607 research outputs found
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Reflectance spectra of Mesosiderites: Implications for asteroid 4 Vesta
Oxygen isotopic data argues that HEDs and mesosiderites may be from the same parent body. A spectral survey of mesosiderites was done to determine their spectral properties in the visible and near-infrared and compare to HEDs
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The origin and significance of the CCAM line: Evidence from chondrules and dark inclusions in Allende (CV3)
The process responsible for the mass independent oxygen isotope variation observed in Solar System materials remains poorly understood. While self-shielding of CO, either in the early solar nebula, or precursor molecular cloud, appears to be a viable mechanism, alternative models have also been proposed
Characterization and application of two RANK-specific antibodies with different biological activities.
Antibodies play an important role in therapy and investigative biomedical research. The TNF-family member Receptor Activator of NF-κB (RANK) is known for its role in bone homeostasis and is increasingly recognized as a central player in immune regulation and epithelial cell activation. However, the study of RANK biology has been hampered by missing or insufficient characterization of high affinity tools that recognize RANK. Here, we present a careful description and comparison of two antibodies, RANK-02 obtained by phage display (Newa, 2014 [1]) and R12-31 generated by immunization (Kamijo, 2006 [2]). We found that both antibodies recognized mouse RANK with high affinity, while RANK-02 and R12-31 recognized human RANK with high and lower affinities, respectively. Using a cell apoptosis assay based on stimulation of a RANK:Fas fusion protein, and a cellular NF-κB signaling assay, we showed that R12-31 was agonist for both species. R12-31 interfered little or not at all with the binding of RANKL to RANK, in contrast to RANK-02 that efficiently prevented this interaction. Depending on the assay and species, RANK-02 was either a weak agonist or a partial antagonist of RANK. Both antibodies recognized human Langerhans cells, previously shown to express RANK, while dermal dendritic cells were poorly labeled. In vivo R12-31 agonist activity was demonstrated by its ability to induce the formation of intestinal villous microfold cells in mice. This characterization of two monoclonal antibodies should now allow better evaluation of their application as therapeutic reagents and investigative tools
Monkey-based Research on Human Disease: The Implications of Genetic Differences
Assertions that the use of monkeys to investigate human diseases is valid scientifically are frequently based on a reported 90–93% genetic similarity between the species. Critical analyses of the relevance of monkey studies to human biology, however, indicate that this genetic similarity does not result in sufficient physiological similarity for monkeys to constitute good models for research, and that monkey data do not translate well to progress in clinical practice for humans. Salient examples include the failure of new drugs in clinical trials, the highly different infectivity and pathology of SIV/HIV, and poor extrapolation of research on Alzheimer’s disease, Parkinson’s disease and stroke. The major molecular differences underlying these inter-species phenotypic disparities have been revealed by comparative genomics and molecular biology — there are key differences in all aspects of gene expression and protein function, from chromosome and chromatin structure to post-translational modification. The collective effects of these differences are striking, extensive and widespread, and they show that the superficial similarity between human and monkey genetic sequences is of little benefit for biomedical research. The extrapolation of biomedical data from monkeys to humans is therefore highly unreliable, and the use of monkeys must be considered of questionable value, particularly given the breadth and potential of alternative methods of enquiry that are currently available to scientists
Subclinical giant cell arteritis in new onset polymyalgia rheumatica:A systematic review and meta-analysis of individual patient data
Objectives: To determine the prevalence and predictors of subclinical giant cell arteritis (GCA) in patients with newly diagnosed polymyalgia rheumatica (PMR). Methods: PubMed, Embase, and Web of Science Core Collection were systematically searched (date of last search July 14, 2021) for any published information on any consecutively recruited cohort reporting the prevalence of GCA in steroid-naïve patients with PMR without cranial or ischemic symptoms. We combined prevalences across populations in a random-effect meta-analysis. Potential predictors of subclinical GCA were identified by mixed-effect logistic regression using individual patient data (IPD) from cohorts screened with PET/(CT). Results: We included 13 cohorts with 566 patients from studies published between 1965 to 2020. Subclinical GCA was diagnosed by temporal artery biopsy in three studies, ultrasound in three studies, and PET/(CT) in seven studies. The pooled prevalence of subclinical GCA across all studies was 23% (95% CI 14%-36%, I2=84%) for any screening method and 29% in the studies using PET/(CT) (95% CI 13%-53%, I2=85%) (n=266 patients). For seven cohorts we obtained IPD for 243 patients screened with PET/(CT). Inflammatory