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Induction of Human Anti-Human Antibody Responses (Ab2) after Application of a Humanized Lewis Y Carbohydrate Specific Antibody (Ab1): Connection of Prolonged Disease Stabilization with Ab3 Induction?

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Journal of Cancer Therapy 2012年第4期3卷 269-277页

作者： Andreas Nechansky Stefan Stranner Oliver Scheiber Nicole Halanek ralf kircheis Apeiron Biologics AG Igeneon GmbH Vienna Austria Virologik GmbH Erlangen Germany

Purpose: Detailed analysis of a patient with epithelial Lewis Y (LeY) positive cancer who received twice 50 mg of the humanized Lewis Y carbohydrate specific mAb IGN311 and developed a clinically significant human anti-human antibody (HAHA) response (Ab2). Results: Clinical stabilization of the disease was assigned to in this patient. The HAHA response consisted mainly of IgG1 and was found to be directed against the IGN311 binding site. Consistent with the induction of the HAHA response, CDC activity against Lewis Y positive target cells was completely abolished at day 8 and could not be restored by the second 50 mg infusion indicating complete neutralization of applied IGN311. The ADCC reactivity was also significantly reduced and anti-anti idiotype-specific antibodies (Ab3) were detectable at day 65. Conclusions: Induction of Ab3 antibodies should be considered as an additional factor influencing the efficacy of humanized antibodies. In this context, the potential threat of induced HAHA responses against therapeutic mAbs might have to be reconsidered because they might actually have also beneficial immunological long-term effects leading to an active immunization component induced by therapeutic antibodies.

关键词： Lewis Y Carbohydrate Immunotherapy Immunogenicity Anti-Idiotype HAHA (Human Anti-Human Antibodies)

Laser-induced plasma formation in water with up to 400 mJ double-pulse LIBS

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Plasma Science and Technology 2024年第1期26卷 93-100页

作者： Marion HENKEL Michelle SIEMENS ralf METHLING Benjamin EMDE Jörg HERMSDORF Steffen FRANKE Diego GONZALEZ Leibniz Institute for Plasma Science and Technology(INP) Felix-Hausdorff-Straße 2Greifswald 17489Germany Laser Zentrum Hannover e.V.(LZH) Hollerithallee 8Hannover 30419Germany

Double-pulse LIBS is a promising technique for deep-sea *** measurements in shallow water with up to 400 mJ each pulse were done to select laser parameters which promote optimized spectral line emission from plasma even at elevated pressures,where line broadening until loss of most of the spectral information can *** emission spectroscopy,using a Czerny-Turner spectrometer,has been applied to investigate the dependence of the emitted radiation on laser parameters and hydrostatic *** has been found,that higher laser pulse energies,especially with short pulse delay as required in high water pressure,can also have an adverse effect on the measured spectrum.

关键词： double-pulse LIBS underwater plasma formation emission spectrosocpy

Unraveling the gut-brain axis:the impact of steroid hormones and nutrition on Parkinson's disease

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Neural Regeneration Research 2024年第10期19卷 2219-2228页

作者： Paula Maria Neufeld ralf A.Nettersheim Veronika Matschke Matthias Vorgerd Sarah Stahlke Carsten Theiss Department of Cytology Institute of AnatomyMedical FacultyRuhr-University BochumBochumGermany Department of Visceral Surgery University Hospital BergmannsheilRuhr-University BochumBochumGermany Department of Neurology Heimer Institute for Muscle ResearchUniversity Hospital BergmannsheilRuhr-University BochumBochumGermany

This comprehensive review explores the intricate relationship between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the context of the gut-brain *** gut-brain axis plays a pivotal role in neurodegenerative diseases like Parkinson's disease,encompassing diverse components such as the gut microbiota,immune system,metabolism,and neural *** gut microbiome,profoundly influenced by dietary factors,emerges as a key *** during the first 1000 days of life shapes the gut microbiota composition,influencing immune responses and impacting both child development and adult ***-fat,high-sugar diets can disrupt this delicate balance,contributing to inflammation and immune *** nutritional strategies,the Mediterranean diet's anti-inflammatory and antioxidant properties show promise in reducing Parkinson's disease ***-targeted dietary approaches and the ketogenic diet hold the potential in improving brain *** nutrition,emerging research uncovers potential interactions between steroid hormones,nutrition,and Parkinson's ***,with its anti-inflammatory properties and presence in the nervous system,offers a novel option for Parkinson's disease *** ability to enhance neuroprotection within the enteric nervous system presents exciting *** review addresses the hypothesis thatα-synuclein aggregates originate from the gut and may enter the brain via the vagus *** symptoms preceding motor symptoms support this *** gut-brain signaling during gut dysbiosis contributes to inflammation and neurotransmitter imbalances,emphasizing the potential of microbiota-based *** summary,this review uncovers the complex web of interactions between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the gut-brain axis *** these connections not only offers novel therapeutic insi

