Very Extended X-ray and H-alpha Emission in M82: Implications for the Superwind Phenomenon

We discuss the properties and implications of a 3.7x0.9 kpc region of spatially-coincident X-ray and H-alpha emission about 11.6 kpc to the north of the galaxy M82 previously discussed by Devine and Bally (1999). The PSPC X-ray spectrum is fit by thermal plasma (kT=0.80+-0.17 keV) absorbed by only the Galactic foreground column density. We evaluate the relationship of the X-ray/H-alpha ridge to the M82 superwind. The main properties of the X-ray emission can all be explained as being due to shock-heating driven as the superwind encounters a massive ionized cloud in the halo of M82. This encounter drives a slow shock into the cloud, which contributes to the excitation of the observed H-alpha emission. At the same time, a fast bow-shock develops in the superwind just upstream of the cloud, and this produces the observed X-ray emission. This interpretation would imply that the superwind has an outflow speed of roughly 800 km/s, consistent with indirect estimates based on its general X-ray properties and the kinematics of the inner kpc-scale region of H-alpha filaments. The gas in the M82 ridge is roughly two orders-of-magnitude hotter than the minimum "escape temperature" at this radius, so this gas will not be retained by M82. (abridged)Comment: 24 pages (latex), 3 figures (2 gif files and one postscript), accepted for publication in Part 1 of The Astrophysical Journa

Absorption-Line Probes of Gas and Dust in Galactic Superwinds

We discuss moderate resolution spectra of the NaD absorption-line in a sample of 32 far-IR-bright starburst galaxies. In 18 cases, the line is produced primarily by interstellar gas, and in 12 of these it is blueshifted by over 100 km/s relative to the galaxy systemic velocity. The absorption-line profiles in these outflow sources span the range from near the galaxy systemic velocity to a maximum blueshift of 400 to 600 km/s. The outflows occur in galaxies systematically viewed more nearly face-on than the others. We therefore argue that the absorbing material consists of ambient interstellar gas accelerated along the minor axis of the galaxy by a hot starburst-driven superwind. The NaD lines are optically-thick, but indirect arguments imply total Hydrogen column densities of N_H = few X 10^{21} cm^{-2}. This implies that the superwind is expelling matter at a rate comparable to the star-formation rate. This outflowing material is very dusty: we find a strong correlation between the depth of the NaD profile and the line-of-sight reddening (E(B-V) = 0.3 to 1 over regions several-to-ten kpc in size). The estimated terminal velocities of superwinds inferred from these data and extant X-ray data are typically 400 to 800 km/s, are independent of the galaxy rotation speed, and are comparable to (substantially exceed) the escape velocities for $L_*$ (dwarf) galaxies. The resulting loss of metals can establish the mass-metallicity relation in spheroids, produce the observed metallicity in the ICM, and enrich a general IGM to 10$^{-1}$ solar metallicity. If the outflowing dust grains survive their journey into the IGM, their effect on observations of cosmologically-distant objects is significant.Comment: 65 pages, including 16 figures. ApJ, in pres

Comparative venom-gland transcriptomics and venom proteomics of four Sidewinder Rattlesnake (\u3ci\u3eCrotalus cerastes\u3c/i\u3e) lineages reveal little differential expression despite individual variation

Changes in gene expression can rapidly influence adaptive traits in the early stages of lineage diversification. Venom is an adaptive trait comprised of numerous toxins used for prey capture and defense. Snake venoms can vary widely between conspecific populations, but the influence of lineage diversification on such compositional differences are unknown. To explore venom differentiation in the early stages of lineage diversification, we used RNA-seq and mass spectrometry to characterize Sidewinder Rattlesnake (Crotalus cerastes) venom. We generated the first venom-gland transcriptomes and complementary venom proteomes for eight individuals collected across the United States and tested for expression differences across life history traits and between subspecific, mitochondrial, and phylotranscriptomic hypotheses. Sidewinder venom was comprised primarily of hemorrhagic toxins, with few cases of differential expression attributable to life history or lineage hypotheses. However, phylotranscriptomic lineage comparisons more than doubled instances of significant expression differences compared to all other factors. Nevertheless, only 6.4% of toxins were differentially expressed overall, suggesting that shallow divergence has not led to major changes in Sidewinder venom composition. Our results demonstrate the need for consensus venom-gland transcriptomes based on multiple individuals and highlight the potential for discrepancies in differential expression between different phylogenetic hypotheses

