Cooperative action in eukaryotic gene regulation: physical properties of a viral example

The Epstein-Barr virus (EBV) infects more than 90% of the human population, and is the cause of several both serious and mild diseases. It is a tumorivirus, and has been widely studied as a model system for gene (de)regulation in human. A central feature of the EBV life cycle is its ability to persist in human B cells in states denoted latency I, II and III. In latency III the host cell is driven to cell proliferation and hence expansion of the viral population, but does not enter the lytic pathway, and no new virions are produced, while the latency I state is almost completely dormant. In this paper we study a physico-chemical model of the switch between latency I and latency III in EBV. We show that the unusually large number of binding sites of two competing transcription factors, one viral and one from the host, serves to make the switch sharper (higher Hill coefficient), either by cooperative binding between molecules of the same species when they bind, or by competition between the two species if there is sufficient steric hindrance.Comment: 7 pages, 6 figures, 1 tabl

The MAGIC of CINEMA: First in-flight science results from a miniaturised anisotropic magnetoresistive magnetometer

We present the first in-flight results from a novel miniaturised anisotropic magnetoresistive space magnetometer, MAGIC (MAGnetometer from Imperial College), aboard the first CINEMA (CubeSat for Ions, Neutrals, Electrons and MAgnetic fields) spacecraft in low Earth orbit. An attitude-independent calibration technique is detailed using the International Geomagnetic Reference Field (IGRF), which is temperature dependent in the case of the outboard sensor. We show that the sensors accurately measure the expected absolute field to within 2% in attitude mode and 1% in science mode. Using a simple method we are able to estimate the spacecraft's attitude using the magnetometer only, thus characterising CINEMA's spin, precession and nutation. Finally, we show that the outboard sensor is capable of detecting transient physical signals with amplitudes of ~ 20–60 nT. These include field-aligned currents at the auroral oval, qualitatively similar to previous observations, which agree in location with measurements from the DMSP (Defense Meteorological Satellite Program) and POES (Polar-orbiting Operational Environmental Satellites) spacecraft. Thus, we demonstrate and discuss the potential science capabilities of the MAGIC instrument onboard a CubeSat platform

In Defense of the Epistemic Imperative

Sample (2015) argues that scientists ought not to believe that their theories are true because they cannot fulfill the epistemic obligation to take the diachronic perspective on their theories. I reply that Sample’s argument imposes an inordinately heavy epistemic obligation on scientists, and that it spells doom not only for scientific theories but also for observational beliefs and philosophical ideas that Samples endorses. I also delineate what I take to be a reasonable epistemic obligation for scientists. In sum, philosophers ought to impose on scientists only an epistemic standard that they are willing to impose on themselves

Radiative Muon Capture on Hydrogen and the Induced Pseudoscalar Coupling

The first measurement of the elementary process $\mu^- p \rightarrow \nu_{\mu} n \gamma$ is reported. A photon pair spectrometer was used to measure the partial branching ratio ($2.10 \pm 0.22) \times 10^{-8}$ for photons of k > 60 MeV. The value of the weak pseudoscalar coupling constant determined from the partial branching ratio is $g_p(q^{2}=-0.88m_{\mu}^2) = (9.8 \pm 0.7 \pm 0.3) \cdot g_a(0)$, where the first error is the quadrature sum of statistical and systematic uncertainties and the second error is due to the uncertainty in $\lambda_{op}$, the decay rate of the ortho to para $p \mu p$ molecule. This value of g_p is $\sim$1.5 times the prediction of PCAC and pion-pole dominance.Comment: 13 pages, RevTeX type, 3 figures (encapsulated postscript), submitted to Phys. Rev. Let

Parity Violation in Elastic Electron-Proton Scattering and the Proton's Strange Magnetic Form Factor

