Funcionalització regioselectiva d'una cetona amb metal·lacarborans polianiònics

L’ús de metal·lacarborans en la síntesi de compostos polianiònics amb un alt contingut en bor i amb bons rendiments és un tema d’alt interès i estudi al grup de Síntesi Inorgànica i Catàlisi de l’ICMAB. Els metal·lacarborans presenten diverses aplicacions innovadores com la BNCT (Boron Neutron Capture Therapy),1 tractament d’aigües residuals,2 activitats catalítiques3 i com a agents dopants de membranes polimèriques conductores.4 Amb la perspectiva d’emprar clústers de bor per materials moleculars funcionalitzats, hem iniciat una investigació que busca la síntesi de productes híbrids amb múltiples elements electroactius (metal·lacarborans) i el grup funcional carbonil, que gràcies a la seva reactivitat coneguda ens permetrà aplicar les molècules sintetitzades a futures reaccions i aplicacions. Una de les condicions inicials plantejades en aquesta investigació és l’ús de productes químics assequibles i de gran disponibilitat, per tal de poder assegurar l’obtenció de precursors per a futures aplicacions amb bons rendiments i ràpids de sintetitzar. Per assolir aquest objectiu es van iniciar les investigacions amb la cetona més simple coneguda, l’acetona (CH3-CO-CH3) (pKa = 19.3) com a producte de partida. A partir de la reacció d’aquesta amb una base forta no nucleòfila es genera CH3-COCH2 (-). Si s’aconsegueix prevenir o minimitzar la reacció d’addició aldòlica, l’anió CH3- CO-CH2 (-) pot atacar nucleofílicament al carboni contigu al catió oxoni5 de la molècula de cobaltabisdicarballur dioxanat (cosà dioxanat), [3,3’-Co(8-(OCH2CH2)2-1,2- C2B9H10)(1’,2’-C2B9H11)], generant un derivat del cosà dioxanat que conté un grup carbonil. Aquest procediment pot ser repetit per introduir diverses unitats de metal·lacarborans (cosà, fesà, etc.), tot i que aquest procés presenta una gran dispersió de subproductes, fet que fa baixar el rendiment global i li resta interès. Un procediment molt més efectiu i que dóna un control de la regioselectivitat molt major dels centres electroactius incorporats és la síntesi acetoacètica (pKa H intercarbonílic = 10.7). Múltiples molècules homo i hetero polianiòniques amb metal·lacarborans han estat sintetitzades amb èxit en aquest treball, amb un control regioselectiu molt precís mitjançant aquest mètode sintètic, i caracteritzades per mètodes electroquímics.

Käyttäjäystävällisen mobiilipalvelun suunnittelu : WAP-sivuston rakentaminen visuaalisen ja käyttöliittymäsuunnittelun keinoin

Opinnäytteeni käsittelee mobiilipalveluiden sekä visuaalista että käyttöliittymäsuunnittelua. Lähden liikkeelle siitä olettamuksesta, että näiden osa-alueiden suunnitteluun kannattaa panostaa. Totean myös, että näin ei kuitenkaan vielä nykyään tehdä. Käsittelen mobiilipalveluja yleisemmällä tasolla, mutta keskityn erityisesti WAP-pohjaisiin palveluihin. Samat periaatteet ja vinkit soveltuvat kuitenkin myös muilla alustoilla toimivien palveluiden suunnitteluun, ja koska minulla on kokemusta myös näistä, olen tuonut tätäkin puolta esiin. Työssäni puhutaan visuaalisesta suunnittelusta ja käytettävyydestä yleisellä tasolla, mutta se toimii samalla eräänlaisena ohjekirjana suunnittelijalle. Uskon, että vielä toistaiseksi yritykset siirtyvät WAPiin pitkälti samalla sisällöllä ja rakenteella kuin web-palvelussaan, ja esittelen työssäni syitä sille, miksi tämä menetelmä on huono. Työhöni kokoamani pikamanuaali kokoaa tärkeimmät käytännön vinkit, joiden avulla voidaan tarvittaessa nopeallakin aikataululla suunnitella käyttäjäystävällinen WAP-palvelu. Kiinnostus aiheeseen nousi omista kokemuksistani työelämässä, ja kirjatiedon lisäksi tärkeänä lähteenä on toiminut oma kokemusmaailmani ja yrityksen ja erehdyksen kautta opitut taidot. Uskon että myös nämä tuovat hyvän lisän oppaaseen. Käsittelen ensin matkaviestinalan yleistä kehitystä ja esittelen syitä sille, miksi mobiilipalveluiden suunnitteluun kannattaa panostaa. Käyn sitten läpi sellaisia mobiililaitteiden erityisominaisuuksia, jotka asettavat työlle omat rajoituksensa. Lopuksi listaan tärkeimmät huomioitavat seikat ja annan käytännön vinkkejä suunnitteluprosessiin.

