The Write Stuff: The Plausible Capability of Jesus’ Followers to Author the Gospels

It is common for critics of the New Testament to cite William Harris’ 10% literacy rate for first-century Greco-Romans as evidence for the implausibility of Jesus’ followers to write, publish, and circulate the New Testament. This “evidence” is often used to dismiss the entire New Testament as a second-century fabrication that cannot accurately represent the true teachings of Jesus. Is this an accurate portrayal of Galilee during the time of Jesus? The purpose of this article is to demonstrate that Jesus’ followers possessed the “‘Write’ Stuff”—the ability to read, write, and memorize, as well as, access to the technology needed to produce and publish the New Testament

Multitissue molecular, genomic, and developmental effects of the deepwater horizon oil spill on resident Gulf killifish (Fundulus grandis)

The Deepwater Horizon oil rig disaster resulted in crude oil contamination along the Gulf coast in sensitive estuaries. Toxicity from exposure to crude oil can affect populations of fish that live or breed in oiled habitats as seen following the Exxon Valdez oil spill. In an ongoing study of the effects of Deepwater Horizon crude oil on fish, Gulf killifish (Fundulus grandis) were collected from an oiled site (Grande Terre, LA) and two reference locations (coastal MS and AL) and monitored for measures of exposure to crude oil. Killifish collected from Grande Terre had divergent gene expression in the liver and gill tissue coincident with the arrival of contaminating oil and up-regulation of cytochrome P4501A (CYP1A) protein in gill, liver, intestine, and head kidney for over one year following peak landfall of oil (August 2011) compared to fish collected from reference sites. Furthermore, laboratory exposures of Gulf killifish embryos to field-collected sediments from Grande Terre and Barataria Bay, LA, also resulted in increased CYP1A and developmental abnormalities when exposed to sediments collected from oiled sites compared to exposure to sediments collected from a reference site. These data are predictive of population-level impacts in fish exposed to sediments from oiled locations along the Gulf of Mexico coast. © 2013 American Chemical Society

A common founding clone with TP53 and PTEN mutations gives rise to a concurrent germ cell tumor and acute megakaryoblastic leukemia

We report the findings from a patient who presented with a concurrent mediastinal germ cell tumor (GCT) and acute myeloid leukemia (AML). Bone marrow pathology was consistent with a diagnosis of acute megakaryoblastic leukemia (AML M7), and biopsy of an anterior mediastinal mass was consistent with a nonseminomatous GCT. Prior studies have described associations between hematological malignancies, including AML M7 and nonseminomatous GCTs, and it was recently suggested that a common founding clone initiated both cancers. We performed enhanced exome sequencing on the GCT and the AML M7 from our patient to define the clonal relationship between the two cancers. We found that both samples contained somatic mutations in PTEN (C136R missense) and TP53 (R213 frameshift). The mutations in PTEN and TP53 were present at ∼100% variant allele frequency (VAF) in both tumors. In addition, we detected and validated five other shared somatic mutations. The copy-number analysis of the AML exome data revealed an amplification of Chromosome 12p. We also identified a heterozygous germline variant in FANCA (S858R), which is known to be associated with Fanconi anemia but is of uncertain significance here. In summary, our data not only support a common founding clone for these cancers but also suggest that a specific set of distinct genomic alterations (in PTEN and TP53) underlies the rare association between GCT and AML. This association is likely linked to the treatment resistance and extremely poor outcome of these patients. We cannot resolve the clonal evolution of these tumors given limitations of our data

Chandra/HETGS Spectroscopy of the Galactic Black Hole GX 339-4: A Relativistic Iron Line and Evidence for a Seyfert-like Warm Absorber

