Representations of Circular Words

In this article we give two different ways of representations of circular words. Representations with tuples are intended as a compact notation, while representations with trees give a way to easily process all conjugates of a word. The latter form can also be used as a graphical representation of periodic properties of finite (in some cases, infinite) words. We also define iterative representations which can be seen as an encoding utilizing the flexible properties of circular words. Every word over the two letter alphabet can be constructed starting from ab by applying the fractional power and the cyclic shift operators one after the other, iteratively.Comment: In Proceedings AFL 2014, arXiv:1405.527

MisPred: a resource for identification of erroneous protein sequences in public databases

Correct prediction of the structure of protein-coding genes of higher eukaryotes is still a difficult task; therefore, public databases are heavily contaminated with mispredicted sequences. The high rate of misprediction has serious consequences because it significantly affects the conclusions that may be drawn from genome-scale sequence analyses of eukaryotic genomes. Here we present the MisPred database and computational pipeline that provide efficient means for the identification of erroneous sequences in public databases. The MisPred database contains a collection of abnormal, incomplete and mispredicted protein sequences from 19 metazoan species identified as erroneous by MisPred quality control tools in the UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, NCBI/RefSeq and EnsEMBL databases. Major releases of the database are automatically generated and updated regularly. The database (http://www.mispred.com) is easily accessible through a simple web interface coupled to a powerful query engine and a standard web service. The content is completely or partially downloadable in a variety of formats

Selection criteria for preoperative endoscopic retrograde cholangiopancreatography before laparoscopic cholecystectomy and endoscopic treatment of bile duct stones. Results of a retrospective; single center study between 1996-2002

AIM: The optimal treatment for bile duct stones (in terms of cost, complications and accuracy) is unclear. The aim of our study was to determine the predictive factors for preoperative endoscopic retrograde cholangiopancreatography (ERCP). METHODS: Patients undergoing preoperative ERCP (= 8 mm) and/or stone at US examination, coexisting acute pancreatitis and/or acute pancreatitis or jaundice in patient's history. Suspected prognostic factors and the combination of factors were compared to the result of ERCP. RESULTS: Two hundred and six preoperative ERCPs were performed during the observed period. The rate of successful cannulation for ERC was (97.1%). Bile duct stones were detected in 81 patients (39.3%), and successfully removed in 79 (97.5%). The number of prognostic factors correlated with the presence of bile duct stones. The positive predictive value for one prognostic factor was 1.2%, for two 43%, for three 72.5%, for four or more 91.4%. CONCLUSION: Based on our data preoperative ERCP is highly recommended in patients with three or more positive factors (high risk patients). In contrast, ERCP is not indicated in patients with zero or one factor (low risk patients). Preoperative ERCP should be offered to patients with two positive factors (moderate risk patients), however the practice should also be based on the local conditions (e.g. skill of the endoscopist, other diagnostic tools)

