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Development of a Ready-to-Use PSMA-11 Kit Formulation and Biological Evaluation of Binding Affinity

Advances in Molecular Imaging 2024年第2期13卷 7-22页

作者： Maria Renata Valente Brandão Freire Natália Marchesan Bexiga Marco Antonio Stephano João Ezequiel Oliveira Carlos Roberto Jorge Soares Ana Cláudia Camargo Miranda Anna Carolina de Alcântara Barbosa Marycel Figols de Barboza Laura Fernanda Garcia luiz Felipe S. Teixeira Maria Helena Marumo Bellini Natanael Gomes da silva luiza Mascarenhas Balieiro Joel Mendes Elaine Bortoleti de Araújo Centro de Radiofarmcia Instituto de Pesquisas Energticas e Nucleares (IPEN) Cidade Universitria So Paulo Brasil Departamento de Tecnologia Farmacutica Faculdade de Cincias Farmacuticas (USP) Cidade Universitria So Paulo Brasil Centro de Biotecnologia Instituto de Pesquisas Energticas e Nucleares (IPEN) Cidade Universitria So Paulo Brasil Departamento de Medicina Nuclear do Hospital Israelita Albert Einstein So Paulo/SP Brasil

Introduction: 68Ga-PSMA-11 is considered the gold standard in detection of micro and oligometastases in advanced prostate cancer, being used for therapeutic planning, as well as, potentially, for evaluating response to treatment. The development of ready-to-use lyophilized kit of PSMA-11 adds quality and safety to the routine use of this radiopharmaceutical and represents a pharmacotechnical challenge as it must preserve the integrity and specificity of the ligand. Methods: PSMA-11 kit formulation was proposed, considering radiolabeling parameters and the preservation of the peptide during the lyophilization process, using mannitol as an excipient. Critical temperature characterization studies were carried out using DSC equipment and the freeze-drying process was developed. The direct radiolabeling conditions were evaluated and standardized using 68Ge/68Ga generator eluate from two different manufacturers (ITG and Eckert & Ziegler). The radiochemical purity was evaluated by TLC and HPLC. Biological evaluation was carried out with lyophilized PSMA-11 to demonstrate the integrity of the peptide and preservation of biological activity after the lyophilization process. Results: Based on critical temperature characterization studies, the freeze-drying cycle was designed to reach a freezing temperature of around −40˚C and primary drying at 2˚C. Using 20 mg of mannitol, an intact and elegant lyophilized cake was obtained. PSMA-11 lyophilized kit was directly labeled with 68Ga eluate from 68Ge/68Ga GMP generators (ITG and Eckert & Ziegler) resulting in % RP > 95% at pH 4.0 to 4.5. The results obtained from in vitro and in vivo biological competition studies confirmed the preservation of PSMA-11 affinity for the receptor after lyophilization. Conclusion: A lyophilized formulation (Kit) of PSMA-11 was successfully obtained, which preserved the integrity and biological activity of the peptide and guaranteed radiolabeling efficiency.

关键词： 68Ga-PSMA-11 Prostate-Specific Membrane Antigen (PSMA) Ready-to-Use Kit GMP-Grade Generators Metastatic Prostate Cancer PET Imaging

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The interplay between leaf water potential and osmotic adjustment on photosynthetic and growth parameters of tropical dry forest trees

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Journal of Forestry Research 2023年第1期34卷 177-186页

作者： Tiago de Sousa Leite Romulo Magno Oliveira de Freitas Nildo da silva Dias Jeferson luiz Dallabona Dombroski Narjara Walessa Nogueira Federal University of Mato Grosso CuiabáMTBrazil Federal Institute of Education Science and Technology of Rio Grande do NortePau dos FerrosRNBrazil Federal Rural University of the Semi-Arid Region MossoróRNBrazil