We observed the Galactic black hole GX 339-4 with the Chandra High Energy Transmission Grating Spectrometer (HETGS) for 75 ksec during the decline of its 2002-2003 outburst. The sensitivity of this observation provides an unprecedented glimpse of a Galactic black hole at about a tenth of the luminosity of the outburst peak. The continuum spectrum is well described by a model consisting of multicolor disk blackbody (kT = 0.6 keV) and power-law (Gamma = 2.5) components. X-ray reflection models yield improved fits. A strong, relativistic Fe K-alpha emission line is revealed, indicating that the inner disk extends to the innermost stable circular orbit. The breadth of the line is sufficient to suggest that GX 339-4 may harbor a black hole with significant angular momentum. Absorption lines from H-like and He-like O, and He-like Ne and Mg are detected, as well as lines which are likely due to Ne II and Ne III. The measured line properties make it difficult to associate the absorption with the coronal phase of the interstellar medium. A scenario wherein the absorption lines are due to an intrinsic AGN-like warm-absorber geometry -- perhaps produced by a disk wind in an extended disk-dominated state -- may be more viable. We compare our results to Chandra observations of the Galactic black hole candidate XTE J1650-500, and discuss our findings in terms of prominent models for Galactic black hole accretion flows and connections to supermassive black holes.Comment: 20 pages, 11 postscript figure files (many in color), uses emulateapj.sty and apjfonts.sty, slightly expanded, accepted for publication in Ap

Impaired β-glucocerebrosidase activity and processing in frontotemporal dementia due to progranulin mutations.

Loss-of-function mutations in progranulin (GRN) are a major autosomal dominant cause of frontotemporal dementia. Most pathogenic GRN mutations result in progranulin haploinsufficiency, which is thought to cause frontotemporal dementia in GRN mutation carriers. Progranulin haploinsufficiency may drive frontotemporal dementia pathogenesis by disrupting lysosomal function, as patients with GRN mutations on both alleles develop the lysosomal storage disorder neuronal ceroid lipofuscinosis, and frontotemporal dementia patients with GRN mutations (FTD-GRN) also accumulate lipofuscin. The specific lysosomal deficits caused by progranulin insufficiency remain unclear, but emerging data indicate that progranulin insufficiency may impair lysosomal sphingolipid-metabolizing enzymes. We investigated the effects of progranulin insufficiency on sphingolipid-metabolizing enzymes in the inferior frontal gyrus of FTD-GRN patients using fluorogenic activity assays, biochemical profiling of enzyme levels and posttranslational modifications, and quantitative neuropathology. Of the enzymes studied, only β-glucocerebrosidase exhibited impairment in FTD-GRN patients. Brains from FTD-GRN patients had lower activity than controls, which was associated with lower levels of mature β-glucocerebrosidase protein and accumulation of insoluble, incompletely glycosylated β-glucocerebrosidase. Immunostaining revealed loss of neuronal β-glucocerebrosidase in FTD-GRN patients. To investigate the effects of progranulin insufficiency on β-glucocerebrosidase outside of the context of neurodegeneration, we investigated β-glucocerebrosidase activity in progranulin-insufficient mice. Brains from Grn-/- mice had lower β-glucocerebrosidase activity than wild-type littermates, which was corrected by AAV-progranulin gene therapy. These data show that progranulin insufficiency impairs β-glucocerebrosidase activity in the brain. This effect is strongest in neurons and may be caused by impaired β-glucocerebrosidase processing

A Long, Hard Look at the Low-Hard State in Accreting Black Holes

We present the first results of coordinated multi-wavelength observations of the Galactic black hole GX 339-4 in a canonical low-hard state, obtained during its 2004 outburst. XMM-Newton observed the source for 2 revolutions, or approximately 280 ksec; RXTE monitored the source throughout this long stare. The resulting data offer the best view yet obtained of the inner accretion flow geometry in the low-hard state, which is thought to be analogous to the geometry in low-luminosity active galactic nuclei. The XMM-Newton spectra clearly reveal the presence of a cool accretion disk component, and a relativistic Fe K emission line. The results of fits made to both components strongly suggest that a standard thin disk remains at or near to the innermost stable circular orbit, at least in bright phases of the low-hard state. These findings indicate that potential links between the inner disk radius and the onset of a steady compact jet, and the paradigm of a radially-recessed disk in the low-hard state, do not hold universally. The results of our observations can best be explained if a standard thin accretion disk fuels a corona which is closely related to, or consistent with, the base of a compact jet. In a brief examination of archival data, we show that Cygnus X-1 supports this picture of the low/hard state. We discuss our results within the context of disk-jet connections and prevailing models for accretion onto black holes.Comment: 13 pages, 10 figures (6 in color), ApJ, in pres

