Fluid structure interaction in fully collapsible tubes

Paper presented at the 8th International Conference on Heat Transfer, Fluid Mechanics and Thermodynamics, Mauritius, 11-13 July, 2011.The main goal of the developed theory is to formulate the biomechanical conditions (geometrical dimensions, viscoelastic properties of veins and blood fluid flow conditions) at which an unstable behavior or even the vein collapse can occur. The above problems are numerically modeled by the finite element method. The weak formulation of the tube deformation is based on the virtual work principle. The mixed formulation of the finite element method with the separately interpolated pressure is used for the structure. The strong coupling of both structure and fluid solvers allow us to simulate self-induced large deflection oscillations of the tube. Provided that the Neo-Hook’s material model was applied the analytical formula for the collapse conditions was found. It was proved that for the brain vein contraction about 5%, the vein collapse can occurs even under normal physiological condition – the angiosynizesis. The fluid structure interaction is studied experimentally on the special experimental line. The fluid structure phenomenon is investigated both for the continuous and pulsating flow and it is evaluated by a non-invasive optical. The method is based on optical measurements of radial displacement of the pulsating tube wall. The simultaneous clinics observation (histological findings), in vitro experiments and numerical modeling gives sufficient data to predict biomechanical conditions of the angiosynizesis.mp201

The C-Terminal Domain of the Arabinosyltransferase Mycobacterium tuberculosis EmbC Is a Lectin-Like Carbohydrate Binding Module

The D-arabinan-containing polymers arabinogalactan (AG) and lipoarabinomannan (LAM) are essential components of the unique cell envelope of the pathogen Mycobacterium tuberculosis. Biosynthesis of AG and LAM involves a series of membrane-embedded arabinofuranosyl (Araf) transferases whose structures are largely uncharacterised, despite the fact that several of them are pharmacological targets of ethambutol, a frontline drug in tuberculosis therapy. Herein, we present the crystal structure of the C-terminal hydrophilic domain of the ethambutol-sensitive Araf transferase M. tuberculosis EmbC, which is essential for LAM synthesis. The structure of the C-terminal domain of EmbC (EmbCCT) encompasses two sub-domains of different folds, of which subdomain II shows distinct similarity to lectin-like carbohydrate-binding modules (CBM). Co-crystallisation with a cell wall-derived di-arabinoside acceptor analogue and structural comparison with ligand-bound CBMs suggest that EmbCCT contains two separate carbohydrate binding sites, associated with subdomains I and II, respectively. Single-residue substitution of conserved tryptophan residues (Trp868, Trp985) at these respective sites inhibited EmbC-catalysed extension of LAM. The same substitutions differentially abrogated binding of di- and penta-arabinofuranoside acceptor analogues to EmbCCT, linking the loss of activity to compromised acceptor substrate binding, indicating the presence of two separate carbohydrate binding sites, and demonstrating that subdomain II indeed functions as a carbohydrate-binding module. This work provides the first step towards unravelling the structure and function of a GT-C-type glycosyltransferase that is essential in M. tuberculosis. Author Summary Top Tuberculosis (TB), an infectious disease caused by the bacillus Mycobacterium tuberculosis, burdens large swaths of the world population. Treatment of active TB typically requires administration of an antibiotic cocktail over several months that includes the drug ethambutol. This front line compound inhibits a set of arabinosyltransferase enzymes, called EmbA, EmbB and EmbC, which are critical for the synthesis of arabinan, a vital polysaccharide in the pathogen's unique cell envelope. How precisely ethambutol inhibits arabinosyltransferase activity is not clear, in part because structural information of its pharmacological targets has been elusive. Here, we report the high-resolution structure of the C-terminal domain of the ethambutol-target EmbC, a 390-amino acid fragment responsible for acceptor substrate recognition. Combining the X-ray crystallographic analysis with structural comparisons, site-directed mutagenesis, activity and ligand binding assays, we identified two regions in the C-terminal domain of EmbC that are capable of binding acceptor substrate mimics and are critical for activity of the full-length enzyme. Our results begin to define structure-function relationships in a family of structurally uncharacterised membrane-embedded glycosyltransferases, which are an important target for tuberculosis therapy

La geografia a la Universitat Autònoma de Barcelona : un projecte d'Enric Lluch (II)

