AMNIS - DESIGN AND IMPLEMENTATION OF AN ADAPTIVE WORKFLOW MANAGEMENT SYSTEM

The experiences of introduction and operation of ERP systems have revealed that update of these software due to the constantly changing business processes demand huge resources. That is why the demand was formulated for a method that enables introducing new features in software system without any modification in program code according to the evolution of the organization. The objective of Amnis development project is to create a system with this adaptation capability using the basic idea of workflows that create documents during evaluation. In this article design and programming challenges are shown that had to be met during the development of Amnis, focusing on topics of effective data storage and queries, workflow control structures and workflow evaluation techniques

Területpolitika helyi szociális ellátórendszert érintő döntéseinek hatása a vidéki helyi társadalmak (falvak és kisvárosok) népesség megtartó képességére és a helyi hatalom érdekérvényesítésére = Decision of the Regional Policy effect on the Local Organisation of Social Services an the preservation of the population ability of the Rural Local Society (village, small-town) and the Assertion of the Interests of Local Governments

A kutatás rávilágított arra, hogy a területpolitika "beavatkozási" kísérletei 1990-2002 között, a kistérségek életvilágára; társadalmi dinamikájára, s a településeinek fejlődési trendjére, vagy azok gazdaságára igen csekély számszerűsíthető hatással voltak: Az elemzésekből kitetszik, hogy a decentralizált forrásallokáció inkább kedvez a vidékies kistérségeknek, míg inkább a centralizáltan kezelt fejlesztési támogatások a városias kistérségekbe, városokba jutottak el. Feltételezhető, amennyiben ha a terület- és településfejlesztési források nagyobb arányban jutnak decentralizált elosztási rendszerbe (a megfigyelt időszakban 14% volt), akkor abban az esetben a vidékies kistérségek nagyobb arányban juthatnának támogatáshoz, de a forrásallokáció decentralizációja önmagában nem garantálja a hátrányok leküzdését, mert a fejlettség szintje és fejlesztési források mértéke között nem mutatható ki közvetlen kapcsolat. Minden bizonnyal, a hatékony település- és területfejlesztés nem a centralizált és a decentralizált szintek prioritásán múlik egyedül. A struktúra egészét szükséges érinteni, hogy a rendelkezésre álló fejlesztési források a kívánt eredményt elérjék; a leszakadó kistérségek felzárkózását, a fejlettebb kistérségek számának gyarapodását. A fejlesztési források hatékonyabb felhasználását minden bizonnyal az endogén források alaposabb feltárása és ehhez időben rendelt külső források csatlakoztatása jelentené. E fejlesztési stratégia erősebb kooperációt követel meg a helyi társadalmak szintjén, és nyitottabb, reflexívebb politikát igényelne a kormányzati szintek irányából. | The research revealed that intervention of regional policy between 1990 and 2002 took only a little effect on the life-world and social dynamics of small regions and on the development or economy of their settlements. It is obvious from the analysis that decentralised resource allocation was rather propitious for rurality small regions while urbanity small regions and cities benefit more from centralised development subsidy. Presumably if regional and settlement development resources would get into decentralised allocation in a higher rate (14% in the observed period) rurality small regions may get more subsidy. However, decentralisation of resource allocation itself will not ensure overcoming the disadvantages because it cannot be shown that there is a direct connection between developmental level and the amount of development resources. In all conscience effective regional and settlement development do not depend only on the priority of centralised and decentralised levels. The whole structure should be concerned so that the available development resources have the required effect on improving the underdeveloped small regions and increasing the number of developed small regions. In all conscience development resources could be used more efficiently by a deeper revelation of inner resources and connecting outer resources to them. This development strategy requires closer cooperation in local society and opener and more reflexive governmental policy

Metabolic syndrome influences cardiac gene expression pattern at the transcript level in male ZDF rats