Mimosa tenuiflora and Piptadenia stipulacea are commonly accepted as drought-tolerant species but little is known about their response to drought followed by ***,the interplay between leaf water potential and osmotic adjustment on photo synthetic and growth parameters of these species was examined.A greenhouse study was conducted in a split-plot design with two water conditions in the main plots(control;drought followed by rehydration),and eight sampling times in the subplots(1,4and 7 days of drought,and 1,3,6,12,and 17 days of rehydration).Plant water status and biochemical changes were assessed as well as leaf gas exchange and subsequent *** drought stress,both species maintained a low leaf water potential throughout the day by accumulating compatible solutes,thus allowing a rapid and full recovery of water status when *** these plants minimized water loss by closing their stomata,neither showed stomatal limitations to *** inhibition of this process during drought was possibly related to mesophyll limitations as well as to a reversible downregulation of photo systems,along with adjustments of their *** deficits also triggered morphological adaptations at the whole plant level,leading to reduced growth,mainly of the shoots in *** and the roots in ***.

关键词： Drought stress Rehydration Gas exchange Plant biomass

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Pericyte Plasticity in the Brain

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Neuroscience Bulletin 2019年第3期35卷 551-560页

作者： Gabryella S.P.Santos luiz A.V.Magno Marco A.Romano-silva Akiva Mintz Alexander Birbrair Departamento de Patologia Universidade Federal de Minas GeraisBelo HorizonteMG 31270-901Brazil Department of Mental Health Federal University of Minas GeraisBelo HorizonteMG 30130-100Brazil Department of Radiology Columbia University Medical CenterNew YorkNY 10032USA

Cerebral pericytes are perivascular cells that stabilize blood vessels. Little is known about the plasticity of pericytes in the adult brain in vivo. Recently, using stateof-the-art technologies, including two-photon microscopy in combination with sophisticated Cre/loxP in vivo tracing techniques, a novel role of pericytes was revealed in vascular remodeling in the adult brain. Strikingly, after pericyte ablation, neighboring pericytes expand their processes and prevent vascular dilatation. This new knowledge provides insights into pericyte plasticity in the adult brain.

关键词： Pericytes Brain Blood vessel Plasticity

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Bartter's syndrome:clinical findings,genetic causes and therapeutic approach

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World Journal of Pediatrics 2021年第1期17卷 31-39页

作者： Flavia Cristina Carvalho Mrad Sílvia Bouissou Morais Soares luiz Alberto Wanderley de Menezes silva Pedro Versiani dos Anjos Menezes Ana Cristina Simoes-e-silva Interdisciplinary Laboratory of Medical Investigation Faculty of MedicineFederal University of Minas Gerais(UFMG)Av.Alfredo Balena190Room#281Belo HorizonteMG 30130-100Brazil Pediatric Nephrology Unit Faculty of MedicineUFMGBelo HorizonteBrazil

Backgound Bartter's syndrome(BS)is a rare group of salt losing tubulopathies due to the impairment of transport mecha-nisms at the thick ascending limb of the Henle's *** sources Literature reviews and original research articles were collected from database,including PubMed and *** According to the time of onset and symptoms,BS can be classified into antenatal and classic *** studies have identified different subtypes of *** types Ⅰ,Ⅱ and Ⅲ are caused by mutations on genes encoding the luminal Na^(+)-K^(+)-2Cl^(-) co-transporter,the luminal K+ channel ROMK,and the basolateral chloride channel ClC-Kb(CLCNKB),***-of-function mutations of Barttin CLCNK type accessory beta subunit cause BS type Ⅳ*** mutations of CLCNKB and CLCNKA cause BS type Ⅳ*** type Ⅴ consists in a novel transient form characterized by antenatal presentation due to mutations in the MAGE family member *** gain-of-function mutations of the extracellular calcium sensing receptor gene can result in an autosomal dominant condition of *** clinical and biochemical alterations in BS include polyuria,dehydration,hypokalemia,hypochloremic metabolic alka-losis,hyperreninemia,high levels of prostaglandins,normal or low blood pressure,hypercalciuria and failure to *** focuses mainly at correcting dehydration and electrolyte disturbances and in measures to reduce polyuria,including the use of nonsteroidal anti-inflammatory medications to control excessive renal prostaglandin E2 *** Early diagnosis and treatment of BS may prevent long-term consequences such as growth failure,nephrocal-cinosis and end-stage renal disease.

