Crystal Structure of Staphylococcus aureus Metallopeptidase (Sapep) Reveals Large Domain Motions between the Manganese-bound and Apo-states

Proteases belonging to the M20 family are characterized by diverse substrate specificity and participate in several metabolic pathways. The Staphylococcus aureus metallopeptidase, Sapep, is a member of the aminoacylase-I/M20 protein family. This protein is a Mn2+-dependent dipeptidase. The crystal structure of this protein in the Mn2+-bound form and in the open, metal-free state suggests that large interdomain movements could potentially regulate the activity of this enzyme. We note that the extended inactive conformation is stabilized by a disulfide bond in the vicinity of the active site. Although these cysteines, Cys(155) and Cys(178), are not active site residues, the reduced form of this enzyme is substantially more active as a dipeptidase. These findings acquire further relevance given a recent observation that this enzyme is only active in methicillin-resistant S. aureus. The structural and biochemical features of this enzyme provide a template for the design of novel methicillin-resistant S. aureus-specific therapeutics.

Activity–Composition Relations in the Nickel Oxide–Magnesium Oxide System at 1300 K by the Solid-State Galvanic Cell Technique

The activity of NiO in NiO-MgO rock salt solid solution has been measured at 1300 K by employing a solid-state galvanic cell: Pt,Ni+ NiO||(CaO)ZrO2||Ni + (Nix,Mgl-x)O, Pt. A high-density tube of Zr02-15 mol% CaO has been used as the solid electrolyte for the emf measurements. The activities of the component oxides in the rock salt solid solution exhibit negative deviation from ideality at the temperature of investigation. The solid solution obeys regular solution behavior at 1300 K. The value of the regular solution parameter is found to be -12000 ((l000) J mol-1. The composition dependence of ΔGEx obtained in this study agrees reasonably well with the calorimetric data reported in the literature for NiO-MgO solid solution.

Phase relations in the system BiO1.5–SrO–CuO at 1123 K

Phase relations in the system Bi-Sr-Cu-O at 1123 K have been investigated using optical microscopy, electron-probe microanalysis (EPMA) and powder X-ray diffraction (XRD) of equilibrated samples. Differential thermal analysis (DTA) was used to confirm liquid formation for compositions rich in BiO1.5. Compositions along the three pseudo-binary sections and inside the pseudo-ternary triangle have been examined. The attainment of equilibrium was facilitated by the use of freshly prepared SrO as the starting material. The loss of Bi2O3 from the sample was minimized by double encapsulation. A complete phase diagram at 1123 K is presented. It differs significantly from versions of the phase diagram published recently.

Basic Income Grant in Namibia, a Viewpoint on the Proposal and on the Work of the BIG Coalition

This thesis studies the basic income grant proposal in Namibia. The proposal suggests a monthly grant of N$100 (approximately 10€) to all those Namibian citizens who do not receive the state pension. This thesis concentrates on the Basic Income Grant (BIG) Coalition and on its work. The formation and transformation of the coalition during the time period between 2003 and 2009 is analyzed with the help of data collected during two field work periods in 2008 and 2009. The data includes interviews, newspaper articles, observations and other background material. The analysis of this material is mainly conducted from organizational viewpoint. The final part of the thesis applies the results to the theory of Mosse, whose propositions about policy and practice will be discussed in relation to the basic income grant pilot project. The thesis argues that social legitimacy has been a vital resource for the work of the BIG Coalition and it has sought for it in various ways. The concept of social legitimacy originates from the resource dependence perspective of Pfeffer and Salancik, who propose that organizations are dependent on their environments, and on the resources provided by the surrounding environment. This thesis studies the concept of social legitimacy in the context of resource dependence theory. Social legitimacy is analyzed in the relations between the coalition and its environment, in the formation of the coalition, in the responses towards criticism, and finally in relation to the propositions concerning policy and practice. The work of the coalition in the pilot project will be analyzed through the propositions of Mosse concerning policy and practice. The results will describe and analyze key events in the formation of the BIG Coalition from the South African proposal until the end of the basic income pilot project. This BIG pilot project conducted in 2008-2009 is one of the most well-known activities of the coalition. The clashes between the coalition and its environment will be analyzed through four case studies. It will be shown that the project has been conducted in order to gain more legitimacy to the basic income grant proposal. The conclusion questions the legitimacy of the BIG Coalition as a research and development organization, and requests for more transparent research on the basic income proposal in Namibia.

