A Tool for optimum design of Waste Water Treatment Plants under uncertainty

L’objectiu principal és presentar un nou prototipus d’eina per al disseny de les plantes de tractament d’aigües residuals utilitzant models mecànics dinàmics quantificant la incertesa

RTM mould design and construction for a DN 50 PN 16 flansch

The objective of this project consists of designing and constructing a RTM mould for a loose flange of glass fibre reinforced plastic (GRP). The design phase has the mission to realise a quality and simple design of the RTM mould, with the objective to obtain an easy and economic phase of construction and the more possible great characteristics of the loose flange. In fact this RTM mould will be a mould prototype, which will be developed in the future to obtain an RTM mould able to support a loose flange production. Therefore when more steps are developed in this project, then the future objective will be near

SwissBioisostere: a database of molecular replacements for ligand design.

The SwissBioisostere database (http://www.swissbioisostere.ch) contains information on molecular replacements and their performance in biochemical assays. It is meant to provide researchers in drug discovery projects with ideas for bioisosteric modifications of their current lead molecule, as well as to give interested scientists access to the details on particular molecular replacements. As of August 2012, the database contains 21 293 355 datapoints corresponding to 5 586 462 unique replacements that have been measured in 35 039 assays against 1948 molecular targets representing 30 target classes. The accessible data were created through detection of matched molecular pairs and mining bioactivity data in the ChEMBL database. The SwissBioisostere database is hosted by the Swiss Institute of Bioinformatics and available via a web-based interface.

Analysis and Design of a secure WLAN solution for Cobre Las Cruces

Cobre Las Cruces is a renowned copper mining company located in Sevilla, with unexpected problems in wireless communications that have a direct affectation in production. Therefore, the main goals are to improve the WiFi infrastructure, to secure it and to detect and prevent from attacks and from the installation of rogue (and non-authorized) APs. All of that integrated with the current ICT infrastructure.This project has been divided into four phases, although only two of them have been included into the TFC; they are the analysis of the current situation and the design of a WLAN solution.Once the analysis part was finished, some weaknesses were detected. Subjects such as lack of connectivity and control, ignorance about installed WiFi devices and their localization and state and, by and large, the use of weak security mechanisms were some of the problems found. Additionally, due to the fact that the working area became larger and new WiFi infrastructures were added, the first phase took more time than expected.As a result of the detailed analysis, some goals were defined to solve and it was designed a centralized approach able to cope with them. A solution based on 802.11i and 802.1x protocols, digital certificates, a probe system running as IDS/IPS and ligthweight APs in conjunction with a Wireless LAN Controller are the main features.

Design of potent inhibitors of human RAD51 recombinase based on BRC motifs of BRCA2 protein: modeling and experimental validation of a chimera peptide.

We have previously shown that a 28-amino acid peptide derived from the BRC4 motif of BRCA2 tumor suppressor inhibits selectively human RAD51 recombinase (HsRad51). With the aim of designing better inhibitors for cancer treatment, we combined an in silico docking approach with in vitro biochemical testing to construct a highly efficient chimera peptide from eight existing human BRC motifs. We built a molecular model of all BRC motifs complexed with HsRad51 based on the crystal structure of the BRC4 motif-HsRad51 complex, computed the interaction energy of each residue in each BRC motif, and selected the best amino acid residue at each binding position. This analysis enabled us to propose four amino acid substitutions in the BRC4 motif. Three of these increased the inhibitory effect in vitro, and this effect was found to be additive. We thus obtained a peptide that is about 10 times more efficient in inhibiting HsRad51-ssDNA complex formation than the original peptide.

Ionotropic and metabotropic mechanisms in chemoreception: 'chance or design'?

