A newly discovered infectious disease of amphibians, chytridiomycosis, caused by the fungal pathogen Batrachochytrium dendrobatidis, is implicated in population declines and possible extinctions ...throughout the world. The purpose of our study was to examine the effects of B. dendrobatidis on the mountain yellow-legged frog (Rana muscosa) in the Sierra Nevada of California (USA). We (1) quantified the prevalence and incidence of B. dendrobatidis through repeat surveys of several hundred R. muscosa populations in the southern Sierra Nevada; (2) described the population-level effects of B. dendrobatidis on R. muscosa population abundance; and (3) compared the mortality rates of infected and uninfected R. muscosa individuals from pre- through post-metamorphosis using both laboratory and field experiments. Mouthpart inspections conducted in 144 and 132 R. muscosa populations in 2003 and 2004, respectively, indicated that 19% of R. muscosa populations in both years showed indications of chytridiomycosis. Sixteen percent of populations that were uninfected in 2003 became infected by 2004. Rana muscosa population sizes were reduced by an average of 88% following B. dendrobatidis outbreaks at six sites, but at seven B. dendrobatidis-negative sites, R. muscosa population sizes increased by an average of 45% over the same time period. In the laboratory, all infected R. muscosa developed fatal chytridiomycosis after metamorphosis, while all uninfected individuals remained healthy. In the field experiment in which R. muscosa tadpoles were caged at infected and uninfected sites, 96% of the individuals that metamorphosed at infected sites died vs. 5% at the uninfected sites. These studies indicate that chytridiomycosis causes high mortality in post-metamorphic R. muscosa, that this emerging disease is the proximate cause of numerous observed R. muscosa population declines, and that the disease threatens this species with extirpation at numerous sites in California's Sierra Nevada.
Generative social science Epstein, Joshua M; Epstein, Joshua M
2011., 20120102, 2012, 2007, 2007-01-01, 20060101, Letnik:
21
eBook
Agent-based computational modeling is changing the face of social science. In Generative Social Science, Joshua Epstein argues that this powerful, novel technique permits the social sciences to meet ...a fundamentally new standard of explanation, in which one "grows" the phenomenon of interest in an artificial society of interacting agents: heterogeneous, boundedly rational actors, represented as mathematical or software objects. After elaborating this notion of generative explanation in a pair of overarching foundational chapters, Epstein illustrates it with examples chosen from such far-flung fields as archaeology, civil conflict, the evolution of norms, epidemiology, retirement economics, spatial games, and organizational adaptation. In elegant chapter preludes, he explains how these widely diverse modeling studies support his sweeping case for generative explanation.
The detection of diffuse radio emission associated with clusters of galaxies indicates populations of relativistic leptons infusing the intracluster medium (ICM). Those electrons and positrons are ...either injected into and accelerated directly in the ICM, or produced as secondary pairs by cosmic-ray ions scattering on ambient protons. Radiation mechanisms involving the energetic leptons together with the decay of neutral pions produced by hadronic interactions have the potential to produce abundant GeV photons. Here, we report on the search for GeV emission from clusters of galaxies using data collected by the Large Area Telescope on the Fermi Gamma-ray Space Telescope from 2008 August to 2010 February. Thirty-three galaxy clusters have been selected according to their proximity and high mass, X-ray flux and temperature, and indications of non-thermal activity for this study. We report upper limits on the photon flux in the range 0.2-100 GeV toward a sample of observed clusters (typical values (1-5) x 10(-9) photon cm(-2) s(-1)) considering both point-like and spatially resolved models for the high-energy emission and discuss how these results constrain the characteristics of energetic leptons and hadrons, and magnetic fields in the ICM. The volume-averaged relativistic-hadron-to-thermal energy density ratio is found to be <5%-10% in several clusters.
Biocompatible silk optical waveguides are fabricated by direct‐write assembly and demonstrated to guide light in both straight and curved architectures. These waveguides can easily be doped or ...functionalized with bioactive molecules, and are promising materials for biophotonic devices.
The project as a whole represents a landmark publication for modernist studies, bringing together, in a ground-breaking format, a number of critical readings of The Cantos by the world's leading ...Pound and modernist scholars. In each chapter a contributor approaches either a single Canto or a defined small group of Cantos in isolation, providing a clear, informative, and interpretive 'reading' that includes an up-to-date assessment of sources and an idea of recent critical approaches to the work. Most importantly, each essay offers guidance to those wishing to understand the works while contributing to the creation of a new manner of reading The Cantos as a remarkably diverse but coherent work. This first volume illuminates the gestation of the Cantos-technique and includes essays on the most important Cantos and groups of Cantos from the Ur-Cantos (early, discarded versions of the beginning of Pound's poem), A Draft of XVI Cantos (1924),A Draft of the Cantos 17-27 (1928), and Eleven New Cantos XXXI-XLI, also known as "Jefferson-Nuevo Mundo," (1934).
