Multiple, weak hits confuse complex systems: A transcriptional regulatory network as an example

Robust systems, like the molecular networks of living cells are often resistant to single hits such as those caused by high-specificity drugs. Here we show that partial weakening of the Escherichia coli and Saccharomyces cerevisiae transcriptional regulatory networks at a small number (3-5) selected nodes can have a greater impact than the complete elimination of a single selected node. In both cases, the targeted nodes have the greatest possible impact; still the results suggest that in some cases broad specificity compounds or multitarget drug therapies may be more effective than individual high-affinity, high-specificity ones. Multiple but partial attacks mimic well a number of in vivo scenarios and may be useful in the efficient modification of other complex systems.Comment: 8 pages, 3 figures, 2 table

CVaR minimization by the SRA algorithm

Using the risk measure CV aR in �nancial analysis has become more and more popular recently. In this paper we apply CV aR for portfolio optimization. The problem is formulated as a two-stage stochastic programming model, and the SRA algorithm, a recently developed heuristic algorithm, is applied for minimizing CV aR

Donorszelekciós kritériumok vizsgálata a debreceni veseátültetési programban

Absztrakt Bevezetés: A donorszervhiány, a donorok életkorának növekedése és a társbetegségek gyakoribbá válása arra ösztönzi a transzplantálóközpontokat, hogy olyan donorvesék elfogadását is mérlegeljék, amelyeket korábban elutasítottak volna. A donorszelekciós kritériumok segíthetnek ennek eldöntésében. Célkitűzés: A különböző kritériumok hasznosságát illetően nincs egységes álláspont, ezért a szerzők megvizsgálták az expanded criteria donor, a deceased donor score és a kidney donor risk index donorszelekciós kritériumok hatását a posztoperatív vesefunkcióra és grafttúlélésre. Módszer: Ötéves intervallumban 205 donor paramétereinek és 138 veseátültetés kimenetelének retrospektív elemzését végezték el. Eredmények: Az expanded criteria donor rendszer szerint optimálisnak véleményezett donorok negyede a magas kockázatú csoportba került a deceased donor score alapján. A magas kockázatú csoportokban rosszabb volt a műtét utáni graftfunkció. A deceased donor score segítségével tovább lehetett bontani a magas kockázatú csoportot. Az így létrejött legmagasabb kockázatú csoport grafttúlélése és műtét utáni graftműködése elmaradt a többi csoportéhoz képest. Következtetések: A vizsgált pontrendszerek segíthetnek a donorpool biztonságos növelésében. Orv. Hetil., 2016, 157(24), 946–955

Multi-component Transparent Conducting Oxides: Progress in Materials Modelling

Transparent conducting oxides (TCOs) play an essential role in modern optoelectronic devices through their combination of electrical conductivity and optical transparency. We review recent progress in our understanding of multi-component TCOs formed from solid-solutions of ZnO, In2O3, Ga2O3 and Al2O3, with a particular emphasis on the contributions of materials modelling, primarily based on Density Functional Theory. In particular, we highlight three major results from our work: (i) the fundamental principles governing the crystal structures of multi-component oxide structures including (In2O3)(ZnO)n, named IZO, and (In2O3)m(Ga2O3)l(ZnO)n, named IGZO; (ii) the relationship between elemental composition and optical and electrical behaviour, including valence band alignments; (iii) the high-performance of amorphous oxide semiconductors. From these advances, the challenge of the rational design of novel electroceramic materials is discussed.Comment: Part of a themed issue of Journal of Physics: Condensed Matter on "Semiconducting Oxides". In Press (2011

Eredményeink a teljes jogú Eurotransplant-tagság óta. A Debreceni Vesetranszplantációs Központ tapasztalatai

Absztrakt Bevezetés: A Debreceni Egyetemen 1991-ben végezték el az első veseátültetést. Hazánk 2013-ban csatlakozott az Eurotransplanthoz. Célkitűzés: A szerzők elemezték a tapasztalatokat. Módszer: 2008. január 1. és 2013. augusztus 31. között (A csoport = 163) és 2013. szeptember 1. és 2015. október 22. között végzett cadavervese-átültetések (B csoport = 90) adatait elemezték. Eredmények: Az élődonorok aránya 3,5%-ról 9,1%-ra nőtt. 2013 óta a recipiensek 25%-a 60 évesnél idősebb, a >30 kg/m2 testtömegindex aránya 31%-ra, a diabetesesek aránya kétszeresére emelkedett. Az ureteroneocystostomia mellett bevezetésre került a vég az oldalhoz ureteroureteralis anastomosis. Indukciós kezelés mellett az akut rejectiós epizód jelentősen csökkent (34%-ról 8%-ra). A technikai szövődmények aránya nem változott. A bakteriális fertőzések aránya csökkent (41%-ról 33%-ra). Az 1, 3 és 5 éves veseallograft-túlélések 86,6%, 85% és 82,7%, valamint 88%, 84% és 84% voltak a két csoportban. Következtetések: Az extended criteria donor arány emelkedett. 2013 óta lehetségessé vált az akut humoralis rejectio kezelése. Az esetszám-növekedés mellett az eredmények jók. Orv. Hetil., 2016, 157(24), 925–937