From ‘Afflicted’ to Activists: Structural Violence and Climate Change Discourse in the States of Pernambuco and Paraíba in Northeast Brazil

This study approaches the problem of poverty in the hinterlands of Northeast Brazil through the concept of structural violence, linking the environmental threats posed by climate change, especially those related to droughts, to the broader social struggles in the region. When discussions about potentials and rights are incorporated into the problematic of poverty, a deeper insight is obtained regarding the various factors behind the phenomenon. It is generally believed that climate change is affecting the already marginalized and poor more than those of higher social standing, and will increasingly do so in the future. The data for this study was collected during a three month field work in the states of Pernambuco and Paraíba in Northeast Brazil. The main methods used were semi-structured interviews and participant observation, including attending seminars concerning climate change on the field. The focus of the work is to compare both layman and expert perceptions on what climate change is about, and question the assumptions about its effects in the future, mainly that of increased numbers of ‘climate refugees’ or people forced to migrate due to changes in climate. The focus on droughts, as opposed to other manifestations of climate change, arises from the fact that droughts are not only phenomena that develop over a longer time span than floods or hurricanes, but is also due to the historical persistence of droughts in the region, and both the institutional and cultural linkages that have evolved around it. The instances of structural violence that are highlighted in this study; the drought industry, land use, and the social and power relations present in the region, including those between the civil society, the state and the private agribusiness sector, all work against a backdrop of symbolic and moral realms of value production, where relations between the different actors are being negotiated anew with the rise of the climate change discourse. The main theoretical framework of the study consists of Johan Galtung’s and Paul Farmer’s theory of structural violence, Ulrich Beck’s theory of the risk society, and James Scott’s theory of everyday peasant resistance.

Phase Relations in the System Cu-Gd-O and Gibbs Energy of Formation of CuGd204

The phase relations in the system Cu-Gd-O have been determined at 1273 K by X-ray diffrac- tion, optical microscopy, and electron microprobe analysis of samples equilibrated in quartz ampules and in pure oxygen. Only one ternary compound, CuGd2O4, was found to be stable. The Gibbs free energy of formation of this compound has been measured using the solid-state cell Pt, Cu2O + CuGd2O4 + Gd2O3 // (Y2O3) ZrO2 // CuO + Cu2O, Pt in the temperature range of 900 to 1350 K. For the formation of CuGd2O4 from its binary component oxides, CuO (s) + Gd2O3 (s) → CuGd2O4 (s) ΔG° = 8230 - 11.2T (±50) J mol-1 Since the formation is endothermic, CuGd2O4 becomes thermodynamically unstable with respect to CuO and Gd2O3 below 735 K. When the oxygen partial pressure over CuGd2O4 is lowered, it decomposes according to the reaction 4CuGd2O4 (s) → 4Gd2O3 (s) + 2Cu2O (s) + O2 (g) for which the equilibrium oxygen potential is given by Δμo 2 = −227,970 + 143.2T (±500) J mol−1 An oxygen potential diagram for the system Cu-Gd-O at 1273 K is presented.

Phase relations in the systems Cu–O–R2O3(R = Tm, Lu) and Gibbs energies of formation of Cu2R2O5 compounds

The phase relations in the systems Cu–O–R2O3(R = Tm, Lu) have been determined at 1273 K by X-ray diffraction, optical microscopy and electron probe microanalysis of samples equilibrated in evacuated quartz ampules and in pure oxygen. Only ternary compounds of the type Cu2R2O5 were found to be stable. The standard Gibbs energies of formation of the compounds have been measured using solid-state galvanic cells of the type, Pt|Cu2O + Cu2R2O5+ R2O3‖(Y2O3)ZrO2‖CuO + Cu2O‖Pt in the temperature range 950–1325 K. The standard Gibbs energy changes associated with the formation of Cu2R2O5 compounds from their binary component oxides are: 2CuO(s)+ Tm2O3(s)→Cu2Tm2O5(s), ΔG°=(10400 – 14.0 T/K)± 100 J mol–1, 2CuO(s)+ Lu2O3(s)→Cu2Lu2O5(s), ΔG°=(10210 – 14.4 T/K)± 100 J mol–1 Since the formation is endothermic, the compounds become thermodynamically unstable with respect to component oxides at low temperatures, Cu2Tm2O5 below 743 K and Cu2Lu2O5 below 709 K. When the chemical potential of oxygen over the Cu2R2O5 compounds is lowered, they decompose according to the reaction, 2Cu2R2O5(s)→2R2O3(s)+ 2Cu2O(s)+ O2(g) The equilibrium oxygen potential corresponding to this reaction is obtained from the emf. Oxygen potential diagrams for the Cu–O–R2O3 systems at 1273 K are presented.