关键词： diet gut-brain axis microbiome neurodegenerative diseases nutrition Parkinson's disease progesterone steroid hormones

Novel C_(sf)/SiBCN composites prepared by densifying C_(sf)/MA-SiBCN with the PIP process:Oxidation behavior and damage mechanism

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Journal of Advanced Ceramics 2024年第5期13卷 666-678页

作者： Wenhao Dou Daxin Li Bingzhu Wang Zhihua Yang Jun Chen Dechang Jia ralf Riedel Yu Zhou Institute for Advanced Ceramics School of Materials Science and EngineeringHarbin Institute of TechnologyHarbin 150001China Key Laboratory of Advanced Structural-Functional Integration Materials and Green Manufacturing Technology Harbin Institute of TechnologyHarbin 150001China Chongqing Research Institute of HIT Chongqing 401135China Beijing Institute of Control Engineering Beijing 100094China Institut für Materialwissenschaft Technische Universität DarmstadtDarmstadt D-64287Germany School of Materials Science and Engineering Harbin Institute of Technology(Shenzhen)Shenzhen 518055China

To improve the oxidation resistance of short carbon fiber(C_(sf))-reinforced mechanically alloyed SiBCN(MA-SiBCN)(C_(sf)/MA-SiBCN)composites,dense amorphous C_(sf)/SiBCN composites containing both MA-SiBCN and polymer-derived ceramics SiBCN(PDCs-SiBCN)were prepared by repeated polymer infiltration and pyrolysis(PIP)of layered C_(sf)/MA-SiBCN composites at 1100℃,and the oxidation behavior and damage mechanism of the as-prepared C_(sf)/SiBCN at 1300–1600℃ were compared and discussed with those of C_(sf)/*** C_(sf)/MA-SiBCN composites resist oxidation attack up to 1400℃ but fail at 1500℃ due to the collapse of the porous framework,while the PIP-densified C_(sf)/SiBCN composites are resistant to static air up to 1600℃.During oxidation,oxygen diffuses through preexisting pores and the pores left by oxidation of carbon fibers and pyrolytic carbon(PyC)to the interior of the *** to the oxidative coupling effect of the MA-SiBCN and PDCs-SiBCN matrices,a relatively continuous and dense oxide layer is formed on the sample surface,and the interfacial region between the oxide layer and the matrix of the as-prepared composite contains an amorphous glassy structure mainly consisting of Si and O and an incompletely oxidized but partially crystallized matrix,which is primarily responsible for improving the oxidation resistance.

关键词： mechanically alloyed SiBCN(MA-SiBCN) polymer-derived ceramics SiBCN(PDCs-SiBCN) short carbon fiber-reinforced SiBCN(C_(sf)/SiBCN)composites polymer infiltration and pyrolysis(PIP) oxidation damage mechanism

Safety and Therapeutic Efficacy of the Lewis Y Carbohydrate Specific Humanized Antibody MB311 in Patients with Malignant Effusion

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Journal of Cancer Therapy 2014年第1期5卷 28-37页

作者： Thomas Bauernhofer Helmut Samonigg Peter Regitnik Werner Weitzer Brigitte Lileg Günter Waxenecker Susanne Wiederkum Manuela Kainer Manfred Schuster Hans Loibner Markus Fido ralf kircheis Andreas Nechansky Igeneon Vienna Austria Medical University Graz Graz Austria

Purpose: Investigation of safety and tolerability as well as therapeutic efficacy of the LeY specific humanized mAb MB311 in cancer pts with malignant effusions in a Phase II clinical trial. Experimental Design: An openlabel, single treatment arm, uncontrolled study with MB311 (100 mg per dose, intravenous infusion on day 1 and 7) in pts with malignant effusion (ascites or pleural effusion) was conducted with the primary objective to examine safety and tolerability as well as pharmacokinetics. Secondary objectives were assessment of pharmacodynamics, volumetric measurement of the malignant effusion and obtaining data for several immunological parameters. Results: Five pts (2 pts with gastric cancer and malignant ascites, 3 pts with breast cancer and malignant pleural effusion/ascites) have completed the study. MB311 was well tolerated with only two pts showing the easily manageable side effects nausea, vomiting (up to grade 2) and one episode of skin rash (grade 2) after the first application. Data of 4 pts were available for evaluating immunologic results and efficacy. In all pts significant levels of MB311 could be detected in the systemic blood circulation and the effusion leading to increased infiltration of CD45 positive immune cells (4/5 pts) and resulting in a reduction of tumor cell counts as detected by immunocytochemistry of effusion samples in 3/5 pts). Most interestingly, the pt with the highest LeY positive tumor showed a significant reduction of effusion volume after treatment—this decrease was also evident for Her2/neu positive tumor cells which were dramatically reduced after MB311 treatment in this breast cancer pt. Conclusion: MB311 was well tolerated in patients with malignant effusions, permeated into malignant effusion and attracted immune cells leading to decreased tumor cell counts in the effusion. In the case of strong LeY expression of malignant cells in the effusion a pronounced decrease in LeY, EpCAM and Her2/neu positive tumor cells and a

