44 research outputs found
Abstract 743: Detection of TERT C228T and C250T promoter mutations in melanoma tumor and plasma samples using novel mutation-specific droplet digital PCR assays
No full textAbstract
Purpose: Detecting mutations in the plasma of patients with solid tumors is becoming a valuable method of diagnosing and monitoring cancer. Mutations in 1 of 2 hot spots in the TERT promoter sequence are found in several cancers, including up to 85% of melanomas and the majority of cases that lack BRAF or NRAS mutations (about one-third of melanomas). Due to the high G-C content of the TERT promoter sequence these mutations can be difficult to detect using NGS approaches. We developed novel droplet digital PCR (ddPCR) assays to detect these 2 mutations with high sensitivity and specificity, and demonstrate the application of these assays in melanoma clinical samples.
Methods: Assays were optimized using cell lines with Sanger sequencing-confirmed mutations: glioblastoma A172 (C228T), and melanoma NYU12-126 (C250T). We varied assay designs and amplification conditions to optimize probe-based detection using the Bio-Rad QX-200 ddPCR system. Assay sensitivities and specificities at various DNA input levels were determined using serial dilutions with 3 replicate wells for each condition. Sensitivity is defined as the lowest mutant allele dilution for which the confidence interval did not overlap with that of the 0% mutant wells. We used normal and cancer-derived DNA sources of different quality (e.g. normal human DNA (Promega), cancer cell lines, plasma and FFPE-derived DNAs) with and without the mutations, and compared the efficiency of detection of amplicons of 88, 113 and 163 base-pairs. We compared efficiencies to assays of similar size for RPP30, a housekeeping gene. Patient-matched metastatic melanoma tumors and plasma samples were analyzed to explore the clinical utility of these assays.
Results: The assays showed greater sensitivity when higher amounts of DNA were analyzed. For C228T the limit of detection (LOD) of the mutant allele was 1%, 0.25% and 0.1% for 6.6ng/well, 33ng/well and 66ng/well respectively; for C250T the LODs were 0.25%, 0.05% and 0.05% respectively. Using normal human DNA, the efficiency of the TERT assays averaged approximately 90% of that for RPP30 across assays of similar size, and no decrease in assay efficiency was observed as amplicon length increased. In contrast, whereas amplicon size had only a modest effect on assay efficiency in plasma cfDNA, it gave a more pronounced effect on FFPE DNA’s, decreasing to 38% for the 163bp amplicon. We observed 100% concordance between TERT mutation detection by SNaPshot and ddPCR in 10 FFPE tumor samples, and in plasma samples from 4 metastatic melanoma patients with matching tumor samples.
Conclusion: We developed robust ddPCR assays to detect TERT promoter mutations with high sensitivity and specificity. Mutated TERT DNA can be detected and quantitated in the plasma of patients with metastatic melanoma, and is likely to be present in the plasma of other cancer patients in whom TERT mutations occur.
Citation Format: Broderick Corless, Gregory Chang, Samantha Cooper, Mahrukh Syeda, Iman Osman, George Karlin-Neumann, David Polsky. Detection of TERT C228T and C250T promoter mutations in melanoma tumor and plasma samples using novel mutation-specific droplet digital PCR assays [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 743. doi:10.1158/1538-7445.AM2017-743</jats:p
Erratum to: Sub-gap defect density characterization of molybdenum oxide: An annealing study for solar cell applications (Nano Research, (2020), 13, 12, (3416-3424), 10.1007/s12274-020-3029-9)
No full textRef. [56] was unfortunately wrong, Instead of [56] Corless, R. M.; Gonnet, G. H.; Hare, D. E. G.; Jeffrey, D. J.; Knuth, D. E. On the Lambert W function. Adv. Comput. Math. 1996, 5, 329–359. It should be changed to Biswas, R. K.; Khan, P.; Mukherjee, S.; Mukhopadhyay, A. K.; Ghosh, J.; Muraleedharan, K. Study of short range structure of amorphous Silica from PDF using Ag radiation in laboratory XRD system, RAMAN and NEXAFS. J. Non. Cryst. Solids 2018, 488, 1–9. Some entries in Table 2 were unfortunately misprinted.Photovoltaic Materials and DevicesElectrical Sustainable Energ
Immolation and critical document
No full textImmolation is a creative text comprised of 58 numbered fragments of dialogue between an unnamed author and editor. Their conversations take place over an extended period as the pair describe and discuss their middle-agedness, whilst the author attempts to create pieces of fiction which the editor critically assesses, and the editor talks about their faltering marriage. The text culminates in an extended story written by the author about a dysfunctional family, which the editor then provides commentary on. The fragments are less structured than a traditional novel and are presented as an intertwined and unconstrained creative experiment. The conversational estrangement and undefined medium of discourse between the author and editor provides a statement on modern relationships and forms of dialogue in contemporary life.
