The institutional transformation of social transformation of social policy in East Central Europe : Poland and Hungary in comparative and historical perspective

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Cyclic triterpenoid production with tailored Saccharomyces cerevisiae

Triterpenoids are secondary plant metabolites derived from squalene and consist of six isoprene units (C30). Many of them or their synthetic derivatives are currently being investigated as medicinal products for various diseases. The cyclic triterpenoid betulinic acid is of special interest for the pharmaceutical and nutritional industry as it has antiretroviral, antimalarial, and anti-inflammatory properties and has potential as an anticancer agent (Muffler et al. 2011, Mullauer et al. 2010). Despite their obvious industrial potential, the application is often hindered by their low abundance in natural plant sources. This poses challenges in a biosustainable production of such compounds due to wasteful and costly product purification. Here, we present a novel biotechnological process for the production of betulinic acid using tailored Saccharomyces cerevisiae strains. The multi-scale optimization of this microbial process included: - pathway engineering by determination of optimal gene combination and dosage, - compartment engineering to increase the reaction space of the betulinic acid pathway, and - strain engineering by implementation of different push, pull and block strategies. In parallel we developed the fermentation process and were able to boost the performance of the engineered yeast by optimization of medium composition, cultivation conditions, carbon source and mode of fermentation operation in lab scale bioreactors. Product purification was achieved by a one-step extraction with acetone. The final process was evaluated in terms of economic and ecological efficiency and rated to be competitive with existing plant extraction procedures with potential for further performance improvement. Please click Additional Files below to see the full abstract

The HTLV-1-encoded protein HBZ directly inhibits the acetyl transferase activity of p300/CBP

The homologous cellular coactivators p300 and CBP contain intrinsic lysine acetyl transferase (termed HAT) activity. This activity is responsible for acetylation of several sites on the histones as well as modification of transcription factors. In a previous study, we found that HBZ, encoded by the Human T-cell Leukemia Virus type 1 (HTLV-1), binds to multiple domains of p300/CBP, including the HAT domain. In this study, we found that HBZ inhibits the HAT activity of p300/CBP through the bZIP domain of the viral protein. This effect correlated with a reduction of H3K18 acetylation, a specific target of p300/CBP, in cells expressing HBZ. Interestingly, lower levels of H3K18 acetylation were detected in HTLV-1 infected cells compared to non-infected cells. The inhibitory effect of HBZ was not limited to histones, as HBZ also inhibited acetylation of the NF-κB subunit, p65, and the tumor suppressor, p53. Recent studies reported that mutations in the HAT domain of p300/CBP that cause a defect in acetylation are found in certain types of leukemia. These observations suggest that inhibition of the HAT activity by HBZ is important for the development of adult T-cell leukemia associated with HTLV-1 infection

Spannungskontrollierbarer Kondensator mit ferroelektrischer Schicht und Verfahren zum Herstellen des spannungskontrollierbaren Kondensators mit ferroelektrischer Schicht

The present invention relates to a voltage-controllable capacitor comprising a first electrode layer (4) composed of a non-ferroelectric material, said first electrode layer being applied on a substrate (6), a ferroelectric interlayer (3) having a thickness that is less than the thickness of the first electrode layer (4), and a second electrode layer (2) composed of a non-ferroelectric material. The ferroelectric interlayer (3) is arranged between the first electrode layer (4) and the second electrode layer (2)

Spannungskontrollierbarer Kondensator und Verfahren zum Herstellen eines spannungskontrollierbaren Kondensators

Die vorliegende Erfindung betrifft einen spannungskontrollierbaren Kondensator mit einem Substrat (5), das mindestens eine gegenüber einer Oberfläche (7) des Substrats (5) vertieft ausgebildete Struktur aufweist. Auf der Oberfläche (7) des Substrats (5) und der Struktur (6) ist eine erste Elektrodenschicht (4) aus einem nicht-ferroelektrischen Werkstoff ausgebildet und auf der ersten Elektrodenschicht (4) eine ferroelektrische Schicht (3) abgeschieden, die eine Dicke aufweist, die kleiner ist als die Dicke der ersten Elektrodenschicht (4). Auf der ferroelektrischen Schicht (3) ist eine zweite Elektrodenschicht (2) aus einem nicht-ferroelektrischen Werkstoff ausgebildet

