255 research outputs found
Epidemiologic Study of Dental Caries Experience and Between-Meal Eating Patterns
The relationship between dental caries and between-meal snacks was investigated in a study of 1,486 high school students. The participants completed a questionnaire on between-meal habits and then were given dental examinations. The lack of differences in dental caries between racial and geographic groups was not related to the frequency of sucrose-containing, between-meal snacks.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66591/2/10.1177_00220345730520022501.pd
Substrate Flexibility of a Mutated Acyltransferase Domain and Implications for Polyketide Biosynthesis
SummaryPolyketides are natural products frequently used for the treatment of various diseases, but their structural complexity hinders efficient derivatization. In this context, we recently introduced enzyme-directed mutasynthesis to incorporate non-native extender units into the biosynthesis of erythromycin. Modeling and mutagenesis studies led to the discovery of a variant of an acyltransferase domain in the erythromycin polyketide synthase capable of accepting a propargylated substrate. Here, we extend molecular rationalization of enzyme-substrate interactions through modeling, to investigate the incorporation of substrates with different degrees of saturation of the malonic acid side chain. This allowed the engineered biosynthesis of new erythromycin derivatives and the introduction of additional mutations into the AT domain for a further shift of the enzyme's substrate scope. Our approach yields non-native polyketide structures with functional groups that will simplify future derivatization approaches, and provides a blueprint for the engineering of AT domains to achieve efficient polyketide synthase diversification
Epidemic spreading with immunization and mutations
The spreading of infectious diseases with and without immunization of
individuals can be modeled by stochastic processes that exhibit a transition
between an active phase of epidemic spreading and an absorbing phase, where the
disease dies out. In nature, however, the transmitted pathogen may also mutate,
weakening the effect of immunization. In order to study the influence of
mutations, we introduce a model that mimics epidemic spreading with
immunization and mutations. The model exhibits a line of continuous phase
transitions and includes the general epidemic process (GEP) and directed
percolation (DP) as special cases. Restricting to perfect immunization in two
spatial dimensions we analyze the phase diagram and study the scaling behavior
along the phase transition line as well as in the vicinity of the GEP point. We
show that mutations lead generically to a crossover from the GEP to DP. Using
standard scaling arguments we also predict the form of the phase transition
line close to the GEP point. It turns out that the protection gained by
immunization is vitally decreased by the occurrence of mutations.Comment: 9 pages, 13 figure
Towards Activity Context using Software Sensors
Service-Oriented Computing delivers the promise of configuring and
reconfiguring software systems to address user's needs in a dynamic way.
Context-aware computing promises to capture the user's needs and hence the
requirements they have on systems. The marriage of both can deliver ad-hoc
software solutions relevant to the user in the most current fashion. However,
here it is a key to gather information on the users' activity (that is what
they are doing). Traditionally any context sensing was conducted with hardware
sensors. However, software can also play the same role and in some situations
will be more useful to sense the activity of the user. Furthermore they can
make use of the fact that Service-oriented systems exchange information through
standard protocols. In this paper we discuss our proposed approach to sense the
activity of the user making use of software
Optical excitations in a one-dimensional Mott insulator
The density-matrix renormalization-group (DMRG) method is used to investigate
optical excitations in the Mott insulating phase of a one-dimensional extended
Hubbard model. The linear optical conductivity is calculated using the
dynamical DMRG method and the nature of the lowest optically excited states is
investigated using a symmetrized DMRG approach. The numerical calculations
agree perfectly with field-theoretical predictions for a small Mott gap and
analytical results for a large Mott gap obtained with a strong-coupling
analysis. Is is shown that four types of optical excitations exist in this Mott
insulator: pairs of unbound charge excitations, excitons, excitonic strings,
and charge-density-wave (CDW) droplets. Each type of excitations dominates the
low-energy optical spectrum in some region of the interaction parameter space
and corresponds to distinct spectral features: a continuum starting at the Mott
gap (unbound charge excitations), a single peak or several isolated peaks below
the Mott gap (excitons and excitonic strings, respectively), and a continuum
below the Mott gap (CDW droplets).Comment: 12 pages (REVTEX 4), 12 figures (in 14 eps files), 1 tabl
Continuity of the Maximum-Entropy Inference
We study the inverse problem of inferring the state of a finite-level quantum
system from expected values of a fixed set of observables, by maximizing a
continuous ranking function. We have proved earlier that the maximum-entropy
