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Zhang, Long, Lihe Chen, Chao Gao, Enuo Chen, Andrea R. Lightle, Llewellyn Foulke, Bihong Zhao, Paul J. Higgins und Wenzheng Zhang. „Loss of Histone H3 K79 Methyltransferase Dot1l Facilitates Kidney Fibrosis by Upregulating Endothelin 1 through Histone Deacetylase 2“. Journal of the American Society of Nephrology 31, Nr. 2 (16.12.2019): 337–49. http://dx.doi.org/10.1681/asn.2019070739.
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BackgroundThe progression rate of CKD varies substantially among patients. The genetic and epigenetic contributions that modify how individual patients respond to kidney injury are largely unknown. Emerging evidence has suggested that histone H3 K79 methyltransferase Dot1l has an antifibrotic effect by repressing Edn1, which encodes endothelin 1 in the connecting tubule/collecting duct.MethodsTo determine if deletion of the Dot1l gene is a genetic and epigenetic risk factor through regulating Edn1, we studied four groups of mice: wild-type mice, connecting tubule/collecting duct–specific Dot1l conditional knockout mice (Dot1lAC), Dot1l and Edn1 double-knockout mice (DEAC), and Edn1 connecting tubule/collecting duct–specific conditional knockout mice (Edn1AC), under three experimental conditions (streptozotocin-induced diabetes, during normal aging, and after unilateral ureteral obstruction). We used several approaches (colocalization, glutathione S-transferase pulldown, coimmunoprecipitation, yeast two-hybrid, gel shift, and chromatin immunoprecipitation assays) to identify and confirm interaction of Dot1a (the major Dot1l splicing variant in the mouse kidney) with histone deacetylase 2 (HDAC2), as well as the function of the Dot1a-HDAC2 complex in regulating Edn1 transcription.ResultsIn each case, Dot1lAC mice developed more pronounced kidney fibrosis and kidney malfunction compared with wild-type mice. These Dot1lAC phenotypes were ameliorated in the double-knockout DEAC mice. The interaction between Dot1a and HDAC2 prevents the Dot1a-HDAC2 complex from association with DNA, providing a counterbalancing mechanism governing Edn1 transcription by modulating H3 K79 dimethylation and H3 acetylation at the Edn1 promoter.ConclusionsOur study confirms Dot1l to be a genetic and epigenetic modifier of kidney fibrosis, reveals a new mechanism regulating Edn1 transcription by Dot1a and HDAC2, and reinforces endothelin 1 as a therapeutic target of kidney fibrosis.
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Meikle, Thomas G., Calum J. Drummond und Charlotte E. Conn. „Microfluidic Synthesis of Rifampicin Loaded PLGA Nanoparticles and the Effect of Formulation on their Physical and Antibacterial Properties“. Australian Journal of Chemistry 73, Nr. 3 (2020): 151. http://dx.doi.org/10.1071/ch19359.
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The encapsulation of drugs in nanoparticles serves as an effective way to modify pharmacokinetics and therapeutic efficacy. Nanoparticles comprised of poly(d,l-lactide-co-glycolide) (PLGA) are well suited for this purpose; they are accessible using multiple synthesis methods, are highly biocompatible and biodegradable, and possess desirable drug release properties. In the present study, we have explored the effects of various formulation parameters on the physical properties of PLGA nanoparticles synthesised using a microfluidic assisted nanoprecipitation method and loaded with a model drug. PLGA nanoparticles, with diameters ranging from 165–364nm, were produced using three alternate stabilisers; poly(vinyl alcohol) (PVA), d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), and didodecyldimethylammonium bromide (DMAB). Three additional formulations used PVA in addition to 20wt-% 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), 1,2-di-O-octadecenyl-3-trimethylammonium propane (DOTMA), and oleic acid. Spectrophotometric analysis demonstrated that the use of PVA increased the loading efficiency over that of TPGS and DMAB formulations, while the inclusion of oleic acid in the PVA formulation resulted in a further 3-fold increase in loading efficiency. Invitro release studies demonstrate that the inclusion of lipid additives significantly alters release kinetics; release was most rapid and complete in the formulation containing oleic acid, while the addition of DOTAP and DOTMA significantly reduced release rates. Finally, the antimicrobial activity of each formulation was tested against Staphylococcus aureus and Bacillus cereus, with minimum inhibitory concentrations nearing or exceeding that of free rifampicin.
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Garda, Zoltán, Tamara Kócs, István Bányai, José A. Martins, Ferenc Krisztián Kálmán, Imre Tóth, Carlos F. G. C. Geraldes und Gyula Tircsó. „Complexes of Bifunctional DO3A-N-(α-amino)propinate Ligands with Mg(II), Ca(II), Cu(II), Zn(II), and Lanthanide(III) Ions: Thermodynamic Stability, Formation and Dissociation Kinetics, and Solution Dynamic NMR Studies“. Molecules 26, Nr. 16 (16.08.2021): 4956. http://dx.doi.org/10.3390/molecules26164956.
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The thermodynamic, kinetic, and structural properties of Ln3+ complexes with the bifunctional DO3A-ACE4− ligand and its amide derivative DO3A-BACE4− (modelling the case where DO3A-ACE4− ligand binds to vector molecules) have been studied in order to confirm the usefulness of the corresponding Gd3+ complexes as relaxation labels of targeted MRI contrast agents. The stability constants of the Mg2+ and Ca2+ complexes of DO3A-ACE4− and DO3A-BACE4− complexes are lower than for DOTA4− and DO3A3−, while the Zn2+ and Cu2+ complexes have similar and higher stability than for DOTA4− and DO3A3− complexes. The stability constants of the Ln(DO3A-BACE)− complexes increase from Ce3+ to Gd3+ but remain practically constant for the late Ln3+ ions (represented by Yb3+). The stability constants of the Ln(DO3A-ACE)4− and Ln(DO3A-BACE)4− complexes are several orders of magnitude lower than those of the corresponding DOTA4− and DO3A3− complexes. The formation rate of Eu(DO3A-ACE)− is one order of magnitude slower than for Eu(DOTA)−, due to the presence of the protonated amine group, which destabilizes the protonated intermediate complex. This protonated group causes the Ln(DO3A-ACE)− complexes to dissociate several orders of magnitude faster than Ln(DOTA)− and its absence in the Ln(DO3A-BACE)− complexes results in inertness similar to Ln(DOTA)− (as judged by the rate constants of acid assisted dissociation). The 1H NMR spectra of the diamagnetic Y(DO3A-ACE)− and Y(DO3A-BACE)− reflect the slow dynamics at low temperatures of the intramolecular isomerization process between the SA pair of enantiomers, R-Λ(λλλλ) and S-Δ(δδδδ). The conformation of the Cα-substituted pendant arm is different in the two complexes, where the bulky substituent is further away from the macrocyclic ring in Y(DO3A-BACE)− than the amino group in Y(DO3A-ACE)− to minimize steric hindrance. The temperature dependence of the spectra reflects slower ring motions than pendant arms rearrangements in both complexes. Although losing some thermodynamic stability relative to Gd(DOTA)−, Gd(DO3A-BACE)− is still quite inert, indicating the usefulness of the bifunctional DO3A-ACE4− in the design of GBCAs and Ln3+-based tags for protein structural NMR analysis.
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Guerra, Cecília, Patrícia Sá, Rebeca Teja und Jaime Ribeiro. „A Permeabilidade entre as Fronteiras das Ciências Sociais e Humanas: A interação de conhecimentos na investigação qualitativa“. Fronteiras: Journal of Social, Technological and Environmental Science 6, Nr. 4 (01.01.2018): 11. http://dx.doi.org/10.21664/2238-8869.2017v6i4.p11-17.
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A abordagem qualitativa nas ciências sociais e humanas enriquece a perspetiva daquele procura saber mais, ir mais fundo, ao amago dos comportamentos e da sua etiologia, na implexa rede que é o Homem e as suas relações. Estes campos da Ciência dotam, ou procuram dotar, o investigador com os instrumentos e do conhecimento para anatomizar o ser social, o Homem, o indivíduo. Não é descurado afirmar que não se pode investigar adequadamente o ser humano, sem a utilização de uma perspetiva multidisciplinar e/ou interdisciplinar, intrínseca às ciências sociais e humanas, bem como às ciências da natureza e da saúde (Chizotti 2006).
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del Olmo-García, Maria Isabel, Maria Angustias Muros, Martín López-de-la-Torre, Marc Agudelo, Pilar Bello, Jose M. Soriano und Juan-Francisco Merino-Torres. „Prevention and Management of Hormonal Crisis during Theragnosis with LU-DOTA-TATE in Neuroendocrine Tumors. A Systematic Review and Approach Proposal“. Journal of Clinical Medicine 9, Nr. 7 (12.07.2020): 2203. http://dx.doi.org/10.3390/jcm9072203.