关键词： Passive Immunotherapy Therapeutic Antibody Circulating Tumor Cells Malignant Effusion Lewis Y Carbohydrate Ascites

Phase I Dose Escalation Study with the Lewis Y Carbohydrate Specific Humanized Antibody IGN311

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Journal of Cancer Therapy 2011年第5期2卷 760-771页

作者： Daniel Oruzio Gunter Waxenecker Christoph Aulmann Bruno Markl Theodor Wagner Geert Mudde Manfred Schuster Norbert Eller Andrea Mayer Stefan Stranner Gottfried Himmler Hans Loibner Günter Schlimok ralf kircheis Andreas Nechansky Zentralklinikum AugsburgGermany Igeneon ViennaAustria AGES Pharmed ViennaAustria S-TARget ViennaAustria Apeiron ViennaAustria CDMS ViennaAustria Immatics TubingenGermany f-Star ViennaAustria ViroLogik ErlangenGermany Meridian Biopharmaceuticals ViennaAustria.

Purpose: Investigation of safety, tolerability, pharmacokinetics, and anti-tumor activity of the Lewis Y-specific, fully humanized monoclonal antibody (mAb) IGN311 in patients with Lewis Y positive tumors in a Phase I clinical trial. Experimental Design: Twelve patients (pts) were enrolled in an open-label, uncontrolled, dose escalating Phase I study. Three pts received 50 mg, three pts 100 mg and six pts 200 mg IGN311 by i.v. infusion on days 1 and 15. Blood samples were taken immediately before infusion, and 0.5, 4, 8, 24 hours post infusion, as well as on days 3, 5 and 8 after the first and second infusion, respectively, and day 29. A final visit was scheduled for day 43. Results: No drug related adverse events were observed in the 50 mg and 100 mg dose groups. Three out of six patients in the 200 mg dose group showed drug related adverse reactions with nausea, vomiting and hypotension in one patient (NCI CTC grade 3) being the dose limiting toxicities. t1/2 of IGN311 was ~20 days after second infusion of IGN311. Sera of patients receiving IGN311 were capable of lysing Lewis Y positive tumor cells in vitro by both, complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). Circulating tumor cells found in the peripheral blood in two out of twelve pts prior to treatment were reduced after treatment to below the quantification limit of the detection method. None of the patients showed an increase in the number of disseminated tumor cells during treatment period. Conclusions: The good safety and PK profile, the biological activity regarding CDC and ADCC mediated tumor cell lysis, and the elimination of circulating tumor cells warrant further clinical investigation of IGN311.

关键词： Passive Immunotherapy Therapeutic Monoclonal Antibody Disseminated Tumor Cells Phase I Study Lewis Y Carbohydrate HAHA (Human Anti-Human Antibodies)

The new kid on the block in insect pest management:sprayable RNAi goes commercial

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Science China(Life Sciences) 2024年第8期67卷 1766-1768页

