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Träfflista för sökning "WFRF:(Howell Craig A.) "

Search: WFRF:(Howell Craig A.)

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1.
  • Shu, Xiang, et al. (author)
  • Associations of obesity and circulating insulin and glucose with breast cancer risk : a Mendelian randomization analysis
  • 2019
  • In: International Journal of Epidemiology. - : OXFORD UNIV PRESS. - 0300-5771 .- 1464-3685. ; 48:3, s. 795-806
  • Journal article (peer-reviewed)abstract
    • Background: In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear. Methods: We conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium. Results: All sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p = 5.09 x 10(-4)], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p = 4.02 x 10(-4)), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p = 5.05 x 10(-19)) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p = 9.22 x 10(-6)). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer. Conclusions: We confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer.
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2.
  • Hosseinzadeh, Griffin, et al. (author)
  • The Early Light Curve of SN 2023bee : Constraining Type Ia Supernova Progenitors the Apian Way
  • 2023
  • In: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 953:1
  • Journal article (peer-reviewed)abstract
    • We present very early photometric and spectroscopic observations of the Type Ia supernova (SN Ia) 2023bee, starting about 8 hr after the explosion, which reveal a strong excess in the optical and nearest UV (U and UVW1) bands during the first several days of explosion. This data set allows us to probe the nature of the binary companion of the exploding white dwarf and the conditions leading to its ignition. We find a good match to the Kasen model in which a main-sequence companion star stings the ejecta with a shock as they buzz past. Models of double detonations, shells of radioactive nickel near the surface, interaction with circumstellar material, and pulsational delayed detonations do not provide good matches to our light curves. We also observe signatures of unburned material, in the form of carbon absorption, in our earliest spectra. Our radio nondetections place a limit on the mass-loss rate from the putative companion that rules out a red giant but allows a main-sequence star. We discuss our results in the context of other similar SNe Ia in the literature.
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3.
  • Irani, I., et al. (author)
  • Less Than 1% of Core-collapse Supernovae in the Local Universe Occur in Elliptical Galaxies
  • 2022
  • In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 927:1
  • Journal article (peer-reviewed)abstract
    • We present observations of three core-collapse supernovae (CCSNe) in elliptical hosts, detected by the Zwicky Transient Facility Bright Transient Survey (BTS). SN 2019ape is a SN Ic that exploded in the main body of a typical elliptical galaxy. Its properties are consistent with an explosion of a regular SN Ic progenitor. A secondary g-band light-curve peak could indicate interaction of the ejecta with circumstellar material (CSM). An Ha-emitting source at the explosion site suggests a residual local star formation origin. SN 2018fsh and SN 2020uik are SNe II which exploded in the outskirts of elliptical galaxies. SN 2020uik shows typical spectra for SNe II, while SN 2018fsh shows a boxy nebular Ha profile, a signature of CSM interaction. We combine these 3 SNe with 7 events from the literature and analyze their hosts as a sample. We present multi-wavelength photometry of the hosts, and compare this to archival photometry of all BTS hosts. Using the spectroscopically complete BTS, we conclude that 0.3%(+0.3)(-0.1) of all CCSNe occur in elliptical galaxies. We derive star formation rates and stellar masses for the host galaxies and compare them to the properties of other SN hosts. We show that CCSNe in ellipticals have larger physical separations from their hosts compared to SNe Ia in elliptical galaxies, and discuss implications for star-forming activity in elliptical galaxies.
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4.
  • Dassie, Justin P., et al. (author)
  • Targeted inhibition of prostate cancer metastases with an RNA aptamer to prostate-specific membrane antigen
  • 2014
  • In: Molecular Therapy. - : Nature Publishing Group. - 1525-0016 .- 1525-0024. ; 22:11, s. 1910-1922
  • Journal article (peer-reviewed)abstract
    • Cell-targeted therapies (smart drugs), which selectively control cancer cell progression with limited toxicity to normal cells, have been developed to effectively treat some cancers. However, many cancers such as metastatic prostate cancer (PC) have yet to be treated with current smart drug technology. Here, we describe the thorough preclinical characterization of an RNA aptamer (A9g) that functions as a smart drug for PC by inhibiting the enzymatic activity of prostate-specific membrane antigen (PSMA). Treatment of PC cells with A9g results in reduced cell migration/invasion in culture and metastatic disease in vivo. Importantly, A9g is safe in vivo and is not immunogenic in human cells. Pharmacokinetic and biodistribution studies in mice confirm target specificity and absence of non-specific on/off-target effects. In conclusion, these studies provide new and important insights into the role of PSMA in driving carcinogenesis and demonstrate critical endpoints for the translation of a novel RNA smart drug for advanced stage PC. © The American Society of Gene amp; Cell Therapy.
