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Signal Transduction and Targeted Therapy 2021年第12期6卷 3369-3370页

作者： natj. haag Hans Zempel Institute of Human Genetics Medical FacultyRWTH Aachen UniversityAachenGermany Institute of Human Genetics Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany Center for Molecular Medicine Cologne(CMMC) Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany

In their new paper,McAlpine and colleagues provide compelling evidence that astrocyte dependent microglial stimulation is crucial for fighting off one of the most prominent Alzheimer disease(AD)pathological hallmarks,namelyβ-amyloid(Aβ)plaque *** find that(i)a subpopulation of astrocytes secrete the classical cytokine interleukin-3(IL-3),(ii)microglia are responsive to this cytokine,(iii)responsiveness(not so much secretion of IL-3)is increased in patients with AD and model systems of AD,and(iv)presence of IL-3 is necessary to allow microglia to counteract some of the detrimental effects of AD:if IL-3 is missing,AD pathology worsens(see Fig.1 for graphical depiction).1 AD and related tauopathies,e.g.,frontotemporal dementia(FTD)or frontotemporal lobar degeneration with tauopathy(FTLDTAU),are detrimental diseases,impose a huge burden on patients and caregivers,and are the scourge of modern healthcare *** recent advances in(immuno-)therapies,a causative cure seems out of range.

关键词： stimulation Alzheimer degeneration

Long-term monitoring of PCDD/PCDF and other unintentionally produced POPs-Concepts and case studies from Europe

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Science China Chemistry 2010年第5期53卷 1017-1024页

作者： REINMANN Jürgen WEBER Roland haag Roland Environnement S.A Deutschland Benzstrasse 1161352 Bad HomburgGermany POPs Environmental Consulting Ulmenstraβe 373035 GppingenGermany TüV Süd Industrie Service GmbH Grabenwiesenstraβe 473072 DonzdorfGermany

During the start-up and unstable combustion periods,even the state-of-the-art incinerators emit polychlorinated dibenzo-p-dioxins and dibenzofurans(PCDD/PCDF) in stack gases at concentrations that are up to 1000 times higher than normal operation. Therefore,incinerators and other sources with variation of PCDD/PCDF release into air cannot be reliably monitored by the conventional short-term sampling that covers only 0.1%to 0.2%of the yearly operating time.A more comprehensive monitoring regime is *** paper describes different applications of continuous PCDD/PCDF sampling in some European *** cases demonstrate that flexible regimes for continuous sampling can be crafted and applied by governments or regional/local *** regimes range from a countrywide,continuous requirement for selected facility types(e.g.,waste incinerators) to a facility-specific regime that applies,for example,to new facilities for a defined time period until the facility has demonstrated continuous compliance with regulatory limits. Countries implementing the Stockholm Convention are suggested to evaluate in their Best available technology/Best environmental practice(BAT/BEP) activities the usefulness of long-term sampling by,for example,designating institutes related to the environmental ministry or regional authorities to supervise long-term sampling regimes at relevant facilities in their country/areas,beginning with priority sources(e.g.,facilities used for destruction of persistent organic pollutants(POPs) or hazardous waste processing) . This paper presents and discusses the results of the AMESA long-term monitoring system having demonstrated that in addition to PCDD/PCDF all other unintentionally produced POPs listed in the Stockholm Convention could be supervised.

关键词： PCDD/PCDF PCB continuous sampling unintentionally produced POPs Stockholm Convention BAT/BEP

Understanding genetics, sex and signaling: Implications of sex-dependent APOE4-neutrophil-microglia interactions for Alzheimer’s and tauopathies

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Signal Transduction and Targeted Therapy 2024年第10期9卷 4167-4169页

作者： natj. haag Juliane Bremer Hans Zempel Institute for Human Genetics and Genomic Medicine University Hospital RWTH AachenAachenGermany Institute of Neuropathology University Hospital RWTH AachenAachenGermany Institute of Human Genetics Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany Center for Molecular Medicine Cologne(CMMC) University of CologneCologneGermany Department of Nuclear Medicine Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany

A recent study published in Nature Medicine uncovers a novel sex-dependent mechanism involving the apolipoprotein E ε4 (APOE4) and in particular neutrophils and their signaling to microglia, which then would mediate cognitive decline in late-onset Alzheimer’s disease (AD).1 We here put the main findings into perspective with current knowledge about APOE4 genotype and neutrophils in the pathogenesis of AD and related tauopathies, and discuss future research directions and therapeutic implications.