We report a new measurement of the parity-violating asymmetry in elastic electron scattering from the proton at backward scattering angles. This asymmetry is sensitive to the strange magnetic form factor of the proton as well as electroweak axial radiative corrections. The new measurement of A = -4.92±0.61±0.73 ppm provides a significant constraint on these quantities. The implications for the strange magnetic form factor are discussed in the context of theoretical estimates for the axial corrections

Effect of analgesic therapy on clinical outcome measures in a randomized controlled trial using client-owned dogs with hip osteoarthritis

BACKGROUND: Pain and impaired mobility because of osteoarthritis (OA) is common in dogs and humans. Efficacy studies of analgesic drug treatment of dogs with naturally occurring OA may be challenging, as a caregiver placebo effect is typically evident. However, little is known about effect sizes of common outcome-measures in canine clinical trials evaluating treatment of OA pain. Forty-nine client-owned dogs with hip OA were enrolled in a randomized, double-blinded placebo-controlled prospective trial. After a 1 week baseline period, dogs were randomly assigned to a treatment (ABT-116 – transient receptor potential vanilloid 1 (TRPV1) antagonist, Carprofen – non-steroidal anti-inflammatory drug (NSAID), Tramadol - synthetic opiate, or Placebo) for 2 weeks. Outcome-measures included physical examination parameters, owner questionnaire, activity monitoring, gait analysis, and use of rescue medication. RESULTS: Acute hyperthermia developed after ABT-116 treatment (P < 0.001). Treatment with carprofen (P ≤ 0.01) and tramadol (P ≤ 0.001) led to improved mobility assessed by owner questionnaire. Nighttime activity was increased after ABT-116 treatment (P = 0.01). Kinetic gait analysis did not reveal significant treatment effects. Use of rescue treatment decreased with treatment in the ABT-116 and Carprofen groups (P < 0.001). Questionnaire score and activity count at the end of treatment were correlated with age, clinical severity at trial entry, and outcome measure baseline status (S(R) ≥ ±0.40, P ≤ 0.005). Placebo treatment effects were evident with all variables studied. CONCLUSION: Treatment of hip OA in client-owned dogs is associated with a placebo effect for all variables that are commonly used for efficacy studies of analgesic drugs. This likely reflects caregiver bias or the phenomenon of regression to the mean. In the present study, outcome measures with significant effects also varied between groups, highlighting the value of using multiple outcome measures, as well as an a priori analysis of effect size associated with each measure. Effect size data from the present study could be used to inform design of future trials studying analgesic treatment of canine OA. Our results suggest that analgesic treatment with ABT-116 is not as effective as carprofen or tramadol for treatment of hip arthritis pain in client-owned dogs

Alien Registration- Sample, Marguerite M. (Strong, Franklin County)

https://digitalmaine.com/alien_docs/19298/thumbnail.jp

Pan-viral serology implicates enteroviruses in acute flaccid myelitis.

Since 2012, the United States of America has experienced a biennial spike in pediatric acute flaccid myelitis (AFM)1-6. Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF)2. CSF from children with AFM (n = 42) and other pediatric neurologic disease controls (n = 58) were investigated for intrathecal antiviral antibodies, using a phage display library expressing 481,966 overlapping peptides derived from all known vertebrate and arboviruses (VirScan). Metagenomic next-generation sequencing (mNGS) of AFM CSF RNA (n = 20 cases) was also performed, both unbiased sequencing and with targeted enrichment for EVs. Using VirScan, the viral family significantly enriched by the CSF of AFM cases relative to controls was Picornaviridae, with the most enriched Picornaviridae peptides belonging to the genus Enterovirus (n = 29/42 cases versus 4/58 controls). EV VP1 ELISA confirmed this finding (n = 22/26 cases versus 7/50 controls). mNGS did not detect additional EV RNA. Despite rare detection of EV RNA, pan-viral serology frequently identified high levels of CSF EV-specific antibodies in AFM compared with controls, providing further evidence for a causal role of non-polio EVs in AFM