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.

Truncating mutations in the last exon of NOTCH2 cause a rare skeletal disorder with osteoporosis.

Hajdu-Cheney syndrome is a rare autosomal dominant skeletal disorder with facial anomalies, osteoporosis and acro-osteolysis. We sequenced the exomes of six unrelated individuals with this syndrome and identified heterozygous nonsense and frameshift mutations in NOTCH2 in five of them. All mutations cluster to the last coding exon of the gene, suggesting that the mutant mRNA products escape nonsense-mediated decay and that the resulting truncated NOTCH2 proteins act in a gain-of-function manner.

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.

Traduir i interpretar les llengües de la immigració a Catalunya: cap a la formació i acreditació d’un perfil professional emergent

El projecte que sol•licitem és el resultat natural d’una recerca iniciada l’any 2008 pel grup de recerca MIRAS (Mediació i Interpretació: Recerca en l’Àmbit Social) de la Universitat Autònoma de Barcelona. La recerca del grup MIRAS ha tingut com a objectiu general, durant els darrers dos anys, la definició del perfil professional del traductor/intèrpret als serveis públics. Aquesta figura emergent i encara poc reconeguda al nostre país va començar a sorgir a partir del boom migratori de les darreres dècades a Catalunya com a resposta als problemes de comunicació freqüents entre la població nouvinguda i els serveis públics locals. Per a assolir l’objectiu esmentat, la primera fase de la recerca del grup MIRAS s’ha centrat en el disseny, distribució, buidatge, anàlisi i creuament de dades de 250 qüestionaris semioberts dirigits als tres principals agents implicats en la interacció comunicativa que estudiem: els traductors/intèrprets, els usuaris i els proveïdors dels serveis. Els resultats d’aquest estudi han demostrat, entre d’altres qüestions rellevants, la manca d’una formació específica per als traductors/intèrprets als serveis públics, així com una absència de regulació de la professió que aquests exerceixen. Un cop realitzat aquest primer estudi pilot, i en vista dels resultats obtinguts, ens sembla doncs evident que el següent pas de la nostra recerca ha d’anar orientat cap a la formació i regulació professional dels traductors/intèrprets als serveis públics. En concret, en el projecte que sol•licitem ens proposem dissenyar una formació especialitzada per a traductors/intèrprets als serveis públics que compleixi amb els següents tres prerequisits: a) estar oberta a tot tipus de persones, independentment del seu nivell d’estudis; b) oferir un ampli ventall de llengües, principalment les llengües de la immigració a Catalunya (per a una primera selecció d’aquestes llengües, vegeu informe demogràfic de la SIM de l’1 de gener de 2010 i resultats de l’estudi pilot de MIRAS), i c) conduir a una acreditació nacional que reguli l’exercici de la professió de traductor/intèrpret als serveis públics de Catalunya. La implementació d’un sistema d’acreditació, segon objectiu del projecte que presentem, és essencial ja que no només permetrà la regulació d’una professió fins avui poc o mal definida, sinó que també garantirà la qualitat dels serveis oferts per aquests professionals en el futur.

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.

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

Design guide

Investigation of the Modified Beam-in-Slab Bridge System, Design Manual, 2004, Vol. 2

Design Manual

Development of a Mix Design Process for Cold-in-Place Rehabilitation Using Foamed Asphalt, December 2005

Report by Iowa Department of Transportation about pavements materials.

Design and evaluation of a panel os single-nucleotide polymorphisms in microRNA genomic regions for association studies in human disease

MicroRNAs (miRNA) are recognized posttranscriptional gene repressors involved in the control of almost every biological process. Allelic variants in these regions may be an important source of phenotypic diversity and contribute to disease susceptibility. We analyzed the genomic organization of 325 human miRNAs (release 7.1, miRBase) to construct a panel of 768 single-nucleotide polymorphisms (SNPs) covering approximately 1 Mb of genomic DNA, including 131 isolated miRNAs (40%) and 194 miRNAs arranged in 48 miRNA clusters, as well as their 5-kb flanking regions. Of these miRNAs, 37% were inside known protein-coding genes, which were significantly associated with biological functions regarding neurological, psychological or nutritional disorders. SNP coverage analysis revealed a lower SNP density in miRNAs compared with the average of the genome, with only 24 SNPs located in the 325 miRNAs studied. Further genotyping of 340 unrelated Spanish individuals showed that more than half of the SNPs in miRNAs were either rare or monomorphic, in agreement with the reported selective constraint on human miRNAs. A comparison of the minor allele frequencies between Spanish and HapMap population samples confirmed the applicability of this SNP panel to the study of complex disorders among the Spanish population, and revealed two miRNA regions, hsa-mir-26a-2 in the CTDSP2 gene and hsa-mir-128-1 in the R3HDM1 gene, showing geographical allelic frequency variation among the four HapMap populations, probably because of differences in natural selection. The designed miRNA SNP panel could help to identify still hidden links between miRNAs and human disease.

A context-based methodology for integrating Web 2.0 services in learning scenarios

The emergence of the Web 2.0 technologies in the last years havechanged the way people interact with knowledge. Services for cooperation andcollaboration have placed the user in the centre of a new knowledge buildingspace. The development of new second generation learning environments canbenefit from the potential of these Web 2.0 services when applied to aneducational context. We propose a methodology for designing learningenvironments that relates Web 2.0 services with the functional requirements ofthese environments. In particular, we concentrate on the design of the KRSMsystem to discuss the components of this methodology and its application.

Collage, a Collaborative Learning Design Editor Based on Patterns

This paper introduces Collage, a high-level IMS-LD compliant authoring tool that is specialized for CSCL (Computer-Supported Collaborative Learning). Nowadays CSCL is a key trend in elearning since it highlights the importance of social interactions as an essential element of learning. CSCL is an interdisciplinary domain, which demands participatory design techniques that allow teachers to get directly involved in design activities. Developing CSCL designs using LD is a difficult task for teachers since LD is a complex technical specification and modelling collaborative characteristics can be tricky. Collage helps teachers in the process of creating their own potentially effective collaborative Learning Designs by reusing and customizing patterns, according to the requirements of a particular learning situation. These patterns, called Collaborative Learning Flow Patterns (CLFPs), represent best practices that are repetitively used by practitioners when structuring the flow of (collaborative) learning activities. An example of an LD that can be created using Collage is illustrated in the paper. Preliminary evaluation results show that teachers, with experience in CL but without LD knowledge, can successfully design real collaborative learning experiences using Collage.