Relationship between the controllability grammian and closed-loop eigenvalues: the single input case

The controllability grammian is important in many control applications. Given a set of closed-loop eigenvalues the corresponding controllability grammian can be obtained by computing the controller which assigns the eigenvalues and then by solving the Lyapunov equation that defines the grammian. The relationship between the controllability grammian, resulting from state feedback, and the closed-loop eigenvalues of a single input linear time invariant (LTI) system is obtained. The proposed methodology does not require the computation of the controller that assigns the specified eigenvalues. The closed-loop system matrix is obtained from the knowledge of the open-loop system matrix, control influence matrix and the specified closed-loop eigenvalues. Knowing the closed-loop system matrix, the grammian is then obtained from the solution of the Lyapunov equation that defines it. Finally the proposed idea is extended to find the state covariance matrix for a specified set of closed-loop eigenvalues (without computing the controller), due to impulsive input in the disturbance channel and to solve the eigenvalue assignment problem for the single input case.

Relationship Between The Impedance Matrix And The Transfer Matrix With Specific Reference To Symmetrical, Reciprocal And Conservative Systems

Impedance matrix and transfer matrix methods are often used in the analysis of linear dynamical systems. In this paper, general relationships between these matrices are derived. The properties of the impedance matrix and the transfer matrix of symmetrical systems, reciprocal systems and conservative systems are investigated. In the process, the following observations are made: (a) symmetrical systems are not a subset of reciprocal systems, as is often misunderstood; (b) the cascading of reciprocal systems again results in a reciprocal system, whereas cascading of symmetrical systems does not necessarily result in a symmetrical system; (c) the determinant of the transfer matrix, being ±1, is a property of both symmetrical systems and reciprocal systems, but this condition, however, is not sufficient to establish either the reciprocity or the symmetry of the system; (d) the impedance matrix of a conservative system is skew-Hermitian.

Dense granular flow down an inclined plane A comparison between the hard particle model and soft particle simulations

The granular flow down an inclined plane is simulated using the discrete element (DE) technique to examine the extent to which the dynamics of an unconfined dense granular flow can be well described by a hard particle model First, we examine the average coordination number for the particles in the flow down an inclined plane using the DE technique using the linear contact model with and without friction, and the Hertzian contact model with friction The simulations show that the average coordination number decreases below 1 for values of the spring stiffness corresponding to real materials, such as sand and glass, even when the angle of inclination is only 10 larger than the angle of repose Additional measures of correlations in the system, such as the fraction of particles with multibody contact, the force ratio (average ratio of the magnitudes of the largest and the second largest force on a particle), and the angle between the two largest forces on the particle, show no evidence of force chains or other correlated motions in the system An analysis of the bond-orientational order parameter indicates that the flow is in the random state, as in event-driven (ED) simulations V Kumaran, J Fluid Mech 632, 107 (2009), J Fluid Mech 632, 145 (2009)] The results of the two simulation techniques for the Bagnold coefficients (ratio of stress and square of the strain rate) and the granular temperature (mean square of the fluctuating velocity) are compared with the theory V Kumaran, J Fluid Mech 632, 107 (2009), J Fluid Mech 632, 145 (2009)] and are found to be in quantitative agreement In addition, we also conduct a comparison of the collision frequency and the distribution of the precollisional relative velocities of particles in contact The strong correlation effects exhibited by these two quantities in event-driven simulations V Kumaran, J Fluid Mech 632, 145 (2009)] are also found in the DE simulations (C) 2010 American Institute of Physics doi 10 1063/1 3504660]

Dynamic coupling between the LID and NMP domain motions in the catalytic conversion of ATP and AMP to ADP by adenylate kinase

The catalytic conversion of adenosine triphosphate (ATP) and adenosine monophosphate (AMP) to adenosine diphosphate (ADP) by adenylate kinase (ADK) involves large amplitude, ligand induced domain motions, involving the opening and the closing of ATP binding domain (LID) and AMP binding domain (NMP) domains, during the repeated catalytic cycle. We discover and analyze an interesting dynamical coupling between the motion of the two domains during the opening, using large scale atomistic molecular dynamics trajectory analysis, covariance analysis, and multidimensional free energy calculations with explicit water. Initially, the LID domain must open by a certain amount before the NMP domain can begin to open. Dynamical correlation map shows interesting cross-peak between LID and NMP domain which suggests the presence of correlated motion between them. This is also reflected in our calculated two-dimensional free energy surface contour diagram which has an interesting elliptic shape, revealing a strong correlation between the opening of the LID domain and that of the NMP domain. Our free energy surface of the LID domain motion is rugged due to interaction with water and the signature of ruggedness is evident in the observed root mean square deviation variation and its fluctuation time correlation functions. We develop a correlated dynamical disorder-type theoretical model to explain the observed dynamic coupling between the motion of the two domains in ADK. Our model correctly reproduces several features of the cross-correlation observed in simulations. (C) 2011 American Institute of Physics. doi:10.1063/1.3516588]