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5.
  • Heindel, Jerrold J., et al. (author)
  • Obesity II : Establishing causal links between chemical exposures and obesity
  • 2022
  • In: Biochemical Pharmacology. - : Elsevier. - 0006-2952 .- 1356-1839 .- 1873-2968. ; 199
  • Research review (peer-reviewed)abstract
    • Obesity is a multifactorial disease with both genetic and environmental components. The prevailing view is that obesity results from an imbalance between energy intake and expenditure caused by overeating and insufficient exercise. We describe another environmental element that can alter the balance between energy intake and energy expenditure: obesogens. Obesogens are a subset of environmental chemicals that act as endocrine disruptors affecting metabolic endpoints. The obesogen hypothesis posits that exposure to endocrine disruptors and other chemicals can alter the development and function of the adipose tissue, liver, pancreas, gastrointestinal tract, and brain, thus changing the set point for control of metabolism. Obesogens can determine how much food is needed to maintain homeostasis and thereby increase the susceptibility to obesity. The most sensitive time for obesogen action is in utero and early childhood, in part via epigenetic programming that can be transmitted to future generations. This review explores the evidence supporting the obesogen hypothesis and highlights knowledge gaps that have prevented widespread acceptance as a contributor to the obesity pandemic. Critically, the obesogen hypothesis changes the narrative from curing obesity to preventing obesity.
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7.
  • Jencson, Jacob E., et al. (author)
  • AT 2019qyl in NGC 300 : Internal Collisions in the Early Outflow from a Very Fast Nova in a Symbiotic Binary
  • 2021
  • In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 920:2
  • Journal article (peer-reviewed)abstract
    • Nova eruptions, thermonuclear explosions on the surfaces of white dwarfs (WDs), are now recognized to be among the most common shock-powered astrophysical transients. We present the early discovery and rapid ultraviolet (UV), optical, and infrared (IR) temporal development of AT 2019qyl, a recent nova in the nearby Sculptor Group galaxy NGC 300. The light curve shows a rapid rise lasting ≲1 day, reaching a peak absolute magnitude of MV = −9.2 mag and a very fast decline, fading by 2 mag over 3.5 days. A steep dropoff in the light curves after 71 days and the rapid decline timescale suggest a low-mass ejection from a massive WD with MWD ≳ 1.2 M⊙. We present an unprecedented view of the early spectroscopic evolution of such an event. Three spectra prior to the peak reveal a complex, multicomponent outflow giving rise to internal collisions and shocks in the ejecta of an He/N-class nova. We identify a coincident IR-variable counterpart in the extensive preeruption coverage of the transient location and infer the presence of a symbiotic progenitor system with an O-rich asymptotic-giant-branch donor star, as well as evidence for an earlier UV-bright outburst in 2014. We suggest that AT 2019qyl is analogous to the subset of Galactic recurrent novae with red-giant companions such as RS Oph and other embedded nova systems like V407 Cyg. Our observations provide new evidence that internal shocks between multiple, distinct outflow components likely contribute to the generation of the shock-powered emission from such systems.
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8.
  • Karp, Melissa A., et al. (author)
  • Increasing the uptake of multispecies models in fisheries management 
  • 2023
  • In: ICES Journal of Marine Science. - : Oxford University Press (OUP). - 1054-3139 .- 1095-9289. ; 80:2, s. 243-257
  • Journal article (peer-reviewed)abstract
    • Multispecies models have existed in a fisheries context since at least the 1970s, but despite much exploration, advancement, and consideration of multispecies models, there remain limited examples of their operational use in fishery management. Given that species and fleet interactions are inherently multispecies problems and the push towards ecosystem-based fisheries management, the lack of more regular operational use is both surprising and compelling. We identify impediments hampering the regular operational use of multispecies models and provide recommendations to address those impediments. These recommendations are: (1) engage stakeholders and managers early and often; (2) improve messaging and communication about the various uses of multispecies models; (3) move forward with multispecies management under current authorities while exploring more inclusive governance structures and flexible decision-making frameworks for handling tradeoffs; (4) evaluate when a multispecies modelling approach may be more appropriate; (5) tailor the multispecies model to a clearly defined purpose; (6) develop interdisciplinary solutions to promoting multispecies model applications; (7) make guidelines available for multispecies model review and application; and (8) ensure code and models are well documented and reproducible. These recommendations draw from a global assemblage of subject matter experts who participated in a workshop entitled “Multispecies Modeling Applications in Fisheries Management”. 