Species- and nestmate brood discrimination in the sibling wood ant species Formica paralugubris and Formica lugubris

Formica lugubris and E paralugubris are sympatric sibling species of wood ants, both of which are widely distributed in Switzerland. Until 1996 they were considered the same species, E lugubris. To investigate whether the two species can be distinguished based on discrimination cues used by the workers we used the pupa-carrying test first introduced by Rainer Rosengren. In this test workers of discriminator colonies are faced with two kinds of pupae and their preferences for one of the types are recorded based on differential retrieval. Interspecific comparisons showed that ants preferred conspecific worker pupae to those of the sibling species regardless whether the pupae were con-colonial or hetero-colonial. Hence, this test can be used as a taxonomic tool to identify wood ants hardly distinguishable by morphological characters. In intraspecific comparisons the highly polygynous (many queens per colony) E paralugubris, the polygynous form of E lugubris and the monogynous (single queen per nest) to weakly polygynous form of E lugubris expressed different trends in their preference behaviour (with nestmate recognition in 14%, 20% and 31% of replicates, respectively). Only F paralugubris presented no significant nestmate recognition.

Proteinaceous infectious behavior in non-pathogenic proteins is controlled by molecular chaperones.

External stresses or mutations may cause labile proteins to lose their distinct native conformations and seek alternatively stable aggregated forms. Molecular chaperones that specifically act on protein aggregates were used here as a tool to address the biochemical nature of stable homo- and hetero-aggregates from non-pathogenic proteins formed by heat-stress. Confirmed by sedimentation and activity measurements, chaperones demonstrated that a single polypeptide chain can form different species of aggregates, depending on the denaturing conditions. Indicative of a cascade reaction, sub-stoichiometric amounts of one fast-aggregating protein strongly accelerated the conversion of another soluble, slow-aggregating protein into insoluble, chaperone-resistant aggregates. Chaperones strongly inhibited seed-induced protein aggregation, suggesting that they can prevent and cure proteinaceous infectious behavior in homo- and hetero-aggregates from common and disease-associated proteins in the cell.

Engineering polyhydroxyalkanoate content and monomer composition in the oleaginous yeast Yarrowia lipolytica by modifying the ß-oxidation multifunctional protein.

Recombinant strains of the oleaginous yeast Yarrowia lipolytica expressing the PHA synthase gene (PhaC) from Pseudomonas aeruginosa in the peroxisome were found able to produce polyhydroxyalkanoates (PHA). PHA production yield, but not the monomer composition, was dependent on POX genotype (POX genes encoding acyl-CoA oxidases) (Haddouche et al. FEMS Yeast Res 10:917-927, 2010). In this study of variants of the Y. lipolytica β-oxidation multifunctional enzyme, with deletions or inactivations of the R-3-hydroxyacyl-CoA dehydrogenase domain, we were able to produce hetero-polymers (functional MFE enzyme) or homo-polymers (with no 3-hydroxyacyl-CoA dehydrogenase activity) of PHA consisting principally of 3-hydroxyacid monomers (>80%) of the same length as the external fatty acid used for growth. The redirection of fatty acid flux towards β-oxidation, by deletion of the neutral lipid synthesis pathway (mutant strain Q4 devoid of the acyltransferases encoded by the LRO1, DGA1, DGA2 and ARE1 genes), in combination with variant expressing only the enoyl-CoA hydratase 2 domain, led to a significant increase in PHA levels, to 7.3% of cell dry weight. Finally, the presence of shorter monomers (up to 20% of the monomers) in a mutant strain lacking the peroxisomal 3-hydroxyacyl-CoA dehydrogenase domain provided evidence for the occurrence of partial mitochondrial β-oxidation in Y. lipolytica.

