Academic literature on the topic 'Doerner Institut'

Any new knowledge that goes beyond the stone tools and techniques used in the Palaeolithic and Mesolithic is most significant as it reveals the cultural and technical capabilities of the people living in these periods. In 1963, two pitch finds were discovered in a lignite open-mining pit in the northern foothills of the Harz Mountains, in a layer the geological age of which was dated as being older than 80,000 years. The great significance of these finds was therefore immediately apparent. One of the finds showed a fingerprint as well as the imprints of a flint stone tool and the structure of wood cells. This was indicative of the pitch piece having served as an adhesive to secure a wooden haft to a flint stone blade.Over 30 years later these finds were transferred to the Doerner Institut for investigation. The GC and GC/MS analyses revealed that, in both cases, birch pitches, well-known historical adhesives, had been used. These consist predominantly of pentacyclic triterpenoid components of the lupane type, with betulin forming the major component. The comparison with birch bark extracts showed that the biological peak profile (bio-marker) was surprisingly well preserved in these pitch finds and that hardly any degradation products were present.Today, comparable pitches can easily be produced with modern technical methods, i.e. using airtight laboratory flasks and temperature control facilities. However, any attempt at simulating the conditions of the Neandertal period and at producing these birch pitches without any of these modern facilities will soon be met with many difficulties. This implies that the Neandertals did not come across these pitches by accident but must have produced them with intent. Conscious action is, however, always a clear sign of considerable technical capabilities.

In this work, the experimental method and the calculation model for the determination of indentation moduli, indentation work, and indentation creep of metallic materials, by means of macroscale-level forces provided by a primary hardness standard machine at the National Institute of Metrological Research (INRIM) at the at room temperature were described. Indentation moduli were accurately determined from measurements of indentation load, displacement, contact stiffness and hardness indentation imaging and from the slope of the indentation unloading curve by applying the Doerner-Nix linear model; indentation work, representing the mechanical work spent during the force application of the indentation procedure, was determined by calculating the areas under the loading–unloading indentation curve, through fitting experimental data with a polynomial law. Measurements were performed with a pyramidal indenter (Vickers test). The applied force was provided by a deadweight machine, and the related displacement was measured by a laser interferometric system. Applied forces and the occurring indentation depths were simultaneously measured: the resulting loading–unloading indentation curve was achieved. Illustrative tests were performed on metals and alloy samples. Discussion and comments on the suitability of the proposed method and analysis were reported.

Introdução: O número crescente de infecções causadas por fungos e o surgimento de microrganismos resistentes tem sinalizado a necessidade da busca por novos agentes antifúngicos, fomentando a pesquisa em moléculas promissoras, como os O-glicosídeos. Objetivo: Partindo dessa premissa, objetivamos a síntese e investigação da atividade antifúngica do benzil 2,3-didesoxi-α-D-eritro-hex-2-enopiranosídeo isolado e quando associado com a anfotericina B. Material e métodos: Inicialmente foi sintetizado o benzil 4,6-di-O-acetil-2,3-didesoxi-α-D-eritro-hex-2-enopiranosídeo a partir da reação entre o 3,4,6-tri-O-acetil-D-glucal e álcool benzílico via catálise ácida e irradiação ultrassônica seguida por sua hidrólise em meio básico para levar ao benzil 2,3-didesoxi-α-D-eritro-hex-2-enopiranosídeo. Este foi submetido à avaliação