374 research outputs found
Systematic variation of the stellar Initial Mass Function with velocity dispersion in early-type galaxies
An essential component of galaxy formation theory is the stellar initial mass
function (IMF), that describes the parent distribution of stellar mass in star
forming regions. We present observational evidence in a sample of early-type
galaxies (ETGs) of a tight correlation between central velocity dispersion and
the strength of several absorption features sensitive to the presence of
low-mass stars. Our sample comprises ~40,000 ETGs from the SPIDER survey
(z<0.1). The data, extracted from the Sloan Digital Sky Survey, are combined,
rejecting both noisy data, and spectra with contamination from telluric lines,
resulting in a set of 18 stacked spectra at high signal-to-noise ratio (S/N>
400 per A). A combined analysis of IMF-sensitive line strengths and spectral
fitting is performed with the latest state-of the art population synthesis
models (an extended version of the MILES models). A significant trend is found
between IMF slope and velocity dispersion, towards an excess of low-mass stars
in the most massive galaxies. Although we emphasize that accurate values of the
IMF slope will require a detailed analysis of chemical composition (such as
[a/Fe] or even individual element abundance ratios), the observed trends
suggest that low-mass ETGs are better fit by a Kroupa-like IMF, whereas massive
galaxies require bottom-heavy IMFs, exceeding the Salpeter slope at velocity
dispersions above 200km/s.Comment: 5 pages, 4 figures, accepted for publication in MNRAS Letter
Inhibition of the Integrin/FAK Signaling Axis and c-Myc Synergistically Disrupts Ovarian Cancer Malignancy
Integrins, a family of heterodimeric receptors for extracellular matrix, are promising therapeutic targets for ovarian cancer, particularly high-grade serous-type (HGSOC), as they drive tumor cell attachment, migration, proliferation and survival by activating focal adhesion kinase (FAK)-dependent signaling. Owing to the potential off-target effects of FAK inhibitors, disruption of the integrin signaling axis remains to be a challenge. Here, we tackled this barrier by screening for inhibitors being functionally cooperative with small-molecule VS-6063, a phase II FAK inhibitor. From this screening, JQ1, a potent inhibitor of Myc oncogenic network, emerged as the most robust collaborator. Treatment with a combination of VS-6063 and JQ1 synergistically caused an arrest of tumor cells at the G2/M phase and a decrease in the XIAP-linked cell survival. Our subsequent mechanistic analyses indicate that this functional cooperation was strongly associated with the concomitant disruption of activation or expression of FAK and c-Myc as well as their downstream signaling through the PI3K/Akt pathway. In line with these observations, we detected a strong co-amplification or upregulation at genomic or protein level for FAK and c-Myc in a large portion of primary tumors in the TCGA or a local HGSOC patient cohort. Taken together, our results suggest that the integrin–FAK signaling axis and c-Myc synergistically drive cell proliferation, survival and oncogenic potential in HGSOC. As such, our study provides key genetic, functional and signaling bases for the small-molecule-based co-targeting of these two distinct oncogenic drivers as a new line of targeted therapy against human ovarian cancer
The Structure of Episodic Memory: Ganeri's ‘Mental Time Travel and Attention’
We offer a framework for assessing what the structure of episodic memory might be, if one accepts the Buddhist denial of persisting selves. This paper is a response to Jonardon Ganeri's paper "Mental time travel and attention", which explores Buddhaghosa's ideas about memory. (It will eventually be published with a reply by Ganeri)
Pristup procjeni zdravstvenoga rizika za ljude prilikom izgradnje gradskoga parka
A Human Health Risk Assessment (HHRA) was undertaken for a proposed park development “River Landing”, to be constructed along the north bank of the South Saskatchewan River in the City of Saskatoon, Saskatchewan, Canada. The purpose of the HHRA was to determine whether chemical constituents identified at the site, including polycyclic aromatic hydrocarbons (PAHs), petroleum hydrocarbons (PHCs), and toxic and heavy metals, would adversely affect the health of construction workers and potential park users. Although more traditional remediation options were considered, the risk assessment approach was chosen since it represented the best available technology. The HHRA was undertaken using protocols and methodologies proposed and readily accepted by the Canadian Council of Ministers of the Environment (CCME), Health Canada, and the United States Environmental Protection Agency (US EPA). Results of the risk assessment revealed that the magnitude and distribution of the chemicals at the site were such that extensive remediation was not required, and that the site could be developed without any significant restrictions on the proposed use. The assessment revealed that potential exposure to soil constituents would not result in adverse health risk to construction workers involved in park development or future park users.Napravljena je procjena zdravstvenoga rizika za ljude (izv. human health risk assessment, HHRA) za projekt gradskoga parka “River Landing” koji bi se trebao izgraditi duž sjeverne obale rijeke South Saskatchewan u Saskatoonu, saveznoj državi Saskatchewan u Kanadi. Svrha je procjene bila utvrditi mogu li kemijski spojevi zatečeni na gradilištu, uključujući policikličke aromatske ugljikovodike, naftne ugljikovodike te toksične i teške metale, štetno utjecati na zdravlje građevinskih radnika i korisnika