Globalization, Transition and the Discourse of Management

Globalization is a heavily debated phenomenon and can be studied from many perspectives. In the present paper the perspective of the discourse of management is presented. Management as an idea and as practice is also a critically contested phenomenon in today's fast changing world. In this paper managerial discourse as an aspect of globalization is studied. The concepts of globalization, managerialism and managerial discourse are introduced and their interdependence is described. Special attention is given to the process of the so-called transition in Slovenia and its connection to the concepts of managerialism and managerial discourse. During the process of transition from one economic and political system to another, managerial discourse became adopted in Slovenia and soon constituted itself as a standard or even dominant discourse in business and economics. Some examples are drawn from Slovene newspapers and other publications to demonstrate first the difference between the socialist (self-management) discourse and managerial discourse, and second, to demonstrate the diffusion of managerial discourse to other spheres of social and political life.managerial discourse, globalization, transition

Synthesis and Biological Evaluation of Fluorescein-Tagged Carborane for Boron Neutron Capture Therapy (BNCT)

Boron Neutron Capture Therapy (BNCT) is a bimodal cancer treatment that involves killing cancer cells through a nuclear reaction of two nontoxic species, boron-10 (10B) and thermal neutrons. There are currently only two FDA-approved drugs for this promising area of cancer therapy, so present research focuses on the synthesis of novel compounds with high boron content as well as methods for their delivery into the tumor cell. A fluorescent tag can allow the observation of the delivery vehicle’s uptake during biodistribution studies. Accordingly, fluorescein was conjugated with iodinated 1-methyl-o-carborane and characterized using Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR), elemental analysis, and mass spectrometry (MS). The biological potential of the fluorescein-tagged 1-methyl-o-carborane conjugate was then evaluated using flow cytometry, cytotoxicity, and biological distribution studies with squamous cell carcinoma (SCC-VII) and pancreatic cancer (MIA PaCa-2) cell lines using phase-contrast, fluorescent, and confocal microscopy.B.S. (Bachelor of Science

An In-Depth Look at DNA Crystals through the Prism of Molecular Dynamics Simulations

X-ray crystallography is the primary tool for biomolecular structural determination. However, contacts formed through the crystal lattice are known to affect structures, especially for small and flexible molecules such as DNA oligomers, by introducing significant structural changes in comparison to solution. Furthermore, why molecules crystallize in certain symmetry groups, which role crystallization additives play, and whether they are just innocuous and unspecific crystallization catalysts remain unclear. By using one of the currently best-performing DNA force fields and applying significant computational effort, we described the nature of intermolecular forces that stabilize B-DNA crystals in various symmetry groups and solvent environments with an unprecedented level of detail. We showed a tight coupling between the lattice stability and the type of crystallization additives and that certain symmetry groups are stable only in the presence of a specific additive. Additives and crystal contacts induce small but non-negligible changes in the physical properties of DNA

Changes in the free-energy landscape of p38α MAP kinase through its canonical activation and binding events as studied by enhanced molecular dynamics simulations

p38α is a Ser/Thr protein kinase involved in a variety of cellular processes and pathological conditions, which makes it a promising pharmacological target. Although the activity of the enzyme is highly regulated, its molecular mechanism of activation remains largely unexplained, even after decades of research. By using state-of-the-art molecular dynamics simulations, we decipher the key elements of the complex molecular mechanism refined by evolution to allow for a fine tuning of p38α kinase activity. Our study describes for the first time the molecular effects of different regulators of the enzymatic activity, and provides an integrative picture of the activation mechanism that explains the seemingly contradictory X-ray and NMR data

Investigating Cryptic Binding Sites by Molecular Dynamics Simulations

This Account highlights recent advances and discusses major challenges in investigations of cryptic (hidden) binding sites by molecular simulations. Cryptic binding sites are not visible in protein targets crystallized without a ligand and only become visible crystallographically upon binding events. These sites have been shown to be druggable and might provide a rare opportunity to target difficult proteins. However, due to their hidden nature, they are difficult to find through experimental screening. Computational methods based on atomistic molecular simulations remain one of the best approaches to identify and characterize cryptic binding sites. However, not all methods are equally efficient. Some are more apt at quickly probing protein dynamics but do not provide thermodynamic or druggability information, while others that are able to provide such data are demanding in terms of time and resources. Here, we review the recent contributions of mixed-solvent simulations, metadynamics, Markov state models, and other enhanced sampling methods to the field of cryptic site identification and characterization. We discuss how these methods were able to provide precious information on the nature of the site opening mechanisms, to predict previously unknown sites which were used to design new ligands, and to compute the free energy landscapes and kinetics associated with the opening of the sites and the binding of the ligands. We highlight the potential and the importance of such predictions in drug discovery, especially for difficult (“undruggable”) targets. We also discuss the major challenges in the field and their possible solutions

X-ray refinement signficantly underestimates the level of microscopic heterogeneity in biomolecular crystals

Biophysical Structural Chemistr

Nonlinearities Influence to RF Satellite Downlink Model with QAM and Raised Square Cosine Filter

Reliability of communications is of vital importance in military applications. Constellations are connecting coded words at different ends of the communication channel that indicate the correctness of the transmitted message. In this paper, we compare the influence of the selected nonlinearity in the transmit amplifier on the constellation diagrams in radio frequency (RF) geostationary satellite downlink and bit-error-rate (BER). Two cases were analyzed: negligible and severe noise in the communication channel. Considering the cubic, hyperbolic tangent, Saleh, Ghorbani, and Raap models, it is shown that the Raap and Saleh models can be used for the lowest BERs when the noise is negligible. In case of severe noise, it is best to use the Raap model from the set of nonlinearities considered. The ANOVA-test showed that there is a dependence between the Raap and Saleh models in the presence of negligible noise, but not in the presence of severe noise

Gas-liquid mass transfer : a comparison of down-and up-pumping axial flow impellers with radial impellers

The performance of a down- and up-pumping pitched blade turbine and A315 for gas-liquid dispersion and mass transfer was evaluated and then compared with that of Rushton and Scaba turbines in a small laboratory scale vessel. The results show that when the axial flow impellers are operated in the up-pumping mode, the overall performance is largely improved compared with the down-pumping configuration. Compared with the radial turbines, the up-pumping A315 has a high gas handling capacity, equivalent to the Scaba turbine and is economically much more efficient in terms of mass transfer than both turbines. On the other hand, the uppumping pitched blade turbine is not as well adapted to such applications. Finally, the axial flow impellers in the down-pumping mode have the lowest performance of all the impellers studied, although the A315 is preferred of the pitched blade turbine