S'ha complert mig segle d'ensenyament de la geografia a la UAB (de 1969 a 2019). Al present article se n'hi expliquen els primers vint anys, fins a completar el desenvolupament de la Llei de reforma universitària (LRU) a la nostra universitat, i s'hi dona a conèixer quin era l'equip acadèmic que va acompanyar Enric Lluch (1928-2012) en aquesta experiència. També s'hi introdueix la geografia que recollia els enfocaments innovadors que arribaven principalment de França, dels països anglosaxons i d'Itàlia, i s'hi mostra la formació docent i investigadora del professorat, a més del desenvolupament de les eines científiques que han fet possible l'assentament de la geografia a la UAB. Bàsicament, es tracta d'explicar-hi la recerca, els contactes internacionals, els laboratoris i la revista Documents d'Anàlisi Geogràfica, entre d'altres qüestions. A les conclusions s'hi valora l'esforç col·lectiu que ha fet possible que aquest procés hagi continuat amb èxit, tant a Bellaterra com a Girona.Se ha cumplido medio siglo de enseñanza de la geografía en la UAB (de 1969 a 2019). En el presente artículo se explican sus primeros veinte años hasta completar el desarrollo de la Ley de reforma universitaria (LRU) en nuestra universidad y se da a conocer cuál era el equipo académico que acompañó a Enric Lluch (1928-2012) en esta experiencia. Se introduce la geografía que recogía los enfoques innovadores que llegaban principalmente de Francia, de los países anglosajones y de Italia, y se muestra la formación docente e investigadora del profesorado, así como el desarrollo de las herramientas científicas que han hecho posible el asentamiento de la geografía en la UAB. Básicamente, se trata de contar la investigación, los contactos internacionales, los laboratorios y la revista Documents d'Anàlisi Geogràfica, entre otros aspectos. En las conclusiones se valora el esfuerzo colectivo que ha hecho posible que este proceso haya continuado con éxito, tanto en Bellaterra como en Girona.Cinquante ans d'enseignement de la Géographie à l'UAB (1969 à 2019) viennent d'être célébrés. Les 20 premières années sont présentées, jusqu'à l'achèvement du développement de la loi sur la réforme de l'université (LRU) à l'UAB, ainsi que l'équipe académique qui a accompagné Enric Lluch (1928-2012) dans cette expérience. On a introduit la géographie qui a rassemblé les approches novatrices venues principalement de la France, des pays anglo-saxons et de l'Italie. Dans cette deuxième partie, nous expliquons la formation des enseignants en matière d'enseignement et de recherche, ainsi que le développement des outils scientifiques qui ont permis l'établissement de la géographie à l'UAB. Il s'agit essentiellement de recherche, de contacts internationaux, de laboratoires et du journal Documents d'Anàlisi Geogràfica, entre autres. Dans les conclusions, l'effort collectif qui a permis à ce processus de se poursuivre avec succès, à Bellaterra comme à Girona, est valorisé.Geography has been taught at the Autonomous University of Barcelona (UAB) for 50 years (1969-2019). This paper explores the first 20 years of geography until the entry into force of the University Reform Law (LRU) at the UAB and the academic team that accompanied Enric Lluch (1928-2012) in this experience. The introduction of geography based on innovative approaches coming mainly from France, English-speaking countries and Italy is discussed. In this second part we also describe the teaching and research training of teachers, and the development of scientific tools that have made the establishment of geography in the UAB possible: basically, research, international contacts, laboratories and the Documents d'Anàlisi Geogràfica journal, among others. To conclude, the collective effort that has contributed to the success of this process both in Bellaterra and in Girona is examined

MAIT cell clonal expansion and TCR repertoire shaping in human volunteers challenged with Salmonella Paratyphi A

Mucosal-associated invariant T (MAIT) cells are innate-like T cells that can detect bacteria-derived metabolites presented on MR1. Here we show, using a controlled infection of humans with live Salmonella enterica serovar Paratyphi A, that MAIT cells are activated during infection, an effect maintained even after antibiotic treatment. At the peak of infection MAIT cell T-cell receptor (TCR)β clonotypes that are over-represented prior to infection transiently contract. Select MAIT cell TCRβ clonotypes that expand after infection have stronger TCR-dependent activation than do contracted clonotypes. Our results demonstrate that host exposure to antigen may drive clonal expansion of MAIT cells with increased functional avidity, suggesting a role for specific vaccination strategies to increase the frequency and potency of MAIT cells to optimize effector function

MAIT cell clonal expansion and TCR repertoire shaping in human volunteers challenged with Salmonella Paratyphi A

Most MAIT cell response to infection studies are of mice. Here the authors characterize MAIT cell population responses to Salmonella Paratyphi A infection of 25 human volunteers using TCR clonotype analysis and mass cytometry of pre-infection matched to post-infection samples

The biomechanic influence on vessel´s physiology and pathophysiology

This action is realized by the project NEXLIZ - CZ.1.07/2.3.00/30.0038, which is co-financed by the European social fund and the state budget of the Czech republic

The Conditions of Vibrations and Collapse of Human Blood Vessels

Biomechanical material properties of arteries and veins are investigated experimentally and theoretically. The main goal of the histological research and the developed theory is to formulate the biomechanical conditions (geometrical dimensions, viskoelastic properties of veins and blood fluid flow conditions) at which an unstable behavior or even the vein collapse can occur. One dimensional fluid structure approximation was starting point for the theoretical analysis of fluid flow through highly elastic collapsible tube. Provided that the neo-Hook’s material model was applied the analytical formula for the collapse conditions was found. It was proved that for the brain vein contraction about 5%, the vein collapse can occurs even under normal physiological condition into vessels – the angiosynizesis. The fluid structure interaction is studied experimentally on the special experimental line. Latex tubes with variable inner diameter and wall thickness are used as specimens