Identification of CT46/HORMAD1, an immunogenic cancer/testis antigen encoding a putative meiosis-related protein.

Transcripts with ESTs derived exclusively or predominantly from testis, and not from other normal tissues, are likely to be products of genes with testis-restricted expression, and are thus potential cancer/testis (CT) antigen genes. A list of 371 genes with such characteristics was compiled by analyzing publicly available EST databases. RT-PCR analysis of normal and tumor tissues was performed to validate an initial selection of 20 of these genes. Several new CT and CT-like genes were identified. One of these, CT46/HORMAD1, is expressed strongly in testis and weakly in placenta; the highest level of expression in other tissues is <1% of testicular expression. The CT46/HORMAD1 gene was expressed in 31% (34/109) of the carcinomas examined, with 11% (12/109) showing expression levels >10% of the testicular level of expression. CT46/HORMAD1 is a single-copy gene on chromosome 1q21.3, encoding a putative protein of 394 aa. Conserved protein domain analysis identified a HORMA domain involved in chromatin binding. The CT46/HORMAD1 protein was found to be homologous to the prototype HORMA domain-containing protein, Hop1, a yeast meiosis-specific protein, as well as to asy1, a meiotic synaptic mutant protein in Arabidopsis thaliana.

The malaria circumsporozoite protein has two functional domains, each with distinct roles as sporozoites journey from mosquito to mammalian host.

Plasmodium sporozoites make a remarkable journey from the mosquito midgut to the mammalian liver. The sporozoite's major surface protein, circumsporozoite protein (CSP), is a multifunctional protein required for sporozoite development and likely mediates several steps of this journey. In this study, we show that CSP has two conformational states, an adhesive conformation in which the C-terminal cell-adhesive domain is exposed and a nonadhesive conformation in which the N terminus masks this domain. We demonstrate that the cell-adhesive domain functions in sporozoite development and hepatocyte invasion. Between these two events, the sporozoite must travel from the mosquito midgut to the mammalian liver, and N-terminal masking of the cell-adhesive domain maintains the sporozoite in a migratory state. In the mammalian host, proteolytic cleavage of CSP regulates the switch to an adhesive conformation, and the highly conserved region I plays a critical role in this process. If the CSP domain architecture is altered such that the cell-adhesive domain is constitutively exposed, the majority of sporozoites do not reach their target organs, and in the mammalian host, they initiate a blood stage infection directly from the inoculation site. These data provide structure-function information relevant to malaria vaccine development.

Differential inhibition of TRAIL-mediated DR5-DISC formation by decoy receptors 1 and 2.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family that induces cancer cell death by apoptosis with some selectivity. TRAIL-induced apoptosis is mediated by the transmembrane receptors death receptor 4 (DR4) (also known as TRAIL-R1) and DR5 (TRAIL-R2). TRAIL can also bind decoy receptor 1 (DcR1) (TRAIL-R3) and DcR2 (TRAIL-R4) that fail to induce apoptosis since they lack and have a truncated cytoplasmic death domain, respectively. In addition, DcR1 and DcR2 inhibit DR4- and DR5-mediated, TRAIL-induced apoptosis and we demonstrate here that this occurs through distinct mechanisms. While DcR1 prevents the assembly of the death-inducing signaling complex (DISC) by titrating TRAIL within lipid rafts, DcR2 is corecruited with DR5 within the DISC, where it inhibits initiator caspase activation. In addition, DcR2 prevents DR4 recruitment within the DR5 DISC. The specificity of DcR1- and DcR2-mediated TRAIL inhibition reveals an additional level of complexity for the regulation of TRAIL signaling.