X-Rays from NGC 3256: High-Energy Emission in Starburst Galaxies and Their Contribution to the Cosmic X-Ray Background

The infrared-luminous galaxy NGC3256 is a classic example of a merger induced nuclear starburst system. We find here that it is the most X-ray luminous star-forming galaxy yet detected (~10^42 ergs/s). Long-slit optical spectroscopy and a deep, high-resolution ROSAT X-ray image show that the starburst is driving a "superwind" which accounts for ~20% of the observed soft (kT~0.3 keV) X-ray emission. Our model for the broadband X-ray emission of NGC3256 contains two additional components: a warm thermal plasma (kT~0.8 keV) associated with the central starburst, and a hard power-law component with an energy index of ~0.7. We find that the input of mechanical energy from the starburst is more than sufficient to sustain the observed level of emission. We also examine possible origins for the power-law component, concluding that neither a buried AGN nor the expected population of high-mass X-ray binaries can account for this emission. Inverse-Compton scattering, involving the galaxy's copious flux of infrared photons and the relativistic electrons produced by supernovae, is likely to make a substantial contribution to the hard X-ray flux. Such a model is consistent with the observed radio and IR fluxes and the radio and X-ray spectral indices. We explore the role of X-ray-luminous starbursts in the production of the cosmic X-ray background radiation. The number counts and spectral index distribution of the faint radio source population, thought to be dominated by star-forming galaxies, suggest that a significant fraction of the hard X-ray background could arise from starbursts at moderate redshift.Comment: 31 pages (tex, epsf), 8 figures (postscript files), accepted for publication in Part 1 of The Astrophysical Journa

Behavioral economic methods to inform infectious disease response: Prevention, testing, and vaccination in the COVID-19 pandemic

The role of human behavior to thwart transmission of infectious diseases like COVID-19 is evident. Psychological and behavioral science are key areas to understand decision-making processes underlying engagement in preventive health behaviors. Here we adapt well validated methods from behavioral economic discounting and demand frameworks to evaluate variables (e.g., delay, cost, probability) known to impact health behavior engagement. We examine the contribution of these mechanisms within a broader response class of behaviors reflecting adherence to public health recommendations made during the COVID-19 pandemic. Four crowdsourced samples (total N = 1,366) completed individual experiments probing a response class including social (physical) distancing, facemask wearing, COVID-19 testing, and COVID-19 vaccination. We also measure the extent to which choice architecture manipulations (e.g., framing, opt-in/opt-out) may promote (or discourage) behavior engagement. We find that people are more likely to socially distance when specified activities are framed as high risk, that facemask use during social interaction decreases systematically with greater social relationship, that describing delay until testing (rather than delay until results) increases testing likelihood, and that framing vaccine safety in a positive valence improves vaccine acceptance. These findings collectively emphasize the flexibility of methods from diverse areas of behavioral science for informing public health crisis management

Ways of Asking, Ways of Telling: A Methodological Comparison of Ethnographic and Research Diagnostic Interviews

The interpretive understanding that can be derived from interviews is highly influenced by methods of data collection, be they structured or semistructured, ethnographic, clinical, life-history or survey interviews. This article responds to calls for research into the interview process by analyzing data produced by two distinctly different types of interview, a semistructured ethnographic interview and the Structured Clinical Interview for DSM, conducted with participants in the Navajo Healing Project. We examine how the two interview genres shape the context of researcher-respondent interaction and, in turn, influence how patients articulate their lives and their experience in terms of illness, causality, social environment, temporality and self/identity. We discuss the manner in which the two interviews impose narrative constraints on interviewers and respondents, with significant implications for understanding the jointly constructed nature of the interview process. The argument demonstrates both divergence and complementarity in the construction of knowledge by means of these interviewing methods