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Neuroendocrine tumors (NETs) frequently overexpress somatostatin receptors (SSTR) on their cell surface. The first-line pharmacological treatment for inoperable metastatic functioning well-differentiated NETs are somatostatin analogs. On second line, Lu-DOTA-TATE (177Lu-DOTA0 Tyr 3 octreotate) has shown stabilization of the disease and an increase in progression free survival, as well as effectiveness in controlling symptoms and increasing quality of life. The management of functional NETs before and during LU-DOTA-TATE treatment is specially challenging, as several complications such as severe carcinoid and catecholamine crisis have been described. The aim of this review is to establish practical guidance for the management and prevention of the most common hormonal crises during radionuclide treatment with Lu-DOTA-TATE: carcinoid syndrome (CS) and catecholamine hypersecretion, as well as to provide a brief commentary on other infrequent metabolic complications. To establish a practical approach, a systematic review was performed. This systematic review was developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and conducted using MEDLINE (accessed from PubMed), Google Scholar and ClinicalTrials.gov. Literature searches found 449 citations, and finally nine were considered for this systematic review.
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Kovács, Attila, und Zoltán Varga. „Metal–ligand interactions in complexes of cyclen-based ligands with Bi and Ac“. Structural Chemistry 32, Nr. 5 (18.08.2021): 1719–31. http://dx.doi.org/10.1007/s11224-021-01816-9.
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AbstractThe structural and bonding properties of Bi and Ac complexes with cyclen-based chelating ligands have been studied using relativistic DFT calculations in conjunction with TZ2P all-electron basis sets. Besides the parent cyclen ligand, the study has covered its extensions with pyridine-type (Lpy), carboxylate (DOTA, DOTPA), picolinate (MeDO2PA) and phosphonate (DOTMP) pendant arms. The effect of the cyclen ring size has been probed by increasing it from [12]aneN4 to [16]aneN4. Additional extensions in the DOTA complexes included the H2O ligand at the 9th coordination site as well as the p-SCN-Bn substituent (a popular linker to the targeting vector). The study focuses on the complex stability, the nature of bonding and the differences between Ac and Bi in the complexes. The metal–ligand interactions have been analysed by the Extended Transition State method combined with Natural Orbitals of Chemical Valence theory and Quantum Theory of Atoms in Molecules models.
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García Dávila, Rocío Elizabeth, Sergio Díaz Bello, Raúl Villanueva Rodríguez, René López León und Luis Valencia Vázquez. „Utilidad de la tomografía por emisión de positrones/tomografía computada (PET/CT) en pacientes con diagnóstico de meduloblastoma“. Revista de la Facultad de Medicina 63, Nr. 1 (10.01.2020): 34–41. http://dx.doi.org/10.22201/fm.24484865e.2020.63.1.06.
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"PET/CT (positron emission tomography/computed tomography, for its acronym in English) is a unique imaging method that provides in vivo evidence of both biochemical and physiological activities of the brain, spinal cord and tumors that involve these structures. Medulloblastoma is the most common malignant tumor of the central nervous system (CNS) in pediatric patients, so PET/CT plays an important role as it provides information on the grade and extent of the tumor as well as to determine the appropriate site for the biopsy, assessing the response to the treatment and the patient’s prognosis. There are different radiopharmaceuticals for the evaluation of central nervous system tumors, but 18F FDG (Fluor-2-fluoro-2-desoxy-D-glucose) and 68Ga-DOTA-NOC (68Ga-DOTA0-1NaI3-octreotide) have been studied to help us evaluate and follow up patients diagnosed with medulloblastoma. Medulloblastoma has an overexpression of glucose transporters, mainly type 1, and an overexpression of predominantly type 2 somatostatin receptors, which allows a high affinity for these radiopharmaceuticals. Key words: Medulloblastoma; positron emission tomography; PET/C; 18F-FDG; 68Ga-DOTA-NOC; brain tumor.
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Stępkowska, Agnieszka. „CHARAKTER ZAKAZU ALIENACJI NIERUCHOMOŚCI POSAGOWYCH W RZYMSKIM PRAWIE KLASYCZNYM“. Zeszyty Prawnicze 11, Nr. 1 (21.12.2016): 295. http://dx.doi.org/10.21697/zp.2011.11.1.16.
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LEGAL CHARACTER OF THE PROHIBITION AGAINST ALIENATION OF DOWRY IMMOVABLES IN THE CLASSICAL ROMAN LAWSummary The well known lex Iulia de fundo dotali prohibited alienation of a Italian land being part of a dowry without women’s consent. The very meaning of this prohibition attracted very much attention of the Roman law scholars in the 20th century. The problem was as follows: was the disposition in breach of the lex Julia null and void (absolute nullity), or was it only voidable by the woman (respective nullity) after the dissolution of her marriage. The later opinion seems to be dominating in 20th century writings on Roman law, since Pierre Noailles had advocated it in his book L’inaliénabilité dotale et la Novelle 61 (Grenoble, 1919). It was subsequently affirmated by such emminent authors like Fritz Pringsheim or Paul Koschaker and became ‘canonic’ oppinion among Roman law scholars. The problem in itself was alien to Romans knowing no difference between absoluteand respective nullity of a disposition, but it looks like, virtual position of Romanlaw in this respect, was not the most attractive to modern scholars. The present paper re-considers the issue taking slightly different departurepoint to that of Noailles and his followers. In the first instance, the category of leges – as regards sanctio of their prohibitory provisions – to which the lex Iulia de fundo dotali belongs is settled. Than the issue, who is entitled to vindicate the land alienated in breach of the lex Iulia, is analysed as well as possibility of convalidation of the invalid disposition. Finally it is considered, whether the statutory provision affected only real transfer of property or it frustrated already husband’s very ability to make a valid contract of sale. In effect, the argument of the present paper is as follows: alienation fundi dotalis without wife’s consent, was beyond any reasonable doubt null and void. Being still the owner of illegally alienated immovables, the husband was bound to vindicate them. For that very reason, he was not able to transfer free and unimpeded possession of the land to the unfortunate purchaser. Consequently, it was not only alienation of the land in dowry, which was null and void by virtue of the lex Iulia de fundo dotali, but also the very contract of it’s sale. Above findings require, the theory of “relative nullity” (i.e. voidability or rescindibility), as advocated by Noailles, Prinzheim and Koschaker, is to be rejected.
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Nussinov, Shmuel. „Yossef Dothan“. Physics Today 44, Nr. 7 (Juli 1991): 73–74. http://dx.doi.org/10.1063/1.2810186.
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Kenoyer, Aimee L., Yukang Lin, Johnnie J. Orozco, Ethan Balkin, Don Hamlin, Alexandra H. Hernandez, Chen Fang et al. „Pre-Targeted Radioimmunotherapy Employing a Recombinant Bispecific Antibody Using a Murine Xenograft Model of Human Leukemia“. Blood 124, Nr. 21 (06.12.2014): 3749. http://dx.doi.org/10.1182/blood.v124.21.3749.3749.
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Abstract Introduction: Acute Myeloid Leukemia (AML) has a high rate of relapse despite hematopoietic cell transplantation (HCT). Pre-targeted radioimmunotherapy (PRIT) prior to HCT offers a promising approach to reduce relapse for high-risk patients. PRIT studies with antibody-streptavidin (Ab-SAV) conjugates have shown promise, but may be limited by SAV immunogenicity. We have developed a recombinant anti-human CD45 bispecific Ab with picomolar affinity to radiolabeled DOTA chelates for targeting AML xenografts in a preclinical model. Methods: We engineered a bispecific Ab recognizing CD45 and DOTA-metal chelates. The light chain sequence from anti-human CD45 Ab (BC8) was cloned into a pFUSE vector along with a single-chain variable region developed to bind to DOTA chelates of multiple radionuclides. Ab was co-transfected into HEK 293 F cells with a pFUSE vector containing heavy chain sequence from Rituximab. Cultures were grown to extinction, and Ab purified via Protein A ion-exchange chromatography. Ab was characterized by SDS-PAGE, HPLC, and flow cytometry to determine specificity and integrity of material. Ab was tested for in vivo targeting in a xenograft model of human AML. Athymic mice bearing flank HEL tumors (30 to 100 µg) were injected with 280 µg bispecific Ab or 300 µg Ab-SAV. Twenty two hours later mice were treated with or without clearing agent (5 µg DOTAY-dextran for bispecific Ab and 50 µg NAGB for Ab-SAV groups). Two hours later mice were given Yttrium-90 (90Y)-DOTA-biotin. Blood was taken at time points over 22 hours post-injection for pharmacokinetic study; xenografts and normal tissues were taken 4, 24, and 48 hours after DOTA-biotin injection for gamma counts. Results: Bispecific Ab targeting CD45 bound to human AML cells in vitro with an increase in mean fluorescence intensity >2 logs compared to control. SDS-PAGE and HPLC demonstrated a construct of expected size. Blood clearance of 90Y-DOTA-biotin was assessed following injection of bispecific Ab with or without clearing agent and compared to mice that received BC8-SAV as the first-step reagent. Even without clearing agent, mice that had received bispecific Ab showed rapid blood clearance of 90Y-DOTA-biotin similar to that of Ab-SAV-injected mice that had received clearing agent, with 8.15 ± 0.56 % ID/g in the blood 5 minutes post-DOTA-biotin injection falling to 1.02 ± 0.62% ID/g within 4 hours and 0.40 ± 0.16 % ID/g at 20 hours. Mice that received BC8-SAV followed by clearing agent had 7.32 ± 2.0 % ID/g in the blood 5 minutes post-injection, falling to 1.13 ± 0.77 % within 4 hours and 0.73 ± 0.46 % at 20 hours. Mice receiving bispecific Ab followed by DOTAY-dextran clearing agent and 90Y-DOTA-biotin showed a rapid blood clearance with a radioactivity concentration of 8.07 ± 3.0% ID/g at 5 minutes and falling to 0.14 ± 0.03 % within 4 hours post-injection. In vivo targeting of the bispecific Ab was similar to Ab-SAV groups; within 4 hours 3.62 ± 0.91 % ID/g was detected in the tumor compared to 0.12 ± 0.05 % in the blood for mice receiving bispecific Ab, while Ab-SAV mice had a tumor value of 3.85 ± 2.5 % and blood was 1.17 ± 0.63 %. Uptake in non-target tissues was low at 4 hours post-injection compared to tumor, with liver and kidney values of 0.05 ± 0.014 % ID/g and 0.518 ± 0.09 % ID/g, respectively. Tumor retention remained steady at 24 and 48 hours with values of 4.13 ± 1.0% ID/g and 4.14 ± 2.47% ID/g respectively. Groups that received bispecific Ab as the first-step agent followed by clearing agent and then 90Y-DOTA-biotin showed slightly higher uptake in normal organs early on, but displayed higher uptake in target tissue. Tumor values at 4, 24, and 48 hours post-injection were 4.65 ± 2.4, 5.89 ± 4.2, and 3.95 ± 2.3 % ID/g, respectively. Conclusion: Recombinant bispecific Ab targeting both human CD45 and radiometal-labeled DOTA is promising as a novel therapeutic approach for AML prior to HCT. Bispecific Ab targets human AML cells in vitro and in vivo with favorable biodistribution showing specific uptake in tumors while normal organs displayed minimal uptake. Blood clearance of the bispecific Ab is rapid and comparable to that of Ab-SAV, even without the addition of a clearing agent. Future studies will assess therapeutic potential of this bispecific Ab PRIT approach in a murine model of AML. Funding Source Acknowledgment: Research reported in this publication was supported by the National Cancer Institute under award numbers R01CA109663, R01CA136639, and R01CA138720. Disclosures No relevant conflicts of interest to declare.
