38 research outputs found
Simulating Heliospheric and Solar Particle Diffusion using the Parker Spiral Geometry
Cosmic Ray transport in curved background magnetic fields is investigated
using numerical Monte-Carlo simulation techniques. Special emphasis is laid on
the Solar system, where the curvature of the magnetic field can be described in
terms of the Parker spiral. Using such geometries, parallel and perpendicular
diffusion coefficients have to be re-defined using the arc length of the field
lines as the parallel displacement and the distance between field lines as the
perpendicular displacement. Furthermore, the turbulent magnetic field is
incorporated using a WKB approach for the field strength. Using a test-particle
simulation, the diffusion coefficients are then calculated by averaging over a
large number of particles starting at the same radial distance from the Sun and
over a large number of turbulence realizations, thus enabling one to infer the
effects due to the curvature of the magnetic fields and associated drift
motions.Comment: accepted for publication at Journal of Geophysical Research - Space
Physic
The Cascadia Initiative : a sea change In seismological studies of subduction zones
Author Posting. © The Oceanography Society, 2014. This article is posted here by permission of The Oceanography Society for personal use, not for redistribution. The definitive version was published in Oceanography 27, no. 2 (2014): 138-150, doi:10.5670/oceanog.2014.49.Increasing public awareness that the Cascadia subduction zone in the Pacific Northwest is capable of great earthquakes (magnitude 9 and greater) motivates the Cascadia Initiative, an ambitious onshore/offshore seismic and geodetic experiment that takes advantage of an amphibious array to study questions ranging from megathrust earthquakes, to volcanic arc structure, to the formation, deformation and hydration of the Juan De Fuca and Gorda Plates. Here, we provide an overview of the Cascadia Initiative, including its primary science objectives, its experimental design and implementation, and a preview of how the resulting data are being used by a diverse and growing scientific community. The Cascadia Initiative also exemplifies how new technology and community-based experiments are opening up frontiers for marine science. The new technology—shielded ocean bottom seismometers—is allowing more routine investigation of the source zone of megathrust earthquakes, which almost exclusively lies offshore and in shallow water. The Cascadia Initiative offers opportunities and accompanying challenges to a rapidly expanding community of those who use ocean bottom seismic data.The Cascadia Initiative is supported by
the National Science Foundation; the
CIET is supported under grants OCE-
1139701, OCE-1238023, OCE‐1342503,
OCE-1407821, and OCE-1427663
to the University of Oregon
Postreproductive lifespans are rare in mammals
A species has a post‐reproductive stage if, like humans, a female entering the adult population can expect to live a substantial proportion of their life after their last reproductive event. However, it is conceptually and statistically challenging to distinguish these true post‐reproductive stages from the usual processes of senescence, which can result in females occasionally surviving past their last reproductive event. Hence, despite considerable interest, the taxonomic prevalence of post‐reproductive stages remains unclear and debated. In this study we use life tables constructed from published data on wild populations of mammals, and statistical measures of post‐reproductive lifespans, to distinguish true post‐reproductive stages from artefacts of senescence and demography in 52 species. We find post‐reproductive stages are rare in mammals and are limited to humans and a few species of toothed whales. By resolving this long‐standing debate, we hope to provide clarity for researchers in the field of evolutionary biology and a solid foundation for further studies investigating the evolution and adaptive significance of this unusual life history trait
Thyroid and pituitary gland development from hatching through metamorphosis of a teleost flatfish, the Atlantic halibut
Fish larval development, not least the spectacular
process of flatfish metamorphosis, appears to be
under complex endocrine control, many aspects of
which are still not fully elucidated. In order to obtain
data on the functional development of two major
endocrine glands, the pituitary and the thyroid, during
flatfish metamorphosis, histology, immunohistochemistry
and in situ hybridization techniques were applied on
larvae of the Atlantic halibut (Hippoglossus hippoglossus),
a large, marine flatfish species, from hatching
through metamorphosis. The material was obtained
from a commercial hatchery. Larval age is defined as
day-degrees (D =accumulated daily temperature from
hatching). Sporadic thyroid follicles are first detected in
larvae at 142 D (27 days post-hatch), prior to the
completion of yolk sack absorption. Both the number
and activity of the follicles increase markedly after yolk
sack absorption and continue to do so during subsequent
development. The larval triiodothyronine (T3)
and thyroxine (T4) content increases, subsequent to yolk
absorption, and coincides with the proliferation of thyroid
follicles. A second increase of both T3 and T4 occurs
around the start of metamorphosis and the T3 content
further increases at the metamorphic climax. Overall,
the T3 content is lower than T4. The pituitary gland can
first be distinguished as a separate organ at the yolk sack
stage. During subsequent development, the gland becomes
more elongated and differentiates into neurohypophysis (NH), pars distalis (PD) and pars intermedia
(PI). The first sporadic endocrine pituitary cells are observed
at the yolk sack stage, somatotrophs (growth
hormone producing cells) and somatolactotrophs (somatolactin
producing cells) are first observed at 121 D
(23 days post-hatch), and lactotrophs (prolactin producing
cells) at 134 D (25 days post-hatch). Scarce
thyrotrophs are evident after detection of the first thyroid
follicles (142 D ), but coincident with a phase in
which follicle number and activity increase (260 D ).
