54 research outputs found
Compound mutations in BCR-ABL1 are not major drivers of primary or secondary resistance to ponatinib in CP-CML patients
No full textBCR-ABL1 kinase domain mutations can confer resistance to first- and second-generation tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML). In preclinical studies, clinically achievable concentrations of the third-generation BCR-ABL1 TKI ponatinib inhibit T315I and all other single BCR-ABL1 mutants except T315M, which generates a single amino acid exchange, but requires 2 sequential nucleotide exchanges. In addition, certain compound mutants (containing ≥2 mutations in cis) confer resistance. Initial analyses based largely on conventional Sanger sequencing (SS) have suggested that the preclinical relationship between BCR-ABL1 mutation status and ponatinib efficacy is generally recapitulated in patients receiving therapy. Thus far, however, such analyses have been limited by the inability of SS to definitively identify compound mutations or mutations representing less than ~20% of total alleles (referred to as "low-level mutations"), as well as limited patient follow-up. Here we used next-generation sequencing (NGS) to define the baseline BCR-ABL1 mutation status of 267 heavily pretreated chronic phase (CP)-CML patients from the PACE trial, and used SS to identify clonally dominant mutants that may have developed on ponatinib therapy (30.1 months median follow-up). Durable cytogenetic and molecular responses were observed irrespective of baseline mutation status and included patients with compound mutations. No single or compound mutation was identified that consistently conferred primary and/or secondary resistance to ponatinib in CP-CML patients. Ponatinib is effective in CP-CML irrespective of baseline mutation status.Michael W. Deininger, J. Graeme Hodgson, Neil P. Shah, Jorge E. Cortes, Dong-Wook Kim, Franck E. Nicolini, Moshe Talpaz, Michele Baccarani, Martin C. Müller, Jin Li, Wendy T. Parker, Stephanie Lustgarten, Tim Clackson, Frank G. Haluska, Francois Guilhot, Hagop M. Kantarjian, Simona Soverini, Andreas Hochhaus, Timothy P. Hughes, Victor M. Rivera and Susan Branfor
Bibliographie
No full textLes abréviations, sauf celles explicitées ci-dessous, sont conformes à l’Année philologique (http%20:/%20www.%20annee-philologique.%20com/aph%20/), au Guide de l’épigraphiste (Bérard Fr., Feisseil D., Petitmengin P., Rousset D. et Sève M. (dir.), Paris, 2000 3) et à la Checklist en ligne (Oates J. F., Bagnall R. S., Clackson S. J., O’Brien A. A., Sosin J. D., Wilfong T. G. et Worp Kl. A., Checklist of Greek, Latin, Demotic and Coptic Papyri, Ostraca and Tablets, http :// scriptorium. lib. duk..
Boise crew portrait, 1994
No full textA group portrait of the smokejumper crew for the Boise Smokejumper Base. Front row: S. Nemore, T. Mason, B. Johnson, S. Ramalingam, E. Reynolds, C. Nebeker, S. Cross, T. Caughlin, J. Hofman, C. Irvine, M. Walmsey, G. Sexton, M. Marquez, R. Blanton Back row: K. Franz, M. Dark, J. Drazinski, D. Mueller, B. Hurley, J. Kitchen, D. Matsuoka, D. Moline, M. Clackson, J. Hubbard, B. Bennett, M. Morgen, M. Burin, K. Rose, R. Johnshoy, J. Weber, P. Brollier, P. Kenny, A. Cushman, E. Magallanes, B. Range, D. Estey, D. Jacobs, T. Pettitt, B. Nachtsheim, W. Wasser, D. Arnold, B. Derham, G. Herkshan, L. Flock, G. Steele, L. Hinojosa, M. Niccoli. Not pictured: G. Beebe, M. Motes, D. Wittke, J. Curd.https://dc.ewu.edu/nsa_crewpics/1253/thumbnail.jp
Designing assisted living technologies 'in the wild' : preliminary experiences with cultural probe methodology
Get PDFBackground
There is growing interest in assisted living technologies to support independence at home. Such technologies should ideally be designed ‘in the wild’ i.e. taking account of how real people live in real homes and communities. The ATHENE (Assistive Technologies for Healthy Living in Elders: Needs Assessment by Ethnography) project seeks to illuminate the living needs of older people and facilitate the co-production with older people of technologies and services. This paper describes the development of a cultural probe tool produced as part of the ATHENE project and how it was used to support home visit interviews with elders with a range of ethnic and social backgrounds, family circumstances, health conditions and assisted living needs.
