Étude en transport électrique d'une double boîte quantique latérale en silicium

Ce mémoire présente des résultats de caractérisation en transport électrique d’une double boîte quantique latérale en silicium de type MOSFET (transistor à effet de champ métal-oxyde-semi- conducteur). La double boîte permet d’isoler des électrons dans les trois dimensions, tout d’abord en formant un gaz bidimensionnel de porteurs de charge près de la surface du substrat sous l’effet d’une grille d’accumulation, puis en déplétant certaines régions du gaz d’électrons avec des grilles de déplétion en polysilicium. Le dispositif a été fabriqué aux Sandia National Laboratories par l’équipe de Malcolm S. Carroll. Les mesures en transport électrique suggèrent l’atteinte du régime à un seul électron à une température relativement élevée de 1.5 K. En effet, des mesures de diamants de Coulomb montrent un diamant associé à la région à zéro électron qui ne se referme pas pour des biais source-drain supérieurs à 30 meV. Il s’agit d’une forte indication que les boîtes quantiques ont bien été vidées, bien que le nombre exact d’électrons n’ait pas pu être confirmé directement par détection de charge. Le diagramme de stabilité obtenu à une température de 8 mK indique la formation d’une double boîte quantique lithographique très stable. Enfin, l’étude des triangles de conduction à fort biais source-drain dans les polarités positive et négative permet d’observer le phénomène du blocage de spin sous l’application d’un champ magnétique parallèle de 450 mT. Une séparation singulet-triplet de ~ 400 μeV en est extraite, indiquant possiblement une levée importante de la dégénérescence de vallée associée au silicium. Les résultats présentés dans ce mémoire constituent l’une des premières observations de l’isolation d’un seul électron dans une double boîte quantique en silicium de type MOSFET. Il s’agit aussi de la première observation du blocage de spin en transport dans ces dispositifs. Ces observations font partie des étapes initiales à réaliser pour obtenir des qubits de spin performants dans le silicium, un matériau pour lequel des longs temps de cohérence sont anticipés

Research Advances for the Conservation of Cultural Heritage

Because European Cultural Heritage is an invaluable legacy, the Ministry for Science and Innovation funded the Spanish Network on Science and Technology for the Conservation of Cultural Heritage (TechnoHeritage), which began its activities in March 2011.Currently seventy five groups participate in the Network, including Spanish National Research Council (CSIC) and Spanish universities teams, cultural institutions, foundations and museums, and private companies. One of the activities of the Network is the organization of annual meetings. This International Congress—organised on behalf of TechnoHeritage by the Universidade de Santiago de Compostela— has a goal of creating an interdisciplinary forum for discussion on all aspects of cultural heritage conservation while providing an up-to-date and comprehensive picture of the state-of-the-art investigations in this field

Structural and functional studies on lysostaphin, an antistaphylococcal endopeptidase

This PhD thesis describes research into the structure and function of lysostaphin (EC 3.4.24.75), a glycylglycine endopeptidase secreted by Staphylococcus simulans biovar staphylolyticus ATCC 1362. Lysostaphin is a member of the M23/M37 zinc metalloprotease family and is a pre-pro-enzyme. The mature form (after removal of the pro-region) contains two distinct domains, the C-terminal cell wall targeting domain of lysostaphin (termed LssTdom in the thesis) facilitates binding to Staphylococcus aureus cells. The endopeptidase domain (termed LssEdom in the thesis) cleaves the pentaglycine crosslinks in the peptidoglycan resulting in cell death through cell rupture of S. aureus. Lysostaphin is a potential therapeutic antibiotic for Methicillin-resistant Staphylococcus aureus (MRSA) for which new antibacterials are required owing to the widespread occurrence of multi-drug resistant strains. To date, the structural requirements for enzymatic activity and the target in the cell wall for lysostaphin have not been fully elucidated. Thus a structure might enable rationally guided design of lysostaphin variants for the generation of new enzymes which would also cleave the non-canonical crosslinks and would thus overcome bacterial resistance. Thus, one approach was to obtain the lysostaphin structure using homology modelling. Lysostaphin shares significant homology with the ALE-1 (83 % identity) and LytM (48 % identity) bacteriocins, and modelling the structure of lysostaphin was achieved using the recently released structures of LytM and ALE-1 derived from X-ray crystallography as templates. In addition, we report the successful production of active recombinant lysostaphin (as well as the endopeptidase and the targeting domains) and initial characterisation of their secondary structure by Fourier-transform infrared spectroscopy. Initially, advanced spectroscopic techniques including X-ray and NMR methods were investigated for molecular interaction studies between Lss and its putative ligands. Significant problems were encountered with these methods and mass spectrometry studies proved more amenable. Lysostaphin targeting domain-ligand complexes have been identified, along with their stoichiometry. The strength of the protein-ligand interactions has also been quantified. Lysostaphin was shown to bind in vitro Gly5 (mimicking the pentaglycine cross-bridge) and Lys-D-Ala-D-Ala (mimicking the stem peptide) with low affinity, but not NAM-L-Ala-D-iGln-Lys. It was also shown that lysostaphin targeting domain affinity for Gly5 was significantly reduced by addition of Gly-Gly-Ser-Gly-Ser (found in the host bacteria resistant to lysostaphin action – S. simulans) in solution. From these studies it could be concluded that resistance due to the incorporation of serine residues in the crossbridge were a result of the endopeptidase domain being unable to cleave this sequence and not due to the targeting domain being unable to bind it