Chemosensory receptors convert an enormous diversity of chemical signals from the external world into a common language of electrical activity in the brain. Mammals and insects use several families of transmembrane receptor proteins to recognize distinct classes of volatile and non-volatile chemicals that are produced by conspecifics or other environmental sources. A comparison of the signalling mechanisms of mammalian and insect receptors has revealed an unexpected functional distinction: mammals rely almost exclusively on metabotropic ligand-binding receptors, which use second messenger signalling cascades to indirectly activate ion channels, whereas insects use ionotropic receptors, which are gated directly by chemical stimuli, thereby leading to neuronal depolarization. In this review, we consider possible reasons for this dichotomy, taking into account biophysical, cell biological, ecological and evolutionary influences on how information is extracted from chemosensory cues by these animal classes.

Public health value of fixed-dose combinations in hypertension.

It is well documented that reducing blood pressure (BP) in hypertensive individuals reduces the risk of cardiovascular (CV) events. Despite this, many patients with hypertension remain untreated or inadequately treated, and fail to reach the recommended BP goals. Suboptimal BP control, whilst arising from multiple causes, is often due to poor patient compliance and/or persistence, and results in a significant health and economic burden on society. The use of fixed-dose combinations (FDCs) for the treatment of hypertension has the potential to increase patient compliance and persistence. When compared with antihypertensive monotherapies, FDCs may also offer equivalent or better efficacy, and the same or improved tolerability. As a result, FDCs have the potential to reduce both the CV event rates and the non-drug healthcare costs associated with hypertension. When FDCs are adopted for the treatment of hypertension, issues relating to copayment, formulary restrictions and therapeutic reference pricing must be addressed.

'Se dire similaire et différent': la (re)présentation de soi et la négociation discursive des références identitaires des ressortissants ex-yougoslaves musulmans au Luxembourg

Cette thèse, qui se base sur des entretiens qualitatifs, porte sur la négociation des références identitaires de musulmans immigrés et réfugiés en provenance de Γ ex-Yougoslavie au Luxembourg et s'intéresse à la pertinence changeante de la religion dans la conception de soi. Selon une approche constructiviste et interactionniste, l'identité est conçue comme un projet constamment négocié, reconstruit dans des processus d'interaction sociale et en fonction des contextes sociaux. Nos données suggèrent l'émergence de constructions identitaires complexes et attestent de la pluridimensionalité et de l'intersectionnalité des références identitaires utilisées dans la conception de soi et témoignent de la non-réduction des individus à des catégories fixes. Différentes catégories sont rendues significatives et de multiples frontières sont établies afin de se différencier de figures d'altérité changeantes, sélectivement choisies pour construire une certaine image de soi. Les discours identitaires témoignent de l'aspiration à une identité positive, dans une situation caractérisée par la perte du statut social et des stigmatisations multiples, en tant que ex-Yougoslaves, demandeurs d'asile et musulmans. Nos interlocuteurs établissent un répertoire identitaire composé de marqueurs transposés, inventés et revalorisés, leur permettant de reconstruire une identité positive pour soi et leurs audiences. Ce travail décrit les manières dont les individus établissent leur répertoire identitaire à l'aide de marqueurs transposés, inventés et revalorisés, leur permettant de reconstruire une identité positive pour soi et leurs audiences et montre comment les processus de différenciation de 'l'autre' dans le pays d'origine et d'accueil sont reliés. - The question addressed in this project with a qualitative design, is how muslim migrants and refugees from the former Socialist Federal Republic of Yugoslavia in Luxemburg negotiate salient identity references in a new social political environment and discusses the changing significance of religion and the way it is integrated in the identity patchwork. According to a constructivist and interactionist approach, conceiving identity as a constantly negotiated project, reconstructed in interaction and with regard to social context, identities are relevant only in relation to particular other groups and in certain situations of interaction. Our data suggest the emergence of complex identity patterns using multiple references for self- description and attest of the intersectionnality of identity references and show that individuals can't be reduced to fixed categories. Different categories are made salient and multiple symbolic boundaries are established in order to differentiate from different "others", selected in order to construct a certain self-concept. The discourses of our participants attest of an aspiration towards a positive identity in a situation characterized by the loss of social status and multiple stigmata. This thesis describes the ways how individuals establish their identity repertoire with invented, transposed and negotiated identity references, that allow them to construct a favourable identity for themselves and their public and shows how différenciation processes in home and host country are related.