back pain (OR 2.73, 1.32-5.64), absence of lower limb pain (OR 2.35, 1.05-5.26), female sex (OR 2.31, 1.17-4.58), temperature >37° (OR 1.83, 0.90-3.71), weight loss (OR 1.83, 0.96-3.51), thrombocyte count (OR 1.51, 1.05-2.18), and haemoglobin level (OR 0.80, 0.64-1.00) were most strongly associated with subclinical GCA in the univariable analysis but not C-reactive protein (OR 1.00, 1.00-1.01) or erythrocyte sedimentation rate (OR 1.01, 1.00-1.02). A prediction model calculated from these variables had an area under the curve of 0.66 (95% CI 0.55-0.75). Conclusion: More than a quarter of patients with PMR may have subclinical GCA. The prediction model from the most extensive IPD set has only modest diagnostic accuracy. Hence, a paradigm shift in the assessment of PMR patients in favour of implementing imaging studies should be discussed
Ecological distribution and population structure of Acantholobulus schmitti (Rathbun, 1930) (Crustacea, Decapoda, Xanthoidea) on the southeastern Brazilian coast
This investigation analyzed the ecological distribution and population structure of A. schmitti on the southeastern coast of Brazil. Crabs were sampled monthly from January 1998 to December 1999 at the following bays: Ubatumirim (UBM), Ubatuba (UBA) and Mar Virado (MV). Water and sediment samples were also collected from all sampling sites for an analysis of environmental factors. Acantholobus schmitti was most abundant at UBM (224), followed by UBA (154) and MV (23) but its abundance showed no association with the environmental factors analyzed. The low abundance of these crabs in MV may be due to the high wave action that moved biodetritic material accumulated on the bottom and frequently removed small crabs from their sheltered positions among the shell fragments. The individuals captured included 269 males and 132 females, of which only 4 specimens were brooding females. Juvenile recruitment occurred throughout the year, but was less intense in the spring. The major abundance of individuals as well as of ovigerous females occurred during 1999, when the entrance of the South Atlantic Central Waters (SACW) was stronger than in previous year. This environmental influence could be the main factor modulating this population
Crises and collective socio-economic phenomena: simple models and challenges
Financial and economic history is strewn with bubbles and crashes, booms and
busts, crises and upheavals of all sorts. Understanding the origin of these
events is arguably one of the most important problems in economic theory. In
this paper, we review recent efforts to include heterogeneities and
interactions in models of decision. We argue that the Random Field Ising model
(RFIM) indeed provides a unifying framework to account for many collective
socio-economic phenomena that lead to sudden ruptures and crises. We discuss
different models that can capture potentially destabilising self-referential
feedback loops, induced either by herding, i.e. reference to peers, or
trending, i.e. reference to the past, and account for some of the phenomenology
missing in the standard models. We discuss some empirically testable
predictions of these models, for example robust signatures of RFIM-like herding
effects, or the logarithmic decay of spatial correlations of voting patterns.
One of the most striking result, inspired by statistical physics methods, is
that Adam Smith's invisible hand can badly fail at solving simple coordination
problems. We also insist on the issue of time-scales, that can be extremely
long in some cases, and prevent socially optimal equilibria to be reached. As a
theoretical challenge, the study of so-called "detailed-balance" violating
decision rules is needed to decide whether conclusions based on current models
(that all assume detailed-balance) are indeed robust and generic.Comment: Review paper accepted for a special issue of J Stat Phys; several
minor improvements along reviewers' comment
Measurement of the B0-anti-B0-Oscillation Frequency with Inclusive Dilepton Events
The - oscillation frequency has been measured with a sample of
23 million \B\bar B pairs collected with the BABAR detector at the PEP-II
asymmetric B Factory at SLAC. In this sample, we select events in which both B
mesons decay semileptonically and use the charge of the leptons to identify the
flavor of each B meson. A simultaneous fit to the decay time difference
distributions for opposite- and same-sign dilepton events gives ps.Comment: 7 pages, 1 figure, submitted to Physical Review Letter
Observation of a new chi_b state in radiative transitions to Upsilon(1S) and Upsilon(2S) at ATLAS
The chi_b(nP) quarkonium states are produced in proton-proton collisions at
the Large Hadron Collider (LHC) at sqrt(s) = 7 TeV and recorded by the ATLAS
detector. Using a data sample corresponding to an integrated luminosity of 4.4
fb^-1, these states are reconstructed through their radiative decays to
Upsilon(1S,2S) with Upsilon->mu+mu-. In addition to the mass peaks
corresponding to the decay modes chi_b(1P,2P)->Upsilon(1S)gamma, a new
structure centered at a mass of 10.530+/-0.005 (stat.)+/-0.009 (syst.) GeV is
also observed, in both the Upsilon(1S)gamma and Upsilon(2S)gamma decay modes.
This is interpreted as the chi_b(3P) system.Comment: 5 pages plus author list (18 pages total), 2 figures, 1 table,
corrected author list, matches final version in Physical Review Letter
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