关键词： Bartter's syndrome Hypercalciuria Hypokalemia Metabolic alkalosis Nephrocalcinosis

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CFD predictions for hazardous area classification

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Chinese Journal of Chemical Engineering 2019年第1期27卷 21-31页

作者： Andrey Oliveira de Souza Aurélio Moreira luiz Ant?nio Tavernard Pereira Neto Ant?nio Carlos Brandao de Araujo Heleno Bispo da silva Sidinei Kebler da silva Jose Jailson Nicacio Alves Federal Institute of Education Science and Technology of Paraiba Petrobras-Petróleo Brasileiro S.A. Federal University of Campina Grande

This study aimed to describe a Computational Fluid Dynamics(CFD) procedure using the ANSYS CFX software 16.1 and Design of Experiments for the determination of volume and extension of explosive atmospheres due to fugitive emissions of flammable *** multidimensional statistical sampling technique Latin Hypercube was used, which defined 100 simulations of random methane gas leak *** CFD model proved to be robust in predicting the extension and volume of the explosive atmosphere for orifice diameters from 0.1 to2.5 mm, pressure from 0.1 MPa to 12 MPa and temperatures from 0 ℃ to 400 ℃.It was found that the calculation domain must be parameterized 8 m in length for each millimeter of the diameter of the source of release to ensure the *** order not to lose precision for very small diameters, the mesh was parameterized with 50 elements along the orifice *** was proved that gravity does not influence the extension and volume of the explosive atmosphere at sonic *** deviation from the ideal gas behavior in the reservoir,achieved by applying the Soave–Redlich–Kwong equation of state, also has not significantly influenced the extension and volume of the explosive *** results showed that the size of the explosive atmosphere varies directly with the diameter of the source emission and reservoir pressure, and inversely with the temperature of the *** diameter of the source is the parameter that has the major effect on the extension of the explosive atmosphere, followed by the pressure and lastly the temperature of the reservoir.

关键词： Computational Fluid Dynamics Computer simulation Safety Fugitive emissions Classified area Flammable gas cloud

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Antiglycation and antioxidant activities of the crude extract and saponin fraction of Tribulus terrestris before and after microcapsule release

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Journal of Integrative Medicine 2022年第2期20卷 153-162页

作者： Célia Cristina Malaguti Figueiredo Amanda da Costa Gomes Filipe Oliveira Granero Joao luiz Bronzel Junior Luciana Pereira silva Valdecir Farias Ximenes Regildo Márcio Goncalves da silva Institute of Chemistry São Paulo State UniversityAraraquaraSão Paulo 14800-060Brazil Educational Foundation of the City of Assis AssisSão Paulo 19807-130Brazil Department of Chemistry School of SciencesSão Paulo State UniversityBauruSão Paulo 17033-360Brazil Department of Biotechnology School of SciencesHumanities and LanguagesSão Paulo State UniversityAssisSão Paulo 19806-900Brazil

Objective:The present study investigated antiglycation and antioxidant activities of crude dry extract and saponin fraction of Tribulus *** also developed a method of microencapsulation and evaluated antiglycation and antioxidant activities of crude dry extract and saponin fraction before and after microcapsule ***:Antiglycation activity was determined by relative electrophoretic mobility(REM),free amino groups and inhibition of advanced glycation end-product(AGE)*** activity was determined by 2,2-diphenyl-1-picrylhydrazyl(DPPH),ferric ion-reducing antioxidant power(FRAP),nitric oxide(NO)and thiobarbituric acid reactive species(TBARS)*** were prepared using maltodextrin as wall material and freeze-drying as encapsulation *** characterization of microcapsules was evaluated by scanning electron microscopy,and encapsulation efficiency and microcapsule release were determined by total saponins *** and antioxidant assays were performed using crude dry extract and saponin fraction of *** before and after ***:Saponin fraction showed an increase of 32.8%total ***-performance liquid chromatography-mass spectrometry analysis showed the presence of saponins in the obtained *** evaluation by REM demonstrated that samples before and after release presented antiglycation activity similar to bovine serum albumin treated with ***,samples inhibited AGE formation,highlighting treatment with saponin fraction after release(89.89%).Antioxidant tests demonstrated antioxidant activity of the *** dry extract before encapsulation presented the highest activities in DPPH(92.00%)and TBARS(32.49%)*** fraction before encapsulation in FRAP test(499μmol Trolox equivalent per gram of dry sample)and NO test(15.13μmol nitrite formed per gram of extract)presented the highest ***:This study presen