Tribos Urbanas da Praia: os casos dos thugs e dos rappers

Às ondas preocupantes da violência urbana com que a cidade da Praia deparou-se na última década do século passado, culpabilizou-se uma nova figura social emergente – os thugs. A eles estão associados os grupos de gangsta rap, surgidos na Praia no início os anos de 2000, subgénero musical do rap que tem funcionado como veículo por onde as reivindicações são transmitidas ao poder instituído e por onde se vangloria a vida desviante e/ou delinquente de alguns jovens resistentes nos bairros periféricos e semi-periféricos da capital, bairros esses auto-denominados de guetos. Neste artigo pretende-se analisar a relação existente entre o fenómeno thug e o gangsta rap, considerados como manifestações de descontentamento social, reivindicação político-social e demarcação identitária através da violência e da música, e apresentar uma breve reflexão sobre duas pesquisas etnográficas sobre as sociabilidades e estilos de vida juvenis na cidade da Praia, em Cabo Verde. Uma, teórica e empiricamente mais madura, iniciada em 2006, no seio de grupos de jovens associados a comportamentos delinquentes, auto e hetero-denominados thugs e, outra, em curso, no seio dos rappers, mais concretamente dos gangsta rappers.

Analysis of patient physical restraints usage in a Swiss emergency service

Introduction: Emergency services (ES) are often faced with agitated,confused or aggressive patients. Such situations may require physicalrestraint. The prevalence of these measures is poorly documented,concerning 1 to 10% of patients admitted in the ES. The indications forrestraint, the context and the related complications are poorly studied.The emergency service and the security service of our hospital havedocumented physical restraint for several years, using specific protocolsintegrated into the medical records. The study evaluated the magnitudeof the problem, the patient characteristics, and degree of adherence tothe restraint protocol.Methods: Retrospective study of physical restraint used on adultpatients in the ES in 2009. The study included analysis of medical anddemographic characteristics, indications justifying restraint and qualityof restraint documentation. Patients were identified from computerizedES and security service records. The data were supplemented byexamination of patients' medical records.Results: In 2009, according to the security service, 390 patients (1%)were physically restrained in the ES. The ES computerized systemidentified only 196 patients. Most patients were male (62%). The medianage was 40 years (15-98 years; P90 = 80 years). 63 % of the situationsoccurred between 18h00 and 6h00, and most frequently on Saturday(19%). Substance or alcohol abuse was present in 48.7% of cases andacute psychiatric crisis was mentioned in 16.7%. In most cases,restraint was motivated by extreme agitation or auto / hetero-aggressiveviolence. Most patients (68 %) were restrained with upper limb andabdominal restraints. More than three anatomic restraints werenecessary in 52 % of the patients. Intervention of security guards wasrequired in 77% of the cases. 61 restraint protocols (31 %) were missingand 57% of the records were incomplete. In many cases, the protocolsdid not include the signature of the physician (22%) or of the nurse(43.8%). Medical records analysis did not allow reliable estimation ofthe number of restraint-induced complications.Conclusions: Physical restraint is most often motivated by majoragitation and/or secondary to substance abuse. Caregivers regularlycall security guards for help. Restraint documentation is often missing orincomplete, requiring major improvement in education and prescription.

Caveolin-1 interacts with the chaperone complex TCP-1 and modulates its protein folding activity.

