Interacció humana amb els ordinadors : Disseny centrat en l'usuari i usabilitat en entorns tàctils

Quan parlem de disseny centrat en l'usuari ens referim al fet de dissenyar pensant en el que vol l'usuari. És per això que se'l consulta, per a saber què vol, què necessita, què i com li agrada més, què no li agrada, què li costa més d'entendre. Es fa, en definitiva, una avaluació del producte la finalitat del qual és ser útil i pràctic per al major nombre possible de persones. En aquest treball parlem de dissenyar pensant en l'usuari en entorns tàctils. Els entorns tàctils només són una de les moltes possibilitats que ens ofereix la interacció humana amb els ordinadors.

C3-symmetric peptide scaffolds are functional mimetics of trimeric CD40L.

Interaction between CD40, a member of the tumor necrosis factor receptor (TNFR) superfamily, and its ligand CD40L, a 39-kDa glycoprotein, is essential for the development of humoral and cellular immune responses. Selective blockade or activation of this pathway provides the ground for the development of new treatments against immunologically based diseases and malignancies. Like other members of the TNF superfamily, CD40L monomers self-assemble around a threefold symmetry axis to form noncovalent homotrimers that can each bind three receptor molecules. Here, we report on the structure-based design of small synthetic molecules with C3 symmetry that can mimic CD40L homotrimers. These molecules interact with CD40, compete with the binding of CD40L to CD40, and reproduce, to a certain extent, the functional properties of the much larger homotrimeric soluble CD40L. Architectures based on rigid C3-symmetric cores may thus represent a general approach to mimicking homotrimers of the TNF superfamily.

Iowa’s Bridge and Highway Climate Change and Extreme Weather Vulnerability Assessment Pilot, HEPN-707, 2015

The Iowa Department of Transportation (DOT) is responsible for approximately 4,100 bridges and structures that are a part of the state’s primary highway system, which includes the Interstate, US, and Iowa highway routes. A pilot study was conducted for six bridges in two Iowa river basins—the Cedar River Basin and the South Skunk River Basin—to develop a methodology to evaluate their vulnerability to climate change and extreme weather. The six bridges had been either closed or severely stressed by record streamflow within the past seven years. An innovative methodology was developed to generate streamflow scenarios given climate change projections. The methodology selected appropriate rainfall projection data to feed into a streamflow model that generated continuous peak annual streamflow series for 1960 through 2100, which were used as input to PeakFQ to estimate return intervals for floods. The methodology evaluated the plausibility of rainfall projections and credibility of streamflow simulation while remaining consistent with U.S. Geological Survey (USGS) protocol for estimating the return interval for floods. The results were conveyed in an innovative graph that combined historical and scenario-based design metrics for use in bridge vulnerability analysis and engineering design. The pilot results determined the annual peak streamflow response to climate change likely will be basin-size dependent, four of the six pilot study bridges would be exposed to increased frequency of extreme streamflow and would have higher frequency of overtopping, the proposed design for replacing the Interstate 35 bridges over the South Skunk River south of Ames, Iowa is resilient to climate change, and some Iowa DOT bridge design policies could be reviewed to consider incorporating climate change information.

Kantavan kehikkorakenteen valmistuksen kehittäminen

Paperikoneen hoitotason muodostaa kantava kehikkorakenne sekä kehikkorakenteiden tuennat. Kantavan kehikkorakenteen valmistuson perinteistä hitsaavaa konepajatuotantoa. Työssä esitetään ratkaisuja valmistuksen kehittämiseen, näiden avulla on tavoitteena pudottaa valmistuksen läpimenoaikaa ja lopullisesti vastata kiristyneeseen kilpailutilanteeseen. Laajempana tavoitteena on osoittaa automaation mahdollisuudet kyseiseen tuotantoon. Alumiinisten rakenteiden toimitukset ovat jatkuvasti kasvaneet. Tähän rakenneryhmään haluttiin panostaa ja tehdä tuotteesta markkinoiden paras sekä kehittää valmistusta, jotta voitaisiin vastata kilpailuun ja lyhyisiin toimitusaikoihin. Työssä esitettävät ratkaisut on suunnattu alumiinisen kantavan kehikon valmistuksen kehittämiseen. Valmistuksen kehittäminen käsittää tuotteen rakennekomponenttien suunnittelemista valmistuksen kannalta, automaation lisäämistä osavalmistukseen sekä hitsauksen kevytmekanisointia.