关键词： Alzheimer tau Medicine

A Deleted Deletion Site in a New Vector Strain and Exceptional Genomic Stability of Plaque-Purified Modified Vaccinia Ankara(MVA)

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Virologica Sinica 2020年第2期35卷 212-226页

作者： Ingo Jordan Deborah Horn Kristin Thiele Lars haag Katharina Fiddeke Volker Sandig ProBioGen AG.Herbert-Bayer-StraBe 8 13086 BerlinGermany Sartorius Stedim Cellca GmbH.Erwin-Rentschler-Str 21 88471 LaupheimGermany Vironova AB Giivlegatan 2211330 StockholmSweden Department of Laboratory Medicine Karolinska Universitetsjukhuset i Huddinge14152 HuddingeSweden

Vectored vaccines based on highly attenuated modified vaccinia Ankara(MVA) are reported to be immunogenic, tolerant to pre-existing immunity, and able to accommodate and stably maintain very large transgenes. MVA is usually produced on primary chicken embryo fibroblasts, but production processes based on continuous cell lines emerge as increasingly robust and cost-effective alternatives. An isolate of a hitherto undescribed genotype was recovered by passage of a nonplaque-purified preparation of MVA in a continuous anatine suspension cell line(***) in chemically defined *** novel isolate(MVA-CR19) replicated to higher infectious titers in the extracellular volume of suspension cultures and induced fewer syncytia in adherent cultures. We now extend previous studies with the investigation of the point mutations in structural genes of MVA-CR19 and describe an additional point mutation in a regulatory gene. We furthermore map and discuss an extensive rearrangement of the left telomer of MVA-CR19 that appears to have occurred by duplication of the right telomer. This event caused deletions and duplications of genes that may modulate immunologic properties of MVACR19 as a vaccine vector. Our characterizations also highlight the exceptional genetic stability of plaque-purified MVA:although the phenotype of MVA-CR19 appears to be advantageous for replication, we found that all genetic markers that differentiate wildtype and MVA-CR19 are stably maintained in passages of recombinant viruses based on either wildtype or MVA-CR.

关键词： Modified vaccinia Ankara(MVA) MVA-CR19 CR.pIX Suspension cell line Vaccine production Genome stability

Management information systems for the information age / Stephen haag, Maeve Cummings, Donald J. McCubbrey. 5th ed.

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Palliative chemotherapy for gastroesophageal cancer in old and very old patients: A retrospective cohort study at the National Center for Tumor Diseases, Heidelberg

2005年

作者： Stephen haag Maeve Cummings Donald J. McCubbrey.

Includes bibliographical references and index.

ISBN: (数字)0072935863

ISBN: (纸本)0072935863

Includes bibliographical references and index.

关键词： Management information systems.

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World Journal of Gastroenterology 2015年第16期21卷 4911-4918页

作者： Anne Katrin Berger Stefanie Zschaebitz Christine Komander Dirk Jger Georg Martin haag National Center for Tumor Diseases Heidelberg University Hospital NCT Clinical Cancer Registry German Cancer Research Center

AIM:To investigate the outcome of palliative chemotherapy in old patients with gastroesophageal cancer at the National Center for Tumor Diseases,***:Using a prospectively generated database,we retrospectively analyzed 55 patients≥70years under palliative chemotherapy for advanced gastroesophageal cancer at the outpatient clinic of the National Center for Tumor Diseases Heidelberg,Germany between January 2006 and *** requirements for inclusion were(1)histologically proven diagnosis of gastroesophageal cancer;(2)advanced(metastatic or inoperable)disease;and(3)no history of radiation or *** clinical information included Eastern Cooperative Oncology Group performance status(ECOG PS),presence and site of metastases at diagnosis,date of previous surgery and perioperative chemotherapy,start and stop date of first-line treatment,toxicities and consecutive dosage reductions of first-line treatment,response to first-line therapy,date of progression,usage of second-line therapies and date and cause of *** times[progression-free survival(PFS),overall survival(OS)and residual survival(RS)]were *** and safety were *** factors including ECOG PS,age and previousperioperative treatment were ***:Median age of our cohort was 76 years.86%of patients received a combination of two cytotoxic drugs.76 percent of patients had an oxaliplatin-based first-line therapy with the oxaliplatin and 5-fluorouracil regimen being the predominantely chosen regimen(69%).Drug modifications due to toxicity were necessary in 56%of patients,and 11%of patients stopped treatment due to *** times of our cohort are in good accordance with the major phaseⅢtrials that included mostly younger patients:PFS and OS were 5.8 and 9.5 mo,*** differed significantly between patient groups with low(≤1)and high(≥2)ECOG PS(12.7 mo vs 3.8 mo,P<0.001).Very old patients(≥75 years)did not sho