Structural and functional studies on lysostaphin, an antistaphylococcal endopeptidase

This PhD thesis describes research into the structure and function of lysostaphin (EC 3.4.24.75), a glycylglycine endopeptidase secreted by Staphylococcus simulans biovar staphylolyticus ATCC 1362. Lysostaphin is a member of the M23/M37 zinc metalloprotease family and is a pre-pro-enzyme. The mature form (after removal of the pro-region) contains two distinct domains, the C-terminal cell wall targeting domain of lysostaphin (termed LssTdom in the thesis) facilitates binding to Staphylococcus aureus cells. The endopeptidase domain (termed LssEdom in the thesis) cleaves the pentaglycine crosslinks in the peptidoglycan resulting in cell death through cell rupture of S. aureus. Lysostaphin is a potential therapeutic antibiotic for Methicillin-resistant Staphylococcus aureus (MRSA) for which new antibacterials are required owing to the widespread occurrence of multi-drug resistant strains. To date, the structural requirements for enzymatic activity and the target in the cell wall for lysostaphin have not been fully elucidated. Thus a structure might enable rationally guided design of lysostaphin variants for the generation of new enzymes which would also cleave the non-canonical crosslinks and would thus overcome bacterial resistance. Thus, one approach was to obtain the lysostaphin structure using homology modelling. Lysostaphin shares significant homology with the ALE-1 (83 % identity) and LytM (48 % identity) bacteriocins, and modelling the structure of lysostaphin was achieved using the recently released structures of LytM and ALE-1 derived from X-ray crystallography as templates. In addition, we report the successful production of active recombinant lysostaphin (as well as the endopeptidase and the targeting domains) and initial characterisation of their secondary structure by Fourier-transform infrared spectroscopy. Initially, advanced spectroscopic techniques including X-ray and NMR methods were investigated for molecular interaction studies between Lss and its putative ligands. Significant problems were encountered with these methods and mass spectrometry studies proved more amenable. Lysostaphin targeting domain-ligand complexes have been identified, along with their stoichiometry. The strength of the protein-ligand interactions has also been quantified. Lysostaphin was shown to bind in vitro Gly5 (mimicking the pentaglycine cross-bridge) and Lys-D-Ala-D-Ala (mimicking the stem peptide) with low affinity, but not NAM-L-Ala-D-iGln-Lys. It was also shown that lysostaphin targeting domain affinity for Gly5 was significantly reduced by addition of Gly-Gly-Ser-Gly-Ser (found in the host bacteria resistant to lysostaphin action – S. simulans) in solution. From these studies it could be concluded that resistance due to the incorporation of serine residues in the crossbridge were a result of the endopeptidase domain being unable to cleave this sequence and not due to the targeting domain being unable to bind it

Inclusion of relatives in stroke rehabilitation : Perception of quality of services they received in the context of early supported discharged (ESD), in- and out-patient services

Background Relatives of stroke patients should be an integral part of the continuum of rehabilitation services. Objective The objective was to describe their perception of the quality of the services they received in the context of early supported discharged (ESD), in- and out-patient rehabilitation services. Methods Descriptive study using the Quality of Services Questionnaire for Relatives post-stroke (QSQR) completed online by relatives after the patient’s discharge. It consists of 22 statements with respect to three subscales: 1) the training/instructions, 2) the information provision and 3) the organizational process of the service offer. Space is allowed for free comments and two open-ended questions. Quantitative data were analyzed descriptively, and we used a content analysis for qualitative data. Results One-third (30/90; 33.3%) of the sample are composed of relatives aged 55 and under, with a majority (81%) of women and 51.3% of spouses. The training/instructions and information provision were perceived positively with a mean % agreement at 85.0 ± 29.6 and 84.8 ± 22.4, respectively. The mean % agreement was 91.4 ± 17.8 for the organizational process subscale. A significantly higher score (p = 0,03; Kruskal Wallis test) was found for out-patient services (n = 20) as compared to ESD (n = 29) or in-patient rehabilitation (n = 41). Qualitatively, a lack of involvement of relatives was mentioned as well as a lack of personalized information about stroke and its consequences and provision of resources available. However, communication between professionals, their availability, and their professionalism were appreciated. Conclusion Despite quantitative high scores, qualitative data allowed the identification of concrete avenues for improvement to truly and systematically include relatives in stroke rehabilitation

Relación entre el déficit sensorial auditivo y depresión en personas mayores: revisión de la literatura