关键词： Glycation Microencapsulation Oxidative stress Saponins Tribulus terrestris

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DAMS:A Distributed Analytics Metadata Schema

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Data Intelligence 2021年第4期3卷 528-547页

作者： Sascha Welten Laurenz Neumann Yeliz Ucer Yediel luiz Olavo Bonino da silva Santos Stefan Decker Oya Beyan Chair Informatik 5 RWTH Aachen University52056 AachenGermany Fraunhofer Institute for Applied Information Techniques(FIT) 53757 Sankt AugustinGermany Faculty of Electrical Engineering Mathematics and Computer ScienceUniversity of Twente7500AE EnschedeThe Netherlands Department of Human Genetics Leiden University Medical CentreLeiden 2333 ZAThe Netherlands Institute of Medical Information Faculty of Medicine&University Hospital CologneUniversity of Cologne50674 CologneGermany

In recent years,implementations enabling Distributed Analytics(DA)have gained considerable attention due to their ability to perform complex analysis tasks on decentralised data by bringing the analysis to the *** concepts propose privacy-enhancing alternatives to data centralisation approaches,which have restricted applicability in case of sensitive data due to ethical,legal or social ***,the immanent problem of DA-enabling architectures is the black-box-alike behaviour of the highly distributed components originating from the lack of semantically enriched descriptions,particularly the absence of basic metadata for data sets or analysis *** approach the mentioned problems,we propose a metadata schema for DA infrastructures,which provides a vocabulary to enrich the involved entities with descriptive *** initially perform a requirement analysis with domain experts to reveal necessary metadata items,which represents the foundation of our ***,we transform the obtained domain expert knowledge into user stories and derive the most significant semantic *** the final step,we enable machine-readability via RDF(S)and SHACL *** deploy our schema in a proof-of-concept monitoring dashboard to validate its contribution to the transparency of DA ***,we evaluate the schema’s compliance with the FAIR *** evaluation shows that the schema succeeds in increasing transparency while being compliant with most of the FAIR *** a common metadata model is critical for enhancing the compatibility between multiple DA infrastructures,our work lowers data access and analysis *** represents an initial and infrastructure-independent foundation for the FAIRification of DA and the underlying scientific data management.

关键词： Distributed analytics Federated analytics Personal Health Train Metadata schema RDF(S) SHACL FAIR

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A Generic Workflow for the Data FAIRification Process

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Data Intelligence 2020年第1期2卷 56-65页

作者： Annika Jacobsen Rajaram Kaliyaperumal luiz Olavo Bonino da silva Santos Barend Mons Erik Schultes Marco Roos Mark Thompson Leiden University Medical Center Leiden2333 ZAThe Netherlands GO FAIR International Support&Coordination Office(GFISCO) LeidenThe Netherlands

The FAIR guiding principles aim to enhance the Findability,Accessibility,Interoperability and Reusability of digital resources such as data,for both humans and *** process of making data FAIR(“FAIRification”)can be described in multiple *** this paper,we describe a generic step-by-step FAIRification workflow to be performed in a multidisciplinary team guided by FAIR data *** FAIRification workflow should be applicable to any type of data and has been developed and used for“Bring Your Own Data”(BYOD)workshops,as well as for the FAIRification of e.g.,rare diseases *** steps are:1)identify the FAIRification objective,2)analyze data,3)analyze metadata,4)define semantic model for data(4a)and metadata(4b),5)make data(5a)and metadata(5b)linkable,6)host FAIR data,and 7)assess FAIR *** each step we describe how the data are processed,what expertise is required,which procedures and tools can be used,and which FAIR principles they relate to.