Investigations for the mechanism of action of novel positive inotropic agents

Az akut szívelégtelenség mortalitása a fejlődő farmakológiai és eszközös kezelés ellenére magas, sőt a Ca2+-mobilizáló inotróp szerek adverz hatásúak a hosszú távú túlélésre. A szarkomert aktiváló szerek új terápiás lehetőséget teremtenek az akut szívelégtelenség kezelésére: a Ca2+-érzékenyítő levosimendan hatékonyságát egyre több klinikai evidencia támasztja alá, míg a miozin aktivátor omecamtiv mecarbil (OM) kapcsán szintén egyre több bíztató eredmény lát napvilágot. Célul tűztük ki, hogy tanulmányozzuk az OM, valamint a levosimendan származék ORM-3819 izolált és permeabilizált szívizomsejtek kontraktilitásának mechanikai és kinetikai paramétereire gyakorolt hatásait, valamint igazoljuk az OM szöveti szelektivitását rekeszizom eredetű vázizomrostokon végzett kontraktilis erőmérésekkel. Az OM növelte a szívizomsejtek Ca2+-érzékenységét, hiszen adott szubmaximális [Ca2+] mellett alacsony és közepes koncentrációban fokozta a preparátumok kontraktilitását, míg inotróp hatása mérsékeltebb volt nagy koncentrációban. Az OM fokozta a szívizomsejtek Fpasszív-ját, illetve az Faktív-ját diasztolés [Ca2+] szinteken. A miozin aktiváció eredményeként lassabb és tartósabb Ca2+-kontraktúrákat regisztráltunk, hiszen csökkent az aktin – miozin kereszthidak sebességi állandója. A szívizomsejteken tapasztaltakhoz hasonló jellegű, de kisebb affinitású OM-hatásokat regisztráltunk lassú endogén kinetikájú vázizomrostok esetében, míg gyors típusú vázizomrostok esetén az OM hatása minimálisnak bizonyult a terápiás dózisokkal identikus koncentráció-tartományban. A levosimendan származék ORM-3819 szintén fokozta a szívizomsejtek Ca2+-érzékenységét az OM-től eltérő mechanikai illetve kinetikai hatásokkal. A cTnC-függő Ca2+-érzékenyítés következtében erőteljesebb és gyorsabb Ca2+-kontraktúrák jöttek létre, hiszen fokozódott az aktin – miozin hidak sebességi állandója. Az ORM-3819 jelenlétében nem alakult ki Ca2+-érzékenyítés diasztolés [Ca2+]-n, valamint nem változott az Fpasszív. Eredményeink alapján az OM Ca2+-érzékenyítő hatású pozitív inotróp szer, mely az aktin – miozin interakció modulálásával az inotrópia szabályozásának „downstream” útvonalán hat. Az OM mechanikai és kinetikai hatásainak köszönhetően erősebb, gyorsabb és lassabb kontrakciók jönnek létre, de alkalmazása fokozott óvatosságot igényel, hiszen felmerülhet a diasztolés diszfunkció veszélye. Az ORM-3819 a cTnC-hez történő kötődésével a Ca2+-érzékenyítés centrális útvonalán hat, de pozitív inotróp hatásában a szelektív PDE III gátlás is szerepet játszhat.While Ca2+-mobilizer positive inotropic agents are nowadays less favored in acute heart failure, direct activation of the cardiac sarcomere became an attractive strategy for the treatment of acute decompensation. The Ca2+-sensitizer levosimendan is now widely accepted to give inotropic support for the failing heart and cardiac myosin activation by omecamtiv mecarbil (OM) is also increasingly considered as a future therapeutic agent in heart failure. Our aim was to assess the mechanical and kinetic effects of OM and the levosimendan-related ORM-3819 on the contractile function of isolated and permeabilized cardiomyocytes. In addition, we also aimed at the clarification of the tissue selectivity of OM during contractile force measurements in skeletal muscle myofiber preparations from the diaphragm. At a given submaximal [Ca2+] OM increased the Ca2+-sensitivity of force production in cardiomyocytes in the presence of low and intermediate OM concentrations, but high OM concentrations did not augment force production. OM dependent Ca2+-sensitization was also observed at very low [Ca2+] levels mimicking diastolic conditions, and it also increased Fpassive. OM decreased the rate of the actin-myosin cross-bridge cycle. Due to the above mechanic and kinetic effects, OM treatment led to strong, slow and long-lasting Ca2+-contractures. OM evoked similar effects in skeletal muscle fibers with slow intrinsic kinetics, nevertheless, OM possessed lower affinity for skeletal muscle fibers than for cardiomyocytes. In fast skeletal muscle preparations, OM-evoked mechanical changes were observed only at high OM concentrations. The levosimendan-related ORM-3819 also increased the Ca2+-sensitivity of force production of the cardiomyocytes, however with a different mechanism of action than OM. ORM-3819-evoked Ca2+-sensitization was accompanied by strong Ca2+-contractures due to increased rates of cross-bridge cycling. ORM-3819 failed to evoke Ca2+-sensitization at very low [Ca2+] and it did not increase Fpassive. Our data demonstrated OM as a Ca2+-sensitizing agent with a downstream mechanism of action in both cardiomyocytes and diaphragmatic muscle fibers. We propose that OM should be administered with care in patients with heart failure because of its potential adverse effects on myocardial relaxation. ORM-3819 was characterized as a cTnC-dependent Ca2+-sensitizer, thereby acting centrally in the contractile process. The positive inotropic effect of ORM-3819 is complemented by its selective inhibition of PDE III isoenzymes.N