Background: Metabolic syndrome (coexisting visceral obesity, dyslipidemia, hyperglycemia, and hypertension) is a prominent risk factor for cardiovascular morbidity and mortality, however, its effect on cardiac gene expression pattern is unclear. Therefore, we examined the possible alterations in cardiac gene expression pattern in male Zucker Diabetic Fatty (ZDF) rats, a model of metabolic syndrome. Methods: Fasting blood glucose, serum insulin, cholesterol and triglyceride levels were measured at 6, 16, and 25 wk of age in male ZDF and lean control rats. Oral glucose tolerance test was performed at 16 and 25 wk of age. At week 25, total RNA was isolated from the myocardium and assayed by rat oligonucleotide microarray for 14921 genes. Expression of selected genes was confirmed by qRT-PCR. Results: Fasting blood glucose, serum insulin, cholesterol and triglyceride levels were significantly increased, glucose tolerance and insulin sensitivity were impaired in ZDF rats compared to leans. In hearts of ZDF rats, 36 genes showed significant up-regulation and 49 genes showed down-regulation as compared to lean controls. Genes with significantly altered expression in the heart due to metabolic syndrome includes functional clusters of metabolism (e.g. 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 2; argininosuccinate synthetase; 2-amino-3ketobutyrate-coenzyme A ligase), structural proteins (e.g. myosin IXA; aggrecan1), signal transduction (e. g. activating transcription factor 3; phospholipase A2; insulin responsive sequence DNA binding protein-1) stress response (e.g. heat shock 70kD protein 1A; heat shock protein 60; glutathione S-transferase Yc2 subunit), ion channels and receptors (e.g. ATPase, (Na+)/K+ transporting, beta 4 polypeptide; ATPase, H+/K+ transporting, nongastric, alpha polypeptide). Moreover some other genes with no definite functional clusters were also changed such as e. g. S100 calcium binding protein A3; ubiquitin carboxy-terminal hydrolase L1; interleukin 18. Gene ontology analysis revealed several significantly enriched functional inter-relationships between genes influenced by metabolic syndrome. Conclusions: Metabolic syndrome significantly alters cardiac gene expression profile which may be involved in development of cardiac pathologies in the presence of metabolic syndrome

Új utak a prosztatarák terápiájában: a genetikai mintázat szerepe a célzott kezelések kiválasztásában = New approaches in the therapy of prostate cancer: The role of genetic patterns in selecting targeted treatments

A prosztatarák genetikai tesztelésének használata egyre elterjedtebb a klinikai gyakorlatban. Ez elsősorban a PARP-inhibitorok megjelenésének köszönhető, amelyek a prosztataráknak a BRCA és más homológ rekombinációs javító (HRR) gének patogén eltéréseit hordozó eseteiben alkalmazhatóak. Ebből kifolyólag a genetikai vizsgálatok elvégzése a prosztatarák előrehaladott eseteinek kezelése során bekerült a rutinvizsgálatok közé. Ezzel párhuzamosan folyamatosan nő az olyan gyógyszeres kezeléseknek a száma, amelyek alkalmazása célzottan egy bizonyos genetikai eltérés jelenléte esetén lehetséges. Ennek eredményeképpen egyre növekszik azon gének száma, amelyek vizsgálata fontos lehet a prosztatadaganatok kezelési stratégiáinak megválasztásánál. Jelen közleményünk- kel szeretnénk áttekintést nyújtani a prosztatarák molekuláris alcsoportjairól, valamint azokról a génekről, amelyek a jelenleg és a közeljövőben potenciálisan alkalmazható kezelések kiválasztásához szükségesek. = The use of genetic testing for prostate cancer is becoming increasingly common in clinical practice, particularly because of the emergence of PARP inhibitors that target tumours with specific genetic abnormalities in their BRCA and other homologous recombination repair (HRR) genes. At the same time, the number of available therapies that target specific subgroups of prostate cancer based on their genetic makeup is continuously growing. Consequently, the selection of treatment for prostate cancer patients may involve testing multiple genes to allow for more tailored treatment plans that take into account the genetic features of the tumour. In this review we aim to provide an overview on the currently relevant genetic alterations in prostate cancer for therapeutic purposes

Glucagon-Like Peptide-1 Excites Firing and Increases GABAergic Miniature Postsynaptic Currents (mPSCs) in Gonadotropin-Releasing Hormone (GnRH) Neurons of the Male Mice via Activation of Nitric Oxide (NO) and Suppression of Endocannabinoid Signaling Pathways