Method
Thirty one people aged 60 to 98 were visited in their homes on three occasions. Following an initial interview, participants were given a set of cultural probe materials, including a digital camera and the ‘Home and Life Scrapbook’ to complete in their own time for one week. Activities within the Home and Life Scrapbook included maps (indicating their relationships to people, places and objects), lists (e.g. likes, dislikes, things they were concerned about, things they were comfortable with), wishes (things they wanted to change or improve), body outline (indicating symptoms or impairments), home plan (room layouts of their homes to indicate spaces and objects used) and a diary. After one week, the researcher and participant reviewed any digital photos taken and the content of the Home and Life Scrapbook as part of the home visit interview.
Findings
The cultural probe facilitated collection of visual, narrative and material data by older people, and appeared to generate high levels of engagement from some participants. However, others used the probe minimally or not at all for various reasons including limited literacy, physical problems (e.g. holding a pen), lack of time or energy, limited emotional or psychological resources, life events, and acute illness. Discussions between researchers and participants about the materials collected (and sometimes about what had prevented them completing the tasks) helped elicit further information relevant to assisted living technology design. The probe materials were particularly helpful when having conversations with non-English speaking participants through an interpreter.
Conclusions
Cultural probe methods can help build a rich picture of the lives and experiences of older people to facilitate the co-production of assisted living technologies. But their application may be constrained by the participant’s physical, mental and emotional capacity. They are most effective when used as a tool to facilitate communication and development of a deeper understanding of older people’s needs
Opening the Frontier: The Gubbio-Perugia Frontier in the Course of History.
No full textThe frontier between Gubbio (ancient Umbria) and Perugia (ancient Etruria), in the northeast part of the modern region of Umbria, was founded in the late sixth century BC. The frontier endured in different forms, most notably in the late antique and medieval periods, as well as fleetingly in 1944, and is fossilized today in the local government boundaries. Archaeological, documentary and philological evidence are brought together to investigate different scales of time that vary from millennia to single days in the representation of a frontier that captured a watershed of geological origins. The foundation of the frontier appears to have been a product of the active agency of the Etruscans, who projected new settlements across the Tiber in the course of the sixth century BC, protected at the outer limit of their territory by the naturally defended farmstead of Col di Marzo. The immediate environs of the ancient abbey of Montelabate have been studied intensively by targeted, systematic and geophysical survey in conjunction with excavation, work that is still in progress. An overview of the development of the frontier is presented here, employing the data currently available.</p
Interrogation of the protein-protein interactions between human BRCA2 BRC repeats and RAD51 reveals atomistic determinants of affinity
