E-commerce und europäische Verbraucherpolitik

Die Schaffung eines Binnenmarktes ohne wirtschaftliche und rechtliche Hemmnisse ist oberstes Ziel der Europäischen Gemeinschaft. Während bereits viele Unternehmen die Möglichkeiten des europäischen Binnenmarktes ausschöpfen, ist das Kaufverhalten der Verbraucher im grenzüberschreitenden Geschäftsverkehr und insbesondere im Bereich des grenzüberschreitenden E-Commerce bislang sehr verhalten. Reichen die vorhandenen und für den E-Commerce relevanten verbraucherschutzrechtlichen Regulierungen aus? Ist der aktuell von der EU-Kommission vorgelegte Entwurf einer Rahmenrichtlinie zur Regelung unlauterer Geschäftspraktiken geeignet, um das Ziel eines Gemeinsamen Marktes über eine Stärkung des E-Commerce zu erreichen? --

Lohnsubventionen zum Abbau von Arbeitslosigkeit im Niedriglohnsektor: kritische Anmerkungen zu Edmund Phelps

Inhaltsverzeichnis: 1 Niedriglohnsektor, Marktversagen und Lohnsubventionen; 2 Ökonomische Begründungen für den Einsatz von Lohnsubventionen zur Korrektur von Marktergebnissen; 2.1 Zutreffende und unzutreffende Rechtfertigungsargumente; 2.2 Nutzen- und Kosteneffekte von Lohnsubventionen; 3 Zu den Beschäftigungseffekten von Lohnsubventionen aus ökonomischer Sicht; 3.1 Theoretische Überlegungen zur Wirksamkeit von Lohnsubventionen; 3.2 Empirische Untersuchungen zur Wirksamkeit von Lohnsubventionen; 4 Bestimmungsfaktoren einer erfolgreichen Arbeitsmarktpolitik

Whole exome sequencing of microdissected splenic marginal zone lymphoma: a study to discover novel tumor-specific mutations

BACKGROUND: Splenic marginal zone lymphoma (SMZL) is an indolent B-cell non-Hodgkin lymphoma and represents the most common primary malignancy of the spleen. Its precise molecular pathogenesis is still unknown and specific molecular markers for diagnosis or possible targets for causal therapies are lacking. METHODS: We performed whole exome sequencing (WES) and copy number analysis from laser-microdissected tumor cells of two primary SMZL discovery cases. Selected somatic single nucleotide variants (SNVs) were analyzed using pyrosequencing and Sanger sequencing in an independent validation cohort. RESULTS: Overall, 25 nonsynonymous somatic SNVs were identified, including known mutations in the NOTCH2 and MYD88 genes. Twenty-three of the mutations have not been associated with SMZL before. Many of these seem to be subclonal. Screening of 24 additional SMZL for mutations at the same positions found mutated in the WES approach revealed no recurrence of mutations for ZNF608 and PDE10A, whereas the MYD88 L265P missense mutation was identified in 15 % of cases. An analysis of the NOTCH2 PEST domain and the whole coding region of the transcription factor SMYD1 in eight cases identified no additional case with a NOTCH2 mutation, but two additional cases with SMYD1 alterations. CONCLUSIONS: In this first WES approach from microdissected SMZL tissue we confirmed known mutations and discovered new somatic variants. Recurrence of MYD88 mutations in SMZL was validated, but NOTCH2 PEST domain mutations were relatively rare (10 % of cases). Recurrent mutations in the transcription factor SMYD1 have not been described in SMZL before and warrant further investigatio