The critical document is comprised of two sections. The first is a series of fragmentary essays concerning my critical research as it relates to Geoff Dyer’s Out of Sheer Rage, a book which describes Dyer’s attempts to write about D. H. Lawrence. As with the creative piece, the section deals with themes of interactivity between pieces of work, experimentations in form, and authorial and editorial insertions as they relate to a finished critical piece. The argument, which is intertwined with and responds to Dyer’s analysis, is that the process of writing can itself become a “means of continuing”, and that there is hope and meaning in the dark patches of the process. The second section is a personal manifesto comprised of motivational writing-related quotations from a variety of sources, taking its major inspiration from Reality Hunger: A Manifesto by David Shields. The text draws on the themes of developing a healthy writing practice
Exploration of the Gartner mound and village site /
No full textImperfect copy: p. 35-43 stained and text of p. 38-39 partially wanting.Stamp of Chillicothe Public Library on front cover and t.p.Inscription on t.p.: To W. H. Hunter. With compliments of the author."Reprint from the Ohio Archaeological and Historical Quarterly, Volume XIII, Number 2."Mode of access: Internet
Hyper-Authorship: The Case of Araki Yasusada
No full textSCUBADIVERS AND CHRYSANTHEMUMS is a collection of essays on the poetry of Araki Yasuada. The book includes essays by Bill Freind, Eliot Weinberger, Marjorie Perloff, Forrest Gander, Mikhail Epstein, Kent Johnson, Brian McHale, Paisley Rekdal, Jenny Boully, Alex Verdolini, Eric R. J. Hayot, Jacob Edmond, Martin Corless-Smith, Farid Matuk, David Rosenberg, David Wojahn, Hosea Hirata and Dan Hoy. "Araki Yasusada, allegedly a survivor of the atomic bombing of Hiroshima, had his work published posthumously and in translation in the mid-1990s. The work was widely praised and seemed to fuse traditional Japanese forms and themes with more innovative North American techniques and a sprinkling of French critical theory. However, Yasusada was an invention, and while no one claimed responsibility for the work, most readers agree that Kent Johnson was the creator, although Johnson insists the actual author is Tosa Motokiyu, the pseudonym for an unnamed writer who is now dead.
Garanteed Exponential Convergence for Uncertain Nonlinear Systems in the Presence of Singular Perturbations
No full text
Chemoenzymatic synthesis of novel cytotoxic epoxyketones using the eponemycin biosynthetic enzyme EpnF
No full textSystematic Review of Escalated Imatinib Doses Compared with Sunitinib or Best Supportive Care, for the Treatment of People with Unresectable/Metastatic Gastrointestinal Stromal Tumours Whose Disease has Progressed on the Standard Imatinib Dose
No full textPMID: 21971958 [PubMed - indexed for MEDLINE] PMCID: PMC3348468 Free PMC Article This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are creditedPeer reviewe
Cuidando do recém-nascido em UTIN: convivendo com a fragilidade do viver/sobreviver à luz da complexidade
No full textDissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Programa de Pós-Graduação em Enfermagem, Florianópolis, 2009.Este estudo trata da elaboração de um modelo que contempla o fenômeno do cuidado em Unidade de Terapia Intensiva Neonatal a partir da compreensão do ser e fazer enquanto enfermeiro neste sistema complexo. Tal compreensão aborda as transformações ocorridas desde a criação das UTINs até a atualidade, vislumbrando sua busca pela integralidade ao oferecer um cuidado sensível e compartilhado. O referencial metodológico da Teoria Fundamentada nos Dados (Grounded theory) associado ao Paradigma da Complexidade de Edgar Morin foi utilizado na análise e na construção do Modelo Teórico: CUIDANDO DO RECÉM-NASCIDO EM UTIN: Convivendo com a fragilidade do viver/sobreviver à luz da complexidade. Participaram da pesquisa 11 sujeitos, entre enfermeiros e mães com bebês internados na UTIN. Utilizou-se a entrevista aberta para coleta dos dados. A análise comparativa dos dados subsidiou o processo de codificação, amostragem, saturação teórica, ordenação e integração dos dados. Os dados foram inseridos no software NVIVO, dando seqüência na organização e agrupamento dos mesmos. A organização dos códigos foi feita de acordo com suas propriedades e, então, agrupados em códigos preliminares, subcategorias e categorias. Através das