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reprogramming cells with synthetic proteins

Asian Journal of Andrology 2015年第3期17卷 394-402页

作者： Xiaoxiao Yang Vikas Malik ralf Jauch Genome regulation Laboratory Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences 190 Kai Yuan Avenue Science Park Guangzhou China

Conversion of one cell type into another cell type by forcibly expressing specific cocktails of transcription factors （TFs） has demonstrated that cell fates are not fixed and that cellular differentiation can be a two-way street with many intersections. These experiments also illustrated the sweeping potential of TFs to ＂read＂ genetically hardwired regulatory information even in cells where they are not normally expressed and to access and open up tightly packed chromatin to execute gene expression programs. Cellular reprogramming enables the modeling of diseases in a dish, to test the efficacy and toxicity of drugs in patient-derived cells and ultimately, could enable cell-based therapies to cure degenerative diseases. Yet, producing terminally differentiated cells that fully resemble their in vivo counterparts in sufficient quantities is still an unmet clinical need. While efforts are being made to reprogram cells nongeneticaUy by using *** molecules, defined TF cocktails still dominate reprogramming protocols. Therefore; the optimization of TFs by protein engineering has emerged as a strategy to enhance reprogramming to produce functional, stable and safe cells for regenerative biomedicine. Engineering approaches focused on Oct4, MyoD, Sox17, Nanog and Mef2c and range from chimeric TFs with added transactivation domains, designer transcription activator-like effectors to activate endogenous TFs to reprogramming TFs with rationally engineered DNA recognition principles. Possibly, applying the complete toolkit of protein design to cellular reprogramming can help to remove the hurdles that, thus far, impeded the clinical use of cells derived from reprogramming technologies.

关键词： cellular reprogramming protein design protein engineering synthetic transcription factors transactivation

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Enterprise applications of semantic technologies for business process management

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Journal of Zhejiang University-Science C(Computers and Electronics) 2012年第4期13卷 308-310页

作者： ralf MUELLEr Oracle BPM Product Development

1 Introduction Today’s business process management (BPM)systems have evolved to provide rich and sophisticated tooling and runtime support for subject

关键词：业务流程管理信息技术企业应用程序语义 Web本体语言 PM系统流程模型基础设施

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Coal petrology,sedimentology and depositional environment of the Parvadeh coais in the Upper Triassic,Tabas Block of Central-East Iran

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International Journal of Coal Science & Technology 2023年第3期10卷 58-77页

作者： Ziba Zamani Hossain rahimpour-Bonab ralf Littke School of Geology College of ScienceUniversity of TehranTehranIran Energy and Mineral resources(EMr) RWTH Aachen UniversityAachenGermany

Peat forming environment strongly influences the economic value of any coal seam and coal-bearing ***,pal-aeoenvironmental studies provide important information for coal resource *** this context,detailed studies on selected coals from the Parvadeh Area,Iran,were conducted using sedimentology,coal petrology,X-ray diffraction(XrD),scanning electron microscopy-energy dispersive X-ray analyzer(SEM-EDX),and proximate *** sedi-mentary facies above and below the coal seams are mainly marine or marine-influenced facies,supporting that the coal-forming mires in the Parvadeh Area developed in a paralic environment,where the base level must be closely related to sea *** contents are moderate to high and mark the influence of brackish/marine water,especially during transgres-sion after peat growth in a lower delta plain *** peat-forming mires extended on coastal/delta plain *** lower delta plain/coastal plain coals are characterized by lateral continuity and substantial thickness,whereas few coals possibly representing the upper delta plain are thin and more *** detrital nature and composition of the numerous partings and the overall high ash yield in the coal seams indicate an active tectonic area with high rates of creation of accommodation space over peat *** petrology and coal facies analysis exhibits a permanently high water table within a forest swamp and mostly rheotrophic conditions,sometimes with connection to the ***-ing to paleoenvironmental reconstructions,it seems that coal layers may be thicker,with less sulfur(pyrite),but more clastic minerals and partings toward the western part of the *** these coal seams presently have low economic potential for the mining operation,partly due to great depth,this humic,high-volatile to medium-volatile bituminous coal may be suitable for exploration of coal bed methane resources.