Spatial learning by rats across visually disconnected environments

Two spatial tasks were designed to test specific properties of spatial representation in rats. In the first task, rats were trained to locate an escape hole at a fixed position in a visually homogeneous arena. This arena was connected with a periphery where a full view of the room environment existed. Therefore, rats were dependent on their memory trace of the previous position in the periphery to discriminate a position within the central region. Under these experimental conditions, the test animals showed a significant discrimination of the training position without a specific local view. In the second task, rats were trained in a radial maze consisting of tunnels that were transparent at their distal ends only. Because the central part of the maze was non-transparent, rats had to plan and execute appropriate trajectories without specific visual feedback from the environment. This situation was intended to encourage the reliance on prospective memory of the non-visited arms in selecting the following move. Our results show that acquisition performance was only slightly decreased compared to that shown in a completely transparent maze and considerably higher than in a translucent maze or in darkness. These two series of experiments indicate (1) that rats can learn about the relative position of different places with no common visual panorama, and (2) that they are able to plan and execute a sequence of visits to several places without direct visual feed-back about their relative position.

Proteomic and transcriptomic profiling of Staphylococcus aureus surface LPXTG-proteins: correlation with agr genotypes and adherence phenotypes.

Staphylococcus aureus infections involve numerous adhesins and toxins, which expression depends on complex regulatory networks. Adhesins include a family of surface proteins covalently attached to the peptidoglycan via a conserved LPXTG motif. Here we determined the protein and mRNA expression of LPXTG-proteins of S. aureus Newman in time-course experiments, and their relation to fibrinogen adherence in vitro. Experiments were performed with mutants in the global accessory-gene regulator (agr), surface protein A (Spa), and fibrinogen-binding protein A (ClfA), as well as during growth in iron-rich or iron-poor media. Surface proteins were recovered by trypsin-shaving of live bacteria. Released peptides were analyzed by liquid chromatography coupled to tandem mass-spectrometry. To unambiguously identify peptides unique to LPXTG-proteins, the analytical conditions were refined using a reference library of S. aureus LPXTG-proteins heterogeneously expressed in surrogate Lactococcus lactis. Transcriptomes were determined by microarrays. Sixteen of the 18 LPXTG-proteins present in S. aureus Newman were detected by proteomics. Nine LPXTG-proteins showed a bell-shape agr-like expression that was abrogated in agr-negative mutants including Spa, fibronectin-binding protein A (FnBPA), ClfA, iron-binding IsdA, and IsdB, immunomodulator SasH, functionally uncharacterized SasD, biofilm-related SasG and methicillin resistance-related FmtB. However, only Spa and SasH modified their proteomic and mRNA profiles in parallel in the parent and its agr- mutant, whereas all other LPXTG-proteins modified their proteomic profiles independently of their mRNA. Moreover, ClfA became highly transcribed and active in fibrinogen-adherence tests during late growth (24 h), whereas it remained poorly detected by proteomics. On the other hand, iron-regulated IsdA-B-C increased their protein expression by >10-times in iron-poor conditions. Thus, proteomic, transcriptomic, and adherence-phenotype demonstrated differential profiles in S. aureus. Moreover, trypsin peptide signatures suggested differential protein domain exposures in various environments, which might be relevant for anti-adhesin vaccines. A comprehensive understanding of the S. aureus physiology should integrate all three approaches.

A Middleware architecture for Unmanned Aircraft Avionics

An Unmanned Aerial Vehicle is a non-piloted airplane designed to operate in dangerous and repetitive situations. With the advent of UAV's civil applications, UAVs are emerging as a valid option in commercial scenarios. If it must be economically viable, the same platform should implement avariety of missions with little reconguration time and overhead.This paper presents a middleware-based architecture specially suited to operate as a exible payload and mission controller in a UAV. The system is composed of low-costcomputing devices connected by network. The functionality is divided into reusable services distributed over a number ofnodes with a middleware managing their lifecycle and communication.Some research has been done in this area; yetit is mainly focused on the control domain and in its realtime operation. Our proposal differs in that we address the implementation of adaptable and reconfigurable unmannedmissions in low-cost and low-resources hardware.

