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

Safety aspects of infliximab in inflammatory bowel disease patients - A retrospective cohort study in 100 patients of a German University Hospital

Background: Infliximab, a chimeric anti-tumour necrosis factor monoclonal antibody with potent anti-inflammatory effects, represents an effective treatment option in patients with severe inflammatory bowel disease (IBD). Serious side-effects of such an immunomodulating therapy are speculated and therefore we reviewed our clinical experience in a retrospective safety study looking upon a single cohort of 100 IBD patients from a large German University Hospital. Methods: 100 patients with severe Crohn's disease (n = 92), ulcerative colitis (n = 7) or indeterminate colitis (n = 1) treated with infliximab (5 mg/kg) from January 2000 to December 2003 were retrospectively analysed for acute and subacute adverse events by chart review. Results: Overall, infliximab therapy was generally well tolerated. No fatal complications, malignancies, autoimmune diseases, neurologic or cardiovascular complications were observed in the cohort during the study period. Overall, adverse events were observed in 10 patients: 2 patients showed an acute infusion reaction, 1 patient a serum sickness-like reaction, in 4 patients a bacterial or viral infection occurred, in 1 patient pancytopenia and 2 patients developed surgical complications. Only 6 patients with adverse events required admission to hospital. A case of tuberculosis after infliximab was not found. The lack of adverse side-effects was associated with young median age and infrequent comorbidities of the cohort. Conclusion: Regarding its strong immunomodulating capacity, infliximab appears to be an efficient and relatively safe therapeutic option for patients with severe IBD. However, the use of infliximab requires careful screening and close patient monitoring to identify patients at risk and the infrequent, but sometimes serious complications of infliximab. Copyright (C) 2004 S. Karger AG, Basel

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

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

VerdictDB: Universalizing Approximate Query Processing

Despite 25 years of research in academia, approximate query processing (AQP) has had little industrial adoption. One of the major causes of this slow adoption is the reluctance of traditional vendors to make radical changes to their legacy codebases, and the preoccupation of newer vendors (e.g., SQL-on-Hadoop products) with implementing standard features. Additionally, the few AQP engines that are available are each tied to a specific platform and require users to completely abandon their existing databases---an unrealistic expectation given the infancy of the AQP technology. Therefore, we argue that a universal solution is needed: a database-agnostic approximation engine that will widen the reach of this emerging technology across various platforms. Our proposal, called VerdictDB, uses a middleware architecture that requires no changes to the backend database, and thus, can work with all off-the-shelf engines. Operating at the driver-level, VerdictDB intercepts analytical queries issued to the database and rewrites them into another query that, if executed by any standard relational engine, will yield sufficient information for computing an approximate answer. VerdictDB uses the returned result set to compute an approximate answer and error estimates, which are then passed on to the user or application. However, lack of access to the query execution layer introduces significant challenges in terms of generality, correctness, and efficiency. This paper shows how VerdictDB overcomes these challenges and delivers up to 171$\times$ speedup (18.45$\times$ on average) for a variety of existing engines, such as Impala, Spark SQL, and Amazon Redshift, while incurring less than 2.6% relative error. VerdictDB is open-sourced under Apache License.Comment: Extended technical report of the paper that appeared in Proceedings of the 2018 International Conference on Management of Data, pp. 1461-1476. ACM, 201

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

Parity-violating Electron Deuteron Scattering and the Proton's Neutral Weak Axial Vector Form Factor

We report on a new measurement of the parity-violating asymmetry in quasielastic electron scattering from the deuteron at backward angles at Q2= 0.038 (GeV/c)2. This quantity provides a determination of the neutral weak axial vector form factor of the nucleon, which can potentially receive large electroweak corrections. The measured asymmetry A=-3.51 +/- 0.57(stat) +/- 0.58(sys)ppm is consistent with theoretical predictions. We also report on updated results of the previous experiment at Q2=0.091 (GeV/c)2, which are also consistent with theoretical predictions.Comment: 4 pages, 2 figures, submitted to Phys. Rev. Let

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