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9.
  • Barna, Barnabas, et al. (author)
  • SN 2019muj-a well-observed Type Iax supernova that bridges the luminosity gap of the class
  • 2021
  • In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 501:1, s. 1078-1099
  • Journal article (peer-reviewed)abstract
    • We present early-time (t < +50 d) observations of SN 2019muj (=ASASSN-19tr), one of the best-observed members of the peculiar SN Iax class. Ultraviolet and optical photometric and optical and near-infrared spectroscopic follow-up started from similar to 5 d before maximum light [t(max)(B) on 58707.8 MJD] and covers the photospheric phase. The early observations allow us to estimate the physical properties of the ejecta and characterize the possible divergence from a uniform chemical abundance structure. The estimated bolometric light-curve peaks at 1.05 x 10(42) erg s(-1) and indicates that only 0.031 M-circle dot of Ni-56 was produced, making SN 2019muj a moderate luminosity object in the Iax class with peak absolute magnitude of M-V = -16.4 mag. The estimated date of explosion is t(0) = 58698.2 MJD and implies a short rise time of t(rise) = 9.6 d in B band. We fit of the spectroscopic data by synthetic spectra, calculated via the radiative transfer code TARDIS. Adopting the partially stratified abundance template based on brighter SNe Iax provides a good match with SN 2019muj. However, without earlier spectra, the need for stratification cannot be stated in most of the elements, except carbon, which is allowed to appear in the outer layers only. SN 2019muj provides a unique opportunity to link extremely low-luminosity SNe Iax to well-studied, brighter SNe Iax.
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10.
  • Galbany, L., et al. (author)
  • Evidence for a Chandrasekhar-mass explosion in the Ca-strong 1991bg-like type la supernova 2016hnk
  • 2019
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 630
  • Journal article (peer-reviewed)abstract
    • Aims. We present a comprehensive dataset of optical and near-infrared photometry and spectroscopy of type Ia supernova (SN) 2016hnk, combined with integral field spectroscopy (IFS) of its host galaxy, MCG -01-06-070, and nearby environment. Our goal with this complete dataset is to understand the nature of this peculiar object.Methods. Properties of the SN local environment are characterized by means of single stellar population synthesis applied to IFS observations taken two years after the SN exploded. We performed detailed analyses of SN photometric data by studying its peculiar light and color curves. SN 2016hnk spectra were compared to other 1991bg-like SNe Ia, 2002es-like SNe Ia, and Ca-rich transients. In addition, we used abundance stratification modeling to identify the various spectral features in the early phase spectral sequence and also compared the dataset to a modified non-LTE model previously produced for the sublumnious SN 1999by.Results. SN 2016hnk is consistent with being a subluminous (M-B = -16.7 mag, S-BV =0.43 +/- 0.03), highly reddened object. The IFS of its host galaxy reveals both a significant amount of dust at the SN location, residual star formation, and a high proportion of old stellar populations in the local environment compared to other locations in the galaxy, which favors an old progenitor for SN 2016hnk. Inspection of a nebular spectrum obtained one year after maximum contains two narrow emission lines attributed to the forbidden [Ca II] lambda lambda 7291,7324 doublet with a Doppler shift of 700 km s(-1). Based on various observational diagnostics, we argue that the progenitor of SN 2016hnk was likely a near Chandrasekhar-mass (M-Ch) carbon-oxygen white dwarf that produced 0.108 M-circle dot of Ni-56. Our modeling suggests that the narrow [Ca II] features observed in the nebular spectrum are associated with Ca-48 from electron capture during the explosion, which is expected to occur only in white dwarfs that explode near or at the M-Ch limit.
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