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Bioactive glass selectively promotes cytotoxicity towards giant cell tumor of bone derived neoplastic stromal cells and induces MAPK signalling dependent autophagy

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Bioactive Materials 2022年第9期7卷 456-468页

作者： Joerg Fellenberg Sarina Losch Burkhard lehner Marcela Arango-Ospina Aldo RBoccaccini Fabian Westhauser Center for Orthopedics Trauma Surgery and Spinal Cord InjuryHeidelberg University HospitalHeidelbergGermany Institute of Biomaterials Department of Materials Science and EngineeringUniversity of Erlangen-NurembergGermany

Giant cell tumors of bone(GCTB)are associated with massive bone destructions and high recurrence *** a previous study,we observed cytotoxic effects of three different compositions of bioactive glasses(BGs)towards GCTSC but not bone marrow derived stromal cells(BMSC)indicating that BGs represent promising candidates for the development of new therapeutic *** the current study we aimed to investigate the molecular mechanisms that are involved in BG induced *** observed,that BG treatment was not associated with any signs of apoptosis,but rather led to a strong induction of mitogen activated protein kinases(MAPK)and,as a consequence,upregulation of several transcription factors specifically in *** wide gene expression profiling further revealed a set of fifteen genes that were exclusively induced in GCTSC or induced significantly stronger in GCTSC compared to *** treatment further induced autophagy that was significantly more pronounced in GCTSC compared to BMSC and could be inhibited by MAPK *** with the known osteogenic properties of BGs our findings support the suitability of BGs as therapeutic agents for the treatment of ***,these data have to be verified under in vivo conditions.

关键词： Bioactive glass Giant cell tumor of bone Mesenchymal stromal cells Mitogen-activated protein kinases Cytotoxicity Autophagy

On fixity of arc-transitive graphs

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Science China Mathematics 2021年第12期64卷 2603-2610页

作者： Florian lehner Primoz Potocnik Pablo Spiga Institute of Discrete Mathematics Graz University of TechnologyGraz 8010Austria Faculty of Mathematics and Physics University of LjubljanaLjubljana 1000Slovenia Dipartimento di Matematica Pura e Applicata University of Milano-BicoccaMilano 20126Italy

The relative xity of a permutation group is the maximum proportion of the points xed by a non-trivial element of the group,and the relative xity of a graph is the relative xity of its automorphism group,viewed as a permutation group on the vertex-set of the *** prove in this paper that the relative xity of connected 2-arc-transitive graphs of a xed valence tends to 0 as the number of vertices grows to in *** prove the same result for the class of arc-transitive graphs of a xed prime valence,and more generally,for any class of arc-transitive locally-L graphs,where L is a xed quasiprimitive graph-restrictive permutation group.

关键词： permutation group xity minimal degree graph automorphism group vertex-transitive arc-transitive xed points

Mapping of liver-enriched transcription factors in the human intestine

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World Journal of Gastroenterology 2010年第31期16卷 3919-3927页

作者： Frank lehner Ulf Kulik Juergen Klempnauer Juergen Borlak Department of General Visceral and Transplantation SurgeryHanover Medical School Molecular Medicine and Medical Biotechnol-ogy Fraunhofer Institute of Toxicology and Experimental Medi-cine Center of Pharmacology and Toxicology Hanover Medical School