Tuotealustapohjaisen suunnittelun vaikutukset risteilijän suunnitteluaikatauluihin

Tuotealustapohjaisella suunnittelulla pyritään hyödyntämään jo kertaalleen hyväksi todettuja kokonaisuuksia ja moduuleja, joiden avulla voidaan nopeasti suunnitella uusia tuotteita. Tarkoituksena on suunnitella asiakkaan näkökulmasta monia erilaisia tuotteita jopa sarjatuotannon kustannustehokkuudella. Tutkimuksessa esitetään risteilijän tuotealustapohjainen suunnitteluprosessi. Lisäksi työn tavoitteena on tutkia uuden suunnitteluprosessin vaikutukset risteilijän suunnitteluaikatauluihin. Tutkimuksessa haastateltiin Turun telakan suunnitteluosaston ja kehitysosaston johtajia. Haastatteluilla selvitettiin nykyisen suunnitteluprosessin haasteita, joiden nähtiin erityisesti viivästyttävät suunnitteluaikatauluja. Keskeisiä haasteita ovat suunnitteluresurssien ylikuormitus ja suunnittelulaadun huonontuminen. Lisäksi kartoitettiin tavoitteet risteilijän tuotealustaratkaisulle ja suunnitteluaikataululle. Haastattelukierroksen pohjalta ja teoriaa soveltaen analysoitiin risteilijän modulaariseen tuotealustaan perustuva suunnitteluprosessi. Tätä suunnitteluprosessia tutkittiin edelleen case-tutkimuksessa jääasemien osalta, jossa haastateltiin kyseisten alueiden suunnittelijoita. Lisäksi case-tutkimuksessa verrattiin jääaseman ja baaripentterin perussuunnittelun vaiheita toisiinsa. Näistä saatuja tutkimustuloksia verrattiin hyttialueen vakioidun perussuunnitteluohjeen vaikutuksiin suunnitteluprosessissa. Onnistunut tuotealustapohjainen suunnittelu vaatii sitoutumista jokaisella organisaation tasolla, jotta tuotealustassa olevien vakioituja moduuleja myös käytettäisiin. Modulaarisesta toiminnasta siirtyminen tuotealustapohjaiseen suunnitteluun vaatii vakioituja moduuleja ja vakioituja rajapintoja risteilijässä. Case-tutkimuksessa ja johtopäätöksissä on todettu uuden suunnitteluprosessin lyhentävän ja tuovan kustannussäästöjä tuotteen valmistusprosessissa.

Field-Programmable Gate Array Card for Readout and Control of Cryoelectronics

The main goal of the present Master’s Thesis project was to create a field-programmable gate array (FPGA) based system for the control of single-electron transistors or other cryoelectronic devices. The FPGA and similar technologies are studied in the present work. The fixed and programmable logic are compared with each other. The main features and limitations of the hardware used in the project are investigated. The hardware and software connections of the device to the computer are shown in detail. The software development techniques for FPGA-based design are described. The steps of design for programmable logic are considered. Furthermore, the results of filters implemented in the software are illustrated.

Mallipohjainen suunnittelu osana aurinkosähkövaihtosuuntaajan tuotekehitystä

Työssä selvitetään mallipohjaisen suunnittelun ja simulointimallista tuotetun ohjelmakoodin kelpoisuutta tuotekehityskäytössä. Työtapoja tutkitaan, koska halutaan selvittää parantavatko esitetyt toimintatavat aurinkosähkövaihtosuuntaajien ohjelmistokehitystä. Työssä käydään läpi mallipohjaisen suunnittelun työvaiheet, niiden sisältö ja tarkoitus. Aurinkosähköjärjestelmästä muodostetaan simulointimalli, josta tuotetaan maksimitehopisteseuraajan ohjelmakoodi, jonka toiminta testataan aurinkosähkövaihtosuuntaajan ohjausalustan simulaattorissa. Mallipohjainen suunnittelu mahdollistaa ohjelmistotuotekehityksen nopeuttamisen käyttämällä samaa järjestelmää useassa työvaiheessa. Ohjelmakoodin tuottaminen simulointimallista on mahdollista ja hyödyllistä, jos yrityksessä käytetään simulointitestausta säätö- ja ohjausjärjestelmän toiminnan suunnitteluun ja varmentamiseen.

Découverte d'inhibiteurs de la dihydrofolate réductase R67 impliquée dans la résistance au triméthoprime.