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Petrovic, Djordje, Nadezda Nikolic, Dragana Stankovic und Divna Djokic. „Electrochemical separation of 90-yttrium in the electrochemical 90Sr/90Y generator and its use for radiolabelling of DOTA-conjugated somatostatin analog [DOTA0, Tyr3] octreotate“. Nuclear Technology and Radiation Protection 27, Nr. 3 (2012): 260–68. http://dx.doi.org/10.2298/ntrp1203260p.
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Radiopharmaceuticals based on 90Y are widely used in the treatment of malignant deseases. In order to meet the requirements for their future application, a 90Sr/90Y generator was developed and 90Y eluted from this locally produced generator was used for the radiolabelling of the DOTA-conjugated somatostatin analog [DOTA0,Tyr3] octreotate and the preparation of [90Y-DOTA0,Tyr3] octreotate (90Y-DOTATATE) for peptide receptore radionuclide therapy. 90Sr/90Y generator was based on the electrochemical separation of 90Y from 90Sr in a two-cycle electrolysis procedure. Three electrode cells were used to perform both electrolyses. In both cycles, working electrodes were kept on constant potential. The pH of the solution was adjusted to 2.7 of the value before the electrolyses. The radionuclidic purity of the 90Y solution was analysed by ITLC and extraction paper chromatography. The labelling of peptide (100 mg DOTATATE) with 90YCl3 was performed at 95?C for 30 minutes. Radiochemical purity was determined by HPLC and chromatographic separation, using a solid SepPak C-18 column. Results obtained confirmed the efficiency of our electrochemical separation technique and quality control methods for 90Y. The achieved efficiency of the 90Sr/90Y generator above 96% of the theoretical value represents a good basis for the further development of this generator. The labelling of the DOTATATE with 90Y exhibited a high efficiency, too: there was less than 1% of 90Y3+in the 90Y-DOTATATE.
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Kirkland, Scotty E. „"Bad, Bad Dothan!": The Dothan Riot and Wiregrass Agrarianism“. Alabama Review 60, Nr. 3 (2007): 163–85. http://dx.doi.org/10.1353/ala.2007.0006.
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HAAS, KARL J. „Subjunctive Masculinities: Making Men Through Music and Ritual in Northern Ghana“. Yearbook for Traditional Music 51 (November 2019): 217–45. http://dx.doi.org/10.1017/ytm.2019.4.
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Abstract (Dagbanli)Dini niŋ ka tuma kalinsi mini pukparigu ni labiri nyanga saha ŋɔ la zuɣu, dabba ban be Tuduyaɣili polo (Northern Region) di niŋdi tom pam tiba zaŋ jandi bɛ biɛhigu ni bɛ laɣi dibo soya diyi ti kana dotali polo. To ayi yuli zaŋ chaŋ kali wahi din jandi Dagbamba Sapashin nim polo, sabbu ŋɔ wuhirila waligimsim din be dotali mini kali wahi yeltɔɣa. Gun Gon nyala kali tuun kpeiŋ din wuhiri dotali tuun tumsa Sapashin nim ni Dagbaŋ pulini, kadi wuhiri ka kpaŋsiri dotali ni nye sheli zaŋ ti dabba ban tumdili.
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Szaj, Patryk. „A jednak dotyka“. Forum Poetyki, Nr. 11-12 (11.06.2018): 164–69. http://dx.doi.org/10.14746/fp.2018.11-12.26815.
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Tekst jest odpowiedzią na polemiczny szkic Grzegorza Pertka Prepozycje. Metafizyka „bliskości”. Stara się on odeprzeć zarzut metafizycznego obciążenia postulatu „bliskości”, wskazując na osłabiającą i „dynamizującą” ów postulat kategorię „dotkliwości”. Autor artykułu wyjaśnia również, że nie zależało mu na odwróceniu relacji między hermeneutyką a dekonstrukcją, ale na jej przemieszczeniu, wynikającym z dostrzeżenia zasadniczego pokrewieństwa obu dyskursów.
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Kaltsas, G. A., D. Papadogias, P. Makras und A. B. Grossman. „Treatment of advanced neuroendocrine tumours with radiolabelled somatostatin analogues“. Endocrine-Related Cancer 12, Nr. 4 (Dezember 2005): 683–99. http://dx.doi.org/10.1677/erc.1.01116.
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Neuroendocrine tumours (NETs) constitute a heterogeneous group of tumours that frequently express cell membrane-specific peptide receptors, such as somatostatin receptors (SSTRs), and of which gastroenteropancreatic (GEP), carcinoid and pancreatic islet cell tumours exhibit the highest expression of SSTRs. Radiolabelled receptor-binding somatostatin analogues (octreotide and lanreotide) act as vehicles to guide radioactivity to tissues expressing SSTRs, and can thus be used for their diagnosis and treatment. After the localization of NETs bearing SSTRs with 111In-octreotide (OctreoScan), a number of radioisotopes with different physical properties have been used for their treatment. The administration of high doses of the Auger electron and γ-emitter 111In-diethylenetriaminepenta-acetic acid (DTPA)0,octreotide in patients with metastatic tumours has been associated with considerable symptomatic improvement but relatively few and short-lived objective tumour responses. The use of another radiolabelled somatostatin analogue coupled with 90Y, a pure β-emitter, 90Y-1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid (DOTA)0,Tyr3,octreotide (90Y-DOTATOC, OctreoTher), was associated with 10–30% objective tumour response rates, and appears to be particularly effective in larger tumours. 111In- and 90Y-DOTA-lanreotide has also been used for the treatment of NETs although its therapeutic efficacy is probably inferior to that of octreotide-based radiopharmaceuticals. More recently, treatment with 177Lu-DOTA0,Tyr3octreotate (177Lu-DOTATATE), which has a higher affinity for the SSTR subtype 2, resulted in approximately 30% complete or partial tumour responses; this radiopharmaceutical is particularly effective in smaller tumours. Furthermore, treatment using both 90Y-DOTATOC and 177Lu-DOTA0,Tyr3octreotate seems promising, as the combination of these radiopharmaceuticals could be effective in tumours bearing both small and large lesions. Tumour regression is positively correlated with a high level of uptake on 111In-octreotide scintigraphy, limited tumour mass and good performance status. In general, better responses have been obtained in GEP tumours than other NETs. The side effects of this form of therapy are relatively few and mild, particularly when kidney-protective agents are used. Treatment with radiolabelled somatostatin analogues presents a promising tool for the management of patients with inoperable or disseminated NETs, and particularly GEP tumours.
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Zhang, Long, und Hui Deng. „Flatland, lineland and dotland“. Nature Materials 19, Nr. 10 (21.09.2020): 1044–45. http://dx.doi.org/10.1038/s41563-020-0770-0.
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Feuerstein, Bernold, und Pieter Groenemeijer. „In memoriam Nikolai Dotzek“. Atmospheric Research 100, Nr. 4 (Juni 2011): 306–9. http://dx.doi.org/10.1016/j.atmosres.2011.02.005.
