Crystal structure of 3-{(E)-[(3, 4-dichloro-phenyl)imino]methyl}benzene-1, 2-diol

The authors acknowledge the provision of funds for the purchase of diffractometer and encouragement by Dr.Muhammad Akram Chaudhary, Vice Chancellor, University of Sargodha, Pakistan.Peer reviewedPublisher PD

A NATIONAL PERSPECTIVE ON LAND USE POLICY ALTERNATIVES AND CONSEQUENCES AT THE RURAL-URBAN FRINGE

Land Economics/Use,

A Resource-Based View Of International Human Resources: Toward A Framework of Integrative and Creative Capabilities

Drawing on organizational learning and MNC perspectives, we extend the resource-based view to address how international human resource management provides sustainable competitive advantage. We develop a framework that emphasizes and extends traditional assumptions of the resource-based view by identifying the learning capabilities necessary for a complex and changing global environment. These capabilities address how MNCs might both create new HR practices in response to local environments and integrate existing HR practices from other parts of the firm (affiliates, regional headquarters, and global headquarters). In an effort to understand the nature of such capabilities, we discuss aspects of human capital, social capital, and organizational capital that might be linked to their development. Page

Seismicity within a propagating ice shelf rift: The relationship between icequake locations and ice shelf structure

Iceberg calving is a dominant mass loss mechanism for Antarctic ice shelves, second only to basal melting. An important process involved in calving is the initiation and propagation of through‐penetrating fractures called rifts; however, the mechanisms controlling rift propagation remain poorly understood. To investigate the mechanics of ice shelf rifting, we analyzed seismicity associated with a propagating rift tip on the Amery Ice Shelf, using data collected during the austral summers of 2004–2007. We apply a suite of passive seismological techniques including icequake locations, back projection, and moment tensor inversion. We confirm previous results that show ice shelf rifting is characterized by periods of relative quiescence punctuated by swarms of intense seismicity of 1 to 3 h. Even during periods of quiescence, we find significant deformation around the rift tip. Moment tensors, calculated for a subset of the largest icequakes ( M w  > −2.0) located near the rift tip, show steeply dipping fault planes, horizontal or shallowly plunging stress orientations, and often have a significant volumetric component. They also reveal that much of the observed seismicity is limited to the upper 50 m of the ice shelf. This suggests a complex system of deformation that involves the propagating rift, the region behind the rift tip, and a system of rift‐transverse crevasses. Small‐scale variations in the mechanical structure of the ice shelf, especially rift‐transverse crevasses and accreted marine ice, play an important role in modulating the rate and location of seismicity associated with the propagating ice shelf rifts. Key Points Rift‐related seismicity controlled by mechanical heterogeneity Back projection reveals that seismic deformation is continuous in region Spacing of rift‐transverse crevasses controls the timing of seismic swarmsPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106935/1/jgrf20203.pd

An antibody raised against a pathogenic serpin variant induces mutant-like behaviour in the wild-type protein

A monoclonal antibody (mAb) that binds to a transient intermediate may act as a catalyst for the corresponding reaction; here we show this principle can extend on a macro molecular scale to the induction of mutant-like oligomerization in a wild-type protein. Using the common pathogenic E342K (Z) variant of α1-antitrypsin as antigen-whose native state is susceptible to the formation of a proto-oligomeric intermediate-we have produced a mAb (5E3) that increases the rate of oligomerization of the wild-type (M) variant. Employing ELISA, gel shift, thermal stability and FRET time-course experiments, we show that mAb5E3 does not bind to the native state of α1-antitrypsin, but recognizes a cryptic epitope in the vicinity of the post-helix A loop and strand 4C that is revealed upon transition to the polymerization intermediate, and which persists in the ensuing oligomer. This epitope is not shared by loop-inserted monomeric conformations. We show the increased amenity to polymerization by either the pathogenic E342K mutation or the binding of mAb5E3 occurs without affecting the energetic barrier to polymerization. As mAb5E3 also does not alter the relative stability of the monomer to intermediate, it acts in a manner similar to the E342K mutant, by facilitating the conformational interchange between these two states

Studying the effect of manager’s Strategic Thinking on Corporate entrepreneurship

