686 research outputs found
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
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 speedup (18.45 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-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
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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 (nβ=β42) and other pediatric neurologic disease controls (nβ=β58) 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 (nβ=β20 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 (nβ=β29/42 cases versus 4/58 controls). EV VP1 ELISA confirmed this finding (nβ=β22/26 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
Radiative Muon Capture on Hydrogen and the Induced Pseudoscalar Coupling
The first measurement of the elementary process is reported. A photon pair spectrometer was used to measure
the partial branching ratio ( for photons of k >
60 MeV. The value of the weak pseudoscalar coupling constant determined from
the partial branching ratio is , where the first error is the quadrature sum of statistical
and systematic uncertainties and the second error is due to the uncertainty in
, the decay rate of the ortho to para molecule. This
value of g_p is 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
Specification of progression in glaucomatous visual field loss, applying locally condensed stimulus arrangements
The goal of this work was to (i) determine patterns of progression in glaucomatous visual field loss, (ii) compare the detection rate of progression between locally condensed stimulus arrangements and conventional 6Β°βΓβ6Β° grid, and (iii) assess the individual frequency distribution of test locations exhibiting a local event (i.e., an abrupt local deterioration of differential luminance sensitivity (DLS) by more than -10dB between any two examinations).
The visual function of 41 glaucomatous eyes of 41 patients (16 females, 25 males, 37 to 75Β years old) was examined with automated static perimetry (Tuebingen Computer Campimeter or Octopus 101-Perimeter). Stimuli were added to locally enhance the spatial resolution in suspicious regions of the visual field. The minimum follow-up was four subsequent sessions with a minimum of 2-month (median 6-month) intervals between each session. Progression was identified using a modified pointwise linear regression (PLR) method and a modified Katz criterion. The presence of events was assessed in all progressive visual fields.
Eleven eyes (27%) showed progression over the study period (median 2.5Β years, range 1.3β8.6Β years). Six (55%) of these had combined progression in depth and size and five eyes (45%) progressed in depth only. Progression in size conformed always to the nerve fiber course. Seven out of 11 (64%) of the progressive scotomata detected by spatially condensed grids would have been missed by the conventional 6Β°βΓβ6Β° grid. At least one event occurred in 64% of all progressive eyes. Five of 11 (46%) progressive eyes showed a cluster of events.
The most common pattern of progression in glaucomatous visual fields is combined progression in depth and size of an existing scotoma. Applying individually condensed test grids remarkably enhances the detection rate of glaucomatous visual field deterioration (at the expense of an increased examination time) compared to conventional stimulus arrangements
Role of Calcitonin Gene-Related Peptide in Bone Repair after Cyclic Fatigue Loading
Calcitonin gene related peptide (CGRP) is a neuropeptide that is abundant in the sensory neurons which innervate bone. The effects of CGRP on isolated bone cells have been widely studied, and CGRP is currently considered to be an osteoanabolic peptide that has effects on both osteoclasts and osteoblasts. However, relatively little is known about the physiological role of CGRP in-vivo in the skeletal responses to bone loading, particularly fatigue loading.We used the rat ulna end-loading model to induce fatigue damage in the ulna unilaterally during cyclic loading. We postulated that CGRP would influence skeletal responses to cyclic fatigue loading. Rats were fatigue loaded and groups of rats were infused systemically with 0.9% saline, CGRP, or the receptor antagonist, CGRP(8-37), for a 10 day study period. Ten days after fatigue loading, bone and serum CGRP concentrations, serum tartrate-resistant acid phosphatase 5b (TRAP5b) concentrations, and fatigue-induced skeletal responses were quantified. We found that cyclic fatigue loading led to increased CGRP concentrations in both loaded and contralateral ulnae. Administration of CGRP(8-37) was associated with increased targeted remodeling in the fatigue-loaded ulna. Administration of CGRP or CGRP(8-37) both increased reparative bone formation over the study period. Plasma concentration of TRAP5b was not significantly influenced by either CGRP or CGRP(8-37) administration.CGRP signaling modulates targeted remodeling of microdamage and reparative new bone formation after bone fatigue, and may be part of a neuronal signaling pathway which has regulatory effects on load-induced repair responses within the skeleton
The Effect of Epstein-Barr Virus Latent Membrane Protein 2 Expression on the Kinetics of Early B Cell Infection
Infection of human B cells with wild-type Epstein-Barr virus (EBV) in vitro leads to activation and proliferation that result in efficient production of lymphoblastoid cell lines (LCLs). Latent Membrane Protein 2 (LMP2) is expressed early after infection and previous research has suggested a possible role in this process. Therefore, we generated recombinant EBV with knockouts of either or both protein isoforms, LMP2A and LMP2B (Ξ2A, Ξ2B, Ξ2A/Ξ2B) to study the effect of LMP2 in early B cell infection. Infection of B cells with Ξ2A and Ξ2A/Ξ2B viruses led to a marked decrease in activation and proliferation relative to wild-type (wt) viruses, and resulted in higher percentages of apoptotic B cells. Ξ2B virus infection showed activation levels comparable to wt, but fewer numbers of proliferating B cells. Early B cell infection with wt, Ξ2A and Ξ2B viruses did not result in changes in latent gene expression, with the exception of elevated LMP2B transcript in Ξ2A virus infection. Infection with Ξ2A and Ξ2B viruses did not affect viral latency, determined by changes in LMP1/Zebra expression following BCR stimulation. However, BCR stimulation of Ξ2A/Ξ2B cells resulted in decreased LMP1 expression, which suggests loss of stability in viral latency. Long-term outgrowth assays revealed that LMP2A, but not LMP2B, is critical for efficient long-term growth of B cells in vitro. The lowest levels of activation, proliferation, and LCL formation were observed when both isoforms were deleted. These results suggest that LMP2A appears to be critical for efficient activation, proliferation and survival of EBV-infected B cells at early times after infection, which impacts the efficient long-term growth of B cells in culture. In contrast, LMP2B did not appear to play a significant role in these processes, and long-term growth of infected B cells was not affected by the absence of this protein. Β© 2013 Wasil et al
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