kytkennät jätettiin malleista pois, mitattujen ja arvoitujen työmäärien välinen ero (ilmaistuna virheenä) kasvoi eräässä tapauksessa 367 % entisestä tarkoittaen sitä, että näin muodostettu malli vastasi toteutusaikoja huonosti annetulla ainestolla. Tämä oli suurin havaitu virhe kaikkien poisjätettyjen ominaisuuksien kesken. Saadun tuloksen perusteella päätettiin, että kyseisen järjestelmän toteutusajat ovat vahvasti riippuvaisia kytkentöjen määrästä, ja näin ollen kytkentöjen määrä oli mitä todennäköisemmin kaikista tärkein työmäärään vaikuttava tekijä tutkitun järjestelmän arkkitehtuurisuunnittelussa.

Kohinan poisto spektrikuvista pehmeillä morfologisilla suodattimilla

Tämän diplomityön tavoitteena oli tutkia kohinan poistoa spektrikuvista käyttäen pehmeitä morfologisia suodattimia. Työssä painotettiin impulssimaisen kohinan suodattamista. Suodattimien toimintaa arvioitiin numeerisesti keskimääräisen itseisarvovirheen, neliövirheen sekä signaali-kohinasuhteen avulla ja visuaalisesti tarkastelemalla suodatettuja kuvia sekä niiden yksittäisiä spektritasoja. Käytettyjä suodatusmenetelmiä olivat suodatus kuvapisteittäin spektrin suunnassa, suodatus koko spektrissä sekä kuutiomenetelmä ja komponenteittainen suodatus. Suodatettavat kuvat sisälsivät joko suola ja pippuri- tai bittivirhekohinaa. Parhaimmat suodatustulokset sekä numeeristen virhekriteerien että visuaalisen tarkastelun perusteella saatiin komponenteittaisella sekä kuvapisteittäisellä menetelmällä. Työssä käytetyt menetelmät on esitetty algoritmimuodossa. Suodatinalgoritmien toteutukset ja suodatuskokeet tehtiin Matlab-ohjelmistolla.

Nanocharacterization of Soft Biological Samples in Shear Mode with Quartz Tuning Fork Probes

Quartz tuning forks are extremely good resonators and their use is growing in scanning probe microscopy. Nevertheless, only a few studies on soft biological samples have been reported using these probes. In this work, we present the methodology to develop and use these nanosensors to properly work with biological samples. The working principles, fabrication and experimental setup are presented. The results in the nanocharacterization of different samples in different ambients are presented by using different working modes: amplitude modulation with and without the use of a Phase-Locked Loop (PLL) and frequency modulation. Pseudomonas aeruginosa bacteria are imaged in nitrogen using amplitude modulation. Microcontact printed antibodies are imaged in buffer using amplitude modulation with a PLL. Finally, metastatic cells are imaged in air using frequency modulation.