Kuvausmenetelmänvalinta ja käyttöönotto ohjelmistotuoteorganisaatiossa

Useiden pitkän kehityskaaren ohjelmistojen ylläpitäminen ja kehittäminen on vaikeaa, sillä niiden dokumentaatio on vajaata tai vanhentunutta. Tässä diplomityössä etsitään ratkaisua tällaisen ohjelmiston ja sen taustalla olevan järjestelmän kuvaukseen. Tavoitteina on tukea nykyisen ohjelmiston ylläpitoa ja uuden työvoiman perehdyttämistä. Tavoitteena on myös pohjustaa uuden korvaavan ohjelmiston suunnittelua kuvaamalla nykyiseen järjestelmään sitoutunutta sovellusalueosaamista. Työssä kehitetään kuvausmenetelmä järjestelmän kuvaamiseen hierarkkisesti laitteistotason yleiskuvauksesta ohjelmiston luokkarakenteeseen sekä toiminnallisuuteen asti. Laite- ja luokkarakennekuvaukset ovat rakenteellisia kuvauksia, joiden tehtävänä on selittää järjestelmän ja sen osien kokoonpano. Toiminnallisuudesta kertovat kuvaukset on toteutettu käyttötapauskuvauksina. Työssä keskityttiin erityisesti kohdejärjestelmän keskeisen ohjelmiston ja tietokannan kuvaamiseen. Ohjelmistosta valittiin tärkeimmät ja eniten sovellusalueen tietotaitoa sisältävät osat, joista työssä luotiin esimerkkikuvaukset. Kuvauksia on kehitettyä menetelmää hyödyntäen helppo laajentaa tarpeiden mukaan paitsi ohjelmiston muihin osiin, myös laitteiston ja järjestelmän kuvaamiseen kokonaisuudessaan syvemmin.

Kunnallisten sähköisten palveluiden mallintaminen

Tämän diplomityön tarkoituksena on kuvata tiettyjen kunnallisten palvelujen rakenne ja prosessikuvaukset. Rakenne kuvataan OWL-mallinnuskielellä ja palvelun käyttäjien suorittamat toiminnot BPML-mallinnuskielen avulla. Työssä on tarkoituksena esittää, kuinka sekä rakenne että toiminnot pystytään kuvaamaan XML-pohjaisen esitystavan avulla, joita nämä OWL- ja BPML-mallinnuskielet ovat. Ensin esitellään työssä käytetyt mallinnuskielet ja ne ominaisuudet, jotka liittyvät tähän tutkimukseen. Tämän jälkeen esitellään työtä varten tehdyt työnkulkukaaviot ja rakennekaaviot,sekä näiden jalostus lopulliseen OWL-muotoon ja BPMN-muotoon . Työ jakautuu kahteen eri osavaiheeseen, joissa ensimmäisessä kerrotaan kuinka kunnallisen palvelun käsitemalli esitetään UML -luokkakaavioiden avulla ja kuinka tämä jalostetaan lopulliseen OWL-muotoon. Toinen osa työstä keskittyy palvelun prosessien mallintamiseen UML-työnkulkukaavioilla ja näiden kaavioiden muokkaamiseen BPMN-muotoon eli liiketoimintaprosessidiagrammeiksi. Kunnallisista palveluista valittiin tähän diplomityöhän tilanvaraus, jonka toimintaa on tarkasteltu haastattelemalla kuntien toimijoita, jotka ovat työssään tekemisissä tilanvaraustoimintojen kanssa. Tilanvarauksen osalta haastattelutiedot olivat valmiiksi saatavilla projektin avulla Päijät-Hämeen osalta, tosin tietojatäydennettiin haastattelemalla Kouvolan tilanvarauksesta huolehtivia henkilöitä.

Acute aphasia after right hemisphere stroke

Right hemispheric stroke aphasia (RHSA) rarely occurs in right- or left-handed patients with their language representation in right hemisphere (RH). For right-handers, the term crossed aphasia is used. Single cases, multiple cases reports, and reviews suggest more variable anatomo-clinical correlations. We included retrospectively from our stroke data bank 16 patients (right- and left-handed, and ambidextrous) with aphasia after a single first-ever ischemic RH stroke. A control group was composed of 25 successive patients with left hemispheric stroke and aphasia (LHSA). For each patient, we analyzed four modalities of language (spontaneous fluency, naming, repetition, and comprehension) and recorded eventual impairment: (1) on admission (hyperacute) and (2) between day 3 and 14 (acute). Lesion volume and location as measured on computed tomography (CT) and magnetic resonance imaging (MRI) were transformed into Talairach stereotaxic space. Nonparametric statistics were used to compare impaired/nonimpaired patients. Comprehension and repetition were less frequently impaired after RHSA (respectively, 56% and 50%) than after LHSA (respectively, 84% and 80%, P = 0.05 and 0.04) only at hyperacute phase. Among RHSA, fewer left-handers/ambidextrous than right-handers had comprehension disorders at second evaluation (P = 0.013). Mean infarct size was similar in RHSA and LHSA with less posterior RHSA lesions (caudal to the posterior commissure). Comprehension and repetition impairments were more often associated with anterior lesions in RHSA (Fisher's exact test, P < 0.05). Despite the small size of the cohort, our findings suggest increased atypical anatomo-functional correlations of RH language representation, particularly in non-right-handed patients.