parka. Premda je razmotrena i uporaba tradicionalnijih metoda sanacije, izabran je ovaj pristup procjeni rizika zbog toga što rabi najbolju dostupnu tehnologiju. Procjena rizika provedena je prema protokolima i metodama koje je odmah usvojio Kanadski savjet ministara za zaštitu okoliša (izv. Canadian Council of Ministers of the Environment, CCME), savezni ured za zdravlje Health Canada te Agencija za zaštitu okoliša Sjedinjenih Država (izv. United States Environmental Protection Agency, US EPA). Procjena rizika pokazala je da količina i rasprostranjenost kemikalija na gradilištu nisu takvi da zahtijevaju opsežniju sanaciju, te da se lokacija može izgraditi bez značajnih ograničenja u namjeni. Procjenom je također utvrđeno da eventualno izlaganje sastavnicama tla neće dovesti do štetnih posljedica za zdravlje građevinskih radnika koji rade na parku, a niti za buduće korisnike parka
Atomic Resonance and Scattering
Contains reports on eight research projects.National Science Foundation (Grant PHY79-09743)National Bureau of Standards (Grant NB-8-NAHA-3017)Joint Services Electronics Program (Contract DAAG29-80-C-0104)National Science Foundation (Grant PHY82-10486)U.S. Navy - Office of Naval Research (Contract N00014-79-C-0183)National Science Foundation (Grant CHE79-02967-A04)U.S. Air Force - Office of Scientific Research (Contract AFOSR-81-0067)Joint Services Electronics Program (Contract DAAG29-83-K-0003
Obesity and Diabetes Cause Cognitive Dysfunction in the Absence of Accelerated β-Amyloid Deposition in a Novel Murine Model of Mixed or Vascular Dementia
Mid-life obesity and type 2 diabetes mellitus (T2DM) confer a modest, increased risk for Alzheimer\u27s disease (AD), though the underlying mechanisms are unknown. We have created a novel mouse model that recapitulates features of T2DM and AD by crossing morbidly obese and diabetic db/db mice with APPΔNL/ΔNLx PS1P264L/P264L knock-in mice. These mice (db/AD) retain many features of the parental lines (e.g. extreme obesity, diabetes, and parenchymal deposition of β-amyloid (Aβ)). The combination of the two diseases led to additional pathologies-perhaps most striking of which was the presence of severe cerebrovascular pathology, including aneurysms and small strokes. Cortical Aβ deposition was not significantly increased in the diabetic mice, though overall expression of presenilin was elevated. Surprisingly, Aβ was not deposited in the vasculature or removed to the plasma, and there was no stimulation of activity or expression of major Aβ-clearing enzymes (neprilysin, insulin degrading enzyme, or endothelin-converting enzyme). The db/AD mice displayed marked cognitive impairment in the Morris Water Maze, compared to either db/db or APPΔNLx PS1P264L mice. We conclude that the diabetes and/or obesity in these mice leads to a destabilization of the vasculature, leading to strokes and that this, in turn, leads to a profound cognitive impairment and that this is unlikely to be directly dependent on Aβ deposition. This model of mixed or vascular dementia provides an exciting new avenue of research into the mechanisms underlying the obesity-related risk for age-related dementia, and will provide a useful tool for the future development of therapeutics
The SAMI Galaxy Survey: Bayesian Inference for Gas Disk Kinematics using a Hierarchical Gaussian Mixture Model
We present a novel Bayesian method, referred to as Blobby3D, to infer gas
kinematics that mitigates the effects of beam smearing for observations using
Integral Field Spectroscopy (IFS). The method is robust for regularly rotating
galaxies despite substructure in the gas distribution. Modelling the gas
substructure within the disk is achieved by using a hierarchical Gaussian
mixture model. To account for beam smearing effects, we construct a modelled
cube that is then convolved per wavelength slice by the seeing, before
calculating the likelihood function. We show that our method can model complex
gas substructure including clumps and spiral arms. We also show that kinematic
asymmetries can be observed after beam smearing for regularly rotating galaxies
with asymmetries only introduced in the spatial distribution of the gas. We
present findings for our method applied to a sample of 20 star-forming galaxies
from the SAMI Galaxy Survey. We estimate the global H gas velocity
dispersion for our sample to be in the range [7, 30] km
s. The relative difference between our approach and estimates using the
single Gaussian component fits per spaxel is for the H flux-weighted mean velocity
dispersion.Comment: 23 pages, 12 figures, accepted for MNRA
Atomic Resonance and Scattering
Contains reports on nine research projects.National Science Foundation (Grant PHY79-09743)National Science Foundation (Grant PHY82-10486)Joint Services Electronics Program (Contract DAAG29-83-K-0003)U.S. Navy - Office of Naval Research (Contract N00014-79-C-0183)National Bureau of Standards (Grant NB83-NAHA-4058)National Science Foundation (Grant CHE79-02967-A04)National Science Foundation (Grant PHY83-07172)Joint Services Electronics Program (Grant DAAG29-83-K-0003
Atomic Resonance and Scattering
Contains reports on eight research projects.National Science Foundation (Grant PHY83-06273)National Bureau of Standards (Grant NB83-NAHA-4058)National Science Foundation (Grant PHY84-11483)Joint Services Electronics Program (Contract DAAG29-83-K-0003)U.S. Navy - Office of Naval Research (Contract NO0014-79-C-0183)U.S. Navy - Office of Naval Research (Contract N00014-83-K-0695)National Science Foundation (Grant PHY83-07172-A01
An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics
For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types
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