Glucagon-like peptide-1 (GLP-1), a metabolic signal molecule, regulates reproduction, although, the involved molecular mechanisms have not been elucidated, yet. Therefore, responsiveness of gonadotropin-releasing hormone (GnRH) neurons to the GLP-1 analog Exendin-4 and elucidation of molecular pathways acting downstream to the GLP-1 receptor (GLP-1R) have been challenged. Loose patch-clamp recordings revealed that Exendin-4 (100 nM-5 μM) elevated firing rate in hypothalamic GnRH-GFP neurons of male mice via activation of GLP-1R. Whole-cell patch-clamp measurements demonstrated increased excitatory GABAergic miniature postsynaptic currents (mPSCs) frequency after Exendin-4 administration, which was eliminated by the GLP-1R antagonist Exendin-3(9-39) (1 μM). Intracellular application of the G-protein inhibitor GDP-β-S (2 mM) impeded action of Exendin-4 on mPSCs, suggesting direct excitatory action of GLP-1 on GnRH neurons. Blockade of nitric-oxide (NO) synthesis by Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME; 100 μM) or N(5)-[Imino(propylamino)methyl]-L-ornithine hydrochloride (NPLA; 1 μM) or intracellular scavenging of NO by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO; 1 mM) partially attenuated the excitatory effect of Exendin-4. Similar partial inhibition was achieved by hindering endocannabinoid pathway using cannabinoid receptor type-1 (CB1) inverse-agonist 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-(1-piperidyl) pyrazole-3-carboxamide (AM251; 1 μM). Simultaneous blockade of NO and endocannabinoid signaling mechanisms eliminated action of Exendin-4 suggesting involvement of both retrograde machineries. Intracellular application of the transient receptor potential vanilloid 1 (TRPV1)-antagonist 2E-N-(2, 3-Dihydro-1,4-benzodioxin-6-yl)-3-[4-(1, 1-dimethylethyl)phenyl]-2-Propenamide (AMG9810; 10 μM) or the fatty acid amide hydrolase (FAAH)-inhibitor PF3845 (5 μM) impeded the GLP-1-triggered endocannabinoid pathway indicating an anandamide-TRPV1-sensitive control of 2-arachidonoylglycerol (2-AG) production. Furthermore, GLP-1 immunoreactive (IR) axons innervated GnRH neurons in the hypothalamus suggesting that GLP-1 of both peripheral and neuronal sources can modulate GnRH neurons. RT-qPCR study confirmed the expression of GLP-1R and neuronal NO synthase (nNOS) mRNAs in GnRH-GFP neurons. Immuno-electron microscopic analysis revealed the presence of nNOS protein in GnRH neurons. These results indicate that GLP-1 exerts direct facilitatory actions via GLP-1R on GnRH neurons and modulates NO and 2-AG retrograde signaling mechanisms that control the presynaptic excitatory GABAergic inputs to GnRH neurons

Meta-analysis of gene expression profiles associated with histological classification and survival in 829 ovarian cancer samples.

Transcriptomic analysis of global gene expression in ovarian carcinoma can identify dysregulated genes capable to serve as molecular markers for histology subtypes and survival. The aim of our study was to validate previous candidate signatures in an independent setting and to identify single genes capable to serve as biomarkers for ovarian cancer progression. As several datasets are available in the GEO today, we were able to perform a true meta-analysis. First, 829 samples (11 datasets) were downloaded, and the predictive power of 16 previously published gene sets was assessed. Of these, eight were capable to discriminate histology subtypes, and none was capable to predict survival. To overcome the differences in previous studies, we used the 829 samples to identify new predictors. Then, we collected 64 ovarian cancer samples (median relapse-free survival 24.5 months) and performed TaqMan Real Time Polimerase Chain Reaction (RT-PCR) analysis for the best 40 genes associated with histology subtypes and survival. Over 90% of subtype-associated genes were confirmed. Overall survival was effectively predicted by hormone receptors (PGR and ESR2) and by TSPAN8. Relapse-free survival was predicted by MAPT and SNCG. In summary, we successfully validated several gene sets in a meta-analysis in large datasets of ovarian samples. Additionally, several individual genes identified were validated in a clinical cohort

Meta-analysis of gene expression profiles associated with histological classification and survival in 829 ovarian cancer samples

Transcriptomic analysis of global gene expression in ovarian carcinoma can identify dysregulated genes capable to serve as molecular markers for histology subtypes and survival. The aim of this study was to validate previous candidate signatures in an independent setting and to identify single genes capable to serve as biomarkers for ovarian cancer progression. As several datasets are available in the GEO today, we were able to perform a true meta-analysis. First, 829 samples (11 datasets) were downloaded, and the predictive power of 16 previously published gene sets was assessed. Of these, 8 were capable to discriminate histology subtypes and none was capable to predict survival. To overcome the differences in previous studies, we used the 829 samples to identify new predictors. Then we collected 64 ovarian cancer samples (median relapse-free survival 24.5 months) and performed TaqMan RT-PCR analysis for the best 40 genes associated with histology subtypes and survival. Over 90% of subtype-associated genes were confirmed. Overall survival was effectively predicted by hormone receptors (PGR and ESR2) and by TSPAN8. Relapse-free survival was predicted by MAPT and SNCG. In summary, we successfully validated several gene sets in a meta-analysis in large datasets of ovarian samples. Additionally, several individual genes identified were validated in a clinical cohort