21,871 research outputs found
Interferon gamma upregulates frataxin and corrects the functional deficits in a Friedreich ataxia model
No full textCopyright © The Author 2012. Published by Oxford University Press.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.Friedreich's ataxia (FRDA) is the most common hereditary ataxia, affecting ∼3 in 100 000 individuals in Caucasian populations. It is caused by intronic GAA repeat expansions that hinder the expression of the FXN gene, resulting in defective levels of the mitochondrial protein frataxin. Sensory neurons in dorsal root ganglia (DRG) are particularly damaged by frataxin deficiency. There is no specific therapy for FRDA. Here, we show that frataxin levels can be upregulated by interferon gamma (IFNγ) in a variety of cell types, including primary cells derived from FRDA patients. IFNγ appears to act largely through a transcriptional mechanism on the FXN gene. Importantly, in vivo treatment with IFNγ increases frataxin expression in DRG neurons, prevents their pathological changes and ameliorates the sensorimotor performance in FRDA mice. These results disclose new roles for IFNγ in cellular metabolism and have direct implications for the treatment of FRDA.AtaxiaUK, National Ataxia Foundation, USA, Friedreich Ataxia Research Alliance
(FARA), USA and Telethon-Italy, FARA, GoFAR, the Wellcome
Trust, the EU FP7 and the Fondazione Telethon
Protecting Animals 36: Author Witi Ihimaera
No full textIn this very special episode of Knowing Animals I am joined by beloved New Zealand author Witi Ihimaera. Witi has written many books featuring nonhuman animals. He offers us a non-colonial lens through which to think about the human/nonhuman relationship
Central Nervous System Involvement in Relapsed Acute Promyelocytic Leukemia
No full text[No abstract available
A review of current induction strategies and emerging prognostic factors in the management of children and adolescents with acute lymphoblastic leukemia
No full textIntroduction: Acute lymphoblastic leukemia is the most frequent hematologic malignancy in children.
Almost 95% of children potentially achieve a complete remission after the induction treatment, but over
the last years, new insights in the genomic disease profile and in minimal residual disease detection
techniques have led to an improvement in the prognostic stratification, identifying selected patients’
subgroups with peculiar therapeutic needs.
Areas covered: According to a comprehensive search of peer-review literature performed in Pubmed, in
this review we summarize the recent evidences on the induction treatment strategies comprised in the
children acute lymphoblastic leukemia scenario, focusing on the role of key drugs such as corticosteroids
and asparaginase and discussing the crucial significance of the genomic characterization at baseline which
may drive the proper induction treatment choice.
Expert opinion: Current induction strategies already produce durable remissions in a significant proportion
of standard-risk children with acute lymphoblastic leukemia. A broader knowledge of the biologic features
related to acute lymphoblastic leukemia subtypes with worse prognosis, and an optimization of targeted
drugs now available, might lead to the achievement of long-term molecular remissions in this setting
Temperaments of young stars : rapid mass accretion rate changes in T Tauri and Herbig Ae stars
No full textFunding: JSV would like to thank the UK Science and Technologies Facility Council (STFC) and the Northern Ireland Department of Culture Arts and Leisure (DCAL) for financial support. AS and TR would like to thank the Science Foundation of Ireland (SFI) for their support under grant numbers 11/RFP/AST/3331 and 10/RFP/AST2780.Variability in emission lines is a characteristic feature in young stars and can be used as a tool to study the physics of the accretion process. Here, we present a study of Hα variability in 15 T Tauri and Herbig Ae stars (K7 - B2) over a wide range of time windows, from minutes, to hours, to days, and years. We assess the variability using linewidth measurements and the time series of line profiles. All objects show gradual, slow profile changes on time-scales of days. In addition, in three cases there is evidence for rapid variations in Hα with typical time-scales of 10 min, which