Ligand entry in human ileal bile acid-binding protein is mediated by histidine protonation

Abstract Human ileal bile acid-binding protein (hI-BABP) has a key role in the intracellular transport of bile salts. To explore the role of histidine protonation in the binding process, the pH-dependence of bile salt binding and internal dynamics in hI-BABP was investigated using NMR spectroscopy and biophysical tools. Thermodynamic and kinetic measurements show an increase in the overall binding affinity and the association rate constant of the first binding step below the pKa of the histidines, suggesting that ligand binding is favoured by the protonated state. The overlap between residues exhibiting a high sensitivity to pH in their backbone amide chemical shifts and protein regions undergoing a global ms conformational exchange indicate a connection between the two processes. According to 15N NMR relaxation dispersion analysis, the slow motion is most pronounced at and above the pKa of the histidines. In agreement with the NMR measurements, MD simulations show a stabilization of the protein by histidine protonation. Hydrogen-bonding and van der Waals interactions mediating the flow of information between the C/D- and G/H-turn regions hosting the three histidines, suggest a complex way of pH-governed allosteric regulation of ligand entry involving a transition between a closed and a more open protein state

Deletion of poly(ADP?ribose) polymerase-1 changes the composition of the microbiome in the gut

L

Workstation Configuration and Process Planning for RLW Operations

The application of Remote Laser Welding (RLW) has become an attractive assembly technology in various branches of industry, as it offers higher efficiency at lower costs compared to traditional Resistance Spot Welding (RSW) when high volumes of sheet metal assemblies are to be produced. However, the introduction of RLW technology raises multiple new issues in designing the configuration, the layout, and the behavior of the assembly system. Since configuring an RLW workstation and planning the welding process are closely interrelated problems, a hierarchical decision process must be applied where configuration and planning go hand in hand. The paper presents a hierarchical workflow forworkstation configuration and process planning for RLW operations, and proposes methods for solving the decision problems related to each step of this workflow. A software toolbox is introduced that has been developed to facilitate a semi-Automatic, mixed-initiative workstation design and t o guide the expert user throughout the configuration, planning, programming, evaluation, and simulation of the RLW workstation. A case study from the automotive industry is presented, where the software tools developed are applied to configuring and planning the behavior of an RLW workstation that replaces RSW technology in assembling a car door

Autonómiák Magyarországon 1848-1998 = Local and Ecclesiastical Autonomies in Hungary 1848-1998

A kutatás célja az 1848-2000 közötti magyarországi közigazgatási, kamarai, társadalombiztosítási, egyházi, egyetemi önkormányzatok és az MTA autonómiája forrásainak, dokumentumainak feltárása, összegyűjtése és publikációjának előkészítése volt. A cél megvalósult, 2005 végén Gergely Jenő szerkesztésében megjelent az "Autonómiák Magyarországon 1848-2000" I-III. kötet. Az I. kötetben található a kutatók által írt, 270 o. terjedelmű elemző tanulmány. Ezt önálló kötetként német nyelven 2006-ban adtuk ki. Ennek célja a nemzetközi szakmai kapcsolataink erősítése. Végül 2006 elején a 3-kötetes művet CD-ROM-ként is megjelentettük. Az anyaggyűjtés nagyobb részének befejezése után, 2004 őszén meghívottakkal konferenciát rendeztünk, amelynek előadásait tanulmánykötetben megjelentettük. A témavezető és doktoranduszok részeredményeiket külön is publikálták. A résztvevő professzorok és doktoranduszok eredményesen dolgoztak együtt, a munka során valóban "tudományos iskolaként" működtek és várhatóan működnek a jövőben is. Az új tudományos eredmény annak dokumentálása, hogy az autonómiák a civil társadalom olyan önszerveződései, amelyek létezése és működése a politikai demokrácia egyik fontos alkotó eleme, biztosítéka. Az új eredményeket, forrásokat a történeti kutatások, az egyetemi oktatás, a mai autonómiák és a közélet egyaránt hasznosíthatják. Eredményeink nyomtatásban közzétett változata hozzáférhető a könyvtárakban, és bárki számára a CD-n. | The aim of the research was the preparation for the exploration, gathering and publication of sources and documents of Hungarian administrative, fiscal, social security-, ecclesiastical, university- and academic autonomies between 1848 and 2000. The aim was realized; in late 2005 "Autonomies in Hungary, 1848-2000." was published, edited by Jenő Gergely. Vol. 1 contains a 270-page analyzing study. In 2006 this study was published as a separate book in German, aiming to strengthen our international scientific ties. Finally, the above-mentioned 3-volume work was released in early 2006 as a CD-ROM. After the material gathering, a conference was held in 2004, the talks of which were published in a study collection. The leading consultant and the PhD students published their partial results in scientific periodicals. The professors and doctoral candidates worked together successfully, functioned as a real ?school of science? and are expected to do so in the future. The novel scientific achievement of the project is the documentation of autonomies as such self-organizing bodies of civil society whose existence and function is a basic guarantee of political democracy. The recent results and sources will be useful for reseachers of history, tertiary and especially PhD instructors, the present-day autonomies, and social life. The printed version of our work is available in libraries and the CD version is on general sale

