On the universality of small scale turbulence

The proposed universality of small scale turbulence is investigated for a set of measurements in a cryogenic free jet with a variation of the Reynolds number (Re) from 8500 to 10^6. The traditional analysis of the statistics of velocity increments by means of structure functions or probability density functions is replaced by a new method which is based on the theory of stochastic Markovian processes. It gives access to a more complete characterization by means of joint probabilities of finding velocity increments at several scales. Based on this more precise method our results call in question the concept of universality.Comment: 4 pages, 4 figure

Theoretical study on the activation mechanism of AMP-kinase by means of Molecular Dynamics Simulations

Mammalian AMP-activated protein kinase (AMPK) is a Ser108/Thr132 heterotrimeric enzyme complex (one catalytic subunit a and two regulatory subunits b and g) with a key role as sensor in the cellular energy homeostasis. This function confers AMPK a major role in numerous metabolic disorders, such as type 2 diabetes, obesity and cancer, and explains the progressive interest as a therapeutic target. AMPK is regulated by several mechanisms including indirect and direct activators, which show clear specificity by a particular subunit. We have carried out a series of molecular dynamic simulations of the apo and holo forms of AMPK to gain insight into the mechanism of AMPK activation

Theoretical study on the activation mechanism of AMP-kinase by means of Molecular Dynamics Simulations

Mammalian AMP-activated protein kinase (AMPK) is a Ser108/Thr132 heterotrimeric enzyme complex (one catalytic subunit a and two regulatory subunits b and g) with a key role as sensor in the cellular energy homeostasis. This function confers AMPK a major role in numerous metabolic disorders, such as type 2 diabetes, obesity and cancer, and explains the progressive interest as a therapeutic target. AMPK is regulated by several mechanisms including indirect and direct activators, which show clear specificity by a particular subunit. We have carried out a series of molecular dynamic simulations of the apo and holo forms of AMPK to gain insight into the mechanism of AMPK activation

Electrostatic Tuning of the Ligand Binding Mechanism by Glu27 in Nitrophorin 7.

Nitrophorins (NP) 1-7 are NO-carrying heme proteins found in the saliva of the blood-sucking insect Rhodnius prolixus. The isoform NP7 displays peculiar properties, such as an abnormally high isoelectric point, the ability to bind negatively charged membranes, and a strong pH sensitivity of NO affinity. A unique trait of NP7 is the presence of Glu in position 27, which is occupied by Val in other NPs. Glu27 appears to be important for tuning the heme properties, but its influence on the pH-dependent NO release mechanism, which is assisted by a conformational change in the AB loop, remains unexplored. Here, in order to gain insight into the functional role of Glu27, we examine the effect of Glu27 → Val and Glu27 → Gln mutations on the ligand binding kinetics using CO as a model. The results reveal that annihilation of the negative charge of Glu27 upon mutation reduces the pH sensitivity of the ligand binding rate, a process that in turn depends on the ionization of Asp32. We propose that Glu27 exerts a through-space electrostatic action on Asp32, which shifts the pKa of the latter amino acid towards more acidic values thus reducing the pH sensitivity of the transition between open and closed states

Unified Multifractal Description of Velocity Increments Statistics in Turbulence: Intermittency and Skewness

The phenomenology of velocity statistics in turbulent flows, up to now, relates to different models dealing with either signed or unsigned longitudinal velocity increments, with either inertial or dissipative fluctuations. In this paper, we are concerned with the complete probability density function (PDF) of signed longitudinal increments at all scales. First, we focus on the symmetric part of the PDFs, taking into account the observed departure from scale invariance induced by dissipation effects. The analysis is then extended to the asymmetric part of the PDFs, with the specific goal to predict the skewness of the velocity derivatives. It opens the route to the complete description of all measurable quantities, for any Reynolds number, and various experimental conditions. This description is based on a single universal parameter function D(h) and a universal constant R*.Comment: 13 pages, 3 figures, Extended version, Publishe

Role of PheE15 gate in ligand entry and nitric oxide detoxification function of Mycobacterium tuberculosis truncated hemoglobin N

The truncated hemoglobin N, HbN, of Mycobacterium tuberculosis is endowed with a potent nitric oxide dioxygenase (NOD) activity that allows it to relieve nitrosative stress and enhance in vivo survival of its host. Despite its small size, the protein matrix of HbN hosts a two-branched tunnel, consisting of orthogonal short and long channels, that connects the heme active site to the protein surface. A novel dual-path mechanism has been suggested to drive migration of O(2) and NO to the distal heme cavity. While oxygen migrates mainly by the short path, a ligand-induced conformational change regulates opening of the long tunnel branch for NO, via a phenylalanine (PheE15) residue that acts as a gate. Site-directed mutagenesis and molecular simulations have been used to examine the gating role played by PheE15 in modulating the NOD function of HbN. Mutants carrying replacement of PheE15 with alanine, isoleucine, tyrosine and tryptophan have similar O(2)/CO association kinetics, but display significant reduction in their NOD function. Molecular simulations substantiated that mutation at the PheE15 gate confers significant changes in the long tunnel, and therefore may affect the migration of ligands. These results support the pivotal role of PheE15 gate in modulating the diffusion of NO via the long tunnel branch in the oxygenated protein, and hence the NOD function of HbN