antifúngica por meio do método da microdiluição em caldo e estudo da associação com a anfotericina B pelo método de Checkerboard. Resultados: O benzil 4,6-di-O-acetil-2,3-didesoxi-α-D-eritro-hex-2-enopiranosídeo e o benzil 2,3-didesoxi-α-D-eritro-hex-2-enopiranosídeo foram obtidos em excelentes rendimentos 91 e 94 %, respectivamente. O benzil 2,3-didesoxi-α-D-eritro-hex-2-enopiranosídeo apresentou atividade antifúngica apenas contra as cepas de Candida albicans ATCC 76615, Candida albicans ATCC 76485 e Candida guilliermondiiLM 103, e sua associação com a anfotericina B foi classificada como indiferente. Conclusão: Estes resultados possibilitam futuros estudos envolvendo esta classe de moléculas, avaliação dos possíveis mecanismos de ação e avaliar outras atividades biológicas, uma vez que esta classe molecular sustenta a expectativa de baixa toxicidade, devido ao seu padrão de biocompatibilidade. Descritores: Síntese Química; Metabolismo dos Carboidratos; Fungos; Candida. Referências Silva S, Negri M, Henriques M, Oliveira R, Williams DW, Azeredo J. Candida glabrata, Candida parapsilosis and Candida tropicalis: biology, epidemiology, pathogenicity and antifungal resistance. FEMS Microbiol Rev. 2012;36:288-305. Vieira AJH, Santos JI. Mecanismos de resistência de Candida albicans aos antifúngicos anfotericina B, fluconazol e caspofungina. RBAC. 2017;49:235-9. De Rossi T, Lozovoy MAB, Silva RV, Fernandes EV, Geraldino TH, Costa IC, et al. Interações entre Candida albicans e Hospedeiro. Semina: Cienc Biol Saude. 2011;32:15-28. Ashong CN, Hunter AS, Mansouri MD, Cadle RM, Hamill RJ, Musher DM. Adherence to clinical practice guidelines for the treatment of candidemia at a Veterans Affairs Medical Center. Int J Health Sci. 2017;11:18-23. Kung HC, Huang PY, Chen WT, Ko BS, Chen YC, Chang SC, et al. 2016 guidelines for the use of antifungal agents in patients with invasive fungal diseases in Taiwan. J microbiol Immunol infect. 2018;51:1-17. Patil S, Rao RS, Raj AT, Sanketh DS, Sarode S, Sarode G. Oral Candidal Carriage in Subjects with Pure Vegetarian and Mixed Dietary Habits. J Clin Diagn Res. 2017;11:22-4. Khan H, Khan Z, Amin S, Mabkhot YN, Mubarak MS, Hadda TB, et al. Plant bioactive molecules bearing glycosides as lead compounds for the treatment of fungal infection: A review. Biomed Pharmacother. 2017;93:498-509. Guzzetti LB, Cecília M, Vescina M, Gil F, Gatti BM. Candidemias en pediatría: distribución de especies y sensibilidad a los antifúngicos. Rev Argent Microbiol. 2017;49:320-2. Wiederhold NP. Antifungal resistance: current trends and future strategies to combat. Infect Drug Resist. 2017;10:249-59. World Health Organization. WHO/EMP/IAU/2017.11. 2017. Acesso em: 04 Fev 2019. Disponível em: www.who.int/medicines/areas/rational_use/antibacterial_agents Lúcio Neto MP. Avaliação tóxica, citotóxica, genotóxica e mutagênica do composto 3-(2-cloro-6-flurobenzil) – imidazolidina-2,4-diona em células eucarióticas. Teresina. Dissertação [Mestrado em Ciências Farmacêuticas] – Universidade Federal do Piauí; 2011. Toshima K, Ishizuka T, Matsuo G, Nakata M. Practical Glycosidation Method of Glycals Using Montmorillonite K-10 as an Environmentally Acceptable and Inexpensive Industrial Catalyst. Chem Ver. 1995;4:306-8. Freitas JCR, Freitas Filho JR, Menezes PH. Stereoselective Synthesis of 2,3-unsaturated-O-Glycosides promoted by TeBr4. J Braz Chem Soc. 2010;21:2169-72. Freitas JCR, Couto TR, Paulino AAS, Freitas Filho JR, Malvestiti I, Oliveira RA, et al. Stereoselective synthesis of pseudoglycosides catalyzed by TeCl4 under mild conditions. Tetrahedron. 2012;68:8645-54. Regueira JLLF, Dantas CR, Freitas JJR, Silva AJFS, Freitas Filho JR, Menezes PH, et al. Stereoselective Synthesis of 2,3-Unsaturated Pseudoglycosides Promoted by Ultrasound. Synthesis. 