Get PDFThe breast cancer suppressor BRCA2 controls the recombinase RAD51 in the reactions that mediate homologous DNA recombination, an essential cellular process required for the error-free repair of DNA double-stranded breaks. The primary mode of interaction between BRCA2 and RAD51 is through the BRC repeats, which are ~35 residue peptide motifs that interact directly with RAD51 in vitro. Human BRCA2, like its mammalian orthologues, contains 8 BRC repeats whose sequence and spacing are evolutionarily conserved. Despite their sequence conservation, there is evidence that the different human BRC repeats have distinct capacities to bind RAD51. A previously published crystal structure reports the structural basis of the interaction between human BRC4 and the catalytic core domain of RAD51. However, no structural information is available regarding the binding of the remaining seven BRC repeats to RAD51, nor is it known why the BRC repeats show marked variation in binding affinity to RAD51 despite only subtle sequence variation. To address these issues, we have performed fluorescence polarisation assays to indirectly measure relative binding affinity, and applied computational simulations to interrogate the behaviour of the eight human BRC-RAD51 complexes, as well as a suite of BRC cancer-associated mutations. Our computational approaches encompass a range of techniques designed to link sequence variation with binding free energy. They include MM-PBSA and thermodynamic integration, which are based on classical force fields, and a recently developed approach to computing binding free energies from large-scale quantum mechanical first principles calculations with the linear-scaling density functional code ONETEP. Our findings not only reveal how sequence variation in the BRC repeats directly affects affinity with RAD51 and provide significant new insights into the control of RAD51 by human BRCA2, but also exemplify a palette of computational and experimental tools for the analysis of protein-protein interactions for chemical biology and molecular therapeutics.<br/
Natural killer cell evolution: cellular and molecular studies on Xenopus
Get PDFThe presence of natural killer cells at lower evolutionary levels was investigated in the amphibian Xenopus laevis. Chromium release microcytotoxicity assays revealed that fresh splenocytes from early-thymectomised Xenopus displayed significant spontaneous cytotoxicity against allogeneic B(_3)B(_7) thymic tumor cell targets, unlike those from control Xenopus, suggesting that 'NK-like' activity is greater in thymectomised (T cell-deficient) animals. Addition of Concanavalin A- derived active supernatants to splenocytes from a thymectomised animal caused a significant increase in cytolytic activity, but had no effect on cells from a control animal. This finding of enhanced cytotoxicity was indicative of lymphokine-activated killing in Xenopus, and supported the concept that tumour cell lysis was mediated by NK - like cells. Attempts were made to enrich the splenocytes for natural killer cells through the selective depletion of other lymphocyte subsets, using the techniques of 'panning’ and 'magnetic bead' separation following monoclonal antibody labelling of cells. On comparison of the two techniques, it was found that both were able to deplete a splenocyte culture of B cells to the same extent, but that magnetic sorting produced far superior results for depletion of T cells. Optimum conditions for magnetic sorting were determined, and used to generate 'purified' populations which were tested for their cytolytic activity. Such preliminary investigations suggested that natural killer like activity in Xenopus is likely to be mediated by a 'non-T / non-B' lymphoid