324 research outputs found
The Quaking RNA-binding proteins as regulators of cell differentiation
First published: 17 March 2022The RNA-binding protein Quaking (QKI) has emerged as a potent regulator of cellular differentiation in developmental and pathological processes. The QKI gene is itself alternatively spliced to produce three major isoforms, QKI-5, QKI-6, and QKI-7, that possess very distinct functions. Here, we highlight roles of the different QKI isoforms in neuronal, vascular, muscle, and monocyte cell differentiation, and during epithelial-mesenchymal transition in cancer progression. QKI isoforms control cell differentiation through regulating alternative splicing, mRNA stability and translation, with activities in gene transcription now also becoming evident. These diverse functions of the QKI isoforms contribute to their broad influences on RNA metabolism and cellular differentiation.
This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications RNA Processing > Splicing Regulation/Alternative Splicing RNA in Disease and Development > RNA in Development.Daniel P. Neumann, Gregory J. Goodall, Philip A. Gregor
Entanglement of a qubit with a single oscillator mode
We solve a model of a qubit strongly coupled to a massive environmental
oscillator mode where the qubit backaction is treated exactly. Using a
Ginzburg-Landau formalism, we derive an effective action for this well known
localization transition. An entangled state emerges as an instanton in the
collective qubit-environment degree of freedom and the resulting model is shown
to be formally equivalent to a Fluctuating Gap Model (FGM) of a disordered
Peierls chain. Below the transition, spectral weight is transferred to an
exponentially small energy scale leaving the qubit coherent but damped. Unlike
the spin-boson model, coherent and effectively localized behaviors may coexist.Comment: 4 pages, 1 figure; added calculation of entanglement entrop
Mixed micelles and gels of a hydrophilic poloxamine (Tetronic 1307) and miltefosine: Structural characterization by small-angle neutron scattering and in vitro evaluation for the treatment of leishmaniasis
Hypothesis/background: Tetronic is a family of four-armed amphiphilic block copolymers of polyethylene
oxide (PEO) and polypropylene oxide (PPO) that self-aggregate to form micelles and hydrogels. Due to
their temperature and pH-responsiveness, they are emerging as smart nanomaterials in the area of drug
delivery. Here we propose the use of Tetronic 1307 (T1307) as a nanocarrier of miltefosine (MF), a zwitterionic alkylphospholipid highly active against leishmaniasis, one of the most threating neglected tropical diseases. Given the amphiphilic nature of the drug, both surfactants can combine to form mixed
micelles, reducing the cytotoxicity of MF by lowering its dose and improving its internalization, hence
its antileishmanial effect.
Experiments: The structure of the T1307 micelles, MF micelles, mixed micelles and hydrogels, formed in
buffered solution (pH = 7.4) at different concentrations has been investigated in-depth by a combination
of small-angle neutron scattering (SANS), dynamic light scattering (DLS), fluorescence spectroscopy and
nuclear magnetic resonance methods (1D, 2D NOESY, and diffusion NMR). The cytotoxicity of the aggregates in macrophages has been assessed, as well as the antileishmanial activity in both Leishmania major
promastigotes and amastigotes.
Findings: T1307 and MF combine into mixed aggregates over a wide range of temperatures and compositions, forming ellipsoidal core–shell mixed micelles. The shell is highly hydrated and comprises most
of the PEO blocks, while the hydrophobic core contains the PO blocks and the MF along with a fraction of
EO and water molecules, depending on the molar ratio in the mixture. The combination with T1307
amplified the leishmanicidal activity of the drug against both forms of the parasite and dramatically
reduced drug cytotoxicity. T1307 micelles also showed a considerable leishmanicidal activity without
exhibiting macrophage toxicity. These results support the use of T1307 as a MF carrier for the treatment
of human and animal leishmaniasis, in its different clinical forms
USO DO DUBLIN CORE NA DESCRIÇÃO DE OBRAS RARAS NA WEB: \ud A COLEÇÃO DA BIBLIOTECA BRASILIANA DIGITAL
Acessível ao público desde junho de 2009, a Biblioteca Brasiliana Digital, da Universidade de \ud
São Paulo tem por objetivo facultar para a pesquisa, a maior Brasiliana custodiada por uma \ud
universidade. Sua intenção é disponibilizar virtualmente parte do acervo da Universidade \ud
oferecendo-se como um instrumento útil e funcional para a pesquisa e o estudo dos temas e \ud
cultura brasileiros, além de oferecer um modelo tecnológico de gestão que possa ser difundido \ud
a outras coleções, acervos e instituições. Este trabalho apresenta os resultado da implantação \ud