a study to discover novel tumor-specific mutations

Background Splenic marginal zone lymphoma (SMZL) is an indolent B-cell non- Hodgkin lymphoma and represents the most common primary malignancy of the spleen. Its precise molecular pathogenesis is still unknown and specific molecular markers for diagnosis or possible targets for causal therapies are lacking. Methods We performed whole exome sequencing (WES) and copy number analysis from laser-microdissected tumor cells of two primary SMZL discovery cases. Selected somatic single nucleotide variants (SNVs) were analyzed using pyrosequencing and Sanger sequencing in an independent validation cohort. Results Overall, 25 nonsynonymous somatic SNVs were identified, including known mutations in the NOTCH2 and MYD88 genes. Twenty-three of the mutations have not been associated with SMZL before. Many of these seem to be subclonal. Screening of 24 additional SMZL for mutations at the same positions found mutated in the WES approach revealed no recurrence of mutations for ZNF608 and PDE10A, whereas the MYD88 L265P missense mutation was identified in 15 % of cases. An analysis of the NOTCH2 PEST domain and the whole coding region of the transcription factor SMYD1 in eight cases identified no additional case with a NOTCH2 mutation, but two additional cases with SMYD1 alterations. Conclusions In this first WES approach from microdissected SMZL tissue we confirmed known mutations and discovered new somatic variants. Recurrence of MYD88 mutations in SMZL was validated, but NOTCH2 PEST domain mutations were relatively rare (10 % of cases). Recurrent mutations in the transcription factor SMYD1 have not been described in SMZL before and warrant further investigation

Einfluss der Transkriptionsfaktoren Dach1, MafB und Foxc2 auf die Differenzierung Parietaler Epithelzellen (PECs) zu Podozyten

Bei der Untersuchung verschiedener chronischer Nierenerkrankungen in den letzten Jahrzehnten zeigte sich, dass Podozyten als Bestandteil der glomerulären Filtrationsbarriere häufig in die Pathomechanismen involviert sind, wobei ein Verlust ihrer besonderen Architektur aus interdigitierenden Fußfortsätzen (effacement) und auch die Ablösung einzelner Podozyten von der glomerulären Basalmembran beobachtet werden können. Da es sich um postmitotische Zellen handelt, kann ein Verlust nur durch eine Hypertrophie verbleibender Zellen ausgeglichen werden. Nach wie vor ist nicht eindeutig geklärt, ob ein Ersatz stattfindet und wenn ja, welche Zellen dafür verantwortlich sind. Seit einigen Jahren sind die PECs in den Fokus der Aufmerksamkeit gerückt und es konnte gezeigt werden, dass sie sich unter bestimmten Bedingungen zu Podozyten-ähnlichen Zellen differenzieren, aber auch einen negativen Einfluss im vorgeschädigten Glomerulum durch ein profibrotisches Potential ausüben können. In dieser Arbeit wurden drei Transkriptionsfaktoren (Dach1, MafB und Foxc2) in PECs transfiziert. Für alle drei konnte in der Vergangenheit eine Bedeutung in der Nieren-bzw. Podozytenentwicklung gezeigt werden. Es sollte untersucht werden, ob einer der drei Transkriptionsfaktoren eine Differenzierung der PECs zu Podozyten in vitro induzieren könnte. Auch der Einfluss der jeweiligen Faktoren untereinander wurde untersucht. Dabei zeigte sich, dass die Transfektion mit pMafB-tGFP einen signifikanten Dach1-Anstieg in PECs bedingte. Hinsichtlich der Expression von F Aktin, α-Tubulin und dem Podozyten-spezifischen Transkriptionsfaktor WT-1 in PECs zeigte sich bildmorphologisch kein Hinweis für einen möglichen Einfluss von Dach1, MafB und Foxc2 in PECs. Allerdings konnte durch die Überexpression von Dach1 in PECs ein signifikanter Anstieg des Podozyten-spezifischen Proteins Synaptopodin beobachtet werden. Des Weiteren kam es zu einer Herunterregulation von Pax-2, was insofern bedeutsam ist, als dass auch Podozyten eine verminderte Pax-2-Expression aufweisen. Es zeigte sich außerdem eine verminderte Expression von Caveolin-1 und β-Catenin. Während Ersteres eher als ein Zeichen des profibrotischen und somit negativen Potentials gewertet werden könnte, ähnelt die Herunterregulation von β-Catenin wiederum dem Status von Podozyten. Zusammenfassend bestätigt die Arbeit das Differenzierungspotential von PECs zu Podozyten und zeigt, dass Dach1 in vitro ein entscheidender Faktor dafür ist.In the last decades it has been shown that podocytes are involved in the development and progress of chronic kidney diseases. They are part of the glomerular filtration barrier, the loss of their characteristic architecture leads to effacement of foot processes and detachment. Podocytes are postmitotic cells, if they are lost, a cell hypertrophy is the only mechanism proposed for compensation. Today, it is not finally proven whether another kind of compensation exists and which cells could be involved. In the last years, the parietal epithelial cells (PECs) were discussed to be intrarenal progenitor cells. They might have a potential for differentiation, on the other hand it has been shown that an inadequate activation contributes to the development and progression of sclerotic lesions in the glomeruli. In this study the PECs were transfected with three plasmids encoding for Dach1, MafB and Foxc2. The importance for the development of the podocytes has been shown in the past. It was studied whether one of these three factors could initiate a differentiation towards podocytes. In addition, the influence of one transcription factor on the others was studied. After the expression of MafB in PECs a significant higher expression of Dach1 has been detected. No changes in the expression of F-Aktin, α-Tubulin or WT-1 were shown, however, the expression of Dach1 in PECs induced an up-regulation of the podocyte-specific protein synaptopodin. Moreover, the expression of Dach1 required a lower expression of Pax-2, Caveolin-1 and β-Catenin. The down-regulation of Pax-2 and β-Catenin seems to be a remark for a potential for differentiation towards podocytes, whereas the down-regulation of Caveolin-1 could be a kind for a profibrotic potential. In summary, this study confirms the potential for a differentiation from PECs to podocytes and shows that Dach1 is a key factor for this process in vitro