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Schultz, David M. „Dedication to Nikolai Dotzek“. Atmospheric Research 100, Nr. 4 (Juni 2011): 305. http://dx.doi.org/10.1016/j.atmosres.2011.02.006.
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Mora Piña, Paulina Fernada, Vanessa Lorena Valverde González und Sofía Paulina Valle Oñate. „La influencia que tiene el videojuego DOTA2 en el estado de ánimo del jugador aplicado al equipo “AMX”“. Ciencia Digital 4, Nr. 1 (04.01.2020): 142–55. http://dx.doi.org/10.33262/cienciadigital.v4i1.1078.
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Los videojuegos se han convertido en una fuente muy rentable, existiendo gran variedad de ellos, Dota 2 es un videojuego muy conocido que afecta al estado de ánimo de los jugadores, para conocer los problemas médicos que causa la exposición de varias horas a esta actividad, se ha utilizado una investigación aplicativa con el método analítico que busca encontrar respuestas a un problema, para producir aportes que impulsen el campo de la medicina y de la informática. La influencia que ejercen los videojuegos sobre la salud emocional de las personas responde al análisis de resultados, las técnicas aplicadas como son la observación, encuestas y entrevistas. El presente trabajo se basó en el equipo “AMX”, jugadores de DOTA2, los resultados analizados manifestaron el cambio de una conducta pacífica a otra agresiva de los participantes luego de perder un juego de formas especificas aumentando su irritabilidad y tensión, por otra parte, se visualizó a cada uno de los integrantes con un comportamiento más compulsivo ante las diferentes acciones que se presentaron en las partidas jugadas.
Dota 2 como videojuego, tiene algunos niveles que cada jugador debe cruzar para llegar a la meta, aumentando la dificultad a medida que avanza, de tal manera que cada jugador siente la necesidad de dedicarle más tiempo por día, generando un cambio de ánimo, violencia y estrés en cada partida, por lo tanto, se realizará un estudio del cambio que experimenta el jugador antes y después de una partida, ganada o perdida y los daños que se han producido a nivel de nervios y habilidades del jugador.
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Shen, Kuan-Yin, Hsin-Yu Liu, Wan-Lun Yan, Chiao-Chieh Wu, Ming-Hui Lee, Chih-Hsing Leng und Shih-Jen Liu. „Liposomal TLR9 Agonist Combined with TLR2 Agonist-Fused Antigen Can Modulate Tumor Microenvironment through Dendritic Cells“. Cancers 12, Nr. 4 (28.03.2020): 810. http://dx.doi.org/10.3390/cancers12040810.
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Dendritic cells (DCs) are antigen-presenting cells involved in T cell activation and differentiation to regulate immune responses. Lipoimmunogens can be developed as pharmaceutical lipoproteins for cancer immunotherapy to target DCs via toll-like receptor 2 (TLR2) signaling. Previously, we constructed a lipoimmunogen, a lipidated human papillomavirus (HPV) E7 inactive mutant (rlipoE7m), to inhibit the growth of HPV16 E7-expressing tumor cells in a murine model. Moreover, this antitumor effect could be enhanced by a combinatory treatment with CpG oligodeoxynucleotides (ODN). To improve safety, we developed a rlipoE7m plus DOTAP liposome-encapsulated native phosphodiester CpG (POCpG/DOTAP) treatment to target DCs to enhance antitumor immunity. We optimized the formulation of rlipoE7m and POCpG/DOTAP liposomes to promote conventional DC and plasmacytoid DC maturation in vitro and in vivo. Combination of rlipoE7m plus POCpG/DOTAP could activate conventional DCs and plasmacytoid DCs to augment IL-12 production to promote antitumor responses by intravenous injection. In addition, the combination of rlipoE7m plus POCpG/DOTAP could elicit robust cytotoxic T lymphocytes (CTLs) by intravenous immunization. Interestingly, the combination of rlipoE7m plus POCpG/DOTAP could efficiently inhibit tumor growth via intravenous immunization. Moreover, rlipoE7m plus POCpG/DOTAP combined reduced the number of tumor-infiltrating regulatory T cells dramatically due to downregulation of IL-10 production by DCs. These results showed that the combination of rlipoE7m plus POCpG/DOTAP could target DCs via intravenous delivery to enhance antitumor immunity and reduce the number of immunosuppressive cells in the tumor microenvironment.
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Green, Damian J., Jon C. Jones, Yukang Lin, Shani L. Frayo, Aimee L. Kenoyer, Shyril O'Steen, Arianna Peters et al. „A Novel Bispecific CD38 Antibody Eradicates Multiple Myeloma in a Mouse Model Following Yttrium-90-DOTA Capture“. Blood 126, Nr. 23 (03.12.2015): 118. http://dx.doi.org/10.1182/blood.v126.23.118.118.
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Abstract BACKGROUND: Despite high rates of initial response to immunomodulatory agents and proteasome inhibitors, the vast majority patients living with multiple myeloma (MM) will ultimately die of progressive disease that is a function of persistent MM cell clones. The radiosensitivity of malignant plasma cells is well documented in clinical settings, and we have previously reported the therapeutic efficacy of a streptavidin-biotin (SAB) pretargeted radioimmunotherapy (PRIT) system delivering the β-emitter 90Y to CD38 antigen targets (Green, et al. Cancer Res. 2014). While SAB-PRIT is capable of disease eradication in mouse models, SA immunogenicity and interference by endogenous biotin may complicate clinical translation of these findings into human trials. METHODS: To prospectively address these potential limitations and to further enhance therapeutic efficacy of PRIT, we engineered an anti-human CD38 xanti-chelated radiometal fusion protein (FP) specifically designed to trap second-step radiolabeled ligand (Y-DOTA) using a very high affinity anti-Y-DOTA scFv (C825). The bispecific anti-CD38 FP construct (028Fc-C825) expressed in CHO cells was affinity purified, assessed by gel filtration chromatography and binding specificity to both CD38 and Y-DOTA was confirmed. In vivo experiments showed the absence of toxicity of the bispecific construct at a dose range of 0.14-2.8 nmol per mouse (n=5/group). Biodistribution studies were performed in athymic nude mice (n=5/group) bearing s.c. luciferase transduced NCI-H929Luc human MM xenograft tumors. Animals received 2.8 nmol (420 µg) of either 028-Fc-C825 (anti-CD38 FP) or an irrelevant matched negative control bi-specific FP 2H7-Fc-C825 (anti-CD20 FP) with the same modular IgG-scFv structure (NCI-H929Luc are CD20 negative). The bispecific FP was administered 23 hours prior to a synthetic DOTAY-Dextran clearing agent (CA; 5 µg) and 24 hours prior to administration of trace labeled 90Y-DOTA (2 µg). In therapy studies, athymic nude mice (n=10/group) bearing s.c. NCI-H929Luc human MM xenograft tumors received 2.8 nmol of either 028-Fc-C825 (anti-CD38 FP) or 2H7-Fc-C825 (anti-CD20 FP) 23 hours prior to synthetic DOTAY-Dextran CA and 24 hrs prior to 90Y-DOTA (2 µg; 1200 µCi per mouse). An activity range of 800 µCi to 1200 µCi was previously identified as optimal in a MM xenograft model using the high energy beta particle emitter 90Y (t1/2 = 64 hours) [Green, et al. Cancer Res. 2014]. RESULTS: Selective tumor targeting of 90Y ligand to CD38+ xenografts was observed following administration of the bispecific anti-CD38 FP. Blood, tumor and nonspecific organ uptakes of 028-Fc-C825 demonstrated tumor-to-normal organ absorbed ratios that were 15:1; 17:1; 9:1; and 13:1, respectively for blood, lung, liver and kidney; compared to 0.7:1; 1:1; 1:1 and 0.5:1, respectively, in mice pretargeted with 2H7-Fc-C825 (control). The bispecific anti-CD38 FP also resulted in tumor-to-normal organ ratios of absorbed radioactivity that were superior to those measured in animals receiving anti-CD38 SAB-PRIT (OKT10-SA chemical conjugate) in the same study (5:1; 8:1; 5:1 and 2:1 for blood, lung, liver and kidney respectively). In therapy studies, no animal in any group lost >7% of initial body weight and by day 11 anti-CD38 bispecific FP treated animals were 102.4% ± 3.4% of baseline weight. All mice in the control bispecific FP group experienced exponential MM tumor growth and 100% of these control animals required euthanasia within 27 days. All mice pretargeted with 028-Fc-C825 (anti-CD38 bispecific FP) demonstrated tumor response by day 6. After 45 days, 100% of the anti-CD38 bispecific FP treated animals remained alive (Figure A) and objective remissions were observed within 18 days in 100% of the mice treated with 028-Fc-C825 followed by 1200 µCi of 90Y-DOTA, including 90% complete remissions (no detectable tumor in 028Fc-C825 treated mice) compared to tumors that were 2040 ± 1389% of initial tumor volume [p<0.0001, Student's t-test] in untreated control animals by day 12 (Figure B). CONCLUSION: Biodistribution studies demonstrate MM tumor specific targeting after anti-CD38 xanti-chelated radiometal FP with minimal levels of yttrium-90 radioactivity detected in normal organs. Tumor responses are very encouraging in this MM xenograft model and results support clinical evaluation of bispecific anti-CD38 FP PRIT in MM. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.