Performance evaluation of parallel manipulators for milling application

This paper focuses on the performance evaluation of the parallel manipulators for milling of composite materials. For this application the most significant performance measurements, which denote the ability of the manipulator for the machining are defined. In this case, optimal synthesis task is solved as a multicriterion optimization problem with respect to the geometric, kinematic, kinetostatic, elastostostatic, dynamic properties. It is shown that stiffness is an important performance factor. Previous models operate with links approximation and calculate stiffness matrix in the neighborhood of initial point. This is a reason why a new way for stiffness matrix calculation is proposed. This method is illustrated in a concrete industrial problem

Incorporation of fungal cellulases in bacterial minicellulosomes yields viable, synergistically acting celluloytic complexes

Artificial designer minicellulosomes comprise a chimeric scaffoldin that displays an optional cellulose-binding module (CBM) and bacterial cohesins from divergent species which bind strongly to enzymes engineered to bear complementary dockerins. Incorporation of cellulosomal cellulases from Clostridium cellulolyticum into minicellulosomes leads to artificial complexes with enhanced activity on crystalline cellulose, due to enzyme proximity and substrate targeting induced by the scaffoldin-borne CBM. In the present study, a bacterial dockerin was appended to the family 6 fungal cellulase Cel6A, produced by Neocallimastix patriciarum, for subsequent incorporation into minicellulosomes in combination with various cellulosomal cellulases from C. cellulolyticum. The binding of the fungal Cel6A with a bacterial family 5 endoglucanase onto chimeric miniscaffoldins had no impact on their activity toward crystalline cellulose. Replacement of the bacterial family 5 enzyme with homologous endoglucanase Cel5D from N. patriciarum bearing a clostridial dockerin gave similar results. In contrast, enzyme pairs comprising the fungal Cel6A and bacterial family 9 endoglucanases were substantially stimulated (up to 2.6-fold) by complexation on chimeric scaffoldins, compared to the free-enzyme system. Incorporation of enzyme pairs including Cel6A and a processive bacterial cellulase generally induced lower stimulation levels. Enhanced activity on crystalline cellulose appeared to result from either proximity or CBM effects alone but never from both simultaneously, unlike minicellulosomes composed exclusively of bacterial cellulases. The present study is the first demonstration that viable designer minicellulosomes can be produced that include (i) free (noncellulosomal) enzymes, (ii) fungal enzymes combined with bacterial enzymes, and (iii) a type (family 6) of cellulase never known to occur in natural cellulosomes

Molecular simulations of globins: Exploring the relationship between structure, dynamics and function

Podeu consultar el llibre complet a: http://hdl.handle.net/2445/32392The discovery in the last two decades of novel members of the globin superfamily has challenged the conventional view about the structure and function of globins. Thus, peculiar structural differences are expected to have direct influence on properties related to ligand migration, binding affinity and heme reactivity. Molecular simulations are a valuable tool to gain insigth into the molecular mechanisms that underlie those structural differences, and their relationship with the diversity of functional roles. In this work, the impact of molecular simulations in exploring the linkage between structure, dynamics and function is highlighted for three representative cases: the migration of ligands through the protein matrix of truncated hemoglobins, the modulation of binding affinity by heme distortion in protoglobin, and finally the functional implications due to the equilibrium between penta- and hexacoordination of the heme with distal histidine in neuroglobin

Towards a Sustainable Governance of Information Systems: Devising a Maturity Assessment Tool of Eco-Responsibility Inspired by the Balanced Scorecard

Part 3: Section 2: Sustainable and Responsible InnovationInternational audienceThe assessment of the maturity of Information System (IS) regarding its contribution to corporate social responsibility policy is considered as a stake for organizations. However, few research efforts have been dedicated to this evaluation and even less to the elaboration of a management tool. This paper adopts an engineering perspective to develop a performance assessment approach in this field. Theoretically, this communication (1) mobilizes the methodology of engineering research to build a measurement system of the IS maturity in relation to the economic, social and environmental performance, (2) extends the researches about the sustainable balanced scorecard (SBSC) to the field of IS governance. Practically, this study provides organizations with a global approach to this complex phenomenon as well as a guide to assess it. The originality of this research lies in the application of the conceptual framework of the SBSC to a new research domain