Quantifying geocode location error using GIS methods

BACKGROUND: The Metropolitan Atlanta Congenital Defects Program (MACDP) collects maternal address information at the time of delivery for infants and fetuses with birth defects. These addresses have been geocoded by two independent agencies: (1) the Georgia Division of Public Health Office of Health Information and Policy (OHIP) and (2) a commercial vendor. Geographic information system (GIS) methods were used to quantify uncertainty in the two sets of geocodes using orthoimagery and tax parcel datasets. METHODS: We sampled 599 infants and fetuses with birth defects delivered during 1994–2002 with maternal residence in either Fulton or Gwinnett County. Tax parcel datasets were obtained from the tax assessor's offices of Fulton and Gwinnett County. High-resolution orthoimagery for these counties was acquired from the U.S. Geological Survey. For each of the 599 addresses we attempted to locate the tax parcel corresponding to the maternal address. If the tax parcel was identified the distance and the angle between the geocode and the residence were calculated. We used simulated data to characterize the impact of geocode location error. In each county 5,000 geocodes were generated and assigned their corresponding Census 2000 tract. Each geocode was then displaced at a random angle by a random distance drawn from the distribution of observed geocode location errors. The census tract of the displaced geocode was determined. We repeated this process 5,000 times and report the percentage of geocodes that resolved into incorrect census tracts. RESULTS: Median location error was less than 100 meters for both OHIP and commercial vendor geocodes; the distribution of angles appeared uniform. Median location error was approximately 35% larger in Gwinnett (a suburban county) relative to Fulton (a county with urban and suburban areas). Location error occasionally caused the simulated geocodes to be displaced into incorrect census tracts; the median percentage of geocodes resolving into incorrect census tracts ranged between 4.5% and 5.3%, depending upon the county and geocoding agency. CONCLUSION: Geocode location uncertainty can be estimated using tax parcel databases in a GIS. This approach is a viable alternative to global positioning system field validation of geocodes

PRKACA Mediates Resistance to HER2-Targeted Therapy in Breast Cancer Cells and Restores Anti-Apoptotic Signaling

Targeting HER2 with antibodies or small molecule inhibitors in HER2-positive breast cancer leads to improved survival, but resistance is a common clinical problem. To uncover novel mechanisms of resistance to anti-HER2 therapy in breast cancer, we performed a kinase open reading frame (ORF) screen to identify genes that rescue HER2-amplified breast cancer cells from HER2 inhibition or suppression. In addition to multiple members of the MAPK and PI3K signaling pathways, we discovered that expression of the survival kinases PRKACA and PIM1 rescued cells from anti-HER2 therapy. Furthermore, we observed elevated PRKACA expression in trastuzumab-resistant breast cancer samples, indicating that this pathway is activated in breast cancers that are clinically resistant to trastuzumab-containing therapy. We found that neither PRKACA nor PIM1 restored MAPK or PI3K activation after lapatinib or trastuzumab treatment, but rather inactivated the pro-apoptotic protein BAD, thereby permitting survival signaling through BCL-XL. Pharmacological blockade of BCL-XL/BCL-2 partially abrogated the rescue effects conferred by PRKACA and PIM1, and sensitized cells to lapatinib treatment. These observations suggest that combined targeting of HER2 and the BCL-XL/BCL-2 anti-apoptotic pathway may increase responses to anti-HER2 therapy in breast cancer and decrease the emergence of resistant disease

Protein flexibility directs DNA recognition by the papillomavirus E2 proteins

Although DNA flexibility is known to play an important role in DNA–protein interactions, the importance of protein flexibility is less well understood. Here, we show that protein dynamics are important in DNA recognition using the well-characterized human papillomavirus (HPV) type 6 E2 protein as a model system. We have compared the DNA binding properties of the HPV 6 E2 DNA binding domain (DBD) and a mutant lacking two C-terminal leucine residues that form part of the hydrophobic core of the protein. Deletion of these residues results in increased specific and non-specific DNA binding and an overall decrease in DNA binding specificity. Using 15N NMR relaxation and hydrogen/deuterium exchange, we demonstrate that the mutation results in increased flexibility within the hydrophobic core and loop regions that orient the DNA binding helices. Stopped-flow kinetic studies indicate that increased flexibility alters DNA binding by increasing initial interactions with DNA but has little or no effect on the structural rearrangements that follow this step. Taken together these data demonstrate that subtle changes in protein dynamics have a major influence on protein–DNA interactions