AIM: To investigate the gene expression pattern of hepatocyte nuclear factor 6 (HNF6) and other liverenriched transcription factors in various segments of the human intestine to better understand the differentiation of the gut epithelium. METHODS: Samples of healthy duodenum and jejunum were obtained from patients with pancreatic cancer whereas ileum and colon was obtained from patients undergoing right or left hemicolectomy or (recto)sigmoid or rectal resection. All surgical specimens were subjected to histopathology. Excised tissue was shock-frozen and analyzed for gene expression of liver-enriched transcription factors by semiquantitative reverse transcription polymerase chain and compared to the human colon carcinoma cell line Caco-2. Protein expression of major liver-enriched transcription factors was determined by Western blotting while the DNA binding of HNF6 was investigated by electromobility shift assays. RESULTS: The gene expression patterning of liverenriched transcription factors differed in the various segments of the human intestine with HNF6 gene expression being most abundant in the duodenum (P < 0.05) whereas expression of the zinc finger protein GATA4 and of the HNF6 target gene ALDH3A1 was most abundant in the jejunum (P < 0.05). Likewise, expression of FOXA2 and the splice variants 2 and 4 of HNF4α were most abundantly expressed in the jejunum (P < 0.05). Essentially, expression of transcription factors declined from the duodenum towards the colon with the most abundant expression in the jejunum and less in the ileum. The expression of HNF6 and of genes targeted by this factor, i.e. neurogenin 3 (NGN3) was most abundant in the jejunum followed by the ileum and the colon while DNA binding activity of HNF4α and of NGN3 was conf irmed by electromobility shift assays to an optimized probe. Furthermore, Western blotting provided evidence of the expression of several liver-enriched transcription factors in cultures of colon epithelial cells, albeit at

关键词： Liver-enriched transcription factors Human intestine Caco-2 Gene expression

Observation of Offshore Wind Farm Wakes by Spaceborne Synthetic Aperture Radar

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Journal of Geodesy and Geoinformation Science 2021年第1期4卷 38-48页

作者： Xiaoming LI Susanne lehner Key Laboratory of Digital Earth Science Aerospace Information Research InstituteChinese Academy of SciencesBeijing 100094China Hainan Key Laboratory of Earth Observation Sanya 572029China

In this paper,studies on offshore wind farm wakes observed by spaceborne synthetic aperture radar(SAR)are reviewed mainly based on our previous ***,we focus on investigating wind wakes and tidal current wakes observed by spaceborne SAR of Terra SAR-X,Gaofen-3 and Radarsat-2 in high spatial resolution,in two offshores wind farms,i.e.,the Alpha Ventus in the North Sea and the one near Donghai bridge in the East China *** examples of wind wakes and tidal current wakes observed by SAR in the two farms are presented and compared.A preliminary statistical analysis on morphology of wind feature downstream Alpha Ventus is presented as *** these studies on wind wakes generated by a single offshore wind farm,we show an example of wakes downstream multiple wind farms in the North Sea to demonstrate"cluster"effect of multiple offshore wind farms on sea wind.

关键词： offshore wind farm wakes synthetic aperture radar

Color Doppler ultrasound imaging in varicoceles: Is the difference in venous diameter encountered during Valsalva predictive of palpable varicocele grade?

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Asian Journal of Urology 2023年第1期10卷 27-32页

作者： Kelly lehner Catherine Ingram Utsav Bansal Colleen Baca Adithya Balasubramanian Nannan Thirumavalavan Jason M.Scovell Saneal Rajanahally Matthew Pollard Larry I.Lipshultz Baylor College of Medicine Scott Department of UrologyHoustonTXUSA

Objective:The clinical grading system for varicoceles is subjective and dependent on clinician *** Doppler ultrasound(US)has not been standardized in the diagnosis of *** aimed to determine if US measurement of varicocele could be predictive of World Health Organization(WHO)varicocele ***:Men who presented for either scrotal pain or infertility to a tertiary men’s health clinic underwent physical examination,and varicoceles were graded following WHO criteria(0Zsubclinical,1,2,3).US was used to measure largest venous diameter in the pampiniform plexus bilaterally at rest and during Valsalva *** operator characteristic curve analysis was used to determine if resting diameter,diameter during Valsalva,or change in diameter between at rest and during Valsalva provided the highest sensitivity and specificity for determining clinical *** values for diameter were determined from these receiver operator characteristic ***:A total of 102 men(50 with clinical varicocele and 52 with subclinical varicocele)were *** at rest was the best ultrasonographic discriminator between subclinical and clinical varicoceles(area under the curve[AUC]Z0.67)with a diameter threshold of 3.0 mm(sensitivity 79%,specificity 42%).Diameter during Valsalva had the greatest AUC for determining clinical Grades 1 versus 2(AUCZ0.57)with diameter threshold of 5.7 mm(sensitivity 71%,specificity 33%).For differentiating between Grades 2 and 3,diameter at rest had the greatest AUC of 0.65 with a threshold of 3.6 mm(sensitivity 71%,specificity 58%).Conclusion:Our results corroborate other studies that have shown a weak correlation between US and clinical *** use of diameter during Valsalva was less predictive than diameter at rest and was only clinically significant in differentiating between Grade 1 and 2 varicocele.A standardized method for determining clinically relevant varicoceles on US would allow for improved pat

