Synthesis and reactions of 1-amino-1,5,6,10b-tetrahydroimidazo[2,1-a]isoquinolin-2(3H)-ones

1-Amino-1,5,6,10b-tetrahydroimidazo[2,1-a]isoquinolin-2(3H)-ones, as previously unknown ring-annelated isoquinolines with a 3-aminoimidazolidin-4-one scaffold, were selectively prepared upon reacting 2-carbamoylmethyl- or 2-ethoxycarbonylmethyl-3,4-dihydroisoquinolinium salts with hydrazine hydrate. Acylation of the primary amino group with benzoyl chlorides, followed by reductive ring cleavage of the annelated 4-imidazolidinone ring and final cyclodehydration of the N,N'-diacylhydrazines resulted in the synthesis of 1-methyl-2(5-aryl-[1,3,4]oxadiazol-2-ylmethyl)-1,2,3,4-tetrahydroisoquinolines which are of interest due to their potential use as bioisosteres of biologically active N-aryl-2-(1-methyl-3,4-dihydro-1H-isoquinolin-2-yl) acetamides

Wissenschaftliche Weiterbildung im Kontext des Bologna-Prozesses

Welche Implikationen der Bologna-Prozess für die wissenschaftliche Weiterbildung hat, ist beim gegenwärtigen Stand nur begrenzt empirisch zu beantworten. Um das sich wandelnde Verhältnis von grundständigen Studien und wissenschaftlicher Weiterbildung, insbesondere von konsekutivem Master und Weiterbildungsmaster, stärker auszuleuchten, wurde neben einer Analyse von nationalen und europäischen Positionspapieren auch eine Fragebogenerhebung vorgenommen. Erfasst wurden die Einschätzung und bisherigen Erfahrungen der Expertinnen und Experten aus Universitäten und Fachhochschulen. In diesem Beitrag werdenausgewählte Ergebnisse aus der österreichischen Teilstudie - als Beitrag zu einer trinationalen Untersuchung (Deutschland, Österreich und die Schweiz) - vorgestellt und diskutiert. 10.07.2007 | Daniela Holzer & Wolfgang Jütte (Graz, Krems

Highly chemoselective difluoromethylative homologation of iso(thio)cyanates: expeditious access to unprecedented α,α-difluoro(thio)amides

The new motif – α,α-difluoromethyl thioamide – has been assembled starting from isothiocyanate (as thioamide precursor) and a formal difluoromethyl-carbanion generated from commercially available TMSCHF2

Classification of the LHC BLM Ionization Chamber

The LHC beam loss monitoring (BLM) system must prevent the super conducting magnets from quenching and protect the machine components from damage. The main monitor type is an ionization chamber. About 4000 of them will be installed around the ring. The lost beam particles initiate hadronic showers through the magnets and other machine components. These shower particles are measured by the monitors installed on the outside of the accelerator equipment. For the calibration of the BLM system the signal response of the ionization chamber is simulated in GEANT4 for all relevant particle types and energies (keV to TeV range). For validation, the simulations are compared to measurements using protons, neutrons, photons and mixed radiation fields at various energies and intensities. This paper will focus on the signal response of the ionization chamber to various particle types and energies including space charge effects at high ionization densities

Design and Implementation of Community Forum System Based on MVC Model

随着信息技术的发展以及网络的开放性，越来越多的人通过互联网进行沟通 和在线交流，而各式各样的论坛就为上网用户提供了一个很好的线上场所，通过 搜索自己感兴趣的论坛，用户可以在论坛中发表自己的见解并与志同道合的人进 行经验的交流。而随着社区的居民的沟通变得越来越频繁，能否为他们提供一个 在线的社区论坛系统就成为了很多社区管理者面临的一个重要课题。本项目就是 在这样的背景下产生的。 本文以软件工程的设计思想为指导，通过实地的调研对需求分析做了深入的 了解，并通过用例图对需求分析进行了总结，得出了系统的功能模块以及每个功 能模块的具体功能。在需求分析的基础上，通过流程图对每个功能的具体...With the opening and development of network information technology, more and more people communicate and online communication through the Internet, and every kind of forum for Internet users to provide a good online sites, search through their interest in the forum, users can be in on the altar in the opinions of their own and with like-minded people the exchange of experiences. With the resident...学位：工程硕士院系专业：软件学院_工程硕士(软件工程)学号：X201223095

Culture expansion of CAR T cells results in aberrant DNA methylation that is associated with adverse clinical outcome