occurs in 10 per cent of the total covered observing time. The mean accretion rate changes, inferred from the line fluxes, are 0.01–0.07 dex for time-scales of <1 h, 0.04–0.4 dex for time-scales of days, and 0.13–0.52 dex for time-scales of years. In Costigan et al., we derived an upper limit finding that the intermediate (days) variability dominated over longer (years) variability. Here, our new results, based on much higher cadence observations, also provide a lower limit to accretion rate variability on similar time-scales (days), thereby constraining the accretion rate variability physics in a much more definitive way. A plausible explanation for the gradual variations over days is an asymmetric accretion flow resulting in a rotational modulation of the accretion-related emission, although other interpretations are possible as well. In conjunction with our previous work, we find that the time-scales and the extent of the variability is similar for objects ranging in mass from ∼0.1 to ∼5 M⊙. This confirms that a single mode of accretion is at work from T Tauri to Herbig Ae stars – across a wide range of stellar masses.Peer reviewe
Treatment and long-term results in children with acute myeloid leukaemia treated according to the AIEOP AML protocols
No full textSince 1982, four consecutive studies on childhood acute myeloid leukaemia (AML) (namely LAM-82, -87, -87M and -92) have been conducted in Italy by the Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP) group. The induction therapy of the first three studies consisted of daunorubicin and cytarabine structured in a 3+7 backbone. In the most recent protocol (LAM92), patients received two induction courses including idarubicin, cytarabine and etoposide. Patients with acute promyelocytic leukaemia (20% of diagnoses) were included in LAM-87 and 87M studies. Postremissional therapy significantly changed over time, with an ever-increasing role given to stem cell transplantation (SCT). The long-term outcome of patients enrolled in the LAM-82, 87 and 87M studies was comparable, whereas that of children treated according to LAM-92 study was significantly better (P<0.005). Either allogeneic or autologous SCT was employed as consolidation therapy in more than 75% of cases enrolled in this latter study. Patients enrolled in the LAM-92 study were stratified in standard and high-risk groups with different outcome (67 vs 47%, respectively, P=0.04). Altogether, the results obtained in these four studies have permitted a progressive refinement of treatment, contributing to the structure of the ongoing LAM-2002 protocol that stratifies patients according to the presence of definite genetic anomalies and response to induction therapy
I Think I Am Philip K. Dick
No full textFor years, noted writer Laurence A. Rickels often found himself compared to novelist Philip K. Dickthough in fact Rickels had never read any of the science fiction writers work. When he finally read his first Philip K. Dick novel, while researching for his recent book The Devil Notebooks , it prompted a prolonged immersion in Dicks writing as well as a recognition of Rickelss own long-documented intellectual pursuits. The result of this engagement is I Think I Am: Philip K. Dick , a profound thought experiment that charts the wide relevance of the pulp sci-fi author and paranoid visionary. I Think I Am: Philip K. Dick explores the science fiction authors meditations on psychic reality and psychosis, Christian mysticism, Eastern religion, and modern spiritualism. Covering all of Dicks science fiction, Rickels corrects the lack of scholarly interest in the legendary Californian author and, ultimately, makes a compelling case for the philosophical and psychoanalytic significance of Philip K. Dicks popular and influential science fiction.Intro -- Contents -- Introjection -- Part I -- Endopsychic Allegories -- Schreber Guardian -- Belief System Surveillance -- Part II -- Deeper Problems -- Veil of Tears -- Go West -- Dick Manfred -- Timing -- Glimmung -- Part III -- Spiritualism Analogy -- Imitating the Dead -- Indexical Layer -- Ilse -- Hammers and Things -- Crucifictions -- Over There -- Martyrology -- Can't Live, Can't Live -- Lola -- Umwelt, Mitwelt, and Eigenwelt -- Outer Race -- The German Introject -- Part IV -- Materialism, Idealism, and Cybernetics -- Startling