subset. Finally, preliminary work was undertaken into the development of 'phage display' technology for the generation of single chain Fy antibody fragments (ultimately against NK cell surface antigens). PGR amplification of the V(_H) and Kappa chains was attempted on RNA extracted (using various methods) from Carboxypeptidase Y-injected-, B(_3)B(_7)-injected-, and unimmunised mice. Following RNA extraction under optimum conditions. Kappa chains were successfully amplified from experimental spleens, but the heavy chains still require more development
Book reviews published in Arctos 43 (2009)
No full text
Epigrafia 2006. Atti della XIVe Rencontre sur l'épigraphie in onore di Silvio Panciera, con altri contributi di colleghi, allievi e collaboratori. A cura di M. L. Caldelli – G. L. Gregori – S. Orlandi, 2008. (Olli Salomies)
Studi di archeologia in onore di Gustavo Traversari. Volumi I–II. A cura di M. Fano Santi, 2004. (Mika Kajava)
Edizione Nazionale delle Opere di Pirro Ligorio. Libri degli antichi eroi e uomini illustri. A cura di B. P. Venetucci, 2005. (Heikki Solin)
Edizione Nazionale delle Opere di Pirro Ligorio. Libro dell'antica città' di Tivoli e di alcune famose ville. A cura di A. Ten, 2005. (Heikki Solin)
Edizione Nazionale delle Opere di Pirro Ligorio. Libro delle iscrizioni latine e greche. A cura di S. Orlandi, 2008. (Heikki Solin)
Edizione Nazionale delle Opere di Pirro Ligorio. Libro di diversi terremoti. A cura di E. Guidoboni, 2005. (Heikki Solin)
Lettres de Chion d'Héraclée. Texte révisé, traduit et commenté par Pierre-Louis Malosse, avec une Préface de J. Schamp, 2004. (Mika Kajava)
Atti del XII Colloquium Tullianum. Salamanca, 7–9 ottobre 2004 (Ciceroniana N.S. XII). A cura di D. Fogazza – S. Monda, 2006. (Heikki Solin)
N. Horsfall: Virgil, Aeneid 2. A Commentary, 2008. (Hannu Riikonen)
The Early Latin Poetry of Sylvester Johannis Phrygius. Ed., with Intr., Tr. and Comm. by P. Sjökvist, 2007. (Raija Sarasti-Wilenius)
Wandering Poets in Ancient Greek Culture. Travel, Locality and Panhellenism. Ed. by R. Hunter – I. Rutherford, 2009. (Stephen Evans)
J. Heath: The Talking Greeks. Speech, Animals, and the other in Homer, Aeschylus, and Plato, 2005. (Tua Korhonen)
T. Papadopoulou: Heracles and Euripidean Tragedy, 2005. (Sanna-Ilaria Kittelä)
T. Habinek: Ancient Rhetoric and Oratory, 2005. (Manna Satama)
C. W. Marshall: The Stagecraft and Performance of Roman Comedy, 2006. (Kalle Knaapi)
G. Kelly: Ammianus Marcellinus: The Allusive Historian, 2008. (Heimo Vesala)
A History of Ancient Greek. From the Beginnings to Late Antiquity. Ed. by A.-F. Christidis, with M. Arapoulou – M. Chriti, 2007. (Kalle Korhonen)
J. Clackson – G. Horrocks: The Blackwell History of the Latin Language, 2007. (Hilla Halla-aho)
Inscriptiones Graecae. Vol. II et III editio altera, pars V: Inscriptiones Atticae aetatis quae est inter Herulorum incursionem et imp. Mauricii tempora. Edidit E. Sironen, 2008. (Heikki Solin)
M. Segre: Iscrizioni di Cos, 2007. (Olli Salomies)
La ricerca epigrafica e antiquaria nelle Venezie dall'età napoleonica all'unità. A cura di A. Buonopane – M. Buora – A. Marcone, 2007. (Heikki Solin)
F. Reiter: Die Nomarchen des Arsinoites. Ein Beitrag zum Steuerwesen im römischen Ägypten, 2004. (Tiina Purola)
La comunicazione nella storia antica. Fantasie e realtà. A cura di M. G. Angeli Bertinelli – A. Donati, 2008. (Olli Salomies)
The Cambridge Companion to the Age of Pericles. Ed. by L. J. Samons II, 2007. (Hannu Riikonen)
M. R. Christ: The Bad Citizen in Classical Athens, 2006. (Elina Salminen)
N. Luraghi: The Ancient Messenians. Constructions of Ethnicity and Memory, 2008. (Sanna-Ilaria Kittelä)
