190 research outputs found
Agent-Based Modeling of Intracellular Transport
We develop an agent-based model of the motion and pattern formation of
vesicles. These intracellular particles can be found in four different modes of
(undirected and directed) motion and can fuse with other vesicles. While the
size of vesicles follows a log-normal distribution that changes over time due
to fusion processes, their spatial distribution gives rise to distinct
patterns. Their occurrence depends on the concentration of proteins which are
synthesized based on the transcriptional activities of some genes. Hence,
differences in these spatio-temporal vesicle patterns allow indirect
conclusions about the (unknown) impact of these genes.
By means of agent-based computer simulations we are able to reproduce such
patterns on real temporal and spatial scales. Our modeling approach is based on
Brownian agents with an internal degree of freedom, , that represents
the different modes of motion. Conditions inside the cell are modeled by an
effective potential that differs for agents dependent on their value .
Agent's motion in this effective potential is modeled by an overdampted
Langevin equation, changes of are modeled as stochastic transitions
with values obtained from experiments, and fusion events are modeled as
space-dependent stochastic transitions. Our results for the spatio-temporal
vesicle patterns can be used for a statistical comparison with experiments. We
also derive hypotheses of how the silencing of some genes may affect the
intracellular transport, and point to generalizations of the model
Seven fatalities associated with ethylphenidate
Ethylphenidate is a stimulant novel psychoactive substance that is an analogue of the prescription drug methylphenidate (Ritalin®). Methylphenidate is used commonly for the treatment of attention deficit hyperactivity disorder. Due to its stimulant effects ethylphenidate is being abused. There is a single case report of a death associated with ethylphenidate in Germany, and a case series of 19 deaths in the East of Scotland, but otherwise, the contribution of ethylphenidate to death is poorly documented. We report the analytical results of 7 cases (between February 2013 and January 2015) in which ethylphenidate was detected and quantitated with a validated liquid chromatography tandem mass spectrometry method (LC-MS/MS). The individuals (all male) ranged in age from 23 to 49 years (median 25 years). The concentration of ethylphenidate in the cases ranged from 0.026mg/L to 2.18mg/L in unpreserved post-mortem femoral blood. Only one case had ethylphenidate present as a sole drug. All other cases had at least 2 other drug classes present (benzodiazepines, heroin, methadone antipsychotics, other new psychoactive compounds). Ethylphenidate toxicity was the sole contribution to the cause of death in one case. Hanging was the cause of death in 2 cases, with the other 4 cases being reported as having occurred due to mixed drug toxicity. These data will further help with the interpretation of post-mortem ethylphenidate levels
First Observation of Coherent Production in Neutrino Nucleus Interactions with 2 GeV
The MiniBooNE experiment at Fermilab has amassed the largest sample to date
of s produced in neutral current (NC) neutrino-nucleus interactions at
low energy. This paper reports a measurement of the momentum distribution of
s produced in mineral oil (CH) and the first observation of coherent
production below 2 GeV. In the forward direction, the yield of events
observed above the expectation for resonant production is attributed primarily
to coherent production off carbon, but may also include a small contribution
from diffractive production on hydrogen. Integrated over the MiniBooNE neutrino
flux, the sum of the NC coherent and diffractive modes is found to be (19.5
1.1 (stat) 2.5 (sys))% of all exclusive NC production at
MiniBooNE. These measurements are of immediate utility because they quantify an
important background to MiniBooNE's search for
oscillations.Comment: Submitted to Phys. Lett.