作者： Junjie Yan ralf Nauen Stuart Reitz Andrei Alyokhin Jiang Zhang David Mota-Sanchez Yonggyun Kim Subba Reddy Palli Silvia I.Rondon Brian A.Nault Juan Luis Jurat-Fuentes Michael S.Crossley William E.Snyder Angharad M.R.Gatehouse Myron P.Zalucki Bruce E.Tabashnik Yulin Gao State Key Laboratory for Biology of Plant Disease and Insect Pests Institute of Plant ProtectionChinese Academy of Agricultural SciencesBeijing 100193China Bayer AG Crop Science DivisionR&DPest ControlMonheim 40789Germany Department of Crop and Soil Science Oregon State UniversityOntario 97914USA School of Biology and Ecology University of MaineOrono 04469USA Shenzhen Branch Guangdong Laboratory of Lingnan Modern AgricultureKey Laboratory of Synthetic BiologyMinistry of Agriculture and Rural AffairsAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhen 518000China Department of Entomology Michigan State UniversityEast Lansing 48864USA Department of Plant Medicals Andong National UniversityAndong 36729Republic of Korea Department of Entomology University of KentuckyLexington 40503USA Oregon State University Oregon Integrated Pest Management CenterCorvallis 97838USA Department of Entomology Cornell UniversityCornell AgriTechGeneva 14456USA Department of Entomology and Plant Pathology University of TennesseeKnoxville 37996USA Department of Entomology and Wildlife Ecology University of DelawareNewark 19716USA Department of Entomology University of GeorgiaAthensGeorgia 30602USA School of Natural and Environmental Sciences Newcastle UniversityNewcastle upon TyneNE17RUUK School of the Environment University of QueenslandBrisbane 4072Australia Shandong Engineering Research Center for Environment-Friendly Agricultural Pest Management College of Plant Health and MedicineQingdao Agricultural UniversityQingdao 266109China Department of Entomology University of ArizonaTucson 85721USA National Center of Excellence for Tuber and Root Crop Research Chinese Academy of Agricultural SciencesBeijing 100081China

Insect pest damage to crops is a threat to global food security(Tilman et al.,2011).Climate change,the evolution of insecticide resistance,and the phasing out of insecticides due to environmental and safety concerns exacerbate this *** urgently need safe and effective crop protection tools to sustainably generate yields that meet ever-increasing global demand.

关键词： crops damage pest

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Evaluation of acoustic radiation force impulse imaging for determination of liver stiffness using transient elastography as a reference

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World Journal of Gastroenterology 2012年第10期18卷 1077-1084页

作者： Gerald kircheis Abdurrahman Sagir Christoph Vogt Stephan vom Dahl ralf Kubitz Dieter Hussinger Department of Gastroenterology Hepatology and Infectious Diseases Heinrich-Heine-University Düsseldorf Moorenstrasse 5 Düsseldorf 40225 Germany Christoph Vogt St. Josef Hospital Moers Asberger Str. 4 Moers 47441 Germany St. Franziskus Hospital Schnsteinstraβe 63 Kln 50825 Germany

AIM: To evaluate cut-off values and performance of acoustic radiation force impulse imaging (ARFI) using transient elastography [FibroScan■ (FS)] as a reference. METHODS: Six hundred and six patients were enrolled in this *** patients underwent liver stiffness measurement with FS (FS-LS) and ARFI (with shear wave velocity quantification; ARFI-SWV) and the performance of ARFI in comparison to FS was determined. Sixtyeight patients underwent liver biopsy. RESULTS: Significantly higher success rates for the determination of liver stiffness were found using ARFI as compared to FS [604/606 (99.7%) vs 482/606 (79.5%); P 13.0 kPa)). ARFI-SWV cut-off values were identified for no significant fibrosis (1.29 m/s; sensitivity 91.4% and specificity 92.6%) and for liver cirrhosis (1.60 m/s; sensitivity 92.3% and specificity 96.5%). The optimal cut-off value for predicting liver fibrosis (F ≥ 2) was 1.32 m/s (sensitivity 87.0% and specificity 80.0%) and for liver cirrhosis (F4) 1.62 m/s (sensitivity 100% and specificity 85.7%), for patients who underwent liver biopsy. An excellent inter-and intraobserver reproducibility was observed for ARFI-SWV determinations. CONCLUSION: An ARFI-SWV cut-off value of 1.29 m/s seems to be optimal for patients with no significant liver fibrosis and 1.60 m/s for patients with liver cirrhosis.

关键词：硬度测定辐射力肝脏弹性瞬时成像肝纤维化评价

Bottomonium suppression in heavy-ion collisions and the in-medium strong force

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Nuclear Science and Techniques 2023年第4期34卷 185-187页

作者： ralf Rapp Cyclotron Institute and Department of Physics and Astronomy Texas A&M UniversityCollege StationTX 77843-3366USA

A large suppression of various bottomonium states in ultra-relativistic heavy-ion collisions has been reported by the STAR collaboration at the Relativistic Heavy-Ion *** observation is consistent with the formation of a quark-gluon plasma,but similar findings in more energetic collisions at the Large Hadron Collider suggest that a consistent picture requires additional *** states of a heavy quark (charm or bottom) and its antiquark,commonly referred to as quarkonia,have long been recognized as excellent probes of quark-gluon plasma(QGP) formation in high-energy collisions of atomic *** the vacuum,most quarkonium states are dominantly bound by a linearly rising potential (the so-called Cornell potential,see Fig.1),as a direct manifestation of the confinement property of Quantum Chromodynamics (QCD).

关键词： quark linearly vacuum