Geografías familiares bajo la dictadura franquista: exilio, clandestinidad, prisión

Este texto ahonda en las geografías políticas, sociales y familiares de Aurèlia Pijoan, la primera mujer que, médico de profesión, ha accedido a un cargo de representación municipal en Lleida. Casada con Luis Pérez García-Lago –secretario general del PSUC y la UGT en la Lleida de los años trenta y posteriormente máximo responsable del partido en el exilio mejicano-, continuó su compromiso a través de la Unión de Mujeres Españolas de México de la que llegó a convertirse en secretaria general. El artículo pretende, a la vez que reflexionar sobre el diálogo que se establece entre recuerdo y olvido, hacer visible la historia de los sin historia a partir de un centro de gravedad concreto, puesto que los itinerarios personales y familiares de Aurèlia Pijoan permiten recorrer las diversas caras del universo represivo franquista: exilio,clandestinidad y prisión.

Probabilistic electrical resistivity tomography of a CO2 sequestration analog

Electrical resistivity tomography (ERT) is a well-established method for geophysical characterization and has shown potential for monitoring geologic CO2 sequestration, due to its sensitivity to electrical resistivity contrasts generated by liquid/gas saturation variability. In contrast to deterministic inversion approaches, probabilistic inversion provides the full posterior probability density function of the saturation field and accounts for the uncertainties inherent in the petrophysical parameters relating the resistivity to saturation. In this study, the data are from benchtop ERT experiments conducted during gas injection into a quasi-2D brine-saturated sand chamber with a packing that mimics a simple anticlinal geological reservoir. The saturation fields are estimated by Markov chain Monte Carlo inversion of the measured data and compared to independent saturation measurements from light transmission through the chamber. Different model parameterizations are evaluated in terms of the recovered saturation and petrophysical parameter values. The saturation field is parameterized (1) in Cartesian coordinates, (2) by means of its discrete cosine transform coefficients, and (3) by fixed saturation values in structural elements whose shape and location is assumed known or represented by an arbitrary Gaussian Bell structure. Results show that the estimated saturation fields are in overall agreement with saturations measured by light transmission, but differ strongly in terms of parameter estimates, parameter uncertainties and computational intensity. Discretization in the frequency domain (as in the discrete cosine transform parameterization) provides more accurate models at a lower computational cost compared to spatially discretized (Cartesian) models. A priori knowledge about the expected geologic structures allows for non-discretized model descriptions with markedly reduced degrees of freedom. Constraining the solutions to the known injected gas volume improved estimates of saturation and parameter values of the petrophysical relationship. (C) 2014 Elsevier B.V. All rights reserved.