We report that caveolin-1, one of the major structural protein of caveolae, interacts with TCP-1, a hetero-oligomeric chaperone complex present in all eukaryotic cells that contributes mainly to the folding of actin and tubulin. The caveolin-TCP-1 interaction entails the first 32 amino acids of the N-terminal segment of caveolin. Our data show that caveolin-1 expression is needed for the induction of TCP-1 actin folding function in response to insulin stimulation. Caveolin-1 phosphorylation at tyrosine residue 14 induces the dissociation of caveolin-1 from TCP-1 and activates actin folding. We show that the mechanism by which caveolin-1 modulates TCP-1 activity is indirect and involves the cytoskeleton linker filamin. Filamin is known to bind caveolin-1 and to function as a negative regulator of insulin-mediated signaling. Our data support the notion that the caveolin-filamin interaction contributes to restore insulin-mediated phosphorylation of caveolin, thus allowing the release of active TCP-1.

Pain assessment in PICU and NICU: Have we got it right?

Pain assessment in critically ill infants and nonverbal children remains a challenge for health professionals. Despite the numerous pain observational measures that have been developed or adapted for infants and children with impaired communication, pain prevalence in paediatric and neonatal intensive care unit remains too high. As pain assessment has been recognised as a pre-requisite for appropriate pain management, much effort was put in the validation or the adaptation of pain measures with little emphasis on implementation of these instruments into practice. Only a few studies demonstrated the benefit of using standardised protocols for the management of pain to guide practice with variable effects. When standardised protocols are undeniably useful in practice, they do not replace health professionals' clinical reasoning necessary to care for individuals. The diversity of the PICU population makes that pain scores need to be interpreted within its clinical context. This session will present pain assessment as a complex transaction that describes structured clinical reasoning from expert nurses that goes beyond the "silver" standard of hetero-evaluation of pain in non-communicative children. Besides pain scores, several patients and nurses factors play a major role in making decisions about analgesia and/or sedation. Patient's clinical instability, change in patient's clinical status, source for observed agitated behaviour, patient's known reactions to analgesia and sedation and anticipation of risks are factors that should be taken into account when implementing pain assessment and management guidelines in PICU and NICU.

Analysis of patient physical restraints usage in a Swiss emergency service

Introduction: Emergency services (ES) are often faced with agitated,confused or aggressive patients. Such situations may require physicalrestraint. The prevalence of these measures is poorly documented,concerning 1 to 10% of patients admitted in the ES. The indications forrestraint, the context and the related complications are poorly studied.The emergency service and the security service of our hospital havedocumented physical restraint for several years, using specific protocolsintegrated into the medical records. The study evaluated the magnitudeof the problem, the patient characteristics, and degree of adherence tothe restraint protocol.Methods: Retrospective study of physical restraint used on adultpatients in the ES in 2009. The study included analysis of medical anddemographic characteristics, indications justifying restraint and qualityof restraint documentation. Patients were identified from computerizedES and security service records. The data were supplemented byexamination of patients' medical records.Results: In 2009, according to the security service, 390 patients (1%)were physically restrained in the ES. The ES computerized systemidentified only 196 patients. Most patients were male (62%). The medianage was 40 years (15-98 years; P90 = 80 years). 63 % of the situationsoccurred between 18h00 and 6h00, and most frequently on Saturday(19%). Substance or alcohol abuse was present in 48.7% of cases andacute psychiatric crisis was mentioned in 16.7%. In most cases,restraint was motivated by extreme agitation or auto / hetero-aggressiveviolence. Most patients (68 %) were restrained with upper limb andabdominal restraints. More than three anatomic restraints werenecessary in 52 % of the patients. Intervention of security guards wasrequired in 77% of the cases. 61 restraint protocols (31 %) were missingand 57% of the records were incomplete. In many cases, the protocolsdid not include the signature of the physician (22%) or of the nurse(43.8%). Medical records analysis did not allow reliable estimation ofthe number of restraint-induced complications.Conclusions: Physical restraint is most often motivated by majoragitation and/or secondary to substance abuse. Caregivers regularlycall security guards for help. Restraint documentation is often missing orincomplete, requiring major improvement in education and prescription.

Characterization of HbpR binding by site-directed mutagenesis of its DNA-binding site and by deletion of the effector domain.