inter-relações entre categorias, emergente dos dados coletados, identificou-se a categoria central, eixo norteador do Modelo Teórico, e integradora das categorias analíticas denominada: Convivendo com a fragilidade do viver/sobreviver: cuidado altamente complexo, sensível, singular e compartilhado em torno da qual giram as demais categorias: Buscando conhecimentos e competências; Gerenciando o cuidado na UTIN e Vivenciando as singularidades na UTIN. Neste contexto, o cuidado em UTIN se fortalece como uma das áreas da Enfermagem em constante desenvolvimento, visando conciliar os avanços tecnológicos importantes para o sobreviver do bebê prematuro com abordagens que valorizam as inter-relações em seu quotidiano, de modo sistêmico. Busca atuar nas diversas esferas do cuidado complexo em saúde, desde os serviços de apoio da instituição hospitalar e seus gestores até a academia, visando evitar atuações compartimentadas e isoladas, integrando e aplicando conhecimentos científicos, com ganhos para a prática profissional. Oferecer suporte tecnológico já não basta. A pesquisa ressalta que é necessário exercitar as potencialidades já inatas dos profissionais de enfermagem e caminhar para o encontro de outras, um verdadeiro convite a novas percepções de cuidar do neonato, sua família e os membros deste sistema complexo, numa constante inquietação e adaptação para as demandas que surgem. Assim, as indagações norteadoras desta pesquisa convidam para a ampliação de novos horizontes de investigação, de forma que as possibilidades de estudos indicadas permitam o aprofundamento no âmbito das organizações de saúde e da academia.This study deals with the elaboration of a model which contemplates the phenomenon of care in a Neonatal Intensive Care Unit (NICU), based on the comprehension of the human being and human actor as a nurse in this complex system. Such comprehension encompasses the transformations which have occurred since the creation of the NICUs, discerning its search for the entirety to offer sensible and shared care. The methodological reference of the Grounded Theory associated with Edgar Morins Complexity Theory was utilized in analysis and the construction of the Theoretical Model: CARING FOR THE NEWBORN IN THE NICU: Living with the fragility of living/surviving in the light of complexity. The sample was composed of 11 subjects, including nurses and mothers with newborns in the NICU. Open interviews were used in order to collect data. Comparative data analysis subsidized the data codification, sampling, theoretical saturation, ordering, and integration processes. Data was inserted into NVIVO software, providing a sequence in data organization and grouping. Organizing the codes was done according to their properties and thus, grouped in preliminary codes, subcategories, and categories. Through the relationships in these categories which emerged from the data collected, the central category, the guiding axis of the Theoretical Model and the integrating factor of the analytical categories was identified, denominated: Living with the fragility of living/surviving: highly complex, sensitive, singular, and shared care around which are the following categories: Seeking knowledge and competencies; Managing NICU care; and Living the singularities of the NICU. In this context, NICU care is strengthened as one of the Nursing areas in constant development, seeking to conciliate important technological advances towards premature newborn survival with the approaches which systematically value day-to-day relationships. It seeks to enact in the diverse spheres of complex health care, from the support services of the hospital institution and its management to academia, searching to avoid fragmented and isolated care through integrating and applying scientific knowledge with gains for professional practice. Offering technological support is no longer enough. Research highlights that it is necessary to exercise already innate potential in nursing professionals and work towards finding others, a true invitation towards new perceptions for care for the newborn, his/her family, and the members of this complex system in a constant unrest and adaptation of demands which may arise. Thus, the guiding questions of this study invite towards the amplification of new investigative horizons, in such a manner that the possibilities for suggested studies permit more profound in the realm of health care and academic organizations