2016;48:1069-78. Moura AL, Lima LMA, Bezerra GB, Freitas JJR, Belian MF, Ramos CS, et al. O-glicosídeos 2,3-insaturados: aplicações, rearranjo de ferrier e reações. Quím Nova. 2018;41:550-66. Dantas CR. Síntese estereosseletiva e caracterização estrutural de compostos Z-eniínicos acoplados a pseudoglicosídeos. Recife. Dissertação [mestrado em química] – Universidade Federal Rural de Pernambuco; 2017. Nigudkar SS, Demchenko A,V. Stereocontrolled 1,2-cis glycosylation as the driving force of progress in synthetic carbohydrate chemistry. Chem Sci. 2015;6:2687-704. Silva RO, Freitas Filho JR, Freitas JCR. D-Glicose, uma Biomolécula Fascinante: História, Propriedades, Produção e Aplicação. Rev Virt Quim. 2018;10:875-91. Delbianco M, Bharate P, Varela-Aramburu S, Seeberger PH. Carbohydrates in Supramolecular Chemistry. Chem Rev. 2016;116:1693-752. Lima JACL, Mata MMS, Silva RG, da Silva WE, Freitas JCR, Freitas Filho JR. Avanços Recentes na Química de C-Glicosídeos: Aplicaçao, Síntese e Reaçoes. Rev. Virt. Quim. 2018;10:900-39. Silva AF, Silva DA. Fármacos anti-inflamatórios não esteroidais mais dispensados em uma farmácia comercial do município de itaocara, estado do Rio de Janeiro, Brasil. Acta Biomed Bras. 2012;3:1-14. Costa AOC. Estudo in vitro e in silico da atividade antifúngica dos isômeros r-(+) e s-(-)citronelal sobre fungos do gênero Cryptococcus. João Pessoa. Dissertação [Mestrado em Produtos Naturais e Sintéticos Bioativos] – Universidade Federal da Paraíba; 2017. Perrin DD, Amarego WLF. Purifications of laboratory chemicals. 3 ed., Pergamon Press: Oxford, 1996. Santos CS, Dos Santos RS, Silva RO, Freitas Filho JR, Freitas JCR. Uma acetilação eficiente e econômica do 1,2:3,4-di-O-isopropilideno-α-D-galactopiranose utilizando anidrido acético ativado in situ pela argila montmorilonita K10. Ceramica. 2018;64:616-22. Santos JAM, Santos CS, Almeida CLA, Silva TDS, Freitas Filho JR, Militão GCG, et al. Structure-based design, synthesis and antitumoral evaluation of enulosides. Eur J Med Chem. 2017;128:192-201. Clinical and Laboratory Standards Institute. M27-A3: reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard. 3rd ed. Wayne: Clinical and Laboratory Standards Institute; 2008. Oliveira WA, Pereira FO, Luna GCDG, Lima IO, Wanderley PA, Lima RB, et al. Antifungal activity of Cymbopogon winterianus jowitt ex bor against Candida albicans.. Braz J Microbiol. 2011;42:433-41. Pippi B. Avaliação da capacidade de Candida parapsilosis e Candida glabrata desenvolverem resistência fenotípica à própolis vermelha brasileira e ao fluconazol e avaliação de sua atividade antifúngica em associação com fluconazol e anidulafungina. Porto Alegre. Dissertação [Mestrado em Microbiologia Agrícola e do Ambiente] – Instituto de Ciências Básicas da Saúde, Universidade do Rio Grande do Sul; 2014. Doern CD. When Does 2 Plus 2 Equal 5? A Review of Antimicrobial Synergy Testing. J clin microbial. 2014;52:4124-8. Melo ACN, Oliveira RN, Freitas Filho JR, Silva T G, Srivastava RM. Synthesis of anti-inflammatory 2,3-unsaturated O-glycosides using conventional and microwave heating techniques. Heterocycl Commun. 2017;23:205-11. Lima B. Anfotericina B pré-aquecida: avaliação da atividade frente a isolados clínicos de Candida spp. do HU-UFSC. Florianópolis. Dissertação [Mestrado em Farmácia] – Universidade de Santa Catarina; 2017. Cavalcanti IMF, Menezes TGC, Campos LAA, Ferraz MS, Maciel MAV, Caetano MNP, et al. Interaction study between vancomycin and liposomes containing natural compounds against methicillin-resistant Staphylococcus aureus clinical isolates. Braz J Pharm Sci. 2018;54:203-10. Targino CSPC. Estudo da atividade antifúngica e dos mecanismos de ação do peptídeo Ctn[15-34], um fragmento C-terminal da crotalicidina, derivado de uma catelicidina expressa nas glândulas de veneno de cascavéis. Fortaleza. Tese [Doutorado em Ciências Farmacêuticas] – Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará; 2017. Spader TB. Avaliação da suscetibilidade de Rhodotorula mucilaginosa frente a associações de antifúngicos com fármacos diversos. Porto Alegre. Tese [Doutorado em Ciências Pneumológicas] – Faculdade de Medicina, Universidade Federal do Rio Grande do Sul; 2017. Guo J, Wang A, Yang K, Ding H, Hu Y, Yang Y, et al. Isolation, characterization and antimicrobial activities of polyacetylene glycosides from Coreopsis tinctoria Nutt. Phytochemistry. 