Immune evasion is a major obstacle for cancer treatment. Common mechanisms of evasion include impaired antigen presentation caused by mutations or loss of heterozygosity of the major ...histocompatibility complex class I (MHC-I), which has been implicated in resistance to immune checkpoint blockade (ICB) therapy
. However, in pancreatic ductal adenocarcinoma (PDAC), which is resistant to most therapies including ICB
, mutations that cause loss of MHC-I are rarely found
despite the frequent downregulation of MHC-I expression
. Here we show that, in PDAC, MHC-I molecules are selectively targeted for lysosomal degradation by an autophagy-dependent mechanism that involves the autophagy cargo receptor NBR1. PDAC cells display reduced expression of MHC-I at the cell surface and instead demonstrate predominant localization within autophagosomes and lysosomes. Notably, inhibition of autophagy restores surface levels of MHC-I and leads to improved antigen presentation, enhanced anti-tumour T cell responses and reduced tumour growth in syngeneic host mice. Accordingly, the anti-tumour effects of autophagy inhibition are reversed by depleting CD8
T cells or reducing surface expression of MHC-I. Inhibition of autophagy, either genetically or pharmacologically with chloroquine, synergizes with dual ICB therapy (anti-PD1 and anti-CTLA4 antibodies), and leads to an enhanced anti-tumour immune response. Our findings demonstrate a role for enhanced autophagy or lysosome function in immune evasion by selective targeting of MHC-I molecules for degradation, and provide a rationale for the combination of autophagy inhibition and dual ICB therapy as a therapeutic strategy against PDAC.
We present 3.7 arcsec (∼0.05 pc) resolution 3.2 mm dust continuum observations from the Institut de Radioastronomie Millimétrique Plateau de Bure Interferometer, with the aim of studying the ...structure and fragmentation of the filamentary infrared dark cloud (IRDC) G035.39–00.33. The continuum emission is segmented into a series of 13 quasi-regularly spaced (λobs ∼ 0.18 pc) cores, following the major axis of the IRDC. We compare the spatial distribution of the cores with that predicted by theoretical work describing the fragmentation of hydrodynamic fluid cylinders, finding a significant (a factor of ≳ 8) discrepancy between the two. Our observations are consistent with the picture emerging from kinematic studies of molecular clouds suggesting that the cores are harboured within a complex network of independent sub-filaments. This result emphasizes the importance of considering the underlying physical structure, and potentially, dynamically important magnetic fields, in any fragmentation analysis. The identified cores exhibit a range in (peak) beam-averaged column density (3.6 × 1023 cm−2 < N
H, c < 8.0 × 1023 cm−2), mass (8.1 M⊙ < M
c < 26.1 M⊙), and number density (6.1 × 105 cm−3 < n
H, c, eq < 14.7 × 105 cm−3). Two of these cores, dark in the mid-infrared, centrally concentrated, monolithic (with no traceable substructure at our PdBI resolution), and with estimated masses of the order ∼20–25 M⊙, are good candidates for the progenitors of intermediate-to-high-mass stars. Virial parameters span a range 0.2 < αvir < 1.3. Without additional support, possibly from dynamically important magnetic fields with strengths of the order of 230 μG < B < 670 μG, the cores are susceptible to gravitational collapse. These results may imply a multilayered fragmentation process, which incorporates the formation of sub-filaments, embedded cores, and the possibility of further fragmentation.
Adenoviruses are used extensively as gene transfer agents, both experimentally and clinically. However, targeting of liver cells by adenoviruses compromises their potential efficacy. In cell culture, ...the adenovirus serotype 5 fiber protein engages the coxsackievirus and adenovirus receptor (CAR) to bind cells. Paradoxically, following intravascular delivery, CAR is not used for liver transduction, implicating alternate pathways. Recently, we demonstrated that coagulation factor (F)X directly binds adenovirus leading to liver infection. Here, we show that FX binds to the Ad5 hexon, not fiber, via an interaction between the FX Gla domain and hypervariable regions of the hexon surface. Binding occurs in multiple human adenovirus serotypes. Liver infection by the FX-Ad5 complex is mediated through a heparin-binding exosite in the FX serine protease domain. This study reveals an unanticipated function for hexon in mediating liver gene transfer in vivo.
Electrically exploded wires find uses throughout high-energy physics. For example, they are commonly used as high-temperature sources, X-ray generators, and in precision timing detonators. However, ...the detailed and complete physics that occurs is complex and still poorly understood. A full mechanistic description of these complex phenomena is beyond the scope of a single paper. Instead, we focus on the formation of metal vapor and its transition to plasma. This single transition is commonly assumed to comprise "bridge-burst". We use a suite of diagnostics including a novel, fiber-based, high-speed, optical pyrometer to better characterize this transition. The primary finding from this project is that peak light output from an exploding wire does not temporally match the peak temperature. Additionally, it is found that peak light does not align with peak bridge-burst voltage and that the peak temperature is not voltage-dependent. These findings are non-intuitive and will allow for the correction of false assumptions previously made about this topic.
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