MicroRNA-122-dependent and -independent replication of Hepatitis C Virus in Hep3B human hepatoma cells

AbstractThe study of Hepatitis C Virus (HCV) has benefitted from the use of the Huh7 cell culture system, but until recently there were no other widely used alternatives to this cell line. Here we render another human hepatoma cell line, Hep3B, permissive to the complete virus life cycle by supplementation with the liver-specific microRNA miR-122, known to aid HCV RNA accumulation. When supplemented, Hep3B cells produce J6/JFH-1 virus titres indistinguishable from those produced by Huh7.5 cells. Interestingly, we were able to detect and characterize miR-122-independent replication of di-cistronic replicons in Hep3B cells. Further, we show that Argonaute-2 (Ago2) is required for miR-122-dependent replication, but dispensable for miR-122-independent replication, confirming Ago2's role in mediating the activity of miR-122. Thus Hep3B cells are a model system for the study of HCV, and miR-122 independent replication is a model to identify proteins involved in the function of miR-122

Deep dielectric charging of regolith within the Moon\u27s permanently shadowed regions

Abstract Energetic charged particles, such as galactic cosmic rays (GCRs) and solar energetic particles (SEPs), can penetrate deep within the lunar surface, resulting in deep dielectric charging. This charging process depends on the GCR and SEP currents, as well as on the regolith\u27s electrical conductivity and permittivity. In permanently shadowed regions (PSRs) near the lunar poles, the discharging timescales are on the order of a lunation (∼20 days). We present the first predictions for deep dielectric charging of lunar regolith. To estimate the resulting subsurface electric fields, we develop a data-driven, one-dimensional, time-dependent model. For model inputs, we use GCR data from the Cosmic Ray Telescope for the Effects of Radiation on board the Lunar Reconnaissance Orbiter and SEP data from the Electron, Proton, and Alpha Monitor on the Advanced Composition Explorer. We find that during the recent solar minimum, GCRs create persistent electric fields up to ∼700 V/m. We also find that large SEP events create transient but strong electric fields (≥106 V/m) that may induce dielectric breakdown. Such breakdown would likely result in significant modifications to the physical and chemical properties of the lunar regolith within PSRs. Key Points Energetic charged particles deep dielectrically charge the lunar regolithWe model the resulting subsurface electric fieldsThe electric fields may be great enough to induce dielectric breakdown

Radiation modeling in the Earth and Mars atmospheres using LRO/CRaTER with the EMMREM Module

Abstract We expand upon the efforts of Joyce et al. (2013), who computed the modulation potential at the Moon using measurements from the Cosmic Ray Telescope for the Effects of Radiation (CRaTER) instrument on the Lunar Reconnaissance Orbiter (LRO) spacecraft along with data products from the Earth-Moon-Mars Radiation Environment Module (EMMREM). Using the computed modulation potential, we calculate galactic cosmic ray (GCR) dose and dose equivalent rates in the Earth and Mars atmospheres for various altitudes over the course of the LRO mission. While we cannot validate these predictions by directly comparable measurement, we find that our results conform to expectations and are in good agreement with the nearest available measurements and therefore may be used as reasonable estimates for use in efforts in risk assessment in the planning of future space missions as well as in the study of GCRs. PREDICCS (Predictions of radiation from REleASE, EMMREM, and Data Incorporating the CRaTER, COSTEP, and other solar energetic particles measurements) is an online system designed to provide the scientific community with a comprehensive resource on the radiation environments of the inner heliosphere. The data products shown here will be incorporated into PREDICCS in order to further this effort and daily updates will be made available on the PREDICCS website (http://prediccs.sr.unh.edu). Key Points We model GCR dose and dose equivalent rates in Earth and Mars atmospheres Dose rates are in reasonable agreement with nearby measurements Data products will soon be made available on PREDICCS website

Record-setting Cosmic-ray Intensities in 2009 and 2010

We report measurements of record-setting intensities of cosmic-ray nuclei from C to Fe, made with the Cosmic Ray Isotope Spectrometer carried on the Advanced Composition Explorer in orbit about the inner Sun-Earth Lagrangian point. In the energy interval from ~70 to ~450 MeV nucleon^(–1), near the peak in the near-Earth cosmic-ray spectrum, the measured intensities of major species from C to Fe were each 20%-26% greater in late 2009 than in the 1997-1998 minimum and previous solar minima of the space age (1957-1997). The elevated intensities reported here and also at neutron monitor energies were undoubtedly due to several unusual aspects of the solar cycle 23/24 minimum, including record-low interplanetary magnetic field (IMF) intensities, an extended period of reduced IMF turbulence, reduced solar-wind dynamic pressure, and extremely low solar activity during an extended solar minimum. The estimated parallel diffusion coefficient for cosmic-ray transport based on measured solar-wind properties was 44% greater in 2009 than in the 1997-1998 solar-minimum period. In addition, the weaker IMF should result in higher cosmic-ray drift velocities. Cosmic-ray intensity variations at 1 AU are found to lag IMF variations by 2-3 solar rotations, indicating that significant solar modulation occurs inside ~20 AU, consistent with earlier galactic cosmic-ray radial-gradient measurements. In 2010, the intensities suddenly decreased to 1997 levels following increases in solar activity and in the inclination of the heliospheric current sheet. We describe the conditions that gave cosmic rays greater access to the inner solar system and discuss some of their implications

