134 research outputs found
The legal and ethical framework governing Body Donation in Europe-1st update on current practice
Previously, we have reported on the legal and
ethical aspects and current practice of body
donation in several European countries,
reflecting cultural and religious variations as
well as different legal and constitutional
frameworks. We have also established good
practice in body donation. Here we shall further extend the legal and ethical frameworks
in place and also focus on novelties in the law
and different directives. Of particular interest
are points that address the commercialization
of human bodies and body parts and weaknesses in the legal directives. Therefore, it is
important to define what is ethical and what
needs to be considered unethical in body
donation and the subsequent utilisation of
human bodies for teaching and research.peer-reviewe
Superhumps in Cataclysmic Binaries. XXIII. V442 Ophiuchi and RX J1643.7+3402
We report the results of long observing campaigns on two novalike variables:
V442 Ophiuchi and RX J1643.7+3402. These stars have high-excitation spectra,
complex line profiles signifying mass loss at particular orbital phases, and
similar orbital periods (respectively 0.12433 and 0.12056 d). They are
well-credentialed members of the SW Sex class of cataclysmic variables. Their
light curves are also quite complex. V442 Oph shows periodic signals with
periods of 0.12090(8) and 4.37(15) days, and RX J1643.7+3402 shows similar
signals at 0.11696(8) d and 4.05(12) d. We interpret these short and long
periods respectively as a "negative superhump" and the wobble period of the
accretion disk. The superhump could then possibly arise from the heating of the
secondary (and structures fixed in the orbital frame) by inner-disk radiation,
which reaches the secondary relatively unimpeded since the disk is not
coplanar.
At higher frequencies, both stars show another type of variability:
quasi-periodic oscillations (QPOs) with a period near 1000 seconds. Underlying
these strong signals of low stability may be weak signals of higher stability.
Similar QPOs, and negative superhumps, are quite common features in SW Sex
stars. Both can in principle be explained by ascribing strong magnetism to the
white dwarf member of the binary; and we suggest that SW Sex stars are
borderline AM Herculis binaries, usually drowned by a high accretion rate. This
would provide an ancestor channel for AM Hers, whose origin is still
mysterious.Comment: PDF, 41 pages, 4 tables, 16 figures; accepted, in press, to appear
December 2002, PASP; more info at http://cba.phys.columbia.edu
An 8-gene mRNA expression profile in circulating tumor cells predicts response to aromatase inhibitors in metastatic breast cancer patients
Background: Molecular characterization of circulating tumor cells (CTC) is promising for personalized medicine. We aimed to identify a CTC gene expression profile predicting outcome to first-line aromatase inhibitors in metastatic breast cancer (MBC) patients. Methods: CTCs were isolated from 78 MBC patients before treatment start. mRNA expression levels of 96 genes were measured by quantitative reverse transcriptase polymerase chain reaction. After applying predefined exclusion criteria based on lack of sufficient RNA quality and/or quantity, the data from 45 patients were used to construct a gene expression profile to predict poor responding patients, defined as disease progression or death <9 months, by a leave-one-out cross validation. Results: Of the 45 patients, 19 were clinically classified as poor responders. To identify them, the 75 % most variable genes were used to select genes differentially expressed between good and poor responders. An 8-gene CTC predictor was significantly associated with outcome (Hazard Ratio [HR] 4.40, 95 % Confidence Interval [CI]: 2.17-8.92, P < 0.001). This predictor identified poor responding patients with a sensitivity of 63 % and a positive predictive value of 75 %, while good responding patients were correctly predicted in 85 % of the cases. In multivariate Cox regression analysis, including CTC count at baseline, the 8-gene CTC predictor was the only factor independently associated with outcome (HR 4.59 [95 % CI: 2.11-9.56], P < 0.001). This 8-gene signature was not associated with outcome in a group of 71 MBC patients treated with systemic treatments other than AI. Conclusions: An 8-gene CTC predictor was identified which discriminates good and poor outcome to first-line aromatase inhibitors in MBC patients. Although results need to be validated, this study underscores the potential of molecular characterization of CTCs
Superhumps in Cataclysmic Binaries. XXIV. Twenty More Dwarf Novae
We report precise measures of the orbital and superhump period in twenty more
dwarf novae. For ten stars, we report new and confirmed spectroscopic periods -
signifying the orbital period P_o - as well as the superhump period P_sh. These
are GX Cas, HO Del, HS Vir, BC UMa, RZ Leo, KV Dra, KS UMa, TU Crt, QW Ser, and
RZ Sge. For the remaining ten, we report a medley of P_o and P_sh measurements
from photometry; most are new, with some confirmations of previous values.
These are KV And, LL And, WX Cet, MM Hya, AO Oct, V2051 Oph, NY Ser, KK Tel, HV
Vir, and RX J1155.4-5641.
Periods, as usual, can be measured to high accuracy, and these are of special
interest since they carry dynamical information about the binary. We still have
not quite learned how to read the music, but a few things are clear. The
fractional superhump excess epsilon [=(P_sh-P_o)/P_o] varies smoothly with P_o.