关键词： FAIR data FAIRification workflow FAIR data stewardship Hands-on FAIRification FAIR dissemination

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The“A”of FAIR-As Open as Possible,as Closed as Necessary

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Data Intelligence 2020年第1期2卷 47-55,303,304页

作者： Annalisa Landi Mark Thompson Viviana Giannuzzi Fedele Bonifazi Ignasi Labastida luiz Olavo Bonino da silva Santos Marco Roos Fondazione per la Ricerca Farmacologica Gianni Benzi Onlus 30-70010 Valenzano(BA)Italy Leiden University Medical Center Leiden2333 ZAThe Netherlands Learning and Research Resources Centre(CRAI) Universitat de BarcelonaCatalunya 08007Spain GO FAIR International Support&Coordination Office(GFISCO) LeidenThe Netherlands

In order to provide responsible access to health data by reconciling benefits of data sharing with privacy rights and ethical and regulatory requirements,Findable,Accessible,Interoperable and Reusable(FAIR)metadata should be *** to the H2020 Program Guidelines on FAIR Data,data should be"as open as possible and as closed as necessary","open"in order to foster the reusability and to accelerate research,but at the same time they should be"closed"to safeguard the privacy of the *** provisions on the protection of natural persons with regard to the processing of personal data have been endorsed by the European General Data Protection Regulation(GDPR),Reg(EU)2016/679,that came into force in May *** work aims to solve accessibility problems related to the protection of personal data in the digital era and to achieve a responsible access to and responsible use of health *** strongly suggest associating each data set with FAIR metadata describing both the type of data collected and the accessibility conditions by considering data protection obligations and ethical and regulatory ***,an existing FAIR infrastructure component has been used as an example to explain how FAIR metadata could facilitate data sharing while ensuring protection of individuals.

关键词： Accessibility of health data FAIR metadata GDPR Data sharing ELSI

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Effects of aeration on the suspended matter from a tropical and eutrophic estuary

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Journal of Environmental Sciences 2019年第12期31卷 175-186页

作者： Natascha Krepsky Maria das Gracas S.Bispo luiz F.Fontana Frederico S.da silva Jodo P.M.Torres Olaf Malm Cleverson G.silva Mirian A.C.Crapez Laboratory of Marine Geology Fluminense Federal UniuersityAue.Gen.Milton Tauares de Souza s/n°-Gragoata24210-346 NiterdiRJBrazil Radioisotopes Laboratory Eduardo Penna Franca Biophysics Institute Carlos Chagas FilhoFederal University of Rio de JaneiroAu.Carlos Chagas Filho373 CCS-Bl.G21941-902 Rio de JaneiroRJBrazil Marine Biology Department Fluminense Federal UniversityR.Mario Santos Bragas/nNiteroi24.020-141 NiteroiRJBrazil

A comprehensive understanding of the complex biogeochemical interactions between organic matter and persistent contaminants in the suspended matter is vital for ecoefficient estuary ***,little is known regarding aeration effects in suspended particulate ***,this study aimed to investigate the effects of aeration on the suspended matter from a Tropical and Eutrophic estuarine *** water with 60 g/L of suspended particulate matter(SPM)was collected from Guanabara Bay,Rio de Janeiro,Brazil,transferred to experimental boxes and aerated for 61 *** aggregates monitoring included abiotic variables measurements and,determination of total organic matter(TOM),biopolymers composition,bacterial activity,trace metals,and polycyclic aromatic hydrocarbons(PAHs)*** aeration enhanced dissolved oxygen(DO)concentration and the redox potential(Eh).However,from days 0 to 61 the predominant bacterial activities were denitrification and *** transport system activity increased after day 10,and aerobic activity was detected after day *** summary,aeration increased aerobic bacterial activity,lipids(LIP)and trace metal concentrations,although diminished protein/carbohydrate ratio and PAH *** metals concentration(Ni,Pb,Cu,Cr,Mn,and Fe)were the highest on day 19 when the p H was *** presented toxic values(Cu>20.0μg/g).The p H showed a strong negative correlation with Eh(r=-0.94;p<0.001).Acidic environment(p H≤5.9)in marine ecosystems with high loads of toxic trace metals is unsafe for ***,managers must be aware of the environmental and biological risks of introducing the aeration technique into a eutrophic marine environment.

关键词： Mixed-pollution Remediation Acidification Esterases enzymes Biopolymer

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