de um esquema de metadados baseado no formato Dublin Core, para a descrição de obras \ud
raras e especiais na web. Especificamente, apresenta os procedimentos e processos de \ud
descrição de conteúdos das diversas tipologias documentais (livros, periódicos, gravuras etc.) \ud
e formatos digitais (pdf, jpeg entre outros). \ud
Palavras-Chave: Bibliotecas digitais; Metadados; Dublin Core.Available for the public access since June 2009, the University of Sao Paulo Brasiliana \ud
Digital Library, aims to provide to the research the largest Brasiliana guarded by an \ud
University. The purpose is make available online part of the University Collection, as an \ud
useful and functional instrument to the research and study of Brazilian themes and culture, \ud
and also offer a technological management model able to be disseminated to other collections \ud
and institutions. This work shows the results of the implantation of a metadata schema based \ud
on Dublin Core format, for the description of rare and special works on the \ud
web. Specifically, it shows the content description procedures and processes of several \ud
documents typologies (books, journals, images etc) and digital formats (pdf, jpeg and others). \ud
Keywords: Digital Libraries, Metadata, Dublin Core
Two-loop corrections to the decay rate of parapositronium
Order corrections to the decay rate of parapositronium are
calculated. A QED scattering calculation of the amplitude for electron-positron
annihilation into two photons at threshold is combined with the technique of
effective field theory to determine an NRQED Hamiltonian, which is then used in
a bound state calculation to determine the decay rate. Our result for the
two-loop correction is in units of times the
lowest order rate. This is consistent with but more precise than the result
of a previous calculation.Comment: 26 pages, 7 figure
Gravitational radiation from gamma-ray bursts as observational opportunities for LIGO and VIRGO
Gamma-ray bursts are believed to originate in core-collapse of massive stars.
This produces an active nucleus containing a rapidly rotating Kerr black hole
surrounded by a uniformly magnetized torus represented by two counter-oriented
current rings. We quantify black hole spin-interactions with the torus and
charged particles along open magnetic flux-tubes subtended by the event
horizon. A major output of Egw=4e53 erg is radiated in gravitational waves of
frequency fgw=500 Hz by a quadrupole mass-moment in the torus. Consistent with
GRB-SNe, we find (i) Ts=90s (tens of s, Kouveliotou et al. 1993), (ii)
aspherical SNe of kinetic energy Esn=2e51 erg (2e51 erg in SN1998bw, Hoeflich
et al. 1999) and (iii) GRB-energies Egamma=2e50 erg (3e50erg in Frail et al.
2001). GRB-SNe occur perhaps about once a year within D=100Mpc. Correlating
LIGO/Virgo detectors enables searches for nearby events and their spectral
closure density 6e-9 around 250Hz in the stochastic background radiation in
gravitational waves. At current sensitivity, LIGO-Hanford may place an upper
bound around 150MSolar in GRB030329. Detection of Egw thus provides a method
for identifying Kerr black holes by calorimetry.Comment: to appear in PRD, 49
Theory and Applications of Non-Relativistic and Relativistic Turbulent Reconnection
Realistic astrophysical environments are turbulent due to the extremely high
Reynolds numbers. Therefore, the theories of reconnection intended for
describing astrophysical reconnection should not ignore the effects of
turbulence on magnetic reconnection. Turbulence is known to change the nature
of many physical processes dramatically and in this review we claim that
magnetic reconnection is not an exception. We stress that not only
astrophysical turbulence is ubiquitous, but also magnetic reconnection itself
induces turbulence. Thus turbulence must be accounted for in any realistic
astrophysical reconnection setup. We argue that due to the similarities of MHD
turbulence in relativistic and non-relativistic cases the theory of magnetic
reconnection developed for the non-relativistic case can be extended to the
relativistic case and we provide numerical simulations that support this
conjecture. We also provide quantitative comparisons of the theoretical
predictions and results of numerical experiments, including the situations when
turbulent reconnection is self-driven, i.e. the turbulence in the system is
generated by the reconnection process itself. We show how turbulent
reconnection entails the violation of magnetic flux freezing, the conclusion
that has really far reaching consequences for many realistically turbulent
astrophysical environments. In addition, we consider observational testing of
turbulent reconnection as well as numerous implications of the theory. The
former includes the Sun and solar wind reconnection, while the latter include