Ambulatory monitoring of physical activities in patients with Parkinson's disease.

A new ambulatory method of monitoring physical activities in Parkinson's disease (PD) patients is proposed based on a portable data-logger with three body-fixed inertial sensors. A group of ten PD patients treated with subthalamic nucleus deep brain stimulation (STN-DBS) and ten normal control subjects followed a protocol of typical daily activities and the whole period of the measurement was recorded by video. Walking periods were recognized using two sensors on shanks and lying periods were detected using a sensor on trunk. By calculating kinematics features of the trunk movements during the transitions between sitting and standing postures and using a statistical classifier, sit-to-stand (SiSt) and stand-to-sit (StSi) transitions were detected and separated from other body movements. Finally, a fuzzy classifier used this information to detect periods of sitting and standing. The proposed method showed a high sensitivity and specificity for the detection of basic body postures allocations: sitting, standing, lying, and walking periods, both in PD patients and healthy subjects. We found significant differences in parameters related to SiSt and StSi transitions between PD patients and controls and also between PD patients with and without STN-DBS turned on. We concluded that our method provides a simple, accurate, and effective means to objectively quantify physical activities in both normal and PD patients and may prove useful to assess the level of motor functions in the latter.

What is the relationship between fear of falling and gait in well-functioning older persons aged 65 to 70 years?

OBJECTIVE: To investigate the association between fear of falling and gait performance in well-functioning older persons. DESIGN: Survey. SETTING: Community. PARTICIPANTS: Subjects (N=860, aged 65-70y) were a subsample of participants enrolled in a cohort study who underwent gait measurements. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Fear of falling and its severity were assessed by 2 questions about fear and related activity restriction. Gait performance, including gait variability, was measured using body-fixed sensors. RESULTS: Overall, 29.6% (210/860) of the participants reported fear of falling, with 5.2% (45/860) reporting activity restriction. Fear of falling was associated with reduced gait performance, including increased gait variability. A gradient in gait performance was observed from participants without fear to those reporting fear without activity restriction and those reporting both fear and activity restriction. For instance, stride velocity decreased from 1.15+/-.15 to 1.11+/-.17 to 1.00+/-.19 m/s (P<.001) in participants without fear, with fear but no activity restriction and with fear and activity restriction, respectively. In multivariate analysis, fear of falling with activity restriction remained associated with reduced gait performance, independent of sex, comorbidity, functional status, falls history, and depressive symptoms. CONCLUSIONS: In these well-functioning older people, those reporting fear of falling with activity restriction had reduced gait performance and increased gait variability, independent of health and functional status. These relationships suggest that early interventions targeting fear of falling might potentially help to prevent its adverse consequences on mobility and function in similar populations.

The interior designer : Can the physiological agents of homeostasis create the appearance of design in nature?

Review of the book: The Tinkerer's Accomplice: How Design Emerges From Life Itself by J. Scott TurnerHarvard University Press: 2007. 304 pp.

Mobile or fixed bearing for total knee arthroplasty? Ambulatory gait analysis results

