Antibody-deficiency and Acute Nephritic Syndrome in a Patient with Homozygous Disruption of the CD81 Gene

info:eu-repo/semantics/nonPublished

Antibody-deficiency and Acute Nephritic Syndrome in a Patient with Homozygous Disruption of the CD81 Gene

info:eu-repo/semantics/nonPublished

Algoritmos como herramienta en la búsqueda de nuevos datos para la resolución de problemas sobre isometrías del plano

Reconociendo la importancia que tienen los algoritmos en el proceso de resolución de problemas, particularmente en la geometría, se identificaron algunas formas en las que se usan algoritmos que son conocidos para los resolutores, durante la resolución de algún problema. A tales formas se les ha dado el nombre de uso de algoritmos y, específicamente, se describen y se muestran evidencias de los usos relacionados con la obtención de nueva información que permita ampliar los caminos considerados para la solución del problema.

Actividades elementales en la calculadora graficadora (Ti - 89, Ti – 92 Plus, Voyage 200)

Actualmente la influencia que tiene la tecnología en la Educación Matemática como medio facilitador tanto en el proceso de aprendizaje como en el de enseñanza de algunas temáticas de las matemáticas escolares, ha generado su inclusión en las instituciones educativas como es el caso, de las calculadoras graficadoras. No obstante, en general son varios los profesores de matemáticas que aunque cuentan con este tipo de recursos para desarrollar sus clases, se abstienen de utilizarlos porque no saben cómo ni en qué momento hacerlo. Por tanto, se presenta algunas actividades sobre ciertas temáticas de la matemática escolar en donde sea factible el uso de herramientas básicas de la calculadora.

Myeloperoxidase G-463A polymorphism and Alzheimer's disease in the ApoEurope study

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Epidemiological and molecular genetic studies have shown the existence of several genes associated with increased risk of AD, the major genetic susceptibility locus coding for apolipoprotein E (apoE). A polymorphism in the myeloperoxidase gene (MPO) has previously been associated with AD susceptibility. However, results in the literature are controversial and seem to be dependent on several factors such as gender, apoE polymorphism or the genetic structure of the population. We investigated MPO G-463A and apoE polymorphism in 265 cases and 246 controls from the ApoEurope Study. In females, we found a significant association between MPO genotype and AD (P=0.034), GG genotype frequency being lower in cases (52.4%) as compared to controls (64.2%). In men, there was no significant effect of MPO polymorphism. No interaction was found between MPO polymorphism and apoE epsilon 4 allele. In conclusion, the G-463A polymorphism of MPO was statistically associated with AD in a gender-specific manner. However, given the low significance of P value we suggest no causal effect of the MPO gene in AD, as also evidenced in a recent meta-analysis. Our results support the hypothesis of a possible linkage disequilibrium between the MPO G-463A gene polymorphism and another functional variant involved in AD.

A critical appraisal of tools available for monitoring epigenetic changes in clinical samples from patients with myeloid malignancies

Research over the past decade has confirmed that epigenetic alterations act in concert with genetic lesions to deregulate gene expression in acute myeloid leukemia and myelodysplastic syndromes. In addition, we now have the capability to pharmaceutically target epigenetic modifications, and there is an urgent need forearly validation of the efficacy of the drugs. Also, an improved understanding of the functionality of epigenetic modifications may further pave the road towards an individualized therapy. Here, we provide the pros and cons of the currently most feasible methods used for characterizing the methylome in clinical samples, and give a brief introduction to novel approaches to sequencing that may revolutionize our abilities to characterize the genomes and epigenomes in acute myeloid leukemia and myelodysplastic syndrome patients.

Prognostic significance of combined MN1, ERG, BAALC, and EVI1 (MEBE) expression in patients with myelodysplastic syndromes

Overexpression of MN1, ERG, BAALC, and EVI1 (MEBE) genes in cytogenetically normal acute myeloid leukemia (AML) patients is associated with poor prognosis, but their prognostic effect in patients with myelodysplastic syndromes (MDS) has not been studied systematically. Expression data of the four genes from 140 MDS patients were combined in an additive score, which was validated in an independent patient cohort of 110 MDS patients. A high MEBE score, defined as high expression of at least two of the four genes, predicted a significantly shorter overall survival (OS) (HR 2.29, 95 % CI 1.3-4.09, P?=?.005) and time to AML progression (HR 4.83, 95 % CI 2.01-11.57, P?

Relationship between genome and epigenome - challenges and requirements for future research

Understanding the links between genetic, epigenetic and non-genetic factors throughout the lifespan and across generations and their role in disease susceptibility and disease progression offer entirely new avenues and solutions to major problems in our society. To overcome the numerous challenges, we have come up with nine major conclusions to set the vision for future policies and research agendas at the European level.