The purpose of this research is to explore the effect of managers' strategic thinking on corporate entrepreneurship. To this end, one main hypothesis and five secondary hypotheses were proposed. This study is descriptive-applicable and Lidka studies (1998) were employed to measure managers' strategic thinking and Robins and Kutler's questionnaire (1996) was used to measure corporate entrepreneurship. The statistical population included 118 managers and employees of a manufacturing company in Kermanshah industrial estate. The research sample was equal to 90 using Cochran formula. The results disclosed that managers' strategic thinking has a positive and significant effect on corporate entrepreneurship and all hypotheses were confirme

An antibody that prevents serpin polymerisation acts by inducing a novel allosteric behavior

Serpins are important regulators of proteolytic pathways with an antiprotease activity that involves a conformational transition from a metastable to a hyperstable state. Certain mutations permit the transition to occur in the absence of a protease; when associated with an intermolecular interaction, this yields linear polymers of hyperstable serpin molecules, which accumulate at the site of synthesis. This is the basis of many pathologies termed the serpinopathies. We have previously identified a monoclonal antibody (mAb4B12) that, in single-chain form, blocks α1-Antitrypsin (α1-AT) polymerisation in cells. Here, we describe the structural basis for this activity. The mAb4B12 epitope was found to encompass residues Glu32, Glu39 and His43 on helix A and Leu306 on helix I. This is not a region typically associated with the serpin mechanism of conformational change, and correspondingly the epitope was present in all tested structural forms of the protein. Antibody binding rendered β-sheet A - on the opposite face of the molecule - more liable to adopt an 'open' state, mediated by changes distal to the breach region and proximal to helix F. The allosteric propagation of induced changes through the molecule was evidenced by an increased rate of peptide incorporation and destabilisation of a preformed serpin-enzyme complex following mAb4B12 binding. These data suggest that prematurely shifting the β-sheet A equilibrium towards the 'open' state out of sequence with other changes suppresses polymer formation. This work identifies a region potentially exploitable for a rational design of ligands that is able to dynamically influence α1-AT polymerisation

Parametrically excited helicopter ground resonance dynamics with high blade asymmetries

The present work is aimed at verifying the influence of high asymmetries in the variation of in-plane lead-lag stiffness of one blade on the ground resonance phenomenon in helicopters. The periodical equations of motions are analyzed by using Floquet's Theory (FM) and the boundaries of instabilities predicted. The stability chart obtained as a function of asymmetry parameters and rotor speed reveals a complex evolution of critical zones and the existence of bifurcation points at low rotor speed values. Additionally, it is known that when treated as parametric excitations; periodic terms may cause parametric resonances in dynamic systems, some of which can become unstable. Therefore, the helicopter is later considered as a parametrically excited system and the equations are treated analytically by applying the Method of Multiple Scales (MMS). A stability analysis is used to verify the existence of unstable parametric resonances with first and second-order sets of equations. The results are compared and validated with those obtained by Floquet's Theory. Moreover, an explanation is given for the presence of unstable motion at low rotor speeds due to parametric instabilities of the second order

A single-chain variable fragment intrabody prevents intracellular polymerization of Z α1-antitrypsin while allowing its antiproteinase activity.

Mutant Z α1-antitrypsin (E342K) accumulates as polymers within the endoplasmic reticulum (ER) of hepatocytes predisposing to liver disease, whereas low levels of circulating Z α1-antitrypsin lead to emphysema by loss of inhibition of neutrophil elastase. The ideal therapy should prevent polymer formation while preserving inhibitory activity. Here we used mAb technology to identify interactors with Z α1-antitrypsin that comply with both requirements. We report the generation of an mAb (4B12) that blocked α1-antitrypsin polymerization in vitro at a 1:1 molar ratio, causing a small increase of the stoichiometry of inhibition for neutrophil elastase. A single-chain variable fragment (scFv) intrabody was generated based on the sequence of mAb4B12. The expression of scFv4B12 within the ER (scFv4B12KDEL) and along the secretory pathway (scFv4B12) reduced the intracellular polymerization of Z α1-antitrypsin by 60%. The scFv4B12 intrabody also increased the secretion of Z α1-antitrypsin that retained inhibitory activity against neutrophil elastase. MAb4B12 recognized a discontinuous epitope probably located in the region of helices A/C/G/H/I and seems to act by altering protein dynamics rather than binding preferentially to the native state. This novel approach could reveal new target sites for small-molecule intervention that may block the transition to aberrant polymers without compromising the inhibitory activity of Z α1-antitrypsin