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Heyn, C. Clara. „NAOMI FEINBRUN-DOTHAN (1900–1995)“. Israel Journal of Plant Sciences 43, Nr. 4 (13.05.1995): 293–94. http://dx.doi.org/10.1080/07929978.1995.10676615.
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Zhang, Xi, Qiaoling Zhou, Lihe Chen, Stefan Berger, Hongyu Wu, Zhou Xiao, David Pearce, Xiaodong Zhou und Wenzheng Zhang. „Mineralocorticoid receptor antagonizes Dot1a-Af9 complex to increase αENaC transcription“. American Journal of Physiology-Renal Physiology 305, Nr. 10 (15.11.2013): F1436—F1444. http://dx.doi.org/10.1152/ajprenal.00202.2013.
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Aldosterone is a major regulator of Na+ absorption and acts by activating the mineralocorticoid receptor (MR) to stimulate the epithelial Na+ channel (ENaC). MR −/− mice exhibited pseudohypoaldosteronism type 1 (hyponatremia, hyperkalemia, salt wasting, and high levels of aldosterone) and died around postnatal day 10. However, if and how MR regulates ENaC transcription remain incompletely understood. Our earlier work demonstrated that aldosterone activates αENaC transcription by reducing expression of Dot1a and Af9 and by impairing Dot1a-Af9 interaction. Most recently, we reported identification of a major Af9 binding site in the αENaC promoter and upregulation of αENaC mRNA expression in mouse kidneys lacking Dot1a. Despite these findings, the putative antagonism between the MR/aldosterone and Dot1a-Af9 complexes has never been addressed. The molecular defects leading to PHA-1 in MR −/− mice remain elusive. Here, we report that MR competes with Dot1a to bind Af9. MR/aldosterone and Dot1a-Af9 complexes mutually counterbalance ENaC mRNA expression in inner medullary collecting duct 3 (IMCD3) cells. Real-time RT-quantitative PCR revealed that 5-day-old MR −/− vs. MR +/+ mice had significantly lower αENaC mRNA levels. This change was associated with an increased Af9 binding and H3 K79 hypermethylation in the αENaC promoter. Therefore, this study identified MR as a novel binding partner and regulator of Af9 and a novel mechanism coupling MR-mediated activation with relief of Dot1a-Af9-mediated repression via MR-Af9 interaction. Impaired ENaC expression due to failure to inhibit Dot1a-Af9 may play an important role in the early stages of PHA-1 (before postnatal day 8) in MR −/− mice.
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Warnock, Peter. „People of the Sea: The Search for the Philistines. Trude Dothan and Moshe Dothan.“ Biblical Archaeologist 58, Nr. 1 (März 1995): 58. http://dx.doi.org/10.2307/3210470.
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Wood, Lauren Virginia, Siva K. Gandhapudi, Karuna Sundarapandiyan, Frank K. Bedu-Addo, Gregory Conn und Jerold G. Woodward. „R-DOTAP (Versamune): A novel enantiospecific cationic lipid nanoparticle that induces CD4 and CD8 cellular immune responses to whole protein and tumor-specific peptide antigens.“ Journal of Clinical Oncology 38, Nr. 15_suppl (20.05.2020): e15211-e15211. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e15211.
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e15211 Background: Immunotherapy approaches are limited in their ability to induce antigen-specific CD8+ T cells in vivo able to recognize and kill tumor cells. We developed a novel immunotherapy approach using enantiomerically pure, R-DOTAP cationic lipid nanoparticles and tumor-derived T cell antigens, and previously demonstrated that R-DOTAP formulations efficiently prime cytotoxic T cells through enhanced cross presentation and induction of type I interferons.[1] A phase I clinical trial of a R-DOTAP HPV16 peptide formulation confirmed induction of strong in vivo HPV-specific CD8+ cytolytic T-cells without associated systemic toxicities. In this study, we assessed R-DOTAP nanoparticle formulations containing whole protein (ovalbumin) or long multi-epitope peptides from the tumor antigen TARP (T-cell alternate reading frame protein): a 58-residue protein overexpressed in prostate and breast cancers, documented to be immunogenic in humans. Methods: R-DOTAP formulations were prepared containing ovalbumin (OVA) or TARP peptides. C57BL/6K mice were immunized with 10 μg/mouse of OVA plus R-DOTAP, CFA or sucrose on Days 0, 15 and 30. OVA-specific cellular and humoral responses following vaccination were assessed by measuring splenic CD4 and CD8 T cell IFN-γ production and circulating OVA-specific antibodies in serum. HLA-A2 transgenic mice (AAD mice) were vaccinated with long, multi-epitope TARP peptides delivered as an R-DOTAP admixture or with CFA or sucrose on Days 0 and 7. Antigen-specific T cell responses were measured by IFN-γ ELISpot assay. Results: OVA R-DOTAP formulations induced strong antigen-specific effector CD4 and CD8 immune and memory responses detected 7 and 30 days, respectively, following vaccination as well as OVA-specific antibody responses. In TARP peptide vaccinated mice, R-DOTAP formulations were able to present multiple CD8 T cell epitopes and stimulate responses that were superior to CFA. Conclusions: Our results suggest that R-DOTAP is a versatile immune activating therapy that can be formulated with long, multi-epitope tumor-derived peptides or whole proteins. R-DOTAP formulations induce quantitatively robust antigen-specific CD4 and CD8 T cells in vivo compared to well-established immune stimulants. Reference: 1.Gandhapudi SK, Ward M, Bush JP et al. Antigen Priming with Enantiospecific Cationic Lipid Nanoparticles Induces Potent Antitumor CTL Responses through Novel Induction of a Type I IFN Response. J Immunol 2019;202:3524-3536
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Grey, Timothy L., Glenn R. Wehtje, Ben F. Hajek und Robert H. Walker. „Sorption and Mobility of Bentazon in Coastal Plain Soils“. Weed Science 44, Nr. 1 (März 1996): 166–70. http://dx.doi.org/10.1017/s0043174500093723.
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Sorption and mobility of14C-bentazon were evaluated using soil solution and soil-thin-layer chromatography, respectively on three Coastal Plain soils. The proportion of bentazon adsorbed, was pH and concentration dependent and ranged between 28 to 47, 31 to 61, and 17 to 68% for the Dothan loamy sand, Greenville clay, and Troup loamy sand, respectively. Bentazon sorption decreased as soil pH increased from 5.4 to 5.8 on the Troup loamy sand, regardless of bentazon concentration. Sorption of 1 and 10 ppm bentazon decreased as soil pH increased from 5.0 to 5.7 on the Greenville clay and 6.1 to 6.4 on the Dothan loamy sand. Bentazon was least mobile on the Greenville clay and mobility increased as pH increased. Mobility of bentazon was greatest on the Troup loamy sand and was not pH dependent. Bentazon mobility decreased as soil pH increased for the Dothan loamy sand.
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Reisenauer, Mary Rose, Steven W. Wang, Yang Xia und Wenzheng Zhang. „Dot1a contains three nuclear localization signals and regulates the epithelial Na+ channel (ENaC) at multiple levels“. American Journal of Physiology-Renal Physiology 299, Nr. 1 (Juli 2010): F63—F76. http://dx.doi.org/10.1152/ajprenal.00105.2010.
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We have previously reported that Dot1a is located in the cytoplasm and nucleus (Reisenauer MR, Anderson M, Huang L, Zhang Z, Zhou Q, Kone BC, Morris AP, Lesage GD, Dryer SE, Zhang W. J Biol Chem 284: 35659–35669, 2009), widely expressed in the kidney as detected by its histone H3K79 methyltransferase activity (Zhang W, Hayashizaki Y, Kone BC. Biochem J 377: 641–651, 2004), and involved in transcriptional control of the epithelial Na+ channel subunit-α gene ( αENaC) (Zhang W, Xia X, Jalal DI, Kuncewicz T, Xu W, Lesage GD, Kone BC. Am J Physiol Cell Physiol 290: C936–C946, 2006). Aldosterone releases repression of αENaC by reducing expression of Dot1a and its partner AF9 (Zhang W, Xia X, Reisenauer MR, Hemenway CS, Kone BC. J Biol Chem 281: 18059–18068, 2006) and by impairing Dot1a-AF9 interaction via Sgk1-mediated AF9 phosphorylation (Zhang W, Xia X, Reisenauer MR, Rieg T, Lang F, Kuhl D, Vallon V, Kone BC. J Clin Invest 117: 773–783, 2007). This network also appears to regulate transcription of several other aldosterone target genes. Here, we provide evidence showing that Dot1a contains at least three potential nuclear localization signals (NLSs). Deletion of these NLSs causes green fluorescent protein-fused Dot1a fusions to localize almost exclusively in the cytoplasm of 293T cells as revealed by confocal microscopy. Deletion of NLSs abolished Dot1a-mediated repression of αENaC-promoter luciferase construct in M1 cells. AF9 is widely expressed in mouse kidney. Similar to αENaC, the mRNA levels of βENaC, γENaC, and Sgk1 are also downregulated by Dot1a and AF9 overexpression. Small interference RNA-mediated knockdown of Dot1a and AF9 or aldosterone treatment leads to an opposite effect. Using single-cell fluorescence imaging or equivalent short-circuit current in IMCD3 and M1 cells, we show that observed transcriptional alterations correspond to changes in ENaC and Sgk1 protein levels as well as benzamil-sensitive Na+ transport. In brief, Dot1a and AF9 downregulate Na+ transport, most likely by regulating ENaC mRNA and subsequent protein expression and ENaC activity.