2017;136:65-9. Dantas CR, de Freitas JJR, Barbosa QPS, Militão GCG, Silva TDS, da Silva TG, et al. Stereoselective Synthesis and Antitumoral Activity of Z-Enyne Pseudoglycosides Org Biomol Chem. 2016;14:6786-95. Qing-Hu W, Na-Ren-Chao-Ke-Tu H, Na-Yin-Tai D, Xiu-Lan W, Wu-Li-Ji AA. The structural elucidation and antimicrobial activities of two isoflavane glycosides from Astragalus membranaceus (Fisch) Bge. var. mongholicus (Bge) Hsiao. J mol struct. 2014;1076:535-8. Soares GL, Santos CS, Freitas JCR, Oliveira WA. Síntese e avaliação do prop-2-in-1-il 4,6-di-O-acetil-2,3-didesoxi-α-D-eritro-hex-2-enopiranosídeo contra espécies não albicans de Candida e resultados da associação com a anfotericina B ou com o cetoconazol Rev Pan-Amaz Saude. 2018;9:43-50.

AbstractWhat are Cy Twombly’s sculptures made of? This article presents an overview of a non-destructive examination conducted on three sculptures by American artist Cy Twombly (1928–2011) as part of an art-technological research project at the Doerner Institut in Munich. The artworks are part of the collection of the Brandhorst Museum and belong to Twombly’s series of so-called ‘Original Sculptures’: assemblages of individual found objects, which the artist covered and modified with layers of plaster and white paint. To develop a long-term preservation strategy, the research focused on understanding the materials and construction methods used in Twombly's sculptures. In collaboration with the Chair of Non-Destructive Testing at the Technical University of Munich, the artworks were inspected using X-ray radiography and computed tomography. The results showed that Cy Twombly used various everyday objects made from wood, plastics, metal, and paper/cardboard to build the assemblages. Unexpectedly, the examinations revealed that the individual parts are solely held together by the coating of plaster and paint, lacking additional mechanical connections. The overall structure thus proved to be very fragile and highly sensitive to physical stresses, whether due to handling, transport, or strains in the microstructure caused by climatic fluctuations. Since little was known about Cy Twombly´s choice of materials and manufacturing details, the results offer valuable insights into the overall artistic process and decision-making of one of the most influential artists of the 20th/twenty-first centuries. Conservators can use the art-technological findings to monitor the sculptures ‘condition and develop or adapt long-term preservation strategies, including aspects such as ambient climatic conditions and handling storage and transport specifications. In addition, the knowledge generated can be used for further research on the specific materials and transferred to other artworks by Cy Twombly.

Abstract Background Desirability of outcome ranking (DOOR) uses an ordinal ranking system to evaluate global outcomes in clinical trial participants by incorporating safety and efficacy assessments into a single endpoint. In this study, we developed and applied a DOOR endpoint for cIAI clinical trials. Methods We reviewed 10 Phase 3 noninferiority trials for cIAI with electronic patient-level data (n=5473 participants) submitted to the FDA between 2005-2021. Extending previous work [CID. 2019:68(10):1691-8)], we developed an expanded cIAI-specific DOOR endpoint based on clinically meaningful events captured in trial datasets and those that were unique to patients with cIAI. Using this DOOR endpoint, we assigned each participant a DOOR rank, estimated the probability that a participant in the study treatment arm in each trial would have a more desirable DOOR rank than if assigned to the comparator arm, and analyzed individual components of clinical experience in each trial. Results Based on analysis of available data, we noted heterogeneity in definitions of “indeterminate” clinical outcomes, and significant diversity and increased incidence of infectious complications (ICs), serious adverse events (SAEs), and surgical/percutaneous