Le triméthoprime (TMP) est un antibiotique communément utilisé depuis les années 60. Le TMP est un inhibiteur de la dihydrofolate réductase (DHFR) bactérienne chromosomale. Cette enzyme est responsable de la réduction du dihydrofolate (DHF) en tétrahydrofolate (THF) chez les bactéries, qui lui, est essentiel à la synthèse des purines et ainsi, à la prolifération cellulaire. La résistance bactérienne au TMP est documentée depuis plus de 30 ans. Une des causes de cette résistance provient du fait que certaines souches bactériennes expriment une DHFR plasmidique, la DHFR R67. La DHFR R67 n'est pas affectée par le TMP, et peut ainsi remplacer la DHFR chromosomale lorsque celle-ci est inhibée par le TMP. À ce jour, aucun inhibiteur spécifique de la DHFR R67 est connu. En découvrant des inhibiteurs contre la DHFR R67, il serait possible de lever la résistance au TMP que la DHFR R67 confère aux bactéries. Afin de découvrir des inhibiteurs de DHFR R67, les approches de design à base de fragments et de criblage virtuel ont été choisies. L'approche de design à base de fragments a permis d'identifier sept composés simples et de faible poids moléculaire (fragments) inhibant faiblement la DHFR R67. À partir de ces fragments, des composés plus complexes et symétriques, inhibant la DHFR R67 dans l'ordre du micromolaire, ont été élaborés. Des études cinétiques ont montré que ces inhibiteurs sont compétitifs et qu'au moins deux molécules se lient simultanément dans le site actif de la DHFR R67. L'étude d'analogues des inhibiteurs micromolaires de la DHFR R67 a permis de déterminer que la présence de groupements carboxylate, benzimidazole et que la longueur des molécules influencent la puissance des inhibiteurs. Une étude par arrimage moléculaire, appuyée par les résultats in vitro, a permis d'élaborer un modèle qui suggère que les résidus Lys32, Gln67 et Ile68 seraient impliqués dans la liaison avec les inhibiteurs. Le criblage virtuel de la librairie de 80 000 composés de Maybridge avec le logiciel Moldock, et les essais d'inhibition in vitro des meilleurs candidats, a permis d'identifier quatre inhibiteurs micromolaires appartenant à des familles distinctes des composés précédemment identifiés. Un second criblage virtuel, d'une banque de 6 millions de composés, a permis d'identifier trois inhibiteurs micromolaires toujours distincts. Ces résultats offrent la base à partir de laquelle il sera possible de développer iv des composés plus efficaces et possédant des propriétés phamacologiquement acceptables dans le but de développer un antibiotique pouvant lever la résistance au TMP conféré par la DHFR R67.

The calculation of force constants and normal coordinates III: constrained force fields for the methyl halides

A method is discussed for imposing any desired constraint on the force field obtained in a force constant refinement calculation. The application of this method to force constant refinement calculations for the methyl halide molecules is reported. All available data on the vibration frequencies, Coriolis interaction constants and centrifugal stretching constants of CH3X and CD3X molecules were used in the refinements, but despite this apparent abundance of data it was found that constraints were necessary in order to obtain a unique solution to the force field. The results of unconstrained calculations, and of three different constrained calculations, are reported in this paper. The constrained models reported are a Urey—Bradley force field, a modified valence force field, and a constraint based on orbital-following bond-hybridization arguments developed in the following paper. The results are discussed, and compared with previous results for these molecules. The third of the above models is found to reproduce the observed data better than either of the first two, and additional reasons are given for preferring this solution to the force field for the methyl halide molecules.

An Earth Observation Land Data Assimilation System (EO-LDAS)

Current methods for estimating vegetation parameters are generally sub-optimal in the way they exploit information and do not generally consider uncertainties. We look forward to a future where operational dataassimilation schemes improve estimates by tracking land surface processes and exploiting multiple types of observations. Dataassimilation schemes seek to combine observations and models in a statistically optimal way taking into account uncertainty in both, but have not yet been much exploited in this area. The EO-LDAS scheme and prototype, developed under ESA funding, is designed to exploit the anticipated wealth of data that will be available under GMES missions, such as the Sentinel family of satellites, to provide improved mapping of land surface biophysical parameters. This paper describes the EO-LDAS implementation, and explores some of its core functionality. EO-LDAS is a weak constraint variational dataassimilationsystem. The prototype provides a mechanism for constraint based on a prior estimate of the state vector, a linear dynamic model, and EarthObservationdata (top-of-canopy reflectance here). The observation operator is a non-linear optical radiative transfer model for a vegetation canopy with a soil lower boundary, operating over the range 400 to 2500 nm. Adjoint codes for all model and operator components are provided in the prototype by automatic differentiation of the computer codes. In this paper, EO-LDAS is applied to the problem of daily estimation of six of the parameters controlling the radiative transfer operator over the course of a year (> 2000 state vector elements). Zero and first order process model constraints are implemented and explored as the dynamic model. The assimilation estimates all state vector elements simultaneously. This is performed in the context of a typical Sentinel-2 MSI operating scenario, using synthetic MSI observations simulated with the observation operator, with uncertainties typical of those achieved by optical sensors supposed for the data. The experiments consider a baseline state vector estimation case where dynamic constraints are applied, and assess the impact of dynamic constraints on the a posteriori uncertainties. The results demonstrate that reductions in uncertainty by a factor of up to two might be obtained by applying the sorts of dynamic constraints used here. The hyperparameter (dynamic model uncertainty) required to control the assimilation are estimated by a cross-validation exercise. The result of the assimilation is seen to be robust to missing observations with quite large data gaps.