G. D. Farney: Ethnic Identity and Aristocratic Competition in Republican Rome, 2007. (Kaj Sandberg)
L. Canfora: Julius Caesar. The People's Dictator. Tr. by M. Hill – K. Windle, 2007. (Luca Maurizi)
The Cambridge Companion to the Age of Augustus. Ed. by K. Galinsky, 2005. (Kaj Sandberg)
F. Meijer: Emperors Don't Die in Bed, 2004. (Hannu Riikonen)
H. Brandt – F. Kolb: Lycia et Pamphylia. Eine römische Provinz im Südwesten Kleinasiens, 2005. (Kai Juntunen)
C. Marek: Pontus et Bithynia. Die römischen Provinzen im Norden Kleinasiens, 2003. (Kai Juntunen)
The World of the Herods. Vol. 1 of the International Conference The World of the Herods and the Nabataeans. Ed. by N. Kokkinos, 2007. (Zbigniew Fiema)
The World of the Nabataeans. Vol. 2 of the International Conference The World of the Herods and the Nabataeans. Ed. by K. D. Politis, 2007. (Zbigniew Fiema)
S. Halliwell: Greek Laughter. A Study of Cultural Psychology from Homer to Early Christianity, 2008. (Stephen Evans)
R. Langlands: Sexual Morality in Ancient Rome, 2006. (Sari Kivistö)
T. Morgan: Popular Morality in the Early Roman Empire, 2007. (Sari Kivistö)
A. M. Gowing: Empire and Memory. The Representation of the Roman Republic in Imperial Culture, 2005. (Kaj Sandberg)
E. D'Ambra: Roman Women, 2007. (Elina Pyy)
E. A. Hemelrijk: Matrona docta: Educated women in the Roman élite from Cornelia to Julia Domna, 2004. (Elina Pyy)
J. M. Carlon: Pliny's Women: Constructing Virtue and Creating Identity in the Roman World, 2009. (Margherita Carucci)
R. Seaford: Dionysos, 2006. (Elina Salminen)
Ethne e religioni nella Sicilia antica. A cura di P. Anello – G. Martorana – R. Sammartano, 2006. (Kalle Korhonen)
Religion auf dem Lande. Entstehung und Veränderung von Sakrallandschaften unter römischer Herrschaft. Hrsg. von C. Auffarth, 2009. (Olli Salomies)
A. Lanni: Law and Justice in the Courts of Classical Athens, 2006. (Janne Pölönen)
J. Harries: Law and Crime in the Roman World, 2007. (Janne Pölönen)
O. F. Robinson: Penal Practice and Penal Policy in Ancient Rome, 2007. (Janne Pölönen)
D. Roebuck – B. de Loynes de Fumichon: Roman Arbitration, 2004. (Janne Pölönen)
L. A. Scatozza Höricht: Pithecusa. Materiali votivi da Monte Vico a dall'area di Santa Restituta, 2007. (Heikki Solin)
M. Albertocchi: Athana Lindia. Le statuette siceliote con pettorali di età arcaica e classica, 2004. (Mika Kajava)
A. G. Mitchell: Greek Vase-Painting and the Origins of Visual Humour, 2009. (Margherita Carucci)
The Parthenon and Its Sculptures. Ed. by M. B. Cosmopoulos, 2004. (Leena Pietilä-Castrén)
S. I. Rotroff : Hellenistic Pottery: The Plain Wares, 2006. (Janne Ikäheimo)
A. Stewart: Attalos, Athens, and the Akropolis. The Pergamene "Little Barbarians" and their Roman and Renaissance Legacy, 2004. (Mika Kajava)
P. Stewart: The Social History of Roman Art, 2008. (Margherita Carucci)
Edilizia pubblica e privata nelle città romane. A cura di L. Quilici – S. Quilici Gigli, 2008. (Heikki Solin)
A. Alexandridis: Die Frauen des römischen Kaiserhauses. Eine Untersuchung ihrer bildlichen Darstellung von Livia bis Iulia Domna, 2004. (Mika Kajava)
Le scoperte archeologiche di Reggio di Calabria (1882–1888), con una inedita relazione di scavo del 1889 di Domenico Spanò Bolani. A cura di F. Martorano, 2001. (Mika Kajava)
D. Mazzoleni – U. Pappalardo: Pompejanische Wandmalerei. Architektur und illusionistische Dekoration, 2005. (Antero Tammisto)
Verschüttet vom Vesuv. Die letzten Stunden von Herculaneum. Hrsg. von J. Mühlenbrock – D. Richter, 2005. (Antero Tammisto)
 
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