Could successful cryoballoon ablation of paroxysmal atrial fibrillation prevent progressive left atrial remodeling?

<p>Abstract</p> <p>Background</p> <p>Radiofrequency catheter ablation of atrial fibrillation (AF) has been proved to be effective and to prevent progressive left atrial (LA) remodeling. Cryoballoon catheter ablation (CCA), using a different energy source, was developed to simplify the ablation procedure. Our hypothesis was that successful CCA can also prevent progressive LA remodeling.</p> <p>Methods</p> <p>36 patients selected for their first CCA because of nonvalvular paroxysmal AF had echocardiography before and 3, 6 and 12 months after CCA. LA diameters, volumes (LAV) and LA volume index (LAVI) were evaluated. LA function was assessed by: early diastolic velocities of the mitral annulus (Aa_sept, Aa_lat), LA filling fraction (LAFF), LA emptying fraction (LAEF) and the systolic fraction of pulmonary venous flow (PVSF). Detailed left ventricular diastolic function assessment was also performed.</p> <p>Results</p> <p>Excluding recurrences in the first 3-month blanking period, the clinical success rate was 64%. During one-year of follow-up, recurrent atrial arrhythmia was found in 21 patients (58%). In the recurrent group at 12 months after ablation, minimal LAV (38 ± 19 to 44 ± 20 ml; <it>p </it>< 0.05), maximal LAV (73 ± 23 to 81 ± 24 ml; <it>p </it>< 0.05), LAVI (35 ± 10 to 39 ± 11 ml/m²; <it>p </it>= 0.01) and the maximal LA longitudinal diameter (55 ± 5 to 59 ± 6 mm; <it>p </it>< 0.01) had all increased. PVSF (58 ± 9 to 50 ± 10%; <it>p </it>= 0.01) and LAFF (36 ± 7 to 33 ± 8%; <it>p </it>= 0.03) had decreased. In contrast, after successful cryoballoon ablation LA size had not increased and LA function had not declined. In the recurrent group LAEF was significantly lower at baseline and at follow-up visits.</p> <p>Conclusions</p> <p>In patients whose paroxysmal atrial fibrillation recurred within one year after cryoballoon catheter ablation left atrial size had increased and left atrial function had declined. In contrast, successful cryoballoon catheter ablation prevented progressive left atrial remodeling.</p

Lukács György levelezése 1945 és 1971 között = The Correspondence of George Lukács between 1945 and 1971

A kutatás a technikai feltételek megteremtésével kezdődött (számítógép- és szkennervásárlás, korlátlan internethasználat). Elkészült a Lukács Archívum honlapja: www.lua.hu. Megkezdődött, majd más forrásból kapott támogatással befejeződött a Lukács-levelezés digitális katalogizálása. Elvégeztük a Lukács 1945 utáni leveleinek más levéltárakból, archívumokból való fölgyűjtését, a kiadási és szerkesztési koncepció kidolgozását, az előválogatást, továbbá az életrajzi, kapcsolati segédletek elkészítését, a kiadni tervezett magyar nyelvű levelek jelentős részének abc- és időrendi jegyzékét, a magyar anyag annotálását. Megkezdődött a német nyelvű levelezés hasonló szempontú feltérképezése, a további kutatás szempontjainak kidolgozása. | Research began with building the technical infrastructure (purchase of computers, scanners, broadband internet connection). The website of the Lukács Archive has also been created: www.lua.hu. Digital cataloguing of the Lukács correspondence was started. This process was later completed using financial support from other sources. We collected Lukács? post-1945 correspondence from different archives, elaborated the conception for editing and publication, did the pre-selection, and prepared the biographical supplements. We also finished the alphabetical and chronological catalogue of most of the Hungarian letters to be published, as well as the annotation of the Hungarian material. A similar work on the German-language correspondence, along with the preparation of further aspects of research, has been started