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The presence of invasive cell clusters known as tumor budding and the closely related epithelial mesenchymal transition (EMT) have a prognostic impact on cancer patients' overall survival. Interestingly, data quantitatively analyzing and correlating the amount of tumor buds and patient overall survival as well as the impact of expression of epithelial phenotype markers are missing. Periampullary carcinoma samples of 171 patients were immunohistochemically stained for E-Cadherin (ECad). Tumor cell clusters (TCC, defined from one to 50 cells) were manually quantified comprising tumor cell number and subcellular localization of ECad expression (membranous, cytoplasmic or mixed). Data analyses were performed using elastic net feature selection. Hereby, five distinct intervals of TCC sizes and corresponding fractions of cells with distinct ECad expression were identified. Prognostic features of the defined budding categories were entered into a subsequent Cox regression model together with standard clinicopathological parameters and, based on the model prediction, cases were categorized into “low and high budding” grades. Overall median TCC size was 16 cells (range: 2-36 cells). The median number of TCCs per tumor was 42 (range: 3-283). Elastic net feature selection identified TCCs of 6-10 and 31-35 cells as prognostically most relevant negative and positive features, respectively. Regarding ECad expression, cytoplasmic ECad expression in TCCs of 11-15 as well as of 26-30 cells revealed prognostic relevance. Combining TCC numbers and ECad expression, budding grade qualified as independent prognostic factor for patient overall survival (p

Poly(ADP-ribose) polymerase (PARP) is involved in the pathogenesis of cell dysfunction, inflammation and organ failure during septic shock. The goal of the current study was to investigate the efficacy and safety of the clinically approved PARP inhibitor olaparib in experimental models of oxidative stress in vitro and in sepsis in vivo. In mice subjected to cecal ligation and puncture (CLP) organ injury markers, circulating and splenic immune cell distributions, circulating mediators, DNA integrity and survival was measured. In U937 cells subjected to oxidative stress, cellular bioenergetics, viability and DNA integrity were measured. Olaparib was used to inhibit PARP. The results show that in adult male mice subjected to CLP, olaparib (1–10 mg/kg i.p.) improved multiorgan dysfunction. Olaparib treatment reduced the degree of bacterial CFUs. Olaparib attenuated the increases in the levels of several circulating mediators in the plasma. In the spleen, the number of CD4+ and CD8+ lymphocytes were reduced in response to CLP; this reduction was inhibited by olaparib treatment. Treg but not Th17 lymphocytes increased in response to CLP; these cell populations were reduced in sepsis when the animals received olaparib. The Th17/Treg ratio was lower in CLP-olaparib group than in the CLP control group. Analysis of miRNA expression identified a multitude of changes in spleen and circulating white blood cell miRNA levels after CLP; olaparib treatment selectively modulated these responses. Olaparib extended the survival rate of mice subjected to CLP. In contrast to males, in female mice olaparib did not have significant protective effects in CLP. In aged mice olaparib exerted beneficial effects that were less pronounced than the effects obtained in young adult males. In in vitro experiments in U937 cells subjected to oxidative stress, olaparib (1–100 μM) inhibited PARP activity, protected against the loss of cell viability, preserved NAD+ levels and improved cellular bioenergetics. In none of the in vivo or in vitro experiments did we observe any adverse effects of olaparib on nuclear or mitochondrial DNA integrity. In conclusion, olaparib improves organ function and extends survival in septic shock. Repurposing and eventual clinical introduction of this clinically approved PARP inhibitor may be warranted for the experimental therapy of septic shock.

Tanulmányunkban a gázinfrastruktúra-beruházások jóléti és ellátásbiztonsági hatásait elemezzük egy többországos szimulációs modellel, a Duna-régió gázpiaci modellel. Ez a modell figyelembe veszi egyfelől a fizikai-szállítási korlátokat, másfelől a hosszú távú, úgynevezett „vedd át, vagy fizess” szerződések jelentette korlátokat is. A tanulmányban egyedi projekteket, projektcsomagokat (mint például az észak–déli gázfolyosó) és nemzetközi nagynyomásúvezeték-projekteket (mint a Nabucco West) értékelünk tovagyűrűző árhatásaik és a regionális költségkonvergencia indexe alapján. Megmutatjuk, hogy a modell az új európai infrastruktúra-csomag keretében létrehozandó, közös érdekű gázinfrastruktúra-projektek kiválasztását támogató költség–haszon elemzési vizsgálatokban is hasznos eszközként szolgálhat.