Chimeric antigen receptor (CAR) T cells provide new perspectives for treatment of hematological malignancies. Manufacturing of these cellular products includes culture expansion procedures, which may affect cellular integrity and therapeutic outcome. In this study, we investigated culture-associated epigenetic changes in CAR T cells and found continuous gain of DNAm, particularly within genes that are relevant for T cell function. Hypermethylation in many genes, such as TCF7, RUNX1, and TOX, was reflected by transcriptional downregulation. 332 CG dinucleotides (CpGs) showed an almost linear gain in methylation with cell culture time, albeit neighboring CpGs were not coherently regulated on the same DNA strands. An epigenetic signature based on 14 of these culture-associated CpGs predicted cell culture time across various culture conditions. Notably, even in CAR T cell products of similar culture time higher DNAm levels at these CpGs were associated with significantly reduced long-term survival post transfusion. Our data demonstrate that cell culture expansion of CAR T cells evokes DNA hypermethylation at specific sites in the genome and the signature may also reflect loss of potential in CAR T cell products. Hence, reduced cultivation periods are beneficial to avoid dysfunctional methylation programs that seem to be associated with worse therapeutic outcome.This research was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation − 363055819/GRK2415; WA1706/11–1; WA 1706/12–2 within CRU344/417911533; WA1706/14–1; and SFB 1506/1); and the ForTra gGmbH für Forschungstransfer der Else Kröner-Fresenius-Stiftung. Furthermore, we thank CERCA Programme / Generalitat de Catalunya for institutional support. The research leading to these results has received funding from MCIN/AEI/10.13039/501100011033 and European Commission “Next GenerationEU”/PRTR (PDC2022–133476-I00); Ministry of Research and Universities of the Catalan Government (2021 PROD 00020); and the Cellex Foundation.Peer ReviewedPostprint (published version

LHC Machine Protection

For nominal beam parameters at 7 TeV/c each of the two LHC proton beams has a stored energy of 362 MJ threatening to damage accelerator equipment in case of uncontrolled beam loss. The energy stored in the magnet system at 7 TeV/c will exceed 10 GJ. In order to avoid damage of accelerator equipment, complex machine protection systems are required. Magnet protection and powering interlock systems must be operational already before commissioning the magnet powering system. Beam operation, throughout the operational cycle from injection to colliding beams, requires fully operational protection systems, including beam interlock systems, beam dumping system, beam instrumentation (mainly beam loss monitors) as well as collimators and beam absorbers. Details of LHC machine protection have been presented on several occasions and the systems involved in protection are well documented [1]. This paper gives an overview of LHC machine protection, discusses the progress with the implementation and presents first results from the commissioning of some systems

Haploidentical hematopoietic stem cell transplantation as individual treatment option in pediatric patients with very high-risk sarcomas

Background Prognosis of children with primary disseminated or metastatic relapsed sarcomas remains dismal despite intensification of conventional therapies including high-dose chemotherapy. Since haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is effective in the treatment of hematological malignancies by mediating a graft versus leukemia effect, we evaluated this approach in pediatric sarcomas as well. Methods Patients with bone Ewing sarcoma or soft tissue sarcoma who received haplo-HSCT as part of clinical trials using CD3+ or TCRα/β+ and CD19+ depletion respectively were evaluated regarding feasibility of treatment and survival. Results We identified 15 patients with primary disseminated disease and 14 with metastatic relapse who were transplanted from a haploidentical donor to improve prognosis. Three-year event-free survival (EFS) was 18,1% and predominantly determined by disease relapse. Survival depended on response to pre-transplant therapy (3y-EFS of patients in complete or very good partial response: 36,4%). However, no patient with metastatic relapse could be rescued. Conclusion Haplo-HSCT for consolidation after conventional therapy seems to be of interest for some, but not for the majority of patients with high-risk pediatric sarcomas. Evaluation of its future use as basis for subsequent humoral or cellular immunotherapies is necessary

Evaluation of seven European aerosol optical depth retrieval algorithms for climate analysis

Satellite data are increasingly used to provide observation-based estimates of the effects of aerosols on climate. The Aerosol-cci project, part of the European Space Agency's Climate Change Initiative (CCI), was designed to provide essential climate variables for aerosols from satellite data. Eight algorithms, developed for the retrieval of aerosol properties using data from AATSR (4), MERIS (3) and POLDER, were evaluated to determine their suitability for climate studies. The primary result from each of these algorithms is the aerosol optical depth (AOD) at several wavelengths, together with the Ångström exponent (AE) which describes the spectral variation of the AOD for a given wavelength pair. Other aerosol parameters which are possibly retrieved from satellite observations are not considered in this paper. The AOD and AE (AE only for Level 2) were evaluated against independent collocated observations from the ground-based AERONET sun photometer network and against “reference” satellite data provided by MODIS and MISR. Tools used for the evaluation were developed for daily products as produced by the retrieval with a spatial resolution of 10 × 10 km2 (Level 2) and daily or monthly aggregates (Level 3). These tools include statistics for L2 and L3 products compared with AERONET, as well as scoring based on spatial and temporal correlations. In this paper we describe their use in a round robin (RR) evaluation of four months of data, one month for each season in 2008. The amount of data was restricted to only four months because of the large effort made to improve the algorithms, and to evaluate the improvement and current status, before larger data sets will be processed. Evaluation criteria are discussed. Results presented show the current status of the European aerosol algorithms in comparison to both AERONET and MODIS and MISR data. The comparison leads to a preliminary conclusion that the scores are similar, including those for the references, but the coverage of AATSR needs to be enhanced and further improvements are possible for most algorithms. None of the algorithms, including the references, outperforms all others everywhere. AATSR data can be used for the retrieval of AOD and AE over land and ocean. PARASOL and one of the MERIS algorithms have been evaluated over ocean only and both algorithms provide good results