Heat shock partially dissociates the overlapping modules of the yeast protein-protein interaction network: a systems level model of adaptation

Network analysis became a powerful tool in recent years. Heat shock is a well-characterized model of cellular dynamics. S. cerevisiae is an appropriate model organism, since both its protein-protein interaction network (interactome) and stress response at the gene expression level have been well characterized. However, the analysis of the reorganization of the yeast interactome during stress has not been investigated yet. We calculated the changes of the interaction-weights of the yeast interactome from the changes of mRNA expression levels upon heat shock. The major finding of our study is that heat shock induced a significant decrease in both the overlaps and connections of yeast interactome modules. In agreement with this the weighted diameter of the yeast interactome had a 4.9-fold increase in heat shock. Several key proteins of the heat shock response became centers of heat shock-induced local communities, as well as bridges providing a residual connection of modules after heat shock. The observed changes resemble to a "stratus-cumulus" type transition of the interactome structure, since the unstressed yeast interactome had a globally connected organization, similar to that of stratus clouds, whereas the heat shocked interactome had a multifocal organization, similar to that of cumulus clouds. Our results showed that heat shock induces a partial disintegration of the global organization of the yeast interactome. This change may be rather general occurring in many types of stresses. Moreover, other complex systems, such as single proteins, social networks and ecosystems may also decrease their inter-modular links, thus develop more compact modules, and display a partial disintegration of their global structure in the initial phase of crisis. Thus, our work may provide a model of a general, system-level adaptation mechanism to environmental changes.Comment: 24 pages, 6 figures, 2 tables, 70 references + 22 pages 8 figures, 4 tables and 8 references in the enclosed Supplemen

In depth evaluation of the prognostic and predictive utility of PTEN immunohistochemistry in colorectal carcinomas: performance of three antibodies with emphasis on intracellular and intratumoral heterogeneity.

BACKGROUND: Phosphatase and tensin homolog deleted in chromosome 10 (PTEN) loss of function is frequently detected in advanced colorectal cancer. Its detection is thought to have prognostic significance and it is being considered to predict responsiveness to anti-EGFR therapy. Unfortunately, while immunohistochemical assessment of PTEN expression is widespread, it lacks standardization and the results are hardly comparable across the available publications. METHODS: Retrospectively collected, formalin-fixed and paraffin-embedded colorectal tumor tissue samples from 55 patients were combined into tissue microarray (TMA) blocks. We used three different PTEN antibodies to determine the frequency, intensity and intracellular pattern of PTEN immunohistochemical labeling: Neomarkers, Dako and CellSignaling. We evaluated the aforementioned parameters in selected regions of colorectal cancers and in their lymph node metastases by using three scoring methods that take into consideration both staining frequency and intensity (H1-H3-score). We also evaluated intracellular localization. RESULTS: The Dako and CellSignaling antibodies stained predominantly cytoplasms, while the Neomarkers antibody specifically stained cell nuclei. PTEN H-scores were significantly lower in all tumor areas as compared to the normal colonic mucosa based on staining with the DAKO and CellSignaling antibodies. Intratumoral regional differences or differences between matching tumors and metastases were not detected with any of the antibodies. Neither Dako, neither CellSignaling, nor the Neomarkers antibodies revealed a significant correlation between PTEN expression and pT, Dukes/MAC and clinical stage. KRAS status, histological grade correlated with PTEN H-scores based on staining with the Neomarkers antibody. PTEN H-scores did not correlate with MMR status. PTEN H-scores did not show any correlation with relapse-free survival based on staining with either antibody. CONCLUSIONS: While PTEN expression decreased in colorectal cancer according to two antibodies, neither of the three applied PTEN antibodies could justify significant correlation with clinicopathological data, nor had prognostic value. Thus, we might conclude that immunohistochemical PTEN investigation remains a challenge requiring more standardized evaluation on larger number of cases to clarify its utility as a prognostic and predictive tool in CRC. The standardization of immunohistochemical method is key in the evaluation process, which is further discussed