[Resumen] Los avances en las condiciones sanitarias y socioeconómicas de los países desarrollados han incrementado la esperanza de vida y el número de personas mayores. Sin embargo, aunque las condiciones sanitarias han mejorado, las alteraciones de la salud en relación con la edad siguen aumentando, siendo el déficit sensorial auditivo una de las más frecuentes. De origen multifactorial, en donde los cambios morfofuncionales en relación con el envejecimiento van a desempe˜nar su papel, presentará predisposiciones subyacentes en cada individuo. El déficit sensorial auditivo va a influir negativamente sobre la calidad de vida de las personas mayores debido a las interferencias producidas sobre la capacidad para comunicarse, afectando, además, al estado de ánimo y al nivel de participación social, independientemente del estado cognitivo y físico del individuo, lo que a largo plazo, y en muchos casos, desembocará en un trastorno depresivo. Detectar y tratar precozmente dicho déficit generará un importante beneficio bio-psico-social y funcional a la persona.[Abstract] Advances in health, social and economic conditions in the developed countries have increased life expectancy and the number of elderly people. However, although health conditions have improved, age-related diseases are still increasing. One of the most common ailments is the age-related hearing loss, which has several pathophysiological causes and may be influenced by age-related morpho-functional changes. Hearing loss may also have underlying conditions in each individual. Sensory hearing loss tends to negatively affect the quality of life of the elderly, interfering with their capacity to communicate and affecting mood and the level of participation in social life. This may be independent of the cognitive and physical state of individuals, which in the long term and in many cases may end in depression. Detection and early treatment of hearing loss is an important bio-psycho-social benefit to the elderly

Characterisation of the developing heart in a pressure overloaded model utilising RNA sequencing to direct functional analysis

Cardiogenesis is influenced by both environmental and genetic factors, with blood flow playing a critical role in cardiac remodelling. Perturbation of any of these factors could lead to abnormal heart development and hence the formation of congenital heart defects. Although abnormal blood flow has been associated with a number of heart defects, the effects of abnormal pressure load on the developing heart gene expression profile have to date not clearly been defined. To determine the heart transcriptional response to haemodynamic alteration during development, outflow tract (OFT) banding was employed in the chick embryo at Hamburger and Hamilton stage (HH) 21. Stereological and expression studies, including the use of global expression analysis by RNA sequencing with an optimised procedure for effective globin depletion, were subsequently performed on HH29 OFT‐banded hearts and compared with sham control hearts, with further targeted expression investigations at HH35. The OFT‐banded hearts were found to have an abnormal morphology with a rounded appearance and left‐sided dilation in comparison with controls. Internal analysis showed they typically had a ventricular septal defect and reductions in the myocardial wall and trabeculae, with an increase in the lumen on the left side of the heart. There was also a significant reduction in apoptosis. The differentially expressed genes were found to be predominately involved in contraction, metabolism, apoptosis and neural development, suggesting a cardioprotective mechanism had been induced. Therefore, altered haemodynamics during development leads to left‐sided dilation and differential expression of genes that may be associated with stress and maintaining cardiac output

The N-terminus of survivin is a mitochondrial-targeting sequence and Src regulator

Survivin is a cancer-associated protein that exists in several locations in the cell. Its cytoplasmic residence in interphase cells is governed by CRM1-mediated nuclear exportation, and its localisation during mitosis to the centromeres and midzone microtubules is that of a canonical chromosomal passenger protein. In addition to these well-established locations, survivin is also a mitochondrial protein, but how it gets there and its function therein is presently unclear. Here we show that the first 10 amino acids at the NH2 terminus of survivin are sufficient to target GFP to the mitochondria in vivo, and ectopic expression of this decapeptide decreases cell adhesion and accelerates proliferation. The data support a signalling mechanism in which mitochondrial survivin activates the tyrosine kinase, C-Src, leading to reduced focal adhesion plaques and disruption of F-actin organisation. This strongly suggests that the NH2 terminus of survivin is a mitochondrial targeting sequence that regulates C-Src, and that survivin acts in concert with C-Src to promote tumorigenesis

Cognitive impairment as predictor of functional dependence in an elderly sample

[Abstract] This retrospective study determines the role of cognitive decline as a predictor of functional dependence. In a representative 600 community-dwellers aged 65 or older, we examined using a logistic regression model, the association between cognitive status (taking into account age and educational level) and dependence on basic and instrumental activities of daily living (ADL and IADL, resp.), controlling for socio-demographic variables and health conditions. The Mini-Mental State Examination (MMSE) scores were compared in participants with functional disability to perform basic and instrumental activities. Cognitive status influenced functional dependence on activities of daily living, basic (OR = 4.1, 95%CI = 2.7–6.1) and instrumental (OR = 5.7, 95%CI = 3.5–9.3), independently of gender, age, educational level and health conditions. Besides, cognitive impairment was associated with the dependence on certain basic (e.g., bathing, toileting) and instrumental (e.g., using the telephone, taking medications, and handling finances) activities. This was a gradual relationship, the highest cognitive decline implied the highest loss of ability at carrying out activities, with a larger impact on basic activities. These findings suggest that cognitive decline can be a predictor for functional dependence, independently of other variables, and turn into a very useful tool indicating the need for support