Stories -- A Couple of Years -- Android Empathy -- Homunculus and Robot -- ALL OF YOU ARE DEAD. I AM ALIVE. -- Go with the Flow -- Part V -- Room for Thought -- Caduceus -- Jump -- Still -- A Wake -- Spätwerk -- Let the Dead Be -- Play Bally -- Das Hund -- Notes -- BibliographyFor years, noted writer Laurence A. Rickels often found himself compared to novelist Philip K. Dickthough in fact Rickels had never read any of the science fiction writers work. When he finally read his first Philip K. Dick novel, while researching for his recent book The Devil Notebooks , it prompted a prolonged immersion in Dicks writing as well as a recognition of Rickelss own long-documented intellectual pursuits. The result of this engagement is I Think I Am: Philip K. Dick , a profound thought experiment that charts the wide relevance of the pulp sci-fi author and paranoid visionary. I Think I Am: Philip K. Dick explores the science fiction authors meditations on psychic reality and psychosis, Christian mysticism, Eastern religion, and modern spiritualism. Covering all of Dicks science fiction, Rickels corrects the lack of scholarly interest in the legendary Californian author and, ultimately, makes a compelling case for the philosophical and psychoanalytic significance of Philip K. Dicks popular and influential science fiction.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
Il bilancio in passivo del postmoderno italiano
No full textFinito il postmoderno è venuto il tempo dei “bilanci”. Dai molti già licenziati (Ferroni, Luperini, Donnarumma, Spinazzola, Calabrese, Wu Ming) sembrerebbe che sia rimasto ben poco da segnare all’attivo. Alla luce di queste disamine, che forse lasciano inevase troppe questioni, è invece possibile rileggere come narrazioni autobiografiche alcuni saggi critici sulla questione, e i loro assunti (soprattutto quelli degli studiosi della generazione degli anni Quaranta) e come testi teorici alcuni romanzi-campione tra gli anni Sessanta e gli anni Novanta
Liftings for noncomplete probability spaces
No full textThe current state of knowledge concerning liftings for noncomplete probability spaces is discussed. This is a somewhat expanded version of the author's talk given at the 1991 Summer Conference on General Topology and Applications in Honor of Mary Ellen Rudin and Her Work.PT: S; CR: BURKE MR, IN PRESS P AM MATH S BURKE MR, 1991, ISRAEL J MATH, V73, P33 BURKE MR, 1992, ISRAEL J MATH, V79, P289 CARLSON T, THEOREM LIFTING CHRISTENSEN JPR, 1974, TOPOLOGY BOREL STRUC FREMLIN DH, 1989, HDB BOOLEAN ALGEBRAS, P877 INOESCUTULCEA A, 1966, 5TH P BERK S MATH ST, V2 IONESCUTULCEA A, 1967, CONTRIBUTIONS PROB 1, P63 IONESCUTULCEA A, 1969, TOPICS THEORY LIFTIN JECH TJ, 1978, SET THEORY JOHNSON RA, 1980, P AM MATH SOC, V80, P234 JUST W, IN PRESS T AM MATH S KUPKA J, 1983, INDIANA U MATH J, V32, P717 LOSERT V, 1983, LNM, V1080, P95 MAHARAM D, 1958, P AM MATH SOC, V9, P987 SHELAH S, 1983, ISRAEL J MATH, V45, P90 TALAGRAND M, 1982, P AM MATH SOC, V84, P379 VONNEUMANN J, 1931, CRELLES J MATH, V165, P109; NR: 18; TC: 0; J9: ANN N Y ACAD SCI; PG: 4; GA: BZ86BSource type: Electronic(1
The AM Canum Venaticorum binary SDSS J173047.59+554518.5
No full textThe AM Canum Venaticorum (AM CVn) binaries are a rare group of hydrogen-deficient, ultrashort period, mass-transferring white dwarf binaries and are possible progenitors of Type Ia supernovae. We present time-resolved spectroscopy of the recently discovered AM CVn binary SDSS J173047.59+554518.5. The average spectrum shows strong double-peaked helium emission lines, as well as a variety of metal lines, including neon; this is the second detection of neon in an AM CVn binary, after the much brighter system GP Com. We detect no calcium in the accretion disc, a puzzling feature that has been noted in many of the longer period AM CVn binaries. We measure an orbital period, from the radial velocities of the emission lines, of 35.2 ± 0.2 min, confirming the ultracompact binary nature of the system. The emission lines seen in SDSS J1730 are very narrow, although double-peaked, implying a low-inclination, face-on accretion disc; using the measured velocities of the line peaks, we estimate i ≤ 11°. This low inclination makes SDSS J1730 an excellent system for the identification of emission lines
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