关键词： Varicocele Ultrasound Doppler Venous plexus Infertility

Endoscopic third ventriculostomy:a feasible treatment option for pediatric hydrocephalus in a high-risk cohort–a single-center report

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World Journal of Pediatric Surgery 2022年第3期5卷 176-180页

作者： Stefanie Deininger Julia Küppers Dirk Lehnick Peter Esslinger Hermann Winiker Markus lehner Department of Neurosurgery University Hospital UlmUlmGermany Department of Pediatric Surgery Luzerner Kantonsspital Kinderspital LuzernLuzernSwitzerland Department of Health Sciences and Health Policy University of LucerneLuzernSwitzerland

Treating hydrocephalus in young childprimarily either byren and infants is still a demanding procedure with a high rate of surgery-related *** improvement of technology in pediatric intensive care has increased the chance of survival in very low birthweight infants,and therefore the risk for patients with posthemorrhagic hydrocephalus(PHH)has also *** the past 20 years,endoscopic third ventriculostomy(ETV)has become a reasonable option for treating different types of hydrocephalus,especially in the challenging field of PHH after intraventricular hemorrhage(IVH).

关键词： hydrocephalus pediatric surgery

Hepatocellular carcinoma recurrence after acute liver allograft rejection treatment: A multicenter European experience

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Hepatobiliary & Pancreatic Diseases International 2019年第6期18卷 517-524页

作者： Quirino Lai Samuele Iesari Armin Finkenstedt Maria Hoppe-Lotichius Maxime Foguenne Konrad lehner Gerd Otto Jan Lerut Starzl Unit of Abdominal Transplantation University Hospitals Saint LucUniversitécatholique LouvainBrusselsBelgium Hepato-biliary Surgery and Liver Transplantation Unit Sapienza University of RomeUmberto I HospitalRomeItaly Department of Bio-technological and Applied Clinical Sciences University of L’AquilaL’AquilaItaly Department of Internal Medicine I Innsbruck Medical UniversityInnsbruckAustria Department of Transplantation and Hepatobiliary Surgery University of MainzMainzGermany

Background:During the last decades,several risk factors for the recurrence of hepatocellular carcinoma(HCC)after liver transplantation(LT)have been ***,the impact of two important drivers of oncogenesis,namely the immunosuppression and the treatment of acute cellular rejection(ACR)have been marginally *** study aimed at investigating the impact of ACR treatment on the incidence of tumor recurrence in a large European HCC-LT ***:Seven hundred and eighty-one adult patients transplanted between February 1,1985 and June 30,2016 were retrospectively *** propensity score match,116 patients treated for ACR using steroid boluses were compared with 115 patients who did not present any ACR or a histologic but clinical irrelevant ***:Steroid boluses treated patients had a 18-fold higher overall incidence of HCC recurrence than those non-treated patients(16.4%vs.0.9%;P<0.0001).At multivariate Cox regression analysis,steroid boluses used to treat ACR were an independent risk factor for HCC recurrence(HR=14.2;95%CI:1.8–110.4;P=0.010).Conclusions:The decision to treat ACR as well as to reinforce immunosuppression load should be cautiously taken in view of the presented *** studies are needed to further elucidate the clinical impact of immunosuppression on HCC recurrence after transplantation.

