Both means and year-to-year variances of climate variables such as temperature and precipitation are predicted to change. However, the potential impact of changing climatic variability on the fate of ...populations has been largely unexamined. We analyzed multiyear demographic data for 36 plant and animal species with a broad range of life histories and types of environment to ask how sensitive their long-term stochastic population growth rates are likely to be to changes in the means and standard deviations of vital rates (survival, reproduction, growth) in response to changing climate. We quantified responsiveness using elasticities of the long-term population growth rate predicted by stochastic projection matrix models. Short-lived species (insects and annual plants and algae) are predicted to be more strongly (and negatively) affected by increasing vital rate variability relative to longer-lived species (perennial plants, birds, ungulates). Taxonomic affiliation has little power to explain sensitivity to increasing variability once longevity has been taken into account. Our results highlight the potential vulnerability of short-lived species to an increasingly variable climate, but also suggest that problems associated with short-lived undesirable species (agricultural pests, disease vectors, invasive weedy plants) may be exacerbated in regions where climate variability decreases.
Soft-gamma-ray repeaters (SGRs) are galactic X-ray stars that emit numerous short-duration (about 0.1 s) bursts of hard X-rays during sporadic active periods. They are thought to be magnetars: ...strongly magnetized neutron stars with emissions powered by the dissipation of magnetic energy. Here we report the detection of a long (380 s) giant flare from SGR 1806-20, which was much more luminous than any previous transient event observed in our Galaxy. (In the first 0.2 s, the flare released as much energy as the Sun radiates in a quarter of a million years.) Its power can be explained by a catastrophic instability involving global crust failure and magnetic reconnection on a magnetar, with possible large-scale untwisting of magnetic field lines outside the star. From a great distance this event would appear to be a short-duration, hard-spectrum cosmic gamma-ray burst. At least a significant fraction of the mysterious short-duration gamma-ray bursts may therefore come from extragalactic magnetars.
ABSTRACT We present nearly simultaneous Chandra and NuSTAR observations of two actively star-forming galaxies within 50 Mpc: NGC 3256 and NGC 3310. Both galaxies are significantly detected by both ...Chandra and NuSTAR, which together provide the first-ever spectra of these two galaxies spanning 0.3-30 keV. The X-ray emission from both galaxies is spatially resolved by Chandra; we find that hot gas dominates the E < 1-3 keV emission while ultraluminous X-ray sources (ULXs) provide majority contributions to the emission at E > 1-3 keV. The NuSTAR galaxy-wide spectra of both galaxies follow steep power-law distributions with Γ 2.6 at E > 5-7 keV. Using new and archival Chandra data, we search for signatures of heavily obscured or low luminosity active galactic nuclei (AGNs). We find that both NGC 3256 and NGC 3310 have X-ray detected sources coincident with nuclear regions; however, the steep NuSTAR spectra of both galaxies restricts these sources to be either low luminosity AGNs (L2−10 keV/LEdd 10−5) or non-AGNs in nature (e.g., ULXs or crowded X-ray sources that reach L2−10 keV ∼ 1040 erg s−1 cannot be ruled out). Combining our constraints on the 0.3-30 keV spectra of NGC 3256 and NGC 3310 with equivalent measurements for nearby star-forming galaxies M83 and NGC 253, we analyze the star formation rate (SFR) normalized spectra of these starburst galaxies. The spectra of all four galaxies show sharply declining power-law slopes at energies above 3-6 keV primarily due to ULX populations. Our observations therefore constrain the average spectral shape of galaxy-wide populations of luminous accreting binaries (i.e., ULXs). Interestingly, despite a completely different galaxy sample selection, emphasizing here a range of SFRs and stellar masses, these properties are similar to those of super-Eddington accreting ULXs that have been studied individually in a targeted NuSTAR ULX program. We also find that NGC 3310 exhibits a factor of 3-10 elevation of X-ray emission over the other star-forming galaxies due to a corresponding overabundance of ULXs. We argue that the excess of ULXs in NGC 3310 is most likely explained by the relatively low metallicity of the young stellar population in this galaxy, a property that is expected to produce an excess of luminous X-ray binaries for a given SFR.