关键词： Gastroesophageal cancer Old patients Palliative chemotherapy Toxicity Eastern CooperativeOncology Group performance status

Functional Surfactants for Molecular Fishing,Capsule Creation,and Single-Cell Gene Expression

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Nano-Micro Letters 2021年第9期13卷 377-385页

作者： Mohammad Suman Chowdhury Xingcai Zhang Leila Amini Pradip Dey Abhishek Kumar Singh Abbas Faghani Michael Schmueck‑Henneresse Rainer haag Institut Für Chemie Und Biochemie Freie Universität BerlinTakustrasse 314195 BerlinGermany John A.Paulson School of Engineering and Applied Sciences Harvard UniversityCambridgeMA 02138USA School of Engineering Massachusetts Institute of TechnologyCambridgeMA 02139USA Berlin Institute of Health-Center for Regenerative Therapies CharitéUniversitätsmedizin Berlin-CVKFöhrer Str.1513353 BerlinGermany BerlinCenter for Advanced Therapies CharitéUniversitätsmedizin Berlin-CVKFöhrer Str.1513353 BerlinGermany

Creating a single surfactant that is open to manipulation,while maintaining its surface activity,robustness,and compatibility,to expand the landscape of surfactant-dependent assays is extremely *** report an oxidation-responsive precursor with thioethers and multiple 1,2-diols for creating a variety of functional surfactants from one parent *** these multifunctional surfactants,we stabilize microfluidics-generated aqueous *** droplets encapsulate different components and immerse in a bioinert oil with distinct interfaces where an azide-bearing surfactant allow fishing of biomolecules from the droplets,aldehyde-bearing surfactant allow fabrication of microcapsules,and hydroxyl-bearing surfactants,with/without oxidized thioethers,allow monitoring of single-cell gene *** multifunctional surfactants poses opportunities for broad applications,including adsorption,bioanalytics,catalysis,formulations,coatings,and programmable subset of emulsions.

关键词： Dendronized fluorosurfactants Droplet microfluidics Microcapsules Oxidation-responsive fluorosurfactants Cell encapsulation

Mussel-inspired multifunctional coating for bacterial infection prevention and osteogenic induction

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Journal of Materials Science & Technology 2021年第9期68卷 160-171页

作者： Mingjun Li Christoph Schlaich Jianguang Zhang Ievgen S.Donskyi Karin Schwibbert Frank Schreiber Yi Xi Jorg Radnik Tanja Schwerdtle Rainer haag Center for Health Science and Engineering Tianjin Key Laboratory of Materials Laminating Fabrication and Interface Control TechnologySchool of Materials Science and EngineeringHebei University of TechnologyTianjin 300130China Institut fur Chemie und Biochemie Freie Universitat BerlinBerlin 14195Germany Division Biodeterioration and Reference Organisms Federal Institute for Materials Research and Testing(BAM)Berlin 12205Germany Division of Surface Analysis and Interfacial Chemistry Federal Institute for Materials Research and Testing(BAM)Berlin 12205Germany Institute of Nutritional Science Department of Food ChemistryUniversity of PotsdamNuthetal D-14558Germany

Bacterial infection and osteogenic integration are the two main problems that cause severe complications after surgeries. In this study, the antibacterial and osteogenic properties were simultaneously introduced in biomaterials, where copper nanoparticles(Cu NPs) were generated by in situ reductions of Cu ions into a mussel-inspired hyperbranched polyglycerol(MI-h PG) coating via a simple dip-coating *** hyperbranched polyglycerol with 10 % catechol groups’ modification presents excellent antifouling property, which could effectively reduce bacteria adhesion on the surface. In this work, polycaprolactone(PCL) electrospun fiber membrane was selected as the substrate, which is commonly used in biomedical implants in bone regeneration and cardiovascular stents because of its good biocompatibility and easy post-modification. The as-fabricated Cu NPs-incorporated PCL membrane [PCL-(MI-h PG)-Cu NPs]was confirmed with effective antibacterial performance via in vitro antibacterial tests against Staphylococcus aureus(S. aureus), Escherichia coli(E. coli), and multi-resistant E. coli. In addition, the in vitro results demonstrated that osteogenic property of PCL-(MI-h PG)-Cu NPs was realized by upregulating the osteoblast-related gene expressions and protein activity. This study shows that antibacterial and osteogenic properties can be balanced in a surface coating by introducing Cu NPs.