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Zhang, Wenzheng, Zhiyuan Yu, Hongyu Wu, Lihe Chen, Qun Kong und Bruce C. Kone. „An Af9 cis-element directly targets Dot1a to mediate transcriptional repression of the αENaC gene“. American Journal of Physiology-Renal Physiology 304, Nr. 4 (15.02.2013): F367—F375. http://dx.doi.org/10.1152/ajprenal.00537.2011.
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The epithelial Na+ channel subunit-α ( αENaC) of the distal nephron is essential for salt balance. We previously demonstrated that the histone methyltransferase Dot1a and its protein partner Af9 basally repress αENaC transcription in mouse inner medullary collecting duct type 3 (mIMCD3) cells and link aldosterone-elicited chromatin modifications to αENaC transcriptional activation. Af9 DNA-binding activity has never been demonstrated, and whether and where Af9 binds to the αENaC promoter to target Dot1a are unknown. The present study sought to identify functional Af9 cis-element(s) in the −57/+439 “R3” subregion of αENaC, the principal site for Dot1a-Af9 interaction, in mIMCD3 cells. We also exploited connecting tubule/collecting duct-specific Dot1l-deficient mice ( Dot1l AC) to determine the impact of Dot1l inactivation on renal αENaC expression in vivo. mIMCD3 cell lines expressing αENaC promoter-reporter constructs harboring deletion of +74/+107 demonstrated greatly reduced association of Af9 and Dot1a by ChIP/qPCR. Aldosterone treatment resulted in further decrements in Af9 and Dot1a association with the αENaC promoter. Gel shift and antibody competition assays using wild-type and mutant oligomers revealed Af9-containing +78/+92 αENaC DNA-protein complexes in nuclear extracts of mIMCD3 cells. Mutation of the +78/+92 element resulted in higher basal αENaC promoter activity and impaired Dot1a-mediated inhibition in trans-repression assays. In agreement, mice with connecting tubule/collecting duct-specific knockout of Dot1l exhibited greater αENaC mRNA levels in kidney compared with control. Thus, we conclude that +78/+92 of αENaC represents the primary Af9 binding site involved in recruiting Dot1a to repress basal and aldosterone-sensitive αENaC transcription and that Dot1l inactivation promotes αENaC mRNA expression by eliminating Dot1a-mediated repression.
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Dadura, Emilia, Agnieszka Wójcik und Jan Gajewski. „Touch In Professional Practice – View Of Physiotherapists“. Advances in Rehabilitation 27, Nr. 2 (01.06.2013): 9–15. http://dx.doi.org/10.2478/rehab-2014-0009.
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Streszczenie Wstęp: Dotyk obecny jest w każdym obszarze życia człowieka. Za jego pośrednictwem ludzie odbierają i poznają otaczający ich świat, komunikują emocje i tworzą silne więzi. Dotyk jest istotnym elementem każdej relacji, a szczególnie relacji fizjoterapeuta - pacjent, gdyż jest on jednym z podstawowych narzędzi, jakimi fizjoterapeuta posługuje się w pracy na co dzień. Celem niniejszych pilotażowych badań była próba oceny, jak fizjoterapeuci postrzegają dotyk i czy wykorzystują w praktyce wskazówki dotyczące warunków i sposobu jego stosowania. Materiał i metody: Badaniem objęto 80 losowo wybranych fizjoterapeutów (39K/41M). Średni wiek badanych 30,36 lat (SD 6,62), a średni staż pracy 6,62 lat (SD 5,05). Posłużono się autorską ankietą (28 pytań), dotyczącą 3 obszarów: postaw fizjoterapeutów wobec dotyku, psychologicznych aspektów dotyku oraz warunków zapewniających jego właściwy komfort. Wyniki: Uzyskane odpowiedzi wskazują, iż badani fizjoterapeuci traktują dotyk głównie jako techniczne narzędzie do zbierania informacji i prowadzenia terapii. Respondenci są świadomi tego, iż dotyk wpływa na ciało i psychikę pacjenta, oraz że jest to akt dwukierunkowy fizjoterapeuta <=> pacjent. Większość badanych nie doświadcza żadnych emocji, dotykając pacjenta. Badani utrzymują, iż stosują w praktyce zalecenia związane z poszanowaniem prawa pacjenta do autonomii, intymności, informacji oraz zachowaniem właściwej dbałości o higienę, komfort i bezpieczeństwo pacjenta w trakcie prowadzonego zabiegu. Wnioski: Uzyskane dane pozwalają sądzić, iż badani postrzegają dotyk w sposób bardzo techniczny, zaniedbując jednocześnie jego wymiar psychospołeczny. Badani znają i przestrzegają w praktyce zaleceń dotyczących warunków oraz sposobu stosowania dotyku
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Gitin, Seymour. „Trude Dothan (1922–2016): In Memoriam“. Palestine Exploration Quarterly 148, Nr. 2 (02.04.2016): 82–83. http://dx.doi.org/10.1080/00310328.2016.1189166.
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Berthold, G., J. Smoliner, V. Rosskopf, E. Gornik, G. Böhm und G. Weimann. „Magnetoresistance in dotlike and antidotlike structures“. Physical Review B 45, Nr. 19 (15.05.1992): 11350–53. http://dx.doi.org/10.1103/physrevb.45.11350.
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Elmehriki, Adam A. H., Mark Milne, Mojmír Suchý, Robert Bartha und Robert H. E. Hudson. „Complexes of selected late period lanthanide(III) cations with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid amide (DOTAM)-alkyl ligands — A new platform for the development of paramagnetic chemical exchange saturation transfer (PARACEST) magnetic resonance imaging (MRI) contrast agents“. Canadian Journal of Chemistry 91, Nr. 3 (März 2013): 211–19. http://dx.doi.org/10.1139/cjc-2012-0358.
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A series of 18 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid amide (DOTAM)-alkyl derived complexes with selected late lanthanide(III) cations (Dy3+, Tb3+, and Tm3+) has been synthesized; their magnetic properties have been evaluated and compared to those derived from DOTAM. Peralkylation of cyclen with corresponding N-iodoacetyl amines was utilized as the key step in the synthesis. Chemical exchange saturation transfer (CEST) spectra of the complexes have been acquired at 37 °C, revealing that Tm3+-derived DOTAM-alkyl complexes possess the most favorable properties as potential paramagnetic chemical exchange saturation transfer (PARACEST) magnetic resonance imaging (MRI) contrast agents.
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Anderluzzi, Giulia, Gustavo Lou, Simona Gallorini, Michela Brazzoli, Russell Johnson, Derek T. O’Hagan, Barbara C. Baudner und Yvonne Perrie. „Investigating the Impact of Delivery System Design on the Efficacy of Self-Amplifying RNA Vaccines“. Vaccines 8, Nr. 2 (08.05.2020): 212. http://dx.doi.org/10.3390/vaccines8020212.
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messenger RNA (mRNA)-based vaccines combine the positive attributes of both live-attenuated and subunit vaccines. In order for these to be applied for clinical use, they require to be formulated with delivery systems. However, there are limited in vivo studies which compare different delivery platforms. Therefore, we have compared four different cationic platforms: (1) liposomes, (2) solid lipid nanoparticles (SLNs), (3) polymeric nanoparticles (NPs) and (4) emulsions, to deliver a self-amplifying mRNA (SAM) vaccine. All formulations contained either the non-ionizable cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) or dimethyldioctadecylammonium bromide (DDA) and they were characterized in terms of physico-chemical attributes, in vitro transfection efficiency and in vivo vaccine potency. Our results showed that SAM encapsulating DOTAP polymeric nanoparticles, DOTAP liposomes and DDA liposomes induced the highest antigen expression in vitro and, from these, DOTAP polymeric nanoparticles were the most potent in triggering humoral and cellular immunity among candidates in vivo.
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Young, A. T. L., J. R. T. Lakey, A. G. Murray und R. B. Moore. „Gene Therapy: A Lipofection Approach for Gene Transfer into Primary Endothelial Cells“. Cell Transplantation 11, Nr. 6 (September 2002): 573–82. http://dx.doi.org/10.3727/000000002783985495.