Macrophage migration inhibitory factor (MIF) expression in human malignant gliomas contributes to immune escape and tumour progression

Macrophage migration inhibitory factor (MIF), which inhibits apoptosis and promotes angiogenesis, is expressed in cancers suppressing immune surveillance. Its biological role in human glioblastoma is, however, only poorly understood. We examined in-vivo expression of MIF in 166 gliomas and 23 normal control brains by immunohistochemistry. MIF immunoreactivity was enhanced in neoplastic astrocytes in WHO grade II glioma and increased significantly in higher tumour grades (III-IV). MIF expression was further assessed in 12 glioma cell lines in vitro. Quantitative RT-PCR showed that MIF mRNA expression was elevated up to 800-fold in malignant glioma cells compared with normal brain. This translated into high protein levels as assessed by immunoblotting of total cell lysates and by ELISA-based measurement of secreted MIF. Wild-type p53-retaining glioma cell lines expressed higher levels of MIF, which may be connected with the previously described role of MIF as a negative regulator of wild-type p53 signalling in tumour cells. Stable knockdown of MIF by shRNA in glioma cells significantly increased tumour cell susceptibility towards NK cell-mediated cytotoxicity. Furthermore, supernatant from mock-transfected cells, but not from MIF knockdown cells, induced downregulation of the activating immune receptor NKG2D on NK and CD8+ T cells. We thus propose that human glioma cell-derived MIF contributes to the immune escape of malignant gliomas by counteracting NK and cytotoxic T-cell-mediated tumour immune surveillance. Considering its further cell-intrinsic and extrinsic tumour-promoting effects and the availability of small molecule inhibitors, MIF seems to be a promising candidate for future glioma therapy.

The timing and spatiotemporal patterning of Neanderthal disappearance

ThetimingofNeanderthal disappearanceandtheextent to whichthey overlapped with the earliest incoming anatomically modern humans (AMHs)inEurasia arekey questions inpalaeoanthropology1,2 .Deter- mining the spatiotemporal relationship between the two populations is crucial if we are to understand the processes, timing and reasons leading to the disappearance of Neanderthals and the likelihood of cultural and genetic exchange. Serious technical challenges, however, havehinderedreliable datingof the period,as theradiocarbonmethod reaches its limit at 50,000 years ago3 .Herewe apply improved accel- erator mass spectrometry 14C techniques to construct robust chro- nologies from 40 key Mousterian and Neanderthal archaeological sites, ranging fromRussia toSpain.Bayesianagemodellingwas used togenerate probability distributionfunctions todetermine the latest appearancedate.Weshowthat theMousterianendedby41,030–39,260 calibratedyears BP(at95.4%probability) acrossEurope.Wealsodem- onstrate that succeeding ‘transitional’ archaeological industries, one ofwhich has beenlinked withNeanderthals (Cha ˆtelperronian)4 ,end at a similar time. Our data indicate that the disappearance of Nean- derthals occurred at different times in different regions.Comparing the data with results obtained fromthe earliest datedAMHsites in Europe, associated with the Uluzzian technocomplex5 , allows us to quantify the temporal overlap between the two human groups. The results revealasignificantoverlap of 2,600–5,400years (at 95.4%prob- ability).This hasimportant implications formodels seeking toexplain the cultural, technological and biological elements involved in the replacement of Neanderthals byAMHs.Amosaic of populations in Europe during the Middle to Upper Palaeolithic transition suggests that there was ample time for the transmission of cultural and sym- bolic behaviours, as well as possible genetic exchanges, between the two groups.

Cathepsin S Cleavage of Protease-Activated Receptor-2 on Endothelial Cells Promotes Microvascular Diabetes Complications

Endothelial dysfunction is a central pathomechanism in diabetes-associated complications. We hypothesized a pathogenic role in this dysfunction of cathepsin S (Cat-S), a cysteine protease that degrades elastic fibers and activates the protease-activated receptor-2 (PAR2) on endothelial cells. We found that injection of mice with recombinant Cat-S induced albuminuria and glomerular endothelial cell injury in a PAR2-dependent manner. In vivo microscopy confirmed a role for intrinsic Cat-S/PAR2 in ischemia-induced microvascular permeability. In vitro transcriptome analysis and experiments using siRNA or specific Cat-S and PAR2 antagonists revealed that Cat-S specifically impaired the integrity and barrier function of glomerular endothelial cells selectively through PAR2. In human and mouse type 2 diabetic nephropathy, only CD68(+) intrarenal monocytes expressed Cat-S mRNA, whereas Cat-S protein was present along endothelial cells and inside proximal tubular epithelial cells also. In contrast, the cysteine protease inhibitor cystatin C was expressed only in tubules. Delayed treatment of type 2 diabetic db/db mice with Cat-S or PAR2 inhibitors attenuated albuminuria and glomerulosclerosis (indicators of diabetic nephropathy) and attenuated albumin leakage into the retina and other structural markers of diabetic retinopathy. These data identify Cat-S as a monocyte/macrophage-derived circulating PAR2 agonist and mediator of endothelial dysfunction-related microvascular diabetes complications. Thus, Cat-S or PAR2 inhibition might be a novel strategy to prevent microvascular disease in diabetes and other diseases.