Kulmastabiilisuuden mallinnus

Työn tavoitteena oli kartoittaa vaihtoehtoisia menetelmiä perinteiselle aikatasossa tapahtuvalle kulmastabiilisuuden mallinnukselle käyttövarmuustarkastelussa. Vaihtoehtoisiin menetelmiin tutustuttiin kirjallisuuden avulla ja valittiin menetelmä testattavaksi pohjoismaisessa yhteiskäyttöjärjestelmässä. Vaihtoehtoisen menetelmän ominaisuusvaatimuksiin kuului nopeampi laskenta, luotettava stabiilien ja epästabiilien tilanteiden seulontakyky ja menetelmän antama indeksi stabiilisuus-/epästabiilisuusasteesta. Pääasiassa menetelmät, joihin tutustuttiin, arvioivat vain transienttia stabiilisuutta. SIME-menetelmä soveltui myös dynaamisen stabiilisuuden arviointiin. Suomessa voi dynaamisella stabiilisuudella olla tulevaisuudessa merkittävä rooli käyttövarmuustarkasteluissa. SIME-menetelmän toimivuutta testattiin osin yksinkertaistetulla Nordel-verkkomallilla, ja saadut tulokset olivat lupaavia. Menetelmä täytti uudelle menetelmälle asetetut vaatimukset, vaikka ongelmiakin esiintyi. Testauksessa käytetyn menetelmän edelleen kehittäminen ja menetelmän testaaminen täydellisellä verkkomallilla on suositeltavaa.

Exploring Compositional Data with the CoDa-Dendrogram

Within the special geometry of the simplex, the sample space of compositional data, compositional orthonormal coordinates allow the application of any multivariate statistical approach. The search for meaningful coordinates has suggested balances (between two groups of parts)—based on a sequential binary partition of a D-part composition—and a representation in form of a CoDa-dendrogram. Projected samples are represented in a dendrogram-like graph showing: (a) the way of grouping parts; (b) the explanatory role of subcompositions generated in the partition process; (c) the decomposition of the variance; (d) the center and quantiles of each balance. The representation is useful for the interpretation of balances and to describe the sample in a single diagram independently of the number of parts. Also, samples of two or more populations, as well as several samples from the same population, can be represented in the same graph, as long as they have the same parts registered. The approach is illustrated with an example of food consumption in Europe

Llegint Cinema. Anàlisi de la representació de la malaltia mental en el setè art

El present treball és un estudi sobre l'estigma social en la malaltia mental i la representació d'aquest al cinema. Aquesta anàlisi s'ha portat a terme a partir de dues línies de treball. Per una banda amb l'anàlisi interpretativa de dotze pel·lícules utilitzant els indicadors de 'perillositat'; 'incapacitat per a la vida'; 'incurabilitat'; 'pèrdua de rols socials'; 'por al rebuig i/o por a les relacions socials'; i per l'altra banda a partir d'un grup de discussió, en el qual s'han visionat fragments de cinc pel·lícules amb set estudiants del Grau d'Educació Social de la Universitat de Vic. Dels resultats obtinguts es desprèn que la pel·lícula és un mitjà de comunicació mitjançant el qual els estereotips són usats en favor de l'espectacle, estigmatitzant així les persones diagnosticades de malaltia mental. Aquest és un dels motius que fan valorar el cinema com un recurs educatiu a considerar tant en la formació d'educadors i educadores socials com en els projectes d'intervenció socioeducativa.

Investigating the functions of subregions within anterior hippocampus.

Previous functional MRI (fMRI) studies have associated anterior hippocampus with imagining and recalling scenes, imagining the future, recalling autobiographical memories and visual scene perception. We have observed that this typically involves the medial rather than the lateral portion of the anterior hippocampus. Here, we investigated which specific structures of the hippocampus underpin this observation. We had participants imagine novel scenes during fMRI scanning, as well as recall previously learned scenes from two different time periods (one week and 30 min prior to scanning), with analogous single object conditions as baselines. Using an extended segmentation protocol focussing on anterior hippocampus, we first investigated which substructures of the hippocampus respond to scenes, and found both imagination and recall of scenes to be associated with activity in presubiculum/parasubiculum, a region associated with spatial representation in rodents. Next, we compared imagining novel scenes to recall from one week or 30 min before scanning. We expected a strong response to imagining novel scenes and 1-week recall, as both involve constructing scene representations from elements stored across cortex. By contrast, we expected a weaker response to 30-min recall, as representations of these scenes had already been constructed but not yet consolidated. Both imagination and 1-week recall of scenes engaged anterior hippocampal structures (anterior subiculum and uncus respectively), indicating possible roles in scene construction. By contrast, 30-min recall of scenes elicited significantly less activation of anterior hippocampus but did engage posterior CA3. Together, these results elucidate the functions of different parts of the anterior hippocampus, a key brain area about which little is definitely known.