Crystallographic Education in the 21st Century

There are many methods that can be used to incorporate concepts of crystallography into the learning experiences of students, whether they are in elementary school, at university or part of the public at large. It is not always critical that those who teach crystallography have immediate access to diffraction equipment to be able to introduce the concepts of symmetry, packing or molecular structure in an age- and audience-appropriate manner. Crystallography can be used as a tool for teaching general chemistry concepts as well as general research techniques without ever having a student determine a crystal structure. Thus, methods for younger students to perform crystal growth experiments of simple inorganic salts, organic compounds and even metals are presented. For settings where crystallographic instrumentation is accessible (proximally or remotely), students can be involved in all steps of the process, from crystal growth, to data collection, through structure solution and refinement, to final publication. Several approaches based on the presentations in the MS92 Microsymposium at the IUCr 23rd Congress and General Assembly are reported. The topics cover methods for introducing crystallography to undergraduate students as part of a core chemistry curriculum; a successful short-course workshop intended to bootstrap researchers who rely on crystallography for their work; and efforts to bring crystallography to secondary school children and non-science majors. In addition to these workshops, demonstrations and long-format courses, open-format crystallographic databases and three-dimensional printed models as tools that can be used to excite target audiences and inspire them to pursue a deeper understanding of crystallography are described

Switching the Inhibitor‐Enzyme Recognition Profile via Chimeric Carbonic Anhydrase XII

A key part of the optimization of small molecules in pharmaceutical inhibitor development is to vary the molecular design to enhance complementarity of chemical features of the compound with the positioning of amino acids in the active site of a target enzyme. Typically this involves iterations of synthesis, to modify the compound, and biophysical assay, to assess the outcomes. Selective targeting of the anti-cancer carbonic anhydrase isoform XII (CA XII), this process is challenging because the overall fold is very similar across the twelve CA isoforms. To enhance drug development for CA XII we used a reverse engineering approach where mutation of the key six amino acids in the active site of human CA XII into the CA II isoform was performed to provide a protein chimera (chCA XII) which is amenable to structure-based compound optimization. Through determination of structural detail and affinity measurement of the interaction with over 60 compounds we observed that the compounds that bound CA XII more strongly than CA II, switched their preference and bound more strongly to the engineered chimera, chCA XII, based on CA II, but containing the 6 key amino acids from CA XII, behaved as CA XII in its compound recognition profile. The structures of the compounds in the chimeric active site also resembled those determined for complexes with CA XII, hence validating this protein engineering approach in the development of new inhibitors

PLBD: protein–ligand binding database of thermodynamic and kinetic intrinsic parameters

We introduce a protein–ligand binding database (PLBD) that presents thermodynamic and kinetic data of reversible protein interactions with small molecule compounds. The manually curated binding data are linked to protein–ligand crystal structures, enabling structure–thermodynamics correlations to be determined. The database contains over 5500 binding datasets of 556 sulfonamide compound interactions with the 12 catalytically active human carbonic anhydrase isozymes defined by fluorescent thermal shift assay, isothermal titration calorimetry, inhibition of enzymatic activity and surface plasmon resonance. In the PLBD, the intrinsic thermodynamic parameters of interactions are provided, which account for the binding-linked protonation reactions. In addition to the protein–ligand binding affinities, the database provides calorimetrically measured binding enthalpies, providing additional mechanistic understanding. The PLBD can be applied to investigations of protein–ligand recognition and could be integrated into small molecule drug design

Litewski rynek pracy – priorytety polityki w kontekście Unii Europejskiej

The article reviews the situation in the Lithuanian labour market and changes which took place in it from the restoration of state independence to the post-crisis period. Based on the analysis of statistical data and legislation, development stages characteristic of the Lithuanian labour market are identified and decisions related to labour market management are overviewed. The article also provides the analysis of legal regulation of Lithuanian labour relations and reveals the fundamental legal features of labour relations, which may be useful in order to achieve greater flexibility and security in the labour market. The article reveals that the Lithuanian labour market was subjected to a few distinct development stages, which determined the measures of the labour market policy. The changing economic situation resulted in changes in the labour market policy, which are indicators of the relevance of labour market issues and the need for their solution.W artykule dokonano krótkiego przeglądu sytuacji rynku pracy na Litwie oraz zachodzących w nim zmian od odzyskania niepodległości Litwy (1990 r.) do okresu po kryzysie gospodarczym (od 2011 r.). Według danych statystycznych i analizy przepisów prawnych na litewskim rynku pracy są zidentyfikowane etapy rozwoju oraz dokonany przegląd odpowiednich decyzji politycznych. Artykuł również zawiera analizę prawnej regulacji stosunków pracy na Litwie, odsłania podstawowe cechy stosunków pracy, które mogą mieć korzystny wpływ na elastyczność i bezpieczeństwo socjalne na rynku pracy. W artykule zauważa się, że Litewski rynek pracy przechodził przez kilka wyraźnych etapów rozwoju, od których była uzależniona stosowana polityka rynku pracy. Zmiany sytuacji gospodarczej wpływają na zmiany polityki rynku pracy, które wskazują na pilność problemów rynku pracy oraz konieczność podjęcia odpowiednich decyzji by zwiększać efektywność funkcjonowania rynku pracy oraz wykorzystywania wciąż kurczących się zasobów kapitału ludzkiego kraju

Lithuanian labour market – policy priorities in the context of the European Union