The somatotrophs are clustered in the medium ventral
region of the PD, lactotrophs in the anterior part of the
PD and somatolactotrophs are scattered in the mid and
posterior region of the pituitary. At around 600 D ,
coinciding with the start of metamorphosis, somatolactotrophs
are restricted to the interdigitating tissue of the
NH. During larval development, the pituitary endocrine
cells become more numerous. The present data on thyroid
development support the notion that thyroid hormones
may play a significant role in Atlantic halibut
metamorphosis. The time of appearance and the subsequent
proliferation of pituitary somatotrophs, lactotrophs,
somatolactotrophs and thyrotrophs indicate at
which stages of larval development and metamorphosis
these endocrine cells may start to play active regulatory
roles.This work has been carried out within the
projects ‘‘Endocrine Control as a Determinant of Larval Quality in
Fish Aquaculture’’ (CT-96-1422) and ‘‘Arrested development: The
Molecular and Endocrine Basis of Flatfish Metamorphosis’’
(Q5RS-2002-01192), with financial support from the Commission
of the European Communities. However, it does not necessarily
reflect the Commission’s views and in no way anticipates its future
policy in this area. This project was further supported by the
Swedish Council for Agricultural and Forestry Research and Pluriannual
funding to CCMAR by the Portuguese Science and
Technology Council
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The Cascadia Initiative: A Sea Change In Seismological Studies of Subduction Zones
Increasing public awareness that the Cascadia subduction zone in the Pacific Northwest is capable of great earthquakes (magnitude 9 and greater) motivates the Cascadia Initiative, an ambitious onshore/offshore seismic and geodetic experiment that takes advantage of an amphibious array to study questions ranging from megathrust earthquakes, to volcanic arc structure, to the formation, deformation and hydration of the Juan De Fuca and Gorda Plates. Here, we provide an overview of the Cascadia Initiative, including its primary science objectives, its experimental design and implementation, and a preview of how the resulting data are being used by a diverse and growing scientific community. The Cascadia Initiative also exemplifies how new technology and community-based experiments are opening up frontiers for marine science. The new technology—shielded ocean bottom seismometers—is allowing more routine investigation of the source zone of megathrust earthquakes, which almost exclusively lies offshore and in shallow water. The Cascadia Initiative offers opportunities and accompanying challenges to a rapidly expanding community of those who use ocean bottom seismic data.This is the publisher’s final pdf. The published article is copyrighted by the Oceanography Society and can be found at: http://www.tos.org/oceanography/index.html
A factor analytic study of the model of human occupation screening tool of hypothesized variables
The Model of Human Occupation (Kielhofner, 2008) postulates that occupational participation is influenced by volition, habituation, three skill areas, and the environment. The Model of Human Occupation Screening Tool (MOHOST) (Parkinson, Forsyth, & Kielhofner, 2004) was developed to provide a broad assessment of the factors that influence a client's occupational participation. The purpose of this study was to ask whether there was evidence that the items of the MOHOST meaningfully cluster into these theoretical sub-constructs. Nine occupational therapists used the MOHOST with 166 clients in the US and the UK, and a series of confirmatory factor analyses (CFA) were conducted. The six-dimensional model fit better than the one-dimensional model, and the standardized coefficients also indicated that the items were well designed and captured each factor. The results of this study confirmed the hypothesis that the MOHOST contains six factors and provides further evidence of the validity of the MOHOST
Ovulatory cycle effects on tip earnings by lap-dancers: Economic evidence for human estrus?