In the presence of 2-hydroxybiphenyl, the enhancer binding protein, HbpR, activates the sigma54-dependent P(hbpC) promoter and controls the initial steps of 2-hydroxybiphenyl degradation in Pseudomonas azelaica. In the activation process, an oligomeric HbpR complex of unknown subunit composition binds to an operator region containing two imperfect palindromic sequences. Here, the HbpR-DNA binding interactions were investigated by site-directed mutagenesis of the operator region and by DNA-binding assays using purified HbpR. Mutations that disrupted the twofold symmetry in the palindromes did not affect the binding affinity of HbpR, but various mutations along a 60 bp region, and also outside the direct palindromic sequences, decreased the binding affinity. Footprints of HbpR on mutant operator fragments showed that a partial loss of binding contacts occurs, suggesting that the binding of one HbpR 'protomer' in the oligomeric complex is impaired whilst leaving the other contacts intact. An HbpR variant, devoid of its N-terminal sensing A-domain, was unable to activate transcription from the hbpC promoter while maintaining protection of the operator DNA in footprints. Wild-type HbpR was unable to activate transcription from the hbpC promoter when delta A-HbpR was expressed in the same cell, suggesting the formation of (repressing) hetero-oligomers. This model implies that HbpR can self-associate on its operator DNA without effector recognition or ATP binding. Furthermore, our findings suggest that the N-terminal sensing domain of HbpR is needed to activate the central ATPase domain rather than to repress a constitutively active C domain, as is the case for the related regulatory protein XylR.

La Ansiedad como estigma: el estereotipo de la persona ansiosa en la población clínica, sanitaria y general

El objetivo principal de esta investigación fue la evaluación de la teoría implícita o estereotipo que diferentes grupos de población tienen de las personas con ansiedad clínica. Para ello se administró un listado de adjetivos para la heteroevaluación de la persona ansiosa a un total de 400 participantes, distribuidos en cuatro grupos: pacientes con trastorno de ansiedad, población general, médicos y diplomados en enfermería. A los pacientes ansiosos se les volvió a administrar el listado de adjetivos para su autoevaluación. Se llevó a cabo un estudio descriptivo mediante la prueba de χ2 para determinar las diferencias entre grupos en relación a los adjetivos más utilizados. Seguidamente se realizaron dos ANOVAs para establecer diferencias entre grupos a partir de la hetero-evaluación y para comprobar si había diferencias entre la heteroevaluación y la autoevaluación de las personas con trastornos de ansiedad. Los resultados muestran diferencias en la percepción de las personas ansiosas por parte de los 4 grupos; pero solo en el grupo general se detectan creencias prejuiciosas en el estereotipo que muestran de las personas ansiosas. Dichos hallazgos ponen de manifiesto las diferencias en los estereotipos de cada población referentes a las personas con ansiedad clínica

Stoichiometry of Heteromeric BAFF and APRIL Cytokines Dictates Their Receptor Binding and Signaling Properties.

The closely related TNF family ligands B cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL) serve in the generation and maintenance of mature B-lymphocytes. Both BAFF and APRIL assemble as homotrimers that bind and activate several receptors that they partially share. However, heteromers of BAFF and APRIL that occur in patients with autoimmune diseases are incompletely characterized. The N and C termini of adjacent BAFF or APRIL monomers are spatially close and can be linked to create single-chain homo- or hetero-ligands of defined stoichiometry. Similar to APRIL, heteromers consisting of one BAFF and two APRILs (BAA) bind to the receptors B cell maturation antigen (BCMA), transmembrane activator and CAML interactor (TACI) but not to the BAFF receptor (BAFFR). Heteromers consisting of one APRIL and two BAFF (ABB) bind to TACI and BCMA and weakly to BAFFR in accordance with the analysis of the receptor interaction sites in the crystallographic structure of ABB. Receptor binding correlated with activity in reporter cell line assays specific for BAFFR, TACI, or BCMA. Single-chain BAFF (BBB) and to a lesser extent single-chain ABB, but not APRIL or single-chain BAA, rescued BAFFR-dependent B cell maturation in BAFF-deficient mice. In conclusion, BAFF-APRIL heteromers of different stoichiometries have distinct receptor-binding properties and activities. Based on the observation that heteromers are less active than BAFF, we speculate that their physiological role might be to down-regulate BAFF activity.