procedures in participants without clinical cure. These informed the expansion of the DOOR endpoint for cIAI to include clinical efficacy outcomes, ICs, SAEs, and additional procedures (Table 1). The DOOR distributions between treatment and comparator arms in all 10 trials were similar. DOOR probability estimates for the 10 trials ranged from 44.5% to 50.3% but were not nominally statistically significant. Component analyses in two trials showed that the study treatment was nominally statistically inferior to the comparator with regard to SAEs and clinical failure, respectively (Fig. 1b, 1c). Table 1.cIAI-Specific DOOR EndpointFigure 1.Forest plot listing the DOOR probabilities and probability for each DOOR component from 3 trials. Trial 1 has no significant differences between the treatment arms in the component analysis (A). The study treatment arm was shown to be nominally statistically inferior for SAEs in Trial 2 (B) and for clinical failure in Trial 3 (C). Conclusion We developed a cIAI-specific DOOR endpoint to better elucidate the events that participants experienced in these trials. The component analysis allowed more nuanced evaluation of the factors that contributed to the composite DOOR probability estimate and provided a visual display of the risk-benefit assessment of a study treatment vs. the comparator. Our study was limited by its retrospective approach and trial design heterogeneity. Disclosures Deborah Collyar, B.Sci, Apellis Pharmaceuticals, Inc.: Advisor/Consultant|Kinnate Biopharma: Advisor/Consultant|M2GEN: Advisor/Consultant|Maxis Clinical Sciences: Advisor/Consultant|Parexel: Honoraria|Pfizer: Honoraria|Roundtable Analytics, Inc.: Ownership Interest Sarah B. Doernberg, MD, MAS, Basilea: Clincal events committee|Genentech: Advisor/Consultant|Gilead: Grant/Research Support|Regeneron: Grant/Research Support|Shinogi: Clincal events committee Scott R. Evans, Ph.D., M.S., Abbvie: DSMB|Akouos: DSMB|Apellis: DSMB|AstraZeneca: Advisor/Consultant|Atricure: Advisor/Consultant|Becton Dickenson: Advisor/Consultant|Breast International Group: DSMB|Candel: DSMB|ChemoCentrix: Advisor/Consultant|Clover: DSMB|DayOneBio: DSMB|DeGruyter: Editor|Duke University: DSMB|Endologix: Advisor/Consultant|FHI Clinical: DSMB|Genentech: Advisor/Consultant|Horizon: Advisor/Consultant|International Drug Development Institute: Advisor/Consultant|Janssen: Advisor/Consultant|Lung Biotech: DSMB|Neovasc: Advisor/Consultant|NIH: Grant/Research Support|Nobel Pharma: Advisor/Consultant|Nuvelution: DSMB|Pfizer: DSMB|Rakuten: DSMB|Roche: DSMB|Roivant: Advisor/Consultant|SAB Biopharm: DSMB|SVB Leerink: Advisor/Consultant|Takeda: DSMB|Taylor & Francis: Book royalties|Teva: DSMB|Tracon: DSMB|University of Penn: DSMB|Vir: DSMB Thomas L. Holland, MD, Aridis: Advisor/Consultant|Lysovant: Advisor/Consultant Henry Chambers, MD, Merck: DSMB member|Merck: Stocks/Bonds|Moderna: Stocks/Bonds Vance G. Fowler, Jr, MD, MHS, Affinergy: Grant/Research Support|Affinergy: Honoraria|Affinium: Honoraria|Amphliphi Biosciences: Honoraria|ArcBio: Stocks/Bonds|Basilea: Grant/Research Support|Basilea: Honoraria|Bayer: Honoraria|C3J: Honoraria|Cerexa/Forest/Actavis/Allergan: Grant/Research Support|Contrafect: Grant/Research Support|Contrafect: Honoraria|Cubist/Merck: Grant/Research Support|Debiopharm: Grant/Research Support|Deep Blue: Grant/Research Support|Destiny: Honoraria|Genentech: Grant/Research Support|Genentech: Honoraria|Integrated Biotherapeutics: Honoraria|Janssen: Grant/Research Support|Janssen: Honoraria|Karius: Grant/Research Support|Medicines Co.: Honoraria|MedImmune: Grant/Research Support|MedImmune: Honoraria|NIH: Grant/Research Support|Novartis: Grant/Research Support|Novartis: Honoraria|Pfizer: Grant/Research Support|Regeneron: Grant/Research Support|Regeneron: Honoraria|Sepsis diagnostics: Sepsis diagnostics patent pending|UpToDate: Royalties|Valanbio: Stocks/Bonds Sumathi Nambiar, MD MPH, Johnson and Johnson: Stocks/Bonds Helen W. Boucher, MD, American Society of Microbiology: Honoraria|Elsevier: Honoraria|Sanford Guide: Honoraria.