C5a receptor targeting in neointima formation after arterial injury in atherosclerosis-prone mice

Background-Receptor binding of complement C5a leads to proinflammatory activation of many cell types, but the role of receptor-mediated action during arterial remodeling after injury has not been studied. In the present study, we examined the contribution of the C5a receptor (C5aR) to neointima formation in apolipoprotein E-deficient mice employing a C5aR antagonist (C5aRA) and a C5aR-blocking monoclonal antibody. Methods and Results-Mice fed an atherogenic diet were subjected to wire-induced endothelial denudation of the carotid artery and treated with C5aRA and anti-C5aR-blocking monoclonal antibody or vehicle control. Compared with controls, neointima formation was significantly reduced in mice receiving C5aRA or anti-C5aR-blocking monoclonal antibody for 1 week but not for 3 weeks, attributable to an increased content of vascular smooth muscle cells, whereas a marked decrease in monocyte and neutrophil content was associated with reduced vascular cell adhesion molecule-1. As assessed by immunohistochemistry, reverse transcription polymerase chain reaction, and flow cytometry, C5aR was expressed in lesional and cultured vascular smooth muscle cells, upregulated by injury or tumor necrosis factor-alpha, and reduced by C5aRA. Plasma levels and neointimal plasminogen activator inhibitor-1 peaked 1 week after injury and were downregulated in C5aRA-treated mice. In vitro, C5a induced plasminogen activator inhibitor-1 expression in endothelial cells and vascular smooth muscle cells in a C5aRA-dependent manner, possibly accounting for higher vascular smooth muscle cell immigration. Conclusions-One-week treatment with C5aRA or anti-C5aR-blocking monoclonal antibody limited neointimal hyperplasia and inflammatory cell content and was associated with reduced vascular cell adhesion molecule-1 expression. However, treatment for 3 weeks failed to reduce but rather stabilized plaques, likely by reducing vascular plasminogen activator inhibitor-1 and increasing vascular smooth muscle cell migration. (Circulation. 2010;122:1026-1036.

Tuning parameters and their impact on ferroelectric hafnium oxide: Presentation held at Materials Research Society Spring Meeting and Exhibit, 2-6 April 2018, Phoenix, Arizona, USA

The 2011 discovery of a ferroelectric phase in doped hafnium oxide [1] and hafnium zirconium oxide solid solution [2] re-established the competitiveness of ferroelectric memory technologies. Mainly driven by the outstanding scalability and CMOS-compatibility of this new ferroelectric material, classical concepts such as FRAM, FeFET and FTJ are reentering the race for leading edge embedded and stand-alone memory solutions [3-6]. Especially the FeFET concept with its simple one-transistor cell design, non-destructive and low power read operation appears to be the main beneficiary of this new development. Scalability to the 2X nm node [3] and highly yielding memory arrays in the Mbit range are currently being demonstrated for hafnium oxide based FeFETs [7]. Nevertheless, a fundamental material understanding is needed to identify the main parameters improving the ferroelectric performance of the hafnium oxide thin films. In this contribution we give an overview of the main parameters and their impact on the ferroelectric behavior of hafnium oxide. The thickness dependence and the directly associated consequence for the doping concentration of the film will be reviewed. The impact of different thermal treatments will be also discussed in relation to CMOS process flows, illustrating how the thermal budget of subsequent processes in the entire process flow can distinctively change the ferroelectric film properties. Furthermore, specific treatment conditions will be shown, which are further enhancing the ferroelectric properties of hafnium oxide films