关键词： Coal petrology Sedimentology Coal facies analysis Upper Triassic Nayband Formation Tabas Block

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The Martin moving grate technology

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Waste Disposal and Sustainable Energy 2023年第3期5卷 283-293页

作者： ralf Koralewska Ulrich Martin Max Schönsteiner MArTIN GmbH für Umwelt-und Energietechnik Leopoldstrasse 24680807MunichGermany

The thermal treatment of waste using grate-based systems has gained global acceptance as the preferred method for sustainable management of residual *** is because the energy content of the waste is utilized and quality products and residues are *** Waste-to-Energy(WtE)plants are extremely *** knowledge of“fuel”waste and its effects on the design and operation of WtE plants is crucial for the successful planning and operation of these *** respond to new challenges and/or priorities,developing and implementing innovative technologies is *** long-term global partnerships and innovative grate and combustion technologies,Martin guarantees that in future,residual waste will be treated following ecological and economic constraints and in compliance with international legal requirements.

关键词： Waste-to-Energy Combustion Grate technologies Heating value Developing countries

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Endoscopic resection techniques for colorectal neoplasia:Current developments

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World Journal of Gastroenterology 2019年第3期25卷 300-307页

作者： Franz Ludwig Dumoulin ralf Hildenbrand Department of Medicine and Gastroenterology Gemeinschaftskrankenhaus Bonn Institute for Pathology Bonn Duisdorf

Endoscopic polypectomy and endoscopic mucosal resection(EMr) are the established treatment standards for colorectal polyps. Current research aims at the reduction of both complication and recurrence rates as well as on shortening procedure times. Cold snare resection is the emerging standard for the treatment of smaller(r the removal of noncancerous polyps up to 9 mm. The method avoids thermal damage, has reduced procedure times and probably also a lower risk for delayed bleeding. On the other end of the treatment spectrum, endoscopic submucosal dissection(ESD)offers en bloc resection of larger flat or sessile lesions. The technique has obvious advantages in the treatment of high-grade dysplasia and early cancer. Due to its minimal recurrence rate, it may also be an alternative to fractionated EMr of larger flat or sessile lesions. However, ESD is technically demanding and burdened by longer procedure times and higher costs. It should therefore be restricted to lesions suspicious for high-grade dysplasia or early invasive *** latest addition to endoscopic resection techniques is endoscopic fullthickness resection with specifically developed devices for flexible *** method is very useful for the treatment of smaller difficult-to-resect lesions,e.g., recurrence with scar formation after previous endoscopic resections.

关键词： Colorectal neoplasia Colorectal cancer screening Cold snare resection Endoscopic polypectomy Endoscopic mucosal resection Endoscopic submucosal dissection Endoscopic full-thickness resection Adenoma recurrence rate

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Dual Targeting of a Processing Peptidase into Both Endosymbiotic Organelles Mediated by a Transport Signal of Unusual Architecture

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Molecular Plant 2012年第2期5卷 494-503页

作者： Bianca Baudisch ralf Bernd Klosgen Institute of Biology-Plant Physiology Martin Luther University Halle-Wittenberg Weinbergweg 10 06120 Halle/Saale Germany

As a result of the endosymbiotic gene transfer, the majority of proteins of mitochondria and chloroplasts are encoded in the nucleus and synthesized in the cytosol as precursor proteins carrying N-terminal transport signals for the ＇re-import＇ into the respective target organelle. Most of these transport signals are monospecific, although some of them have dual targeting properties, that is, they are recognized both by mitochondria and by chloroplasts as target organelles. We have identified alpha-MPP2, one of the two isoforms of the substrate binding subunit of mitochondrial processing peptidase of Arabidopsis thaliana, as a novel member of this class of nuclear-encoded organelle proteins. As demonstrated by in organello transport experiments with isolated organelles and by in vivo localization studies employing fluorescent chimeric reporter proteins, the N-terminal region of the alpha-MPP2 precursor comprises transport signals for the import into mitochondria as well as into chloroplasts. Both signals are found within the N-terminal 79 residues of the precursor protein, where they occupy partly separated and partly overlapping regions. Deletion mapping combined with in organello and in vivo protein transport studies demonstrate an unusual architecture of this transport signal, suggesting a composition of three functionally separated domains.