关键词： Liver transplantation Recurrence Steroid biopsy Acute rejection

Analysis and handling of bio-nanoparticles and environmental nanoparticles using electrostatic aerosol mobility

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Particuology 2013年第1期11卷 14-19页

作者： Peter Kallinger Victor U.Weiss Angela lehner Gunter Allmaier Wladyslaw W.Szymanski University of Vienna.Faculty of Physics Boltzmanngasse 5A-1090 ViennaAustria Vienna University of Technology Institute of Chemical Technologies and AnalyticsCetreidemarkt 9A-1060 ViennaAustria University of Vienna Faculty of PhysicsBoltzmanngasse 5A-1090 ViennaAustria

The successful application of differential mobility analysis for the characterization and manipulation of nanoparticles at atmospheric pressure has given rise to further development of this technique. The parallel differential mobility analyzer provides the possibility to simultaneously measure a size spec- trum of nanoparticles and select a particular set of nanoparticles with a defined size for collection （as well as enrichment） and further orthogonal analysis （as for example electron microscopy, atomic force microscopy or mass spectrometry）. Performing a high resolution measurement of electrical mobility diameters allows molecular weight determination of species with ultrahigh molecular masses in the mega Dalton range （e.g. protein complexes）. The precise size measurement of the human rhinovirus has confirmed the potential of this technique to analyze even intact infectious human-pathogenic viruses. Moreover, the real-time measurement of nanoparticle occurrence in an urban environment confirms the versatility of the method presented here and its applicability also in other areas of importance.

关键词： Nanoparticles Environmental burden Virus measurement PDMA GEMMA

Development of a sample preparation approach to measure the size of nanoparticle aggregates by electron microscopy

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Particuology 2019年第4期17卷 49-57页

作者： Agnieszka Dudkiewicz Angela lehner Qasim Chaudhry Kristian Molhave Guenter Allmaier Karen Tiede Alistair B.A. Boxall Peter Hofmann John Lewis The Food and Environment Research Agency Sand Hutton York Y041 1LZ UK Department of Environment The University of York Heslington York YO10 5DD UK National Centre for Food Manufacturing The University of Lincoln Holbeach PE12 7AG UK Research Group Bio- and Polymer Analysis Institute of Chemical Technologies and Analytics TU Wien (Vienna University of Technology) Getreidemarkt 9 A-1060 Vienna Austria University of Chester Parkgate Road Chester CH1 4BJ UK Department of Micro and Nanotechnology Technical University of Denmark DTU Bldg 345b Lyngby 2800 Denmark Research Centre for Global Food Security and Ecosystems University of Hohenheim Wollgrasweg 43 70155 Stuttgart Germany Department of Geoinformatics - Z.GIS University of Salzburg Schillerstr. 30 A-5020 Salzburg Austria

Electron microscopy (EM) is widely used for nanoparticle (NP) sizing. Following an initial assessment of two sample preparation protocols described in the current literature as"unperturbed", we found that neither could accurately measure the size of NPs featuring a broad size distribution, e.g., aggregates. Because many real-world NP samples consist of aggregates, this finding was of considerable concern. The data showed that the protocols introduced errors into the measurement by either inducing agglomeration artefacts or providing a skewed size distribution towards small particles (skewing artefact). The focus of this work was to develop and apply a mathematical refinement to correct the skewing artefact. This refinement provided a much improved agreement between EM and a reference methodology, when applied to the measurement of synthetic amorphous silica NPs. Further investigation, highlighted the influence of NP chemistry on the refinement. This study emphasised the urgent need for greater and more detailed consideration regarding the sample preparation of NP aggregates to routinely achieve accurate measurements by EM. This study also provided a novel refinement solution applicable to the size characterisation of silica and c让rate-coated gold NPs featuring broad size distributions. With further research, this approach could be extended to other NP types.

关键词： Nanoparticles Aggregates Measurement Electron microscopy Sample preparation Artefacts