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Despite the great potential of gene therapy to become a new treatment modality in future medicine, there are still many limitations to overcome before this gene approach can pass to the stage of human trial. The foremost obstacle is the development of a safe, efficient, and efficacious vector system for in vivo gene application. This study evaluated the efficacy of lipofection as a gene delivery vehicle into primary endothelial cells. Transfection efficiency of several lipid-based reagents (Effectene, Fugene 6, DOTAP) was examined at experimental temperatures of 37°C, 24°C, and 6°C. Human umbilical vein endothelial cells (HUVECs) were transfected with the enhanced green fluorescent protein (EGFP) using precise amounts of DNA (Effectene, 0.2 μg; Fugene 6, 0.5 μg; DOTAP, 2.5 μg) and lipids (Effectene, 10 μl; Fugene 6, 6 μl; DOTAP, 15 μl) optimized in our laboratory. Duration of incubation in the DNA/lipid transfection mixture varied for each lipid transfectant as follows: 5 h for both Fugene 6 and DOTAP and 3 h for Effectene. Efficiency of transfection was quantified by microscopic evaluation of EFGP expression in a minimum of 100 cells per group. Transfection efficiencies achieved with these lipofection agents were 34 ± 1.3% (mean ± SEM), 33 ± 1.4%, and 18 ± 1.5% for Effectene, Fugene 6, and DOTAP, respectively, at 37°C. Transfection results were lower at 24°C with mean efficiencies of 26 ± 2.4% for Effectene, 14 ± 2.9% for Fugene 6, and 15 ± 3.2% for DOTAP. Furthermore, mean efficiencies at 6°C were 6 ± 0.5%, 8 ± 1.5%, and 6 ± 0.0% for Effectene, Fugene 6, and DOTAP, respectively. Efficiency of transfection appeared to be temperature dependent (ANOVA; p < 0.0001). In spite of a significant decrease (37°C vs. 24°C: p < 0.0001; 37°C vs. 6°C: p < 0.0001; 24°C vs. 6°C: p < 0.0115) in transfection efficiency at low temperatures, the successful in vitro gene manipulation renders lipofection a potential gene delivery strategy for in vivo gene therapy.
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Kim, Bieong-Kil, Guen-Bae Hwang, Young-Bae Seu, Jong-Soo Choi, Kyeong Sik Jin und Kyung-Oh Doh. „DOTAP/DOPE ratio and cell type determine transfection efficiency with DOTAP-liposomes“. Biochimica et Biophysica Acta (BBA) - Biomembranes 1848, Nr. 10 (Oktober 2015): 1996–2001. http://dx.doi.org/10.1016/j.bbamem.2015.06.020.
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Vincent, Carr D., Benjamin A. Buscher, Jonathan R. Friedman, Lee Anne Williams, Patrick Bardill und Joseph P. Vogel. „Identification of Non-dot/icm Suppressors of the Legionella pneumophila ΔdotL Lethality Phenotype“. Journal of Bacteriology 188, Nr. 23 (22.09.2006): 8231–43. http://dx.doi.org/10.1128/jb.00937-06.
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ABSTRACT Legionella pneumophila, a causative agent of bacterial pneumonia, survives inside phagocytic cells by avoiding rapid targeting to the lysosome. This bacterium utilizes a type IVB secretion system, encoded by the dot/icm genes, to replicate inside host cells. DotL, a critical component of the Dot/Icm secretion apparatus, functions as the type IV coupling protein. In contrast to most dot/icm genes, which are dispensable for growth on bacteriological media, dotL is required for the viability of wild-type L. pneumophila. Previously we reported that ΔdotL lethality could be suppressed by inactivation of the Dot/Icm complex via mutations in other dot/icm genes. Here we report the isolation of non-dot/icm suppressors of this phenotype. These ΔdotL suppressors include insertions that disrupt the function of the L. pneumophila homologs of cpxR, djlA, lysS, and two novel open reading frames, lpg0742 and lpg1594, that we have named ldsA and ldsB for lethality of ΔdotL suppressor. In addition to suppressing ΔdotL lethality, inactivation of these genes in a wild-type strain background causes a range of defects in L. pneumophila virulence traits, including intracellular growth, implicating these factors in the proper function of the Dot/Icm complex. Consistent with previous data showing a role for the cpx system in regulating expression of several dot/icm genes, the cpxR insertion mutant produced decreased levels of three Dot/Icm proteins, DotA, IcmV, and IcmW. The remaining four suppressors did not affect the steady-state levels of any Dot/Icm protein and are likely to represent the first identified factors necessary for assembly and/or activation of the Dot/Icm secretion complex.
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Kwekkeboom, Dik J., Boen L. Kam, Martijn van Essen, Jaap J. M. Teunissen, Casper H. J. van Eijck, Roelf Valkema, Marion de Jong, Wouter W. de Herder und Eric P. Krenning. „Somatostatin receptor-based imaging and therapy of gastroenteropancreatic neuroendocrine tumors“. Endocrine-Related Cancer 17, Nr. 1 (März 2010): R53—R73. http://dx.doi.org/10.1677/erc-09-0078.
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Somatostatin receptor imaging (SRI) with [111In-DTPA0]octreotide has proven its role in the diagnosis and staging of gastroenteropancreatic neuroendocrine tumors (GEPNETs). Newer radiolabeled somatostatin analogs which can be used in positron emission tomography (PET) imaging, and which have a higher affinity for the somatostatin receptor, especially receptor subtype-2, have been developed. It would be desirable, however, if one radiolabeled analog became the new standard for PET imaging, because the current application of a multitude of analogs implies a fragmented knowledge on the interpretation of the images that are obtained in clinical practice. In our view, the most likely candidates for such a universal PET tracer for SRI are [68Ga-DOTA0,Tyr3]octreotate or [68Ga-DOTA0,Tyr3]octreotide. Treatment with radiolabeled somatostatin analogs is a promising new tool in the management of patients with inoperable or metastasized neuroendocrine tumors. Symptomatic improvement may occur with all 111In-, 90Y-, or 177Lu-labeled somatostatin analogs that have been used for peptide receptor radionuclide therapy (PRRT). The results that were obtained with [90Y-DOTA0,Tyr3]octreotide and [177Lu-DOTA0,Tyr3]octreotate are very encouraging in terms of tumor regression. Also, if kidney protective agents are used, the side effects of this therapy are few and mild, and the median duration of the therapy response for these radiopharmaceuticals is 30 and 40 months respectively. The patients' self-assessed quality of life increases significantly after treatment with [177Lu-DOTA0,Tyr3]octreotate. Lastly, compared to historical controls, there is a benefit in overall survival of several years from the time of diagnosis in patients treated with [177Lu-DOTA0,Tyr3]octreotate. These data compare favorably with the limited number of alternative treatment approaches. If more widespread use of PRRT can be guaranteed, such therapy may well become the therapy of first choice in patients with metastasized or inoperable GEPNETs.
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Kurosaki, Tomoaki, Takashi Kitahara, Mugen Teshima, Koyo Nishida, Junzo Nakamura, Mikiro Nakashima, Hideto To, Hiromitsu Hukuchi, Tomoyuki Hamamoto und Hitoshi Sasaki. „Exploitation of De Novo Helper-Lipids for Effective Gene Delivery.“ Journal of Pharmacy & Pharmaceutical Sciences 11, Nr. 4 (05.01.2009): 56. http://dx.doi.org/10.18433/j31s3b.
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Purpose: In gene delivery, a fusogenic lipid such as dioleyl phosphatidylethanolamine (DOPE) which is a component of cationic liposomal vector is important factor for effective transfection efficiency. We investigated the effect of penetration enhancers as alternative helper-lipids to DOPE. Methods: Transdermal penetraion enhancers such as N-lauroylsarcosine (LS), (R)-(+)-limonene (LM), vitamin E (VE), and phosphatidyl choline from eggs (EggPC) were used in this experiments as helper-lipids with N-[1-(2, 3-dioleyloxy) propyl]-N, N, N-trimethlylammonium chloride (DOTMA) and cholesterol (CHOL). We examined in vitro transfection efficiency, cytotoxicity, hematotoxicity, and in vivo transfection efficiency of plasmid DNA/cationic liposomes complexes. Results: In transfection experiments in vitro, the cationic lipoplexes containing LS had highest transfection efficiency among the other lipoplexes independently of FBS. Furthermore, the lipoplexes containing LS had lowest cell toxicity among the other lipoplexes in the presence of FBS. As the results of erythrocytes interaction experiment, DOTMA/LS/CHOL, DOTMA/VE/CHOL, and DOTMA/EggPC/CHOL lipoplexes showed extremely lower hematotoxicity. On the basis of these results, the in vivo transfection efficiencies of the lipoplexes were examined. The lipoplexes containing LS had the highest transfection activity among the other lipoplexes. Conclusion: In conclusion, several transdermal penetration enhancers are available for alternative helper-lipids to DOPE in cationic liposomal vectors. Among them, DOTMA/LS/CHOL lipoplexes showed superior characteristics in in vitro transfection efficiency, cell toxicity, hematotoxicity, and in vivo transfection efficiency.
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Guinto-Nishimura, Gerardo Y., Juan L. Gómez-Amador, Nora Kerik-Rotenberg, Rodrigo Uribe-Pacheco, Marcos V. Sangrador-Deitos und José J. Martínez-Manrique. „68Ga-DOTATOC-PET/CT–guided resection of a primary intraosseous meningioma: technical note“. Neurosurgical Focus 50, Nr. 1 (Januar 2021): E6. http://dx.doi.org/10.3171/2020.10.focus20771.