关键词： Protein transport dual targeting mitochondria chloroplasts mitochondrial processing peptidase

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MULTIGrID METHODS FOr OBSTACLE PrOBLEMS

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Journal of Computational Mathematics 2009年第1期27卷 1-44页

作者： Carsten Grser ralf Kornhuber Freie Universitt Berlin Institut für Mathematik

In this review, we intend to clarify the underlying ideas and the relations between various multigrid methods ranging from subset decomposition, to projected subspace decomposition and truncated multigrid. In addition, we present a novel globally convergent inexact active set method which is closely related to truncated multigrid. The numerical properties of algorithms are carefully assessed by means of a degenerate problem and a problem with a complicated coincidence set.

关键词： Multigrid methods Variational inequalities.

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Endocrine and paracrine role of bile acids

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World Journal of Gastroenterology 2008年第37期14卷 5620-5629页

作者： Verena Keitel ralf Kubitz Dieter Hussinger Clinic of Gastroenterology Hepatology and Infectiology Heinrich-Heine-UniversityMoorenstrasse 5 Dsseldorf D-40225 Germany

Bile acids are not only important for the absorption of dietary lipids and fat soluble vitamins but are signalling molecules with diverse endocrine and paracrine functions. Bile acids regulate bile acid, lipid and glucose metabolism and modulate temperature and energy homeostasis. Furthermore, bile acids can not only promote cell proliferation and liver regeneration but can also induce programmed cell death. Bile acid functions are mediated through different pathways which comprise the activation of nuclear hormone receptors, of intracefular kinases and of the plasma membranebound, G-protein coupled bile acid receptor TGrS/Gpbar-1.

关键词： Bile acids Farnesoid X receptor TGr5 Glucose metabolism Lipid metabolism

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Forecasting the effects of EU policy measures on the nitrate pollution of groundwater and surface waters

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Journal of Environmental Sciences 2010年第6期22卷 872-877页

作者： ralf Kunkel Peter Kreins Bjrn Tetzlaff Frank Wendland research Centre Jülich Institute of Chemistry and Dynamics of the Geosphere Institute of rural Studies Federal Agricultural Research Centre

We used the interdisciplinary model network rEGFLUD to predict the actual mean nitrate concentration in percolation water at the scale of the Weser river basin （Germany） using an area differentiated （100 m × 100 m） approach. rEGFLUD combines the agro-economic model rAUMIS for estimating nitrogen surpluses and the hydrological models GrOWA/DENUZ for assessing the nitrate leaching from the soil. For areas showing predicted nitrate concentrations in percolation water above the European Union （EU） groundwater quality standard of 50 mg NO3-N/L, effective agri-environmental reduction measures need to be derived and implemented to improve groundwater and surface water quality by 2015. The effects of already implemented agricultural policy are quantified by a baseline scenario projecting the N-surpluses from agricultural sector to 2015. The rEGFLUD model is used to estimate the effects of this scenario concerning groundwater and surface water pollution by nitrate. From the results of the model analysis the needs for additional measures can be derived in terms of required additional N-surplus reduction and in terms of regional prioritization of measures. research work will therefore directly support the implementation of the Water Framework Directive of the European Union in the Weser basin.

关键词： catchment management diffuse source pollution mitigation methods river basin management Water Framework Directive

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How Can We Make Disaster Management Evaluations More Useful?An Empirical Study of Dutch Exercise Evaluations

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International Journal of Disaster risk Science 2020年第5期11卷 578-591页

作者： ralf Josef Johanna Beerens Henrik Tehler Ben Pelzer Institute for Safety(IFV) 6801 HA ArnhemThe Netherlands Division of risk Management and Societal Safety Lund University22100 LundSweden Lund University Centre for risk Assessment and Management(LUCrAM) Lund University22100 LundSweden Department of Sociology Radboud University Nijmegen6500 HE Nijmegen.The Netherlands

The evaluation of simulated disasters(for example,exercises)and real responses are important ***,little attention has been paid to how reports documenting such events should be written.A key issue is how to make them as useful as possible to professionals working in disaster risk ***,we focus on three aspects of a written evaluation:how the object of the evaluation is described,how the analysis is described,and how the conclusions are *** empirical experiment,based on real evaluation documents,asked 84 Dutch mayors and crisis management professionals to evaluate the perceived usefulness of the three aspects noted *** results showed that how evalua・tions are written does ***,the usefulness of an evaluation intended for learning purposes is improved when its analysis and conclusions are *** contrast,evaluations used for accountability purposes are only improved by the clarity of the con *** findings have implications for the way disaster management evaluations should be documented.

关键词： Disaster management evaluation Evaluation design Evaluation report Exercise evaluation The Netherlands Usefulness

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