Käytäntöyhteisöt ja asiantuntijaorganisaation oppiminen

Työssä lähdetään olettamuksesta, että organisaation oppiminen on keskeinen menestystekijä ja organisaation elinehtona on pystyä vastaamaan muutoksen tuomiin haasteisiin. Muutokseen vastaaminen puolestaan tarkoittaa sitä, että organisaatio oppii tekemään asioita toisin. Työssä on haettu vastausta sille kuinka käytäntöyhteisöillä voidaan tukea asiantuntijaorganisaation oppimista eräässä IT-alan organisaatiossa. Tuloksena syntynyttä mallia ja organisaation oppimisen käsitteitä tarkastelemalla osoitetaan, että käytäntöyhteisöillä pystytään edistämään asiantuntijaorganisaation oppimista tutkimuskohteena olevassa organisaatiossa. Käytäntöyhteisöissä ihmiset yhdistää aihealue, joka muodostaa yhteisölle yhteisen näkemyksen siitä, mitä yhteisö on ja mitä se tekee. Tiedon jakamiseen motivoi se, että yhteisössä henkilöt pystyvät nostamaan omaa arvostustaan tuomalla oman panoksensa yhteisen edun hyväksi. Mitä enemmän tietoa jaetaan, sitä suuremmaksi tulee yhteisen tiedon määrä, ja sen paremmaksi muodostuu organisaation kyky vastaanottaa uutta tietoa. Kyky vaikuttaa ongelmiin ja nähdä ongelmien taustalla todellisuudessa vaikuttavat asiat ovat keskeinen asia organisaation oppimisessa. Mallissa kuvataan esimerkein, miten uuden tiedon luominen yhteisöissä tapahtuu.

Tunnuslukujen monimuotoisuus: ROI, RI ja EVA

Tässä työssä käsitellään sijoitetun pääoman tuottoprosentin, jäännöskatteen ja taloudellisen lisäarvon historiaa, käsitteitä ja käyttöä. Erityisesti keskitytään näistä tunnusluvuista käytettyjen määritelmien moninaisuuteen. Aluksi tutustutaan tunnuslukujen historiaan ja määritelmiin. Tämän jälkeen tutkitaan niiden käyttömahdollisuuksia johdon ja rahoituksen laskentatoimessa. Lopuksi tutkitaan empiirisen aineiston avulla näiden tunnuslukujen käyttöä yrityksissä. Sijoitetun pääoman tuottoprosentti syntyi 1900-luvun alussa Yhdysvalloissa, josta se levisi maailmanlaajuiseksi. Sijoitetun pääoman tuottoprosentti on suosittu tunnusluku sen helppokäyttöisyyden ansiosta. Rahoituksen laskentatoimen puolella on annettu tarkat ohjeet sijoitetun pääoman tuottoprosentin laskemiseksi, koska sen esittäminen ulkoisessa tiedottamisessa on joillekin yrityksille lakisääteistä. Johdon laskentatoimessa ei ole olemassa sääntöjä tämän tunnusluvun laskemiseksi, ja se voidaan laskea yrityksen haluamalla tavalla. Jäännöskate on ensimmäisen kerran mainittu kirjallisuudessa jo 1700-luvun loppupuolella, mutta sen käytöstä tuli yleisempää vasta 1900-luvulla. Jäännöskate ei kuitenkaan koskaan saavuttanut suurta suosiota, eikä sitä nykyään juuri käytetä. Jäännöskatteeseen pohjautuva taloudellinen lisäarvo nousi julkisuuteen, kun Stern Stewart & Co. rekisteröi sen tuotemerkikseen 1980-luvun lopussa. Verrattuna jäännöskatteeseen taloudellinen lisäarvo vastaa paremmin yrityksen todellista arvonmuodostusta. Näiden tunnuslukujen laskenta ei ole lakisääteisiä, joten kaikki yritykset voivat laskea ne omalla tavallaan. Jäännöskatetta ja taloudellista lisäarvoa käytetään lähinnä johdon laskentatoimessa, mutta vähitellen ne ovat siirtymässä myös rahoituksen laskentatoimeen.