Novel methodology for determining the effect of adsorbates on human enamel acid dissolution
Objective: The effect of various interventions on enamel demineralisation can be determined by chemically measuring mineral ions dissolved by the attacking acid. Results are usually expressed as mineral loss per surface area of enamel exposed. Acid resistant varnish or adhesive tape are typically used to delineate an area of enamel. However, enamel surface curvature, rugosity and porosity reduce the reliability of simple area measurements made at the macro scale. Our aim was to develop a simple method for investigating the effect of adsorbates on enamel demineralisation that does not rely on knowing the area of enamel exposed. As an exemplar we have used salivary proteins as a model adsorbate. Design: Natural human tooth enamel surfaces were subjected to five sequential acid challenges and then incubated in adsorbate (whole clarified saliva) followed by a further 15 acid challenges. Demineralisation was determined by measuring the phosphate released into the acid during each exposure by a spectrophotometric assay. The initial five challenges established a mean baseline mineral loss for each tooth against which the effect of subsequently adsorbed proteins could be compared. Results: Salivary proteins significantly reduced the acid demineralisation of human enamel by 43% (p < 0.01). Loss of proteins during each challenge corresponded to a gradual reduction in the degree of protection afforded. Conclusions: The methodology provides a simple and flexible means to investigate the effect of any adsorbate on enamel acid dissolution. Knowledge of the area of exposed enamel is irrelevant as each tooth acts as its own negative control
Alternative BCG delivery strategies improve protection against Mycobacterium tuberculosis in non-human primates: Protection associated with mycobacterial antigen-specific CD4 effector memory T-cell populations
Intradermal (ID) BCG injection provides incomplete protection against TB in humans and experimental models. Alternative BCG vaccination strategies may improve protection in model species, including rhesus macaques. This study compares the immunogenicity and efficacy of BCG administered by ID and intravenous (IV) injection, or as an intratracheal mucosal boost (ID + IT), against aerosol challenge with Mycobacterium tuberculosis Erdman strain. Disease pathology was significantly reduced, and survival improved, by each BCG vaccination strategy, relative to unvaccinated animals. However, IV induced protection surpassed that achieved by all other routes, providing an opportunity to explore protective immunological mechanisms using antigen-specific IFN-γ ELISpot and polychromatic flow cytometry assays. IFN-γ spot forming units and multifunctional CD4 T-cell frequencies increased significantly following each vaccination regimen and were greatest following IV immunisation. Vaccine-induced multifunctional CD4 T-cells producing IFN-γ and TNF-α were associated with reduced disease pathology following subsequent M.tb challenge; however, high frequencies of this population following M.tb infection correlated with increased pathology. Cytokine producing T-cells primarily occupied the CD4 transitional effector memory phenotype, implicating this population as central to the mycobacterial response, potentially contributing to the stringent control observed in IV vaccinated animals. This study demonstrates the protective efficacy of IV BCG vaccination in rhesus macaques, offering a valuable tool for the interrogation of immunological mechanisms and potential correlates of protection
LUXSim: A Component-Centric Approach to Low-Background Simulations
Geant4 has been used throughout the nuclear and high-energy physics community
to simulate energy depositions in various detectors and materials. These
simulations have mostly been run with a source beam outside the detector. In
the case of low-background physics, however, a primary concern is the effect on
the detector from radioactivity inherent in the detector parts themselves. From
this standpoint, there is no single source or beam, but rather a collection of
sources with potentially complicated spatial extent. LUXSim is a simulation
framework used by the LUX collaboration that takes a component-centric approach
to event generation and recording. A new set of classes allows for multiple
radioactive sources to be set within any number of components at run time, with
the entire collection of sources handled within a single simulation run.
Various levels of information can also be recorded from the individual
components, with these record levels also being set at runtime. This
flexibility in both source generation and information recording is possible
without the need to recompile, reducing the complexity of code management and
the proliferation of versions. Within the code itself, casting geometry objects
within this new set of classes rather than as the default Geant4 classes
automatically extends this flexibility to every individual component. No
additional work is required on the part of the developer, reducing development
time and increasing confidence in the results. We describe the guiding
principles behind LUXSim, detail some of its unique classes and methods, and
give examples of usage.
* Corresponding author, [email protected]: 45 pages, 15 figure
Test of Lorentz and CPT violation with Short Baseline Neutrino Oscillation Excesses
The sidereal time dependence of MiniBooNE electron neutrino and anti-electron
neutrino appearance data are analyzed to search for evidence of Lorentz and CPT
violation. An unbinned Kolmogorov-Smirnov test shows both the electron neutrino
and anti-electron neutrino appearance data are compatible with the null
sidereal variation hypothesis to more than 5%. Using an unbinned likelihood fit
with a Lorentz-violating oscillation model derived from the Standard Model
Extension (SME) to describe any excess events over background, we find that the
electron neutrino appearance data prefer a sidereal time-independent solution,
and the anti-electron neutrino appearance data slightly prefer a sidereal
time-dependent solution. Limits of order 10E-20 GeV are placed on combinations
of SME coefficients. These limits give the best limits on certain SME
coefficients for muon neutrino to electron neutrino and anti-muon neutrino to
anti-electron neutrino oscillations. The fit values and limits of combinations
of SME coefficients are provided.Comment: 14 pages, 3 figures, and 2 tables, submitted to Physics Letters
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