Does the worsening galactic cosmic radiation environment observed by CRaTER preclude future manned deep space exploration?

Abstract The Sun and its solar wind are currently exhibiting extremely low densities and magnetic field strengths, representing states that have never been observed during the space age. The highly abnormal solar activity between cycles 23 and 24 has caused the longest solar minimum in over 80 years and continues into the unusually small solar maximum of cycle 24. As a result of the remarkably weak solar activity, we have also observed the highest fluxes of galactic cosmic rays in the space age and relatively small solar energetic particle events. We use observations from the Cosmic Ray Telescope for the Effects of Radiation (CRaTER) on the Lunar Reconnaissance Orbiter to examine the implications of these highly unusual solar conditions for human space exploration. We show that while these conditions are not a show stopper for long-duration missions (e.g., to the Moon, an asteroid, or Mars), galactic cosmic ray radiation remains a significant and worsening factor that limits mission durations. While solar energetic particle events in cycle 24 present some hazard, the accumulated doses for astronauts behind 10 g/cm2 shielding are well below current dose limits. Galactic cosmic radiation presents a more significant challenge: the time to 3% risk of exposure-induced death (REID) in interplanetary space was less than 400 days for a 30 year old male and less than 300 days for a 30 year old female in the last cycle 23–24 minimum. The time to 3% REID is estimated to be ∼20% lower in the coming cycle 24–25 minimum. If the heliospheric magnetic field continues to weaken over time, as is likely, then allowable mission durations will decrease correspondingly. Thus, we estimate exposures in extreme solar minimum conditions and the corresponding effects on allowable durations

Banking from Leeds, not London: regional strategy and structure at the Yorkshire Bank, 1859–1952

Industrial philanthropist Edward Akroyd created the Yorkshire Penny Savings Bank in 1859. Despite competition from the Post Office Savings Bank after 1861 and a serious reserve problem in 1911, it sustained his overall strategy to become a successful regional bank. Using archival and contemporary sources to build on recent scholarship illustrating how savings banks were integrated into local economies and the complementary roles of philanthropy and paternalism, we analyse an English regional bank's strategy, including an assessment of strategic innovation, ownership changes and management structure. This will demonstrate that the founder's vision continued, even though the 1911 crisis radically altered both strategy and structure

Dimensional Crossover in the Large N Limit

We consider dimensional crossover for an $O(N)$ Landau-Ginzburg-Wilson model on a $d$-dimensional film geometry of thickness $L$ in the large $N$-limit. We calculate the full universal crossover scaling forms for the free energy and the equation of state. We compare the results obtained using ``environmentally friendly'' renormalization with those found using a direct, non-renormalization group approach. A set of effective critical exponents are calculated and scaling laws for these exponents are shown to hold exactly, thereby yielding non-trivial relations between the various thermodynamic scaling functions.Comment: 25 pages of PlainTe

Constraining the Kahler Moduli in the Heterotic Standard Model

Phenomenological implications of the volume of the Calabi-Yau threefolds on the hidden and observable M-theory boundaries, together with slope stability of their corresponding vector bundles, constrain the set of Kaehler moduli which give rise to realistic compactifications of the strongly coupled heterotic string. When vector bundles are constructed using extensions, we provide simple rules to determine lower and upper bounds to the region of the Kaehler moduli space where such compactifications can exist. We show how small these regions can be, working out in full detail the case of the recently proposed Heterotic Standard Model. More explicitely, we exhibit Kaehler classes in these regions for which the visible vector bundle is stable. On the other hand, there is no polarization for which the hidden bundle is stable.Comment: 28 pages, harvmac. Exposition improved, references and one figure added, minor correction

Consensus: a framework for evaluation of uncertain gene variants in laboratory test reporting

Accurate interpretation of gene testing is a key component in customizing patient therapy. Where confirming evidence for a gene variant is lacking, computational prediction may be employed. A standardized framework, however, does not yet exist for quantitative evaluation of disease association for uncertain or novel gene variants in an objective manner. Here, complementary predictors for missense gene variants were incorporated into a weighted Consensus framework that includes calculated reference intervals from known disease outcomes. Data visualization for clinical reporting is also discussed