CYP Oxidoreductase (Por) is the essential electron donor for all CYP enzymes and is responsible for the activation of CYP. The Taconic Hepatic CYP Reductase Null (HRN) mouse model possesses a ...targeted mutation that results in liver-specific deletion of the Por gene thereby resulting in a disruption of CYP metabolism in the liver. The objectives of these studies were to further characterize the HRN mouse using probe drugs metabolized by CYP. In addition, tumor exposure in xenograft tumor bearing HRN immune-compromised (nude) mice was also determined. In HRN mice following intravenous (iv) administration of midazolam, clearance (CL) was reduced by ∼ 80% compared to wild-type mice (WT). After oral administration, the AUC of midazolam was increased by ∼ 20-fold in HRN mice compared to WT mice; this greater effect suggests that hepatic first pass plays a role in the oral CL of midazolam. A 50% and an 80% decrease in CL were also observed in HRN mice following iv administration of docetaxel and theophylline, respectively, compared to WT mice. In addition, a 2- to 3-fold increase in tumor concentrations of G4222, a tool compound, were observed in tumor bearing HRN nude mice compared to tumor bearing nude WT mice. The observations from these experiments demonstrate that, for compounds that are extensively metabolized by hepatic CYP, the HRN mouse model could potentially be valuable for evaluating in vivo efficacy of tool compounds in drug discovery where high hepatic CL and low exposure may prevent in vivo evaluation of a new chemical entity.
The Nuclear Spectroscopic Telescope Array (NuSTAR) mission, launched on 2012 June 13, is the first focusing high-energy X-ray telescope in orbit. NuSTAR operates in the band from 3 to 79 keV, ...extending the sensitivity of focusing far beyond the ~10 keV high-energy cutoff achieved by all previous X-ray satellites. The inherently low background associated with concentrating the X-ray light enables NuSTAR to probe the hard X-ray sky with a more than 100-fold improvement in sensitivity over the collimated or coded mask instruments that have operated in this bandpass. Using its unprecedented combination of sensitivity and spatial and spectral resolution, NuSTAR will pursue five primary scientific objectives: (1) probe obscured active galactic nucleus (AGN) activity out to the peak epoch of galaxy assembly in the universe (at z <, ~ 2) by surveying selected regions of the sky; (2) study the population of hard X-ray-emitting compact objects in the Galaxy by mapping the central regions of the Milky Way; (3) study the non-thermal radiation in young supernova remnants, both the hard X-ray continuum and the emission from the radioactive element super(44)Ti; (4) observe blazars contemporaneously with ground-based radio, optical, and TeV telescopes, as well as with Fermi and Swift, to constrain the structure of AGN jets; and (5) observe line and continuum emission from core-collapse supernovae in the Local Group, and from nearby Type Ia events, to constrain explosion models. During its baseline two-year mission, NuSTAR will also undertake a broad program of targeted observations. The observatory consists of two co-aligned grazing-incidence X-ray telescopes pointed at celestial targets by a three-axis stabilized spacecraft. Deployed into a 600 km, near-circular, 6degrees inclination orbit, the observatory has now completed commissioning, and is performing consistent with pre-launch expectations. NuSTAR is now executing its primary science mission, and with an expected orbit lifetime of 10 yr, we anticipate proposing a guest investigator program, to begin in late 2014.
Odontocete cetaceans bioaccumulate high concentrations of endocrine disrupting persistent organic pollutants (POPs), including dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyltrichloroethylene ...(DDE), and dichlorodiphenyldichloroethane (DDD) – collectively DDTs – but few studies have explored DDTs-mediated endocrine disruption in cetaceans. Herein, we use remotely collected blubber biopsies from common bottlenose dolphins (Tursiops truncatus) inhabiting a site with high localized DDTs contamination to study the relationships between DDTs exposure and steroid hormone homeostasis in cetaceans. We quantified blubber steroid hormone concentrations by liquid chromatography-tandem mass spectrometry and blubber POP concentrations by gas chromatography-mass spectrometry. We detected six steroid hormones in blubber, including progesterone (P4), 17-hydroxyprogesterone (17OHP4), androstenedione (AE), testosterone (T), cortisol (F), and cortisone (E). Sampled dolphins (n = 62) exhibited exposure to DDT, DDE, DDD, chlordanes (CHLDs), mirex, dieldrin, hexachlorobenzene, polychlorinated biphenyls (PCBs), and brominated diphenyl ethers (BDEs). Using principal components analysis (PCA), we determined that blubber DDTs primarily loaded to the first principal component (PC1) explaining 81.6% of the total variance in POP exposure, while the remaining POPs primarily loaded to the PC2 (10.4% of variance). PC1 scores were negatively correlated with blubber T in males and blubber F in females, suggesting that exposure to DDTs impacted androgen and corticosteroid homeostasis. These conclusions were further supported by observed negative correlations between T and o,p’-DDE, o,p’-DDD, and p,p’-DDD in males sampled in the fall, and between F and the six individual DDTs and ∑6DDTs in females. Overall, these results suggest that POP-mediated endocrine disruption may have occurred in this stock of dolphins, which could negatively impact their health and fitness. However, this study relied on uncontrolled incidental exposures, making it impossible to establish a causal relationship between DDTs exposure and endocrine effects. Importantly, this study demonstrates that remotely collected blubber biopsies are a useful matrix for studying endocrine disruption in marine mammals.