Scanning electrochemical microscopy (SECM) with coupled potentiometric and amperometric measurement modes is used to study corrosion reactions in aqueous environments. Whereas conventional electrochemical techniques lack spatial resolution and provide little information on behaviour at sites of corrosion initiation or at defects, the advent of scanning electrochemical microscopy is contributing to overcome these limitations when applied to the investigation of corrosion processes in situ. Ion-selective microelectrodes (ISME) and dual amperometric/potentiometric probes have been developed that can be employed as SECM tips as they exhibit sufficiently low resistances and response times. The applicability of this experimental approach is demonstrated by chemically imaging the behaviour of an iron-magnesium galvanic couple immersed in a diluted aqueous electrolyte. The dissolution of metal ions from anodic sites, the consumption of oxygen at the cathodic sites, and the local pH changes associated with both half cell reactions are thus effectively monitored

Claudins are the main protein components of tight junctions (TJs) which function as selective barriers by controlling paracellular diffusion, maintain cellular polarity and play a role in signal transduction. The expression pattern of the 24 known members of the claudin family proved to be organ and tissue specific. The up- or downregulation of individual claudins has been described, especially during carcinogenesis. A significant increase of claudins-1 and -7 was detected in premalignant cervical lesions and invasive cancer compared with normal cervical epithelia. Claudins-3 and -4 were elevated in endometrial cancer. Claudin-1 overexpression characterized type II (seropapillary) endometrial carcinoma, while claudin-2 was elevated in type I (endometrioid) carcinoma. Claudins-3 and -4 were highly expressed in serous ovarian carcinoma. The expression data on claudins in different premalignant and malignant alterations suggest that these proteins might serve as diagnostic and prognostic markers and might be targets for future therapy.

Jelen tanulmányban a hazai áramár utóbbi időben tapasztalt jelentős emelkedésének magyarázatára vonatkozó leggyakrabban említett tényezőt, a balkáni árampiaci helyzetet és annak a hazai árampiacra gyakorolt hatásait elemezzük. Célunk a délkelet-európai árampiaci fejlemények hátterének feltárása, valamint a balkáni és a hazai árampiac összefüggéseit jellemző tényleges viszonyok leírása. Munkánk során árnyalni igyekszünk a „balkáni” árampiacról a szakmai közbeszédben kialakult differenciálatlan és sok tekintetben hamis képet.

Tanulmányunkban a közép- és kelet-európai térség villamosenergia-nagykereskedelmi piacának rövid távú közgazdasági modellezésével foglalkozunk - teljes piacnyitás utáni körülményeket feltételezve. A modell inputjai között becslést adunk az igénybe vehető termelőkapacitások nagyságára és a termelés költségére, a keresleti jellemzőkre és az átviteli hálózat sajátosságaira. Modellezési megközelítésünk előnye, hogy egyszerre vesszük figyelembe a regionális piacok egymáshoz való térbeli viszonyát és a piaci erőfölénnyel rendelkező vállalatok árbefolyásoló képességét. Főbb következtetéseink: 1. a jelenlegi piaci integráció szintjén a nagy áramtermelő vállalatok piaci ereje számottevő; 2. a szorosabb piaci integráció mérsékli az erőfölénnyel való visszaélés lehetőségét, és árcsökkentő hatással jár; viszont 3. a teljes piaci integráció sem korlátozza kielégítő módon a nagy áramtermelők piaci erejét. Modellezési eredményeink gyakorlati jelentőségét azonban egyszerűsítő feltevéseink valószínűségnek vizsgálata nélkül nem tudjuk pontosan megítélni.