the process of reconnection diffusion induced by turbulent reconnection, the
acceleration of energetic particles, bursts of turbulent reconnection related
to black hole sources as well as gamma ray bursts. Finally, we explain why
turbulent reconnection cannot be explained by turbulent resistivity or derived
through the mean field approach.Comment: 66 pages, 24 figures, a chapter of the book "Magnetic Reconnection -
Concepts and Applications", editors W. Gonzalez, E. N. Parke
Heavy quarkonium: progress, puzzles, and opportunities
A golden age for heavy quarkonium physics dawned a decade ago, initiated by
the confluence of exciting advances in quantum chromodynamics (QCD) and an
explosion of related experimental activity. The early years of this period were
chronicled in the Quarkonium Working Group (QWG) CERN Yellow Report (YR) in
2004, which presented a comprehensive review of the status of the field at that
time and provided specific recommendations for further progress. However, the
broad spectrum of subsequent breakthroughs, surprises, and continuing puzzles
could only be partially anticipated. Since the release of the YR, the BESII
program concluded only to give birth to BESIII; the -factories and CLEO-c
flourished; quarkonium production and polarization measurements at HERA and the
Tevatron matured; and heavy-ion collisions at RHIC have opened a window on the
deconfinement regime. All these experiments leave legacies of quality,
precision, and unsolved mysteries for quarkonium physics, and therefore beg for
continuing investigations. The plethora of newly-found quarkonium-like states
unleashed a flood of theoretical investigations into new forms of matter such
as quark-gluon hybrids, mesonic molecules, and tetraquarks. Measurements of the
spectroscopy, decays, production, and in-medium behavior of c\bar{c}, b\bar{b},
and b\bar{c} bound states have been shown to validate some theoretical
approaches to QCD and highlight lack of quantitative success for others. The
intriguing details of quarkonium suppression in heavy-ion collisions that have
emerged from RHIC have elevated the importance of separating hot- and
cold-nuclear-matter effects in quark-gluon plasma studies. This review
systematically addresses all these matters and concludes by prioritizing
directions for ongoing and future efforts.Comment: 182 pages, 112 figures. Editors: N. Brambilla, S. Eidelman, B. K.
Heltsley, R. Vogt. Section Coordinators: G. T. Bodwin, E. Eichten, A. D.
Frawley, A. B. Meyer, R. E. Mitchell, V. Papadimitriou, P. Petreczky, A. A.
Petrov, P. Robbe, A. Vair
Depression prevalence using the HADS-D compared to SCID major depression classification:An individual participant data meta-analysis
Objectives: Validated diagnostic interviews are required to classify depression status and estimate prevalence of disorder, but screening tools are often used instead. We used individual participant data meta-analysis to compare prevalence based on standard Hospital Anxiety and Depression Scale – depression subscale (HADS-D) cutoffs of ≥8 and ≥11 versus Structured Clinical Interview for DSM (SCID) major depression and determined if an alternative HADS-D cutoff could more accurately estimate prevalence. Methods: We searched Medline, Medline In-Process & Other Non-Indexed Citations via Ovid, PsycINFO, and Web of Science (inception-July 11, 2016) for studies comparing HADS-D scores to SCID major depression status. Pooled prevalence and pooled differences in prevalence for HADS-D cutoffs versus SCID major depression were estimated. Results: 6005 participants (689 SCID major depression cases) from 41 primary studies were included. Pooled prevalence was 24.5% (95% Confidence Interval (CI): 20.5%, 29.0%) for HADS-D ≥8, 10.7% (95% CI: 8.3%, 13.8%) for HADS-D ≥11, and 11.6% (95% CI: 9.2%, 14.6%) for SCID major depression. HADS-D ≥11 was closest to SCID major depression prevalence, but the 95% prediction interval for the difference that could be expected for HADS-D ≥11 versus SCID in a new study was −21.1% to 19.5%. Conclusions: HADS-D ≥8 substantially overestimates depression prevalence. Of all possible cutoff thresholds, HADS-D ≥11 was closest to the SCID, but there was substantial heterogeneity in the difference between HADS-D ≥11 and SCID-based estimates. HADS-D should not be used as a substitute for a validated diagnostic interview.This study was funded by the Canadian Institutes of Health Research (CIHR, KRS-144045 & PCG 155468). Ms. Neupane was supported by a G.R. Caverhill Fellowship from the Faculty of Medicine, McGill University. Drs. Levis and Wu were supported by Fonds de recherche du Québec - Santé (FRQS) Postdoctoral Training Fellowships. Mr. Bhandari was supported by a studentship from the Research Institute of the McGill University Health Centre. Ms. Rice was supported by a Vanier Canada Graduate Scholarship. Dr. Patten was supported by a Senior Health