Background: Mobile-bearing knee replacements have some theoretical advantages over fixed-bearing devices. However, very few randomized controlled clinical trials have been published to date, and studies showed little clinical and subjective advantages for the mobile-bearing using traditional systems of scoring. The choice of the ideal outcome measure to assess total joint replacement remains a complex issue. However, gait analysis provides objective and quantifying evidences of treatment evaluation. Significant methodological advances are currently made in gait analysis laboratories and ambulatory gait devices are now available. The goal of this study was to provide gait parameters as a new objective method to assess total knee arthroplasty outcome between patients with fixed- and mobile-bearing, using an ambulatory device with minimal sensor configuration. This randomized controlled double-blind study included to date 14 patients: the gait signatures of four patients with mobile-bearing were compared to the gait signatures of nine patients with fixed-bearing pre-operatively and post-operatively at 6 weeks, 3 months and 6 months. Each participant was asked to perform two walking trials of 30m long at his/her preferred speed and to complete a EQ-5D questionnaire, a WOMAC and Knee Society Score (KSS). Lower limbs rotations were measured by four miniature angular rate sensors mounted respectively, on each shank and thigh. A new method for a portable system for gait analysis has been developed with very encouraging results regarding the objective outcome of total knee arthroplasty using mobile- and fixed-bearings.

Malaria vaccine candidate: design of a multivalent subunit α-helical coiled coil poly-epitope.

A new strategy for the rapid identification of new malaria antigens based on protein structural motifs was previously described. We identified and evaluated the malaria vaccine potential of fragments of several malaria antigens containing α-helical coiled coil protein motifs. By taking advantage of the relatively short size of these structural fragments, we constructed different poly-epitopes in which 3 or 4 of these segments were joined together via a non-immunogenic linker. Only peptides that are targets of human antibodies with anti-parasite in vitro biological activities were incorporated. One of the constructs, P181, was well recognized by sera and peripheral blood mononuclear cells (PBMC) of adults living in malaria-endemic areas. Affinity purified antigen-specific human antibodies and sera from P181-immunized mice recognised native proteins on malaria-infected erythrocytes in both immunofluorescence and western blot assays. In addition, specific antibodies inhibited parasite development in an antibody dependent cellular inhibition (ADCI) assay. Naturally induced antigen-specific human antibodies were at high titers and associated with clinical protection from malaria in longitudinal follow-up studies in Senegal.

Exploring unfrequent events with accelerated molecular dynamics simulations: from photochemistry to drug design

La meva incorporació al grup de recerca del Prof. McCammon (University of California San Diego) en qualitat d’investigador post doctoral amb una beca Beatriu de Pinós, va tenir lloc el passat 1 de desembre de 2010; on vaig dur a terme les meves tasques de recerca fins al darrer 1 d’abril de 2012. El Prof. McCammon és un referent mundial en l’aplicació de simulacions de dinàmica molecular (MD) en sistemes biològics d’interès humà. La contribució més important del Prof. McCammon en la simulació de sistemes biològics és el desenvolupament del mètode de dinàmiques moleculars accelerades (AMD). Les simulacions MD convencionals, les quals estan limitades a l’escala de temps del nanosegon (~10-9s), no son adients per l’estudi de sistemes biològics rellevants a escales de temps mes llargues (μs, ms...). AMD permet explorar fenòmens moleculars poc freqüents però que son clau per l’enteniment de molts sistemes biològics; fenòmens que no podrien ser observats d’un altre manera. Durant la meva estada a la “University of California San Diego”, vaig treballar en diferent aplicacions de les simulacions AMD, incloent fotoquímica i disseny de fàrmacs per ordinador. Concretament, primer vaig desenvolupar amb èxit una combinació dels mètodes AMD i simulacions Car-Parrinello per millorar l’exploració de camins de desactivació (interseccions còniques) en reaccions químiques fotoactivades. En segon lloc, vaig aplicar tècniques estadístiques (Replica Exchange) amb AMD en la descripció d’interaccions proteïna-lligand. Finalment, vaig dur a terme un estudi de disseny de fàrmacs per ordinador en la proteïna-G Rho (involucrada en el desenvolupament de càncer humà) combinant anàlisis estructurals i simulacions AMD. Els projectes en els quals he participat han estat publicats (o estan encara en procés de revisió) en diferents revistes científiques, i han estat presentats en diferents congressos internacionals. La memòria inclosa a continuació conté més detalls de cada projecte esmentat.

Investigation of the Modified Beam-in-Slab Bridge System, Design Guide, 2004, Vol. 3

Design guide