Polymer multilayer tattooing for enhanced DNA vaccination

DNA vaccines have many potential benefits but have failed to generate robust immune responses in humans. Recently, methods such as in vivo electroporation have demonstrated improved performance, but an optimal strategy for safe, reproducible, and pain-free DNA vaccination remains elusive. Here we report an approach for rapid implantation of vaccine-loaded polymer films carrying DNA, immune-stimulatory RNA, and biodegradable polycations into the immune-cell-rich epidermis, using microneedles coated with releasable polyelectrolyte multilayers. Films transferred into the skin following brief microneedle application promoted local transfection and controlled the persistence of DNA and adjuvants in the skin from days to weeks, with kinetics determined by the film composition. These ‘multilayer tattoo’ DNA vaccines induced immune responses against a model HIV antigen comparable to electroporation in mice, enhanced memory T-cell generation, and elicited 140-fold higher gene expression in non-human primate skin than intradermal DNA injection, indicating the potential of this strategy for enhancing DNA vaccination.Howard Hughes Medical Institute (Investigator)Ragon Institute of MGH, MIT, and HarvardNational Institutes of Health (U.S.) (NIH AI095109)United States. Dept. of Defense. Institute for Soldier Nanotechnologies (contract W911NF-07-D-0004)United States. Dept. of Defense. Institute for Soldier Nanotechnologies (contract W911NF-07-0004

Capturing Complete Spatial Context in Satellite Observations of Greenhouse Gases

Scientific consensus from a 2015 pre-Decadal Survey workshop highlighted the essential need for a wide-swath (mapping) low earth orbit (LEO) instrument delivering carbon dioxide (CO_2), methane (CH_4), and carbon monoxide (CO) measurements with global coverage. OCO-2 pioneered space-based CO_2 remote sensing, but lacks the CH_4, CO and mapping capabilities required for an improved understanding of the global carbon cycle. The Carbon Balance Observatory (CARBO) advances key technologies to enable high-performance, cost-effective solutions for a space-based carbon-climate observing system. CARBO is a compact, modular, 15-30° field of view spectrometer that delivers high-precision CO_2, CH_4, CO and solar induced chlorophyll fluorescence (SIF) data with weekly global coverage from LEO. CARBO employs innovative immersion grating technologies to achieve diffraction-limited performance with OCO-like spatial (2x2 km^2) and spectral (λ/Δλ ≈ 20,000) resolution in a package that is >50% smaller, lighter and more cost-effective. CARBO delivers a 25- to 50-fold increase in spatial coverage compared to OCO-2 with no loss of detection sensitivity. Individual CARBO modules weigh < 20 kg, opening diverse new space-based platform opportunities

NuSTAR reveals the hidden nature of SS433

SS433 is the only Galactic binary system known to accrete at highly super-critical rates, analogous to tidal disruption events, and needed to explain the mass of some high redshift quasars. Probing the inner regions of SS433 in the X-rays is crucial to understanding this system, and super-critical accretion in general, but has not yet been possible due to obscuration. NuSTAR observed SS433 in the hard X-ray band across multiple phases of its super-orbital precession period. Spectral-timing tools have allowed us to confirm that the hard X-ray emission from the inner regions is scattered towards us by the walls of the wind-cone. By comparing to numerical models, we determine an intrinsic X-ray luminosity of >= 3x10^37 erg/s and that, if viewed face on, the apparent luminosity would be > 1x10^39 erg/s, confirming its long-suspected nature as an ultraluminous X-ray source (ULX). A lag due to absorption by Fe XXV/XXVI in outflowing material travelling at least 0.14-0.29c matches absorption lines seen in ULXs and - in future - will allow us to map a super-critical outflow for the first time.Comment: 24 pages, 8 figures, submitted for publicatio