Scholar award from Alberta Innovates, Health Solutions. The primary study by Scott et al. was supported by the Cumming School of Medicine and Alberta Health Services through the Calgary Health Trust, and funding from the Hotchkiss Brain Institute. The primary study by Amoozegar et al. was supported by the Alberta Health Services, the University of Calgary Faculty of Medicine, and the Hotchkiss Brain Institute. The primary study by Cheung et al. was supported by the Waikato Clinical School, University of Auckland, the Waikato Medical Research Foundation and the Waikato Respiratory Research Fund. The primary study by Cukor et al. was supported in part by a Promoting Psychological Research and Training on Health-Disparities Issues at Ethnic Minority Serving Institutions Grants (ProDIGs) awarded to Dr. Cukor from the American Psychological Association. The primary study by De Souza et al. was supported by Birmingham and Solihull Mental Health Foundation Trust. The primary study by Honarmand et al. was supported by a grant from the Multiple Sclerosis Society of Canada. The primary study by Fischer et al. was supported as part of the RECODEHF study by the German Federal Ministry of Education and Research (01GY1150). The primary study by Gagnon et al. was supported by the Drummond Foundation and the Department of Psychiatry, University Health Network. The primary study by Akechi et al. was supported in part by a Grant-in-Aid for Cancer Research (11−2) from the Japanese Ministry of Health, Labour and Welfare and a Grant-in-Aid for Young Scientists (B) from the Japanese Ministry of Education, Culture, Sports, Science and Technology. The primary study by Kugaya et al. was supported in part by a Grant-in-Aid for Cancer Research (9–31) and the Second-Term Comprehensive 10-year Strategy for Cancer Control from the Japanese Ministry of Health, Labour and Welfare. The primary study Ryan et al. was supported by the Irish Cancer Society (Grant CRP08GAL). The primary study by Keller et al. was supported by the Medical Faculty of the University of Heidelberg (grant no. 175/2000). The primary study by Love et al. (2004) was supported by the Kathleen Cuningham Foundation (National Breast Cancer Foundation), the Cancer Council of Victoria and the National Health and Medical Research Council. The primary study by Love et al. (2002) was supported by a grant from the Bethlehem Griffiths Research Foundation. The primary study by Löwe et al. was supported by the medical faculty of the University of Heidelberg, Germany (Project 121/2000). The primary study by Navines et al. was supported in part by the Spanish grants from the Fondo de Investigación en Salud, Instituto de Salud Carlos III (EO PI08/90869 and PSIGEN-VHC Study: FIS-E08/00268) and the support of FEDER (one way to make Europe). The primary study by O'Rourke et al. was supported by the Scottish Home and Health Department, Stroke Association, and Medical Research Council. The primary study by Sanchez-Gistau et al. was supported by a grant from the Ministry of Health of Spain (PI040418) and in part by Catalonia Government, DURSI 2009SGR1119. The primary study by Gould et al. was supported by the Transport Accident Commission Grant. The primary study by Rooney et al. was supported by the NHS Lothian Neuro-Oncology Endowment Fund. The primary study by Schwarzbold et al. was supported by PRONEX Program (NENASC Project) and PPSUS Program of Fundaçao de Amparo a esquisa e Inovacao do Estado de Santa Catarina (FAPESC) and the National Science and Technology Institute for Translational Medicine (INCT-TM). The primary study by Simard et al. was supported by IDEA grants from the Canadian Prostate Cancer Research Initiative and the Canadian Breast Cancer Research Alliance, as well as a studentship from the Canadian Institutes of Health Research. The primary study by Singer et al. (2009) was supported by a grant from the German Federal Ministry for Education and Research (no. 01ZZ0106). The primary study by Singer et al. (2008) was supported by grants from the German Federal Ministry for Education and Research (# 7DZAIQTX) and of the University of Leipzig (# formel. 1–57). The primary study by Meyer et al. was supported by the Federal Ministry of Education and Research (BMBF). The primary study by Stone et al. was supported by the Medical Research Council, UK and Chest Heart and Stroke, Scotland. The primary study by Turner et al. was supported by a bequest from Jennie Thomas through Hunter Medical Research Institute. The primary study by Walterfang et al. was supported by Melbourne Health. Drs. Benedetti and Thombs were supported by FRQS researcher salary awards. No other authors reported funding for primary studies or for their work on this study. No funder had any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication
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