Multiple Pathways Promote Dynamical Coupling between Catalytic Domains in <i>Escherichia coli</i> Prolyl-tRNA Synthetase
Aminoacyl-tRNA synthetases are multidomain
enzymes that catalyze
covalent attachment of amino acids to their cognate tRNA. Cross-talk
between functional domains is a prerequisite for this process. In
this study, we investigate the molecular mechanism of site-to-site
communication in <i>Escherichia coli</i> prolyl-tRNA synthetase
(Ec ProRS). Earlier studies have demonstrated that evolutionarily
conserved and/or co-evolved residues that are engaged in correlated
motion are critical for the propagation of functional conformational
changes from one site to another in modular proteins. Here, molecular
simulation and bioinformatics-based analysis were performed to identify
dynamically coupled and evolutionarily constrained residues that form
contiguous pathways of residue–residue interactions between
the aminoacylation and editing domains of Ec ProRS. The results of
this study suggest that multiple pathways exist between these two
domains to maintain the dynamic coupling essential for enzyme function.
Moreover, residues in these interaction networks are generally highly
conserved. Site-directed changes of on-pathway residues have a significant
impact on enzyme function and dynamics, suggesting that any perturbation
along these pathways disrupts the native residue–residue interactions
that are required for effective communication between the two functional
domains. Free energy analysis revealed that communication between
residues within a pathway and cross-talk between pathways are important
for coordinating functions of different domains of Ec ProRS for efficient
catalysis
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Olutasidenib (FT-2102), an IDH1m Inhibitor As a Single Agent or in Combination with Azacitidine, Induces Deep Clinical Responses with Mutation Clearance in Patients with Acute Myeloid Leukemia Treated in a Phase 1 Dose Escalation and Expansion Study
Background: Isocitrate dehydrogenase 1 mutations (IDH1m) occur in 7-14% of AML patients (pts) and approximately 3-4% of MDS pts. Olutasidenib is a highly potent, selective small molecule inhibitor of IDH1m with the therapeutic potential to restore normal cellular differentiation. Azacitidine (AZA) has shown synergistic effects with IDHm inhibitors on releasing differentiation block in IDHm leukemia models in vitro. Methods: The Phase 1 study (NCT02719574) assessed the safety, PK/PD, and clinical activity of olutasidenib in patients with IDH1m AML or MDS. Eligibility criteria included: IDH1m AML or MDS [relapsed/refractory (R/R) or treatment naïve (TN) pts not eligible for or refusing standard therapy], adequate liver and renal function. There were no restrictions for concomitant non-anticancer medications. IDH1m variant allele frequency (VAF) and co-mutations were measured at baseline and during treatment. Available safety data are presented for all pts (AML/MDS); efficacy data are presented for AML pts only. Results: As of April 12, 2019, 32 pts had been treated with single agent (SA) olutasidenib and 46 pts with olutasidenib in combination (COMBO) with AZA; median time on treatment was 4.2 mo for SA (range: 10% of pts, including thrombocytopenia (28% vs 33%), febrile neutropenia (22% vs 28%), anemia (22% vs 20%), pneumonia (16% vs 11%), and leukocytosis (13% vs 15%); COMBO-treated pts had more Gr 3/4 neutropenia (6% vs 28%), fatigue (6% vs 15%), and nausea (0% vs 9%). No QTcF prolongation was reported in SA while 3 (7%) pts treated with COMBO reported prolonged QTcF (1 Gr 3). Ten (13%) pts had differentiation syndrome (4 SA; 6 COMBO), which resolved with temporary interruption of olutasidenib and treatment with dexamethasone, hydroxyurea, and/or supportive care. None led to treatment discontinuation. Nineteen (24%) pts died on treatment or within 28 days of the last dose, no deaths were considered treatment-related. For AML pts, clinical responses occurred in 39% SA and 54% COMBO (CR 15% and 23%, respectively; Table 1). CRs were durable (up to >27 mo); disease control (SD >13 mo) was observed in pts without an IWG-defined response. Of the 59 AML pts (23 SA; 36 COMBO) who were transfusion-dependent at baseline, 26 (11 [48%] SA; 15 [42%] COMBO) and 21 (9 [39%] SA; 12 [33%] COMBO) became transfusion-independent (seen in all response categories) during 28 and 56 days on treatment, respectively. For R/R AML pts, median survival was 8.7 mo for SA and 12.1 mo for COMBO; for TN AML pts, median survival was 8.8 mo for SA (n=4) and not reached for COMBO. For R/R and TN AML patients with available pre- and on-treatment samples, IDH1m clearance or significant reduction (VAF <1%) was observed in 10/25 