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•First study of DDTs-mediated endocrine disruption in common bottlenose dolphins•Organochlorine pesticide exposure linked to disrupted testosterone and cortisol homeostasis•Remote blubber biopsies are useful for studying marine mammal endocrine disruption
Bottlenose dolphins in Florida, USA continue to be exposed to the banned pesticide DDT and may be exhibiting impaired endocrine (hormone) health as a result.
ABSTRACT We have discovered heavy obscuration in the dual active galactic nucleus (AGN) in the Swift/Burst Alert Telescope (BAT) source SWIFT J2028.5+2543 using Nuclear Spectroscopic Telescope Array ...(NuSTAR). While an early XMM-Newton study suggested the emission was mainly from NGC 6921, the superior spatial resolution of NuSTAR above 10 keV resolves the Swift/BAT emission into two sources associated with the nearby galaxies MCG +04-48-002 and NGC 6921 (z = 0.014) with a projected separation of 25.3 kpc (91″). NuSTAR's sensitivity above 10 keV finds both are heavily obscured to Compton-thick levels (NH (1-2) × 1024 cm−2) and contribute equally to the BAT detection ( L 10 − 50 keV int 6 × 1042 erg s−1). The observed luminosity of both sources is severely diminished in the 2-10 keV band ( L 2 − 10 keV obs < 0.1 × L 2 − 10 keV int ), illustrating the importance of >10 keV surveys like those with NuSTAR and Swift/BAT. Compared to archival X-ray data, MCG +04-48-002 shows significant variability (>3) between observations. Despite being bright X-ray AGNs, they are difficult to detect using optical emission-line diagnostics because MCG +04-48-002 is identified as a starburst/composite because of the high rates of star formation from a luminous infrared galaxy while NGC 6921 is only classified as a LINER using line detection limits. SWIFT J2028.5+2543 is the first dual AGN resolved above 10 keV and is the second most heavily obscured dual AGN discovered to date in the X-rays other than NGC 6240.
Conventional wisdom has rendered patients with brain metastases ineligible for clinical trials for fear that poor survival could mask the benefit of otherwise promising treatments. Our group ...previously published the diagnosis-specific Graded Prognostic Assessment (GPA). Updates with larger contemporary cohorts using molecular markers and newly identified prognostic factors have been published. The purposes of this work are to present all the updated indices in a single report to guide treatment choice, stratify research, and define an eligibility quotient to expand eligibility.
A multi-institutional database of 6,984 patients with newly diagnosed brain metastases underwent multivariable analyses of prognostic factors and treatments associated with survival for each primary site. Significant factors were used to define the updated GPA. GPAs of 4.0 and 0.0 correlate with the best and worst prognoses, respectively.
Significant prognostic factors varied by diagnosis and new prognostic factors were identified. Those factors were incorporated into the updated GPA with robust separation (
< .01) between subgroups. Survival has improved, but varies widely by GPA for patients with non-small-cell lung, breast, melanoma, GI, and renal cancer with brain metastases from 7-47 months, 3-36 months, 5-34 months, 3-17 months, and 4-35 months, respectively.
Median survival varies widely and our ability to estimate survival for patients with brain metastases has improved. The updated GPA (available free at brainmetgpa.com) provides an accurate tool with which to estimate survival, individualize treatment, and stratify clinical trials. Instead of excluding patients with brain metastases, enrollment should be encouraged and those trials should be stratified by the GPA to ensure those trials make appropriate comparisons. Furthermore, we recommend the expansion of eligibility to allow for the enrollment of patients with previously treated brain metastases who have a 50% or greater probability of an additional year of survival (eligibility quotient > 0.50).
One of the largest river systems in South Africa, the Olifants River, has experienced significant changes in water quality due to anthropogenic activities. Since 2005, there have been various ..."outbreaks" of the inflammatory disease pansteatitis in several vertebrate species. Large-scale pansteatitis-related mortality events have decimated the crocodile population at Lake Loskop and decreased the population at Kruger National Park. Most pansteatitis-related diagnoses within the region are conducted post-mortem by either gross pathology or histology. The application of a non-lethal approach to assess the prevalence and pervasiveness of pansteatitis in the Olifants River region would be of great importance for the development of a management plan for this disease. In this study, several plasma-based biomarkers accurately classified pansteatitis in Mozambique tilapia (Oreochromis mossambicus) collected from Lake Loskop using a commercially available benchtop blood chemistry analyzer combined with data interpretation via artificial neural network analysis. According to the model, four blood chemistry parameters (calcium, sodium, total protein and albumin), in combination with total length, diagnose pansteatitis to a predictive accuracy of 92 percent. In addition, several morphometric traits (total length, age, weight) were also associated with pansteatitis. On-going research will focus on further evaluating the use of blood chemistry to classify pansteatitis across different species, trophic levels, and within different sites along the Olifants River.
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