Human melioidosis, Malawi, 2011

A case of human melioidosis caused by a novel sequence type of Burkholderia pseudomallei occurred in a child in Malawi, southern Africa. A literature review showed that human cases reported from the continent have been increasing.

Modos r de oscilação em estrelas de neutrões

Tese dout., Física - Astrofísica, Universidade do Algarve, 2007

Makerspace in der Stadtbibliothek Göttingen : Machbarkeitsstudie und Risikoanalyse

Bei dem Konzept Makerspace handelt es sich um ein niedrigschwelliges Angebot, das für alle Besucher Anreize, Ideen und Unterstützung bieten kann. Durch den Faktor des gemeinsamen Lernens werden soziale Grenzen überbrückt und neue Netzwerke gebildet, implizites Wissen wird ausgetauscht und Lernen neu erfahren. Der Makerspace bietet eine Bühne, um eigene Erfahrungen auszutauschen, Wissen an Interessierte weiterzugeben oder gemeinschaftlich an einem kreativen Projekt zu arbeiten. Als Ort des Lernens und der Information, aber auch als Treffpunkt bieten öffentliche Bibliotheken einen idealen Rahmen für ein entsprechendes Angebot. Das modulare Makerspace-Konzept ermöglicht ihnen, die Angebote ganz nach ihren Bedürfnissen und Ansprüchen auszurichten. Vorhandene Medienbestände können in die Makerspace-Aktivitäten eingebunden werden. Makerspaces sind vielversprechende Zukunftsmodelle kollektiver Erfahrungsräume und bieten Platz für eine inklusive Lernwerkstatt für die Gemeinschaft. Aufgrund der vorliegenden Analyse empfiehlt das Projektteam für die Stadtbibliothek Göttingen mit dem Koffermodul zu starten, um die Teilnehmer und Mitarbeiter nicht zu überfordern. Die räumlichen Gegebenheiten lassen aber in einem späteren Stadium auch die Module Schrank und Raum zu. Diese Erweiterungen sollten von der Nutzung und der Nachfrage abhängig gemacht werden.

Déterminants et significations des conduites d’hypertravail : une approche psychosociale et systémique- le cas des travailleurs et des travailleuses des secteurs du multimédia et des services informatiques

Loin de la réduction pressentie du temps de travail et de l’émergence d’une société des loisirs, est plutôt observé, depuis une trentaine d’années, un accroissement du temps consacré au travail pour les travailleurs les plus qualifiés, au Québec comme dans la plupart des sociétés occidentales (Burke et Cooper, 2008; Lapointe, 2005; Lee, 2007). Dans un contexte où les « arrangements temporels » (Thoemmes, 2000) tendent à s’individualiser de façon à mieux prendre en compte les réalités et les besoins des salariés et salariées tout comme ceux des organisations, cette thèse interroge le caractère « volontaire » des conduites d’hypertravail observées chez les travailleurs et les travailleuses des secteurs des services informatiques et du multimédia. Elle s’attarde plus particulièrement aux processus psychosociaux qui sous-tendent la construction de ces conduites. Inscrite au sein d’une approche psychosociale et systémique, notre recherche articule une théorie qui met en résonance les fonctionnements individuel et organisationnel, soutenue par le modèle du Système psychique organisationnel (Aubert et de Gaulejac, 1991), et une théorie de la socialisation plurielle et active, soutenue par le modèle du Système des activités (Baubion-Broye et Hajjar, 1998; Curie, 2000). Opérationnalisée selon une grille articulée autour de cinq niveaux d’analyse (intra-individuel, interpersonnel, positionnel, idéologique et de la tâche et de l’organisation du travail), nous avons mené 34 entretiens biographiques (26 hommes et 8 femmes) auprès de salariés et salariées des secteurs des services informatiques et du multimédia. Les résultats mettent en évidence trois types de processus menant à l’adoption de conduites d’hypertravail ; un cas-type qui illustre un processus de renforcement d’une identité professionnelle de « grand travailleur » ; un cas-type qui rend compte d’un processus de suraffiliation organisationnelle et d’assujettissement de la vie hors-travail; et un cas-type qui expose le maintien d’une conduite d’hypertravail défensive, dans un contexte de mise à l’épreuve organisationnelle. Au final, les résonances particulières observées entre ces niveaux et facteurs nous amènent à souligner l’intérêt de mieux comprendre l’hypertravail en prenant en compte les significations que les individus donnent à leurs conduites, à partir d’un regard diachronique et synchronique. Nous discutons également du caractère dynamique et évolutif de la relation individu-collectif-organisation et du rôle différencié des organisations et des collectifs de travail dans la construction des conduites d’hypertravail. Nous relevons enfin certaines implications des nouvelles pratiques et normes de temps de travail observées dans ces organisations, favorables au développement et au maintien de l’hypertravail. Mots-clés : temps de travail, longues heures de travail, conduites d’hypertravail, articulation travail-vie personnelle, socialisation plurielle et active, domination au travail.