The scatter of the points about that smooth curve is quite low, and can be used
to limit the intrinsic scatter in M_1, the white dwarf mass, and the
mass-radius relation of the secondary. The dispersion in M_1 does not exceed
24%, and the secondary-star radii scatter by no more than 11% from a fixed
mass-radius relation. For the well-behaved part of epsilon(P_o) space, we
estimate from superhump theory that the secondaries are 18+-6% larger than
theoretical ZAMS stars. This affects some other testable predictions about the
secondaries: at a fixed P_o, it suggests that the secondaries are (compared
with ZAMS predictions) 40+-14% less massive, 12+-4% smaller, 19+-6% cooler, and
less luminous by a factor 2.5(7). The presence of a well-defined mass-radius
relation, reflected in a well-defined epsilon(P_o) relation, strongly limits
effects of nuclear evolution in the secondaries.Comment: PDF, 62 pages, 7 tables, 21 figures; accepted, in press, to appear
November 2003, PASP; more info at http://cba.phys.columbia.edu
Cells of the human intestinal tract mapped across space and time
Acknowledgements We acknowledge support from the Wellcome Sanger Cytometry Core Facility, Cellular Genetics Informatics team, Cellular Generation and Phenotyping (CGaP) and Core DNA Pipelines. This work was financially supported by the Wellcome Trust (W1T20694, S.A.T.; 203151/Z/16/Z, R. A. Barker.); the European Research Council (646794, ThDefine, S.A.T.); an MRC New Investigator Research Grant (MR/T001917/1, M.Z.); and a project grant from the Great Ormond Street Hospital Childrenâs Charity, Sparks (V4519, M.Z.). The human embryonic and fetal material was provided by the Joint MRC/Wellcome (MR/R006237/1) Human Developmental Biology Resource (https://www.hdbr.org/). K.R.J. holds a Non-Stipendiary Junior Research Fellowship from Christâs College, University of Cambridge. M.R.C. is supported by a Medical Research Council Human Cell Atlas Research Grant (MR/S035842/1) and a Wellcome Trust Investigator Award (220268/Z/20/Z). H.W.K. is funded by a Sir Henry Wellcome Fellowship (213555/Z/18/Z). A.F. is funded by a Wellcome PhD Studentship (102163/B/13/Z). K.T.M. is funded by an award from the Chan Zuckerberg Initiative. H.H.U. is supported by the Oxford Biomedical Research Centre (BRC) and the The Leona M. and Harry B. Helmsley Charitable Trust. We thank A. Chakravarti and S. Chatterjee for their contribution to the analysis of the enteric nervous system. We also thank R. Lindeboom and C. Talavera-Lopez for support with epithelium and Visium analysis, respectively; C. Tudor, T. Li and O. Tarkowska for image processing and infrastructure support; A. Wilbrey-Clark and T. Porter for support with Visium library preparation; A. Ross and J. Park for access to and handling of fetal tissue; A. Hunter for assistance in protocol development; D. Fitzpatrick for discussion on developmental intestinal disorders; and J. Eliasova for the graphical images. We thank the tissue donors and their families, and the Cambridge Biorepository for Translational Medicine and Human Developmental Biology Resource, for access to human tissue. This publication is part of the Human Cell Atlas: https://www.humancellatlas.org/publications.Peer reviewedPublisher PD
Cells of the human intestinal tract mapped across space and time.
Funder: Medical Research CouncilThe cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing in response to functional requirements and environmental exposures. Here, to comprehensively map cell lineages, we use single-cell RNA sequencing and antigen receptor analysis of almost half a million cells from up to 5 anatomical regions in the developing and up to 11 distinct anatomical regions in the healthy paediatric and adult human gut. This reveals the existence of transcriptionally distinct BEST4 epithelial cells throughout the human intestinal tract. Furthermore, we implicate IgG sensing as a function of intestinal tuft cells. We describe neural cell populations in the developing enteric nervous system, and predict cell-type-specific expression of genes associated with Hirschsprung's disease. Finally, using a systems approach, we identify key cell players that drive the formation of secondary lymphoid tissue in early human development. We show that these programs are adopted in inflammatory bowel disease to recruit and retain immune cells at the site of inflammation. This catalogue of intestinal cells will provide new insights into cellular programs in development, homeostasis and disease
The rise and fall of the king : the correlation between FO Aquarii's low states and the White Dwarf's Spindown
The intermediate polar FO Aquarii experienced its first-reported low-accretion states in 2016, 2017, and 2018. We establish that these low states occurred shortly after the system's white dwarf (WD) began spinning down, after having spent a quarter-century spinning up. FO Aquarii is the only intermediate polar whose period derivative has undergone a sign change, and it has now done so twice. By combining our spin-pulse timings with previous data, we determine that the WD's spin period has varied quasi-sinusoidally since the system's discovery, and an extrapolation predicts that the white dwarf was spinning down during newly discovered low states in photographic plates from 1964, 1965, and 1974. Thus, FO Aquarii's low states appear to occur exclusively during epochs of spindown. Additionally, our time-series photometry of the 2016-18 low states reveals that the mode of accretion is extremely sensitive to the accretion rate; when the system is fainter than V~14.0, the accretion onto the WD is largely stream-fed, but when it is brighter, it is almost exclusively disk-fed. The system's grazing eclipse remained detectable throughout all observations, confirming the uninterrupted presence of a disk-like structure, regardless of the accretion state. Our observations are consistent with theoretical predictions that during the low states, the accretion disk dissipates into a ring of diamagnetic blobs. Finally, a new XMM-Newton observation from 2017 indicates that the system's anomalously soft X-ray spectrum and diminished X-ray luminosity in the wake of the 2016 low state appear to be long-lasting changes compared to pre-2016 observations.peer-reviewe
The impact of viral mutations on recognition by SARS-CoV-2 specific TÂ cells.
We identify amino acid variants within dominant SARS-CoV-2 TÂ cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific TÂ cells assessed by IFN-Îł and cytotoxic killing assays. Complete loss of TÂ cell responsiveness was seen due to Q213K in the Aâ01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the Bâ27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the Aâ03:01/Aâ11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ TÂ cell lines unable to recognize variant epitopes have diverse TÂ cell receptor repertoires. These data demonstrate the potential for TÂ cell evasion and highlight the need for ongoing surveillance for variants capable of escaping TÂ cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC â IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC
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