关键词： Mussel-inspired coating CuNPs Multi-resistant bacteria Antibacterial Antifouling Osteogenesis

Management information systems for the information age / 6th ed. 6th ed.

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2007年

作者： haag, Stephen.

ISBN: (数字)007305223X

ISBN: (纸本)007305223X

Management Information Systems for the Information Age, 3rd edition maintains the unique overall approach of the successful second edition: the right mix of traditional and leading edge topical coverage along with LOTS of hands-on, problem-solving projects. haag works well for professors (and students) who want a very interactive, engaging experience, and for those who want to see a strong tie to the latest and greatest on the Internet and corresponding textbook website. haag is equally appropriate for both business and non-business majors. This revision now clearly distinguishes between technical and managerial topics key to MIS by organizing the technology coverage into Modules and the managerial material into Chapters. In response to feedback from both users and non-users, the chapters have been slightly reorganized to incorporate increased coverage of E-Commerce and E-Business (now a full chapter 5). Pedagogical features have been retained but fine-tuned and the vibrant design has been toned down to reflect fewer features on a page.

关键词： Management information systems.

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World Journal of Gastrointestinal Oncology 2020年第11期12卷 1288-1295页

作者： Anne Katrin Berger Michael Allgäuer Leonidas Apostolidis Anna Elisa Schulze-Schleithoff Uta Merle Dirk Jaeger Georg Martin haag Department of Medical Oncology National Center for Tumor DiseasesUniversity Hospital of HeidelbergHeidelberg 69120Germany Department of Pathology Institute of PathologyUniversity Hospital of HeidelbergHeidelberg 69120Germany Department of Gastroenterology University Hospital of HeidelbergHeidelberg 69120Germany Department of Gastroenterology and Hepatology University Hospital of HeidelbergHeidelberg 69120Germany

BACKGROUND Microangiopathic hemolytic anemia(MAHA) with thrombocytopenia and organ failure caused by tumor-associated thrombotic microangiopathy(TMA) is a lifethreatening oncological emergency. Rapid diagnosis and precise distinction from other forms of TMA is crucial for appropriate therapy, which aims at treating the underlying malignancy. However, the prognosis of patients with cancer-related(CR)-MAHA is limited. To date, less than 50 patients with gastric cancer and CRMAHA have been reported, mainly as single case reports, and detailed information on treatment strategies and outcome are scarce. We analyzed the characteristics and outcomes data of CR-MAHA patients with gastric cancer treated at our center between 2012 and *** To gain knowledge about CR-MAHA and the course of *** We retrospectively analyzed patients using an institutional prospectively maintained database. Patients who had CR-MAHA but other cancer types or cancer of unknown primary were excluded. The basic requirements for inclusion were: Histologically proven gastric adenocarcinoma;and clinical diagnosis of hemolytic anemia with schistocytes with or without thrombocytopenia. The observation period for each patient started with the first day of documented symptoms. The follow-up period for this analysis ended on February 1, *** We identified eight patients with a median age of 54 years. Histologically, all patients had(partial) diffuse subtypes of gastric adenocarcinoma with partial or complete signet cell morphology. All patients had metastatic disease and one patient had a microsatellite instability-high(MSI-H) tumor. In three patients, clinical signs of MAHA preceded the diagnosis of cancer, and in two patients, CRMAHA indicated recurrent disease. All patients had severe hemolytic anemia and thrombocytopenia. Six patients experienced severe bone pain, and five patients had dyspnea. Systemic, 5-fluorouracil-based combination chemotherapy was initiated in six patients, w

关键词： Microangiopathic hemolytic anemia Gastric cancer Chemotherapy Secondline chemotherapy Thrombocytopenia Microsatellite instability-high tumor