Visegrad Group and its Presence in the Mashriq Region

This paper provides an outline about Hungary’s, Poland’s, Slovakia’s and Czechia’s relationships to the Mashriq region, especially Jordan, Israel and Egypt. The Central and Eastern European countries are considered both individually and collectively in the Visegrád group (V4). Therefore quantitative and qualitative indicators are examined. As one result it was found that in most cases the V4 had no common interests and consequently did not formulate common positions. But finally, the results of this work suggest that the migration crisis has indeed increased the interest of the Visegrád countries in the Mashriq and has accelerated their involvement to some extent both in the Mashriq region and within the European Union

Hypusinated eIF5A Promotes Ribosomal Frameshifting during Decoding of ODC Antizyme mRNA in Saccharomyces cerevisiae

Polyamines are essential biogenic poly-cations with important roles in many cellular processes and diseases such as cancer. A rate-limiting step early in the biosynthesis of polyamines is the conversion of ornithine to putrescine by the homodimeric enzyme ornithine decarboxylase (ODC). In a conserved mechanism of posttranslational regulation, ODC antizyme (OAZ) binds to ODC monomers promoting their ubiquitin-independent degradation by the proteasome. Decoding of OAZ mRNA is unusual in that it involves polyamine-regulated bypassing of an internal translation termination (STOP) codon by a ribosomal frameshift (RFS) event. Using Saccharomyces cerevisiae, we earlier showed that high polyamine concentrations lead to increased efficiency of OAZ1 mRNA translation by binding to nascent Oaz1 polypeptide. The binding of polyamines prevents stalling of the ribosomes on OAZ1 mRNA caused by nascent Oaz1 polypeptide thereby promoting synthesis of full-length Oaz1. Polyamine depletion, however, also inhibits RFS during the decoding of constructs bearing the OAZ1 shift site lacking sequences encoding the Oaz1 parts implicated in polyamine binding. Polyamine depletion is known to impair hypusine modification of translation factor eIF5A. Using a novel set of conditional mutants impaired in the function of eIF5A/Hyp2 or its hypusination, we show here that hypusinated eIF5A is required for efficient translation across the OAZ1 RFS site. These findings identify eIF5A as a part of Oaz1 regulation, and thereby of polyamine synthesis. Additional experiments with DFMO, however, show that depletion of polyamines inhibits translation across the OAZ1 RFS site not only by reducing Hyp2 hypusination, but in addition, and even earlier, by affecting RFS more directly

Briefwechsel, Juli 1739- Juli 1740 : Unter Einschluß des Briefwechsels von Luise Adelgunde Victorie Gottsched /

Mode of access: Internet via World Wide Web.Description based on online resource; title from PDF title page (publisher's Web site, viewed Dec. 14, 2016