The article reviews the situation in the Lithuanian labour market and changes which took place in it from the restoration of state independence to the post-crisis period. Based on the analysis of statistical data and legislation, development stages characteristic of the Lithuanian labour market are identified and decisions related to labour market management are overviewed. The article also provides the analysis of legal regulation of Lithuanian labour relations and reveals the fundamental legal features of labour relations, which may be useful in order to achieve greater flexibility and security in the labour market. The article reveals that the Lithuanian labour market was subjected to a few distinct development stages, which determined the measures of the labour market policy. The changing economic situation resulted in changes in the labour market policy, which are indicators of the relevance of labour market issues and the need for their solution.W artykule dokonano krótkiego przeglądu sytuacji rynku pracy na Litwie oraz zachodzących w nim zmian od odzyskania niepodległości Litwy (1990 r.) do okresu po kryzysie gospodarczym (od 2011 r.). Według danych statystycznych i analizy przepisów prawnych na litewskim rynku pracy są zidentyfikowane etapy rozwoju oraz dokonany przegląd odpowiednich decyzji politycznych. Artykuł również zawiera analizę prawnej regulacji stosunków pracy na Litwie, odsłania podstawowe cechy stosunków pracy, które mogą mieć korzystny wpływ na elastyczność i bezpieczeństwo socjalne na rynku pracy. W artykule zauważa się, że Litewski rynek pracy przechodził przez kilka wyraźnych etapów rozwoju, od których była uzależniona stosowana polityka rynku pracy. Zmiany sytuacji gospodarczej wpływają na zmiany polityki rynku pracy, które wskazują na pilność problemów rynku pracy oraz konieczność podjęcia odpowiednich decyzji by zwiększać efektywność funkcjonowania rynku pracy oraz wykorzystywania wciąż kurczących się zasobów kapitału ludzkiego kraju

A System of Indicators for Evaluating the Motivation of Employees for Work in Telecommunication Enterprises

The article examines the main problem dealing with the evaluation of the motivation level of employees for work in telecommunication enterprises. The paper considers motivation factors taken into account for the purpose of establishing the general motivation level of the employee. The article describes the classification of the presented factors and determines their significance. SAW method has been used for creating a system of indicators for evaluating the level of motivation. Telekomunikacijų įmonių darbuotojų darbo motyvacijos vertinimo rodiklių sistema Santrauka Straipsnyje  nagrinėjamos  telekomunikacijų  bendrovių  darbuotojų  motyvacijos  problemos,  atskleista  motyvacijos  veiksnių vertinimo problematika. Išnagrinėti motyvaciniai veiksniai, pagal kuriuos nustatomas bendras darbuotojo motyvacijos lygis. Pateiktas motyvacijos veiksnių klasifikavimas, nustatyti veiksnių reikšmingumai. Išnagrinėjus teorinius ir praktinius ska­tinimo veiksnių vertinimo aspektus, taikant daugiakriterį SAW metodą, suformuota motyvacijos sistemos vertinimo rodiklių sistema. Reikšminiai žodžiai: darbuotojų darbo motyvacija, vertinimas, metodas, rodiklis

Discovery and characterization of novel selective inhibitors of carbonic anhydrase IX

Human carbonic anhydrase IX (CA IX) is highly expressed in tumor tissues, and its selective inhibition provides a potential target for the treatment of numerous cancers. Development of potent, highly selective inhibitors against this target remains an unmet need in anticancer therapeutics. A series of fluorinated benzenesulfonamides with substituents on the benzene ring was designed and synthesized. Several of these exhibited a highly potent and selective inhibition profile against CA IX. Three fluorine atoms significantly increased the affinity by withdrawing electrons and lowering the pKa of the benzenesulfonamide group. The bulky ortho substituents, such as cyclooctyl or even cyclododecyl groups, fit into the hydrophobic pocket in the active site of CA IX but not CA II, as shown by the compound's co-crystal structure with chimeric CA IX. The strongest inhibitor of recombinant human CA IX's catalytic domain in human cells achieved an affinity of 50 pM. However, the high affinity diminished the selectivity. The most selective compound for CA IX exhibited 10 nM affinity. The compound that showed the best balance between affinity and selectivity bound with 1 nM affinity. The inhibitors described in this work provide the basis for novel anticancer therapeutics targeting CA IX

Crystallographic education in the 21st century

There are many methods that can be used to incorporate concepts of crystallography into the learning experiences of students, whether they are in elementary school, at university or part of the public at large. It is not always critical that those who teach crystallography have immediate access to diffraction equipment to be able to introduce the concepts of symmetry, packing or molecular structure in an age- and audience-appropriate manner. Crystallography can be used as a tool for teaching general chemistry concepts as well as general research techniques without ever having a student determine a crystal structure. Thus, methods for younger students to perform crystal growth experiments of simple inorganic salts, organic compounds and even metals are presented. For settings where crystallographic instrumentation is accessible (proximally or remotely), students can be involved in all steps of the process, from crystal growth, to data collection, through structure solution and refinement, to final publication. Several approaches based on the presentations in the MS92 Microsymposium at the IUCr 23rd Congress and General Assembly are reported. The topics cover methods for introducing crystallography to undergraduate students as part of a core chemistry curriculum; a successful short-course workshop intended to bootstrap researchers who rely on crystallography for their work; and efforts to bring crystallography to secondary school children and non-science majors. In addition to these workshops, demonstrations and long-format courses, open-format crystallographic databases and three-dimensional printed models as tools that can be used to excite target audiences and inspire them to pursue a deeper understanding of crystallography are described