pts (40%) achieving an objective response and in 3/6 pts (50%) with stable disease. Mutation and 2-HG analyses suggest that pts who progressed on olutasidenib had a non-IDH1m-driven mechanism; updated analyses will be presented. Conclusions: SA and COMBO olutasidenib has shown favorable safety and clinical activity in IDH1m R/R AML with a SA ORR of 41% (95% CI: 21, 64) and a COMBO ORR of 46% (27, 67), and durable disease control. Olutasidenib induces deep responses with IDH1 mutation clearance in a subset of treated pts. Phase 2 investigations of SA and COMBO olutasidenib at the RP2D are ongoing in multiple IDH1m AML populations. Additional combinations are also being explored. Disclosures Watts: Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding. Baer:Forma: Research Funding; Kite: Research Funding; Astellas: Research Funding; Incyte: Research Funding; Takeda: Research Funding; Abbvie: Research Funding; Al Therapeutics: Research Funding. Yang:Agios: Consultancy; AstraZeneca: Research Funding. Prebet:pfizer: Honoraria; novartis: Honoraria; pfizer: Honoraria; Boehringer Ingelheim: Research Funding; novartis: Honoraria. Lee:Helsinn: Consultancy; Jazz Pharmaceuticals, Inc: Consultancy; Roche Molecular Systems: Consultancy; AstraZeneca Pharmaceuticals: Consultancy; Karyopharm Therapeutics: Consultancy; Ai Therapeutics: Research Funding. Schiller:Biomed Valley Discoveries: Research Funding; Bristol Myer Squibb: Research Funding; Astellas: Research Funding; Agios: Research Funding, Speakers Bureau; Celgene: Research Funding, Speakers Bureau; Constellation Pharmaceutical: Research Funding; Daiichi Sankyo: Research Funding; Eli Lilly and Company: Research Funding; FujiFilm: Research Funding; Genzyme: Research Funding; Gilead: Research Funding; Incyte: Research Funding; J&J: Research Funding; Jazz Pharmaceuticals: Honoraria, Research Funding; Karyopharm: Research Funding; Novartis: Research Funding; Onconova: Research Funding; Pfizer Pharmaceuticals: Equity Ownership, Research Funding; Sangamo Therapeutics: Research Funding; Amgen: Other, Research Funding. Dinner:Agios: Consultancy; Pfizer: Consultancy; AstraZeneca: Consultancy. Pigneux:Roche: Honoraria; F. Hoffmann-La Roche Ltd: Honoraria; Pfizer: Honoraria; Abbvie: Honoraria; Jazz: Honoraria; Amgen: Honoraria; Daichi: Honoraria; Astellas: Honoraria; Novartis: Honoraria. Montesinos:Abbvie: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Research support, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Research support, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Research support, Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Other: Research support; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Research support, Research Funding, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Other: Research support, Research Funding, Speakers Bureau; Teva: Membership on an entity's Board of Directors or advisory committees, Other: Research support, Research Funding, Speakers Bureau. Wang:Stemline: Other: Advisory role, Speakers Bureau; Daiichi: Other: Advisory role; Amgen: Other: Advisory role; Abbvie: Other: Advisory role; Kite: Other: Advisory role; Jazz: Other: Advisory role; Astellas: Other: Advisory role, Speakers Bureau; celyad: Other: Advisory role; Pfizer: Other: Advisory role, Speakers Bureau; Agios: Other: Advisory role. Seiter:Novartis, Incyte, Celgene, Astellas, Sanofi: Speakers Bureau; Novartis, Astellas,: Consultancy; Novartis, Forma, Sun Pharma, Celgene, Jazz, Roche: Research Funding. Wei:Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Macrogenics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra Zeneca: Honoraria, Research Funding; Janssen: Honoraria; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: AHW is a former employee of the Walter and Eliza Hall Institute and receives a fraction of its royalty stream related to venetoclax, Research Funding, Speakers Bureau; Astellas: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. De Botton:Agios: Consultancy, Research Funding; Celgene: Consultancy, Speakers Bureau; Pierre Fabre: Consultancy; Servier: Consultancy; Pfizer: Consultancy; Novartis: Consultancy; Janssen: Consultancy; FORMA: Consultancy, Research Funding; Syros: Consultancy; Bayer: Consultancy; Abbvie: Consultancy; Daiichi: Consultancy; Astellas: Consultancy. Jonas:AbbVie, Accelerated Medical Diagnostics, AROG, Celgene, Daiichi Sankyo, Esanex, Forma, Genentech/Roche, GlycoMimetics, Incyte, LP Therapeutics, Pharmacyclics: Research Funding; AbbVie, Amgen, GlycoMimetics: Other: Travel expenses; AbbVie, Amgen, Celgene, GlycoMimetics, Jazz, Pharmacyclics, Tolero: Consultancy, Membership on an entity's Board of Directors or advisory committees. Ferrell:Astex Pharmaceuticals: Re