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Primary intraosseous meningiomas (PIMs) are rare tumors that present with a variable radiological appearance and a clinical behavior that is considerably different from that of intracranial meningiomas. Treatment of PIMs consists of complete resection, which may be difficult to achieve due to the lack of clear tumor margins on conventional imaging studies. PET/CT using 68Ga-DOTA–conjugated peptides has been used for the diagnosis and treatment planning of different types of meningiomas due to these tracers’ affinity to somatostatin receptors, which are found in most meningiomas. However, this imaging modality’s use as an intraoperative adjunct has not been reported for PIMs. In this technical note, the authors describe a [68Ga-DOTA0-Tyr3]octreotide (68Ga-DOTATOC)-PET/CT–guided resection of a PIM. In this case, the area of increased uptake in the 68Ga-DOTATOC-PET/CT study extended well beyond the tumor margins identified on MRI. The patient’s pathology report confirmed the presence of tumor cells within peripheral bone, which macroscopically appeared normal. The authors propose 68Ga-DOTATOC-PET/CT as a valuable adjunct in the surgical management of PIMs and offer a reasonable justification for its use based on current evidence. Its use for intraoperative image guidance may aid neurosurgeons in achieving a complete resection, thus minimizing the risk of recurrence of this complex pathological entity.
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Radinja, Darko. „Problematika sonaravnega razvoja v slovenskem alpskem svetu (na primeru Rateške pokrajine)“. Dela, Nr. 13 (01.12.1999): 115–33. http://dx.doi.org/10.4312/dela.13.115-133.
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Poročilo osvetljuje obseg in strukturo nekdanje agrarne preobrazbe obravnavane alpske pokrajine predvsem z vidika hudourniške problematike. Z okoljevarstvenega vidika se dotika njenih navzkrižij tudi v zadnjih desetletjih.
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Djumaev, Alexander, und Jean During. „Asie Centrale: Les maitres du dotar [Central Asia: The Masters of the Dotar]“. Yearbook for Traditional Music 26 (1994): 187. http://dx.doi.org/10.2307/768269.
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Miglio, Adam E. „Iron Age Epigraphic Artifacts from Tel Dothan“. Bulletin of the American Schools of Oriental Research 371 (Mai 2014): 129–39. http://dx.doi.org/10.5615/bullamerschoorie.371.0129.
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Schrieber, Jorn, Dominic Schuhmacher und Carsten Gottschlich. „DOTmark – A Benchmark for Discrete Optimal Transport“. IEEE Access 5 (2017): 271–82. http://dx.doi.org/10.1109/access.2016.2639065.
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Junier, T., und M. Pagni. „Dotlet: diagonal plots in a Web browser“. Bioinformatics 16, Nr. 2 (01.02.2000): 178–79. http://dx.doi.org/10.1093/bioinformatics/16.2.178.
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Gavoille, G. „Dotlike magnetic structure in CoCr films“. Journal of Magnetism and Magnetic Materials 88, Nr. 3 (August 1990): 275–80. http://dx.doi.org/10.1016/0304-8853(90)90649-b.
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Mueller, Thomas C., Philip A. Banks und William C. Steen. „Microbial Degradation of Flurtamone in Three Georgia Soils“. Weed Science 39, Nr. 2 (Juni 1991): 270–74. http://dx.doi.org/10.1017/s0043174500071599.
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Degradation of flurtamone in a Greenville sandy clay loam, a Cecil loam, and a Dothan loamy sand with 0, 1, or 2 yr of previous flurtamone field use was evaluated under controlled conditions. Soil sterilization by autoclaving significantly reduced flurtamone dissipation rate in all soils. Enhanced degradation of flurtamone was observed in a Greenville sandy clay loam after 1 yr of previous flurtamone field use and in a Cecil loam after 2 yr of previous flurtamone field use. No enhancement of flurtamone degradation was observed in a Dothan loamy sand. Flurtamone degradation kinetics in these studies was described as a first-order process. Microbial populations in each soil showed no major changes in total bacterial numbers due to preexposure to flurtamone in the field.
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Juchnowicz, Marta. „Najlepsze praktyki w zarządzaniu kapitałem ludzkim; metodyka badania, opisy przypadków“. Kwartalnik Ekonomistów i Menedżerów 24, Nr. 2 (30.04.2012): 0. http://dx.doi.org/10.5604/01.3001.0009.5849.
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Recenzowane opracowanie naukowe dotyka problematyki tyleż szerokiej co słabo zdefiniowanej: dobrych praktyk w zakresie funkcji personalnej organizacji. Eksplorowane zagadnienie ma charakter problemu „wyłaniającego się” co stawia recenzowane opracowanie w rzędzie prekursorskich.
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Hattori, Yoshiyuki, Masataka Date, Shohei Arai, Kumi Kawano, Etsuo Yonemochi und Yoshie Maitani. „Transdermal Delivery of Small Interfering RNA with Elastic Cationic Liposomes in Mice“. Journal of Pharmaceutics 2013 (26.12.2013): 1–6. http://dx.doi.org/10.1155/2013/149695.
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We developed elastic cationic liposomal vectors for transdermal siRNA delivery. These liposomes were prepared with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) as a cationic lipid and sodium cholate (NaChol) or Tween 80 as an edge activator. When NaChol or Tween 80 was included at 5, 10, and 15% (w/w) into DOTAP liposomal formulations (C5-, C10-, and C15-liposomes and T5-, T10-, and T15-liposomes), C15- and T10-liposomes showed 2.4- and 2.7-fold-higher elasticities than DOTAP liposome, respectively. Although the sizes of all elastic liposomes prepared in this study were about 80–90 nm, the sizes of C5-, C10- and C15-liposome/siRNA complexes (lipoplexes) were about 1,700–1,800 nm, and those of T5-, T10-, and T15-lipoplexes were about 550–780 nm. Their elastic lipoplexes showed strong gene suppression by siRNA without cytotoxicity when transfected into human cervical carcinoma SiHa cells. Following skin application of the fluorescence-labeled lipoplexes in mice, among the elastic lipoplexes, C15- and T5-lipoplexes showed effective penetration of siRNA into skin, compared with DOTAP lipoplex and free siRNA solution. These data suggest that elastic cationic liposomes containing an appropriate amount of NaChol or Tween 80 as an edge activator could deliver siRNA transdermally.
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Putzer, Daniel, Alexander Kroiss, Dietmar Waitz, Michael Gabriel, Tatjana Traub-Weidinger, Christian Uprimny, Elisabeth von Guggenberg et al. „Somatostatin receptor PET in neuroendocrine tumours: 68Ga-DOTA0,Tyr3-octreotide versus 68Ga-DOTA0-lanreotide“. European Journal of Nuclear Medicine and Molecular Imaging 40, Nr. 3 (14.11.2012): 364–72. http://dx.doi.org/10.1007/s00259-012-2286-6.
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Villard, Linda, Anna Romer, Nicolas Marincek, Philippe Brunner, Michael T. Koller, Christian Schindler, Quinn K. T. Ng et al. „Cohort Study of Somatostatin-Based Radiopeptide Therapy With [90Y-DOTA]-TOC Versus [90Y-DOTA]-TOC Plus [177Lu-DOTA]-TOC in Neuroendocrine Cancers“. Journal of Clinical Oncology 30, Nr. 10 (01.04.2012): 1100–1106. http://dx.doi.org/10.1200/jco.2011.37.2151.
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Purpose Radiopeptide therapy is commonly performed with a single radioisotope. We aimed to compare the effectiveness of somatostatin-based radiopeptide therapy with a single versus a combination of radioisotopes. Patients and Methods In a cohort study, patients with metastasized neuroendocrine cancer were treated with repeated cycles of 90yttrium-labeled tetraazacyclododecane-tetraacetic acid modified Tyr-octreotide ([90Y-DOTA]-TOC) or with cycles alternating between [90Y-DOTA]-TOC and 177lutetium-labeled DOTA-TOC ([177Lu-DOTA]-TOC) until tumor progression or permanent toxicity. Multivariable Cox regression and competing risk regression were used to study predictors of survival and renal toxicity in patients completing three or more treatment cycles. Results A total of 486 patients completed three or more treatment cycles; 237 patients received [90Y-DOTA]-TOC and 249 patients received [90Y-DOTA]-TOC + [177Lu-DOTA]-TOC. Patients receiving [90Y-DOTA]-TOC + [177Lu-DOTA]-TOC had a significantly longer survival than patients receiving [90Y-DOTA]-TOC alone (5.51 v 3.96 years; hazard ratio, 0.64; 95% CI, 0.47 to 0.88; P = .006). The rates of severe hematologic toxicities (6.3% v 4.4%; P = .25) and severe renal toxicity (8.9% v 11.2%; P = .47) were comparable in both groups. Conclusion [90Y-DOTA]-TOC + [177Lu-DOTA]-TOC was associated with improved overall survival compared with [90Y-DOTA]-TOC alone in patients completing three or more cycles of treatment. Contrary to the current practice in radiopeptide therapy, our results suggest an advantage of using a combination of radioisotopes.