Cortical hot spots and labyrinths: why cortical neuromodulation for episodic migraine with aura should be personalized

Stimulation protocols for medical devices should be rationally designed. For episodic migraine with aura we outline model-based design strategies toward preventive and acute therapies using stereotactic cortical neuromodulation. To this end, we regard a localized spreading depression (SD) wave segment as a central element in migraine pathophysiology. To describe nucleation and propagation features of the SD wave segment, we define the new concepts of cortical hot spots and labyrinths, respectively. In particular, we firstly focus exclusively on curvature-induced dynamical properties by studying a generic reaction-diffusion model of SD on the folded cortical surface. This surface is described with increasing level of details, including finally personalized simulations using patient's magnetic resonance imaging (MRI) scanner readings. At this stage, the only relevant factor that can modulate nucleation and propagation paths is the Gaussian curvature, which has the advantage of being rather readily accessible by MRI. We conclude with discussing further anatomical factors, such as areal, laminar, and cellular heterogeneity, that in addition to and in relation to Gaussian curvature determine the generalized concept of cortical hot spots and labyrinths as target structures for neuromodulation. Our numerical simulations suggest that these target structures are like fingerprints, they are individual features of each migraine sufferer. The goal in the future will be to provide individualized neural tissue simulations. These simulations should predict the clinical data and therefore can also serve as a test bed for exploring stereotactic cortical neuromodulation.

Classical and hologram QSAR studies on a series of inhibitors of trypanosomatid Glyceraldehyde-3-Phosphate Dehydrogenase

Leishmaniasis and trypanosomiasis are major causes of morbidity and mortality in both tropical and subtropical regions of the world. The current available drugs are limited, ineffective, and require long treatment regimens. Due to the high dependence of trypanosomatids on glycolysis as a source of energy, some glycolytic enzymes have been identified as attractive targets for drug design. In the present work, classical Two-Dimensional Quantitative Structure -Activity Relationships (2D QSAR) and Hologram QSAR (HQSAR) studies were performed on a series of adenosine derivatives as inhibitors of Leishmania mexicana Glyceraldehyde-3-Phosphate Dehydrogenase (LmGAPDH). Significant correlation coefficients (classical QSAR, r(2)=0.83 and q(2) =0.81; HQSAR, r(2)=0.91 and q(2) =0.86) were obtained for the 56 training set compounds, indicating the potential of the models for untested compounds. The models were then externally validated using a test set of 14 structurally related compounds and the predicted values were in good agreement with the experimental results (classical QSAR, r(pred)(2) = 0.94; HQSAR, r(pred)(2) = 0.92).

Structural basis for selective inhibition of trypanosomatid glyceraldehyde-3-phosphate dehydrogenase: Molecular docking and 3D QSAR studies

The glycolytic enzyme glyceraldehyde-3 -phosphate dehydrogenase (GAPDH) is as an attractive target for the development of novel antitrypanosomatid agents. In the present work, comparative molecular field analysis and comparative molecular similarity index analysis were conducted on a large series of selective inhibitors of trypanosomatid GAPDH. Four statistically significant models were obtained (r(2) > 0.90 and q(2) > 0.70), indicating their predictive ability for untested compounds. The models were then used to predict the potency of an external test set, and the predicted values were in good agreement with the experimental results. Molecular modeling studies provided further insight into the structural basis for selective inhibition of trypanosomatid GAPDH.

Structural basis for selective inhibition of purine nucleoside phosphorylase from Schistosoma mansoni: Kinetic and structural studies

Selectivity plays a crucial role in the design of enzyme inhibitors as novel antiparasitic agents, particularly in cases where the target enzyme is also present in the human host. Purine nucleoside phosphorylase from Schistosoma mansoni (SmPNP) is an attractive target for the discovery of potential antischistosomal agents. In the present work, kinetic studies were carried out in order to determine the inhibitory potency, mode of action and enzyme selectivity of a series of inhibitors of SmPNP. In addition, crystallographic studies provided important structural insights for rational inhibitor design, revealing consistent structural differences in the binding mode of the inhibitors in the active sites of the SmPNP and human PNP (HsPNP) structures. The molecular information gathered in this work should be useful for future medicinal chemistry efforts in the design of new inhibitors of SmPNP having increased affinity and selectivity. (C) 2010 Elsevier Ltd. All rights reserved.