inference can be a discontinuous map from the convex set of expected values to
the convex set of states because the image contains states of reduced support,
while this map restricts to a smooth parametrization of a Gibbsian family of
fully supported states. Here we prove for arbitrary ranking functions that the
inference is continuous up to boundary points. This follows from a continuity
condition in terms of the openness of the restricted linear map from states to
their expected values. The openness condition shows also that ranking functions
with a discontinuous inference are typical. Moreover it shows that the
inference is continuous in the restriction to any polytope which implies that a
discontinuity belongs to the quantum domain of non-commutative observables and
that a geodesic closure of a Gibbsian family equals the set of maximum-entropy
states. We discuss eight descriptions of the set of maximum-entropy states with
proofs of accuracy and an analysis of deviations.Comment: 34 pages, 1 figur
Anomalous c-axis charge dynamics in copper oxide materials
Within the t-J model, the c-axis charge dynamics of the copper oxide
materials in the underdoped and optimally doped regimes is studied by
considering the incoherent interlayer hopping. It is shown that the c-axis
charge dynamics is mainly governed by the scattering from the in-plane
fluctuation. In the optimally doped regime, the c-axis resistivity is a linear
in temperatures, and shows the metallic-like behavior for all temperatures,
while the c-axis resistivity in the underdoped regime is characterized by a
crossover from the high temperature metallic-like behavior to the low
temperature semiconducting-like behavior, which are consistent with experiments
and numerical simulations.Comment: 6 pages, Latex, Three figures are adde
Quantum Monte Carlo and variational approaches to the Holstein model
Based on the canonical Lang-Firsov transformation of the Hamiltonian we
develop a very efficient quantum Monte Carlo algorithm for the Holstein model
with one electron. Separation of the fermionic degrees of freedom by a
reweighting of the probability distribution leads to a dramatic reduction in
computational effort. A principal component representation of the phonon
degrees of freedom allows to sample completely uncorrelated phonon
configurations. The combination of these elements enables us to perform
efficient simulations for a wide range of temperature, phonon frequency and
electron-phonon coupling on clusters large enough to avoid finite-size effects.
The algorithm is tested in one dimension and the data are compared with
exact-diagonalization results and with existing work. Moreover, the ideas
presented here can also be applied to the many-electron case. In the
one-electron case considered here, the physics of the Holstein model can be
described by a simple variational approach.Comment: 18 pages, 11 Figures, v2: one typo correcte
The exposure of the hybrid detector of the Pierre Auger Observatory
The Pierre Auger Observatory is a detector for ultra-high energy cosmic rays.
It consists of a surface array to measure secondary particles at ground level
and a fluorescence detector to measure the development of air showers in the
atmosphere above the array. The "hybrid" detection mode combines the
information from the two subsystems. We describe the determination of the
hybrid exposure for events observed by the fluorescence telescopes in
coincidence with at least one water-Cherenkov detector of the surface array. A
detailed knowledge of the time dependence of the detection operations is
crucial for an accurate evaluation of the exposure. We discuss the relevance of
monitoring data collected during operations, such as the status of the
fluorescence detector, background light and atmospheric conditions, that are
used in both simulation and reconstruction.Comment: Paper accepted by Astroparticle Physic
PTPA variants and impaired PP2A activity in early-onset parkinsonism with intellectual disability
The protein phosphatase 2A complex (PP2A), the major Ser/Thr phosphatase in the brain, is involved in a number of signalling pathways and functions, including the regulation of crucial proteins for neurodegeneration, such as alpha-synuclein, tau and LRRK2. Here, we report the identification of variants in the PTPA/PPP2R4 gene, encoding a major PP2A activator, in two families with early-onset parkinsonism and intellectual disability. We carried out clinical studies and genetic analyses, including genome-wide linkage analysis, whole-exome sequencing, and Sanger sequencing of candidate variants. We next performed functional studies on the disease-associated variants in cultured cells and knock-down of ptpa in Drosophila melanogaster. We first identified a homozygous PTPA variant, c.893T>G (p.Met298Arg), in patients from a South African family with early-onset parkinsonism and intellectual disability. Screening of a large series of additional families yielded a second homozygous variant, c.512C>A (p.Ala171Asp), in a Libyan family with a similar phenotype. Both variants co-segregate with disease in the respective families. The affected subjects display juvenile-onset parkinsonism and intellectual disability. The motor symptoms were responsive to treatment with levodopa and deep brain stimulation of the subthalamic nucleus. In overexpression studies, both the PTPA p.Ala171Asp and p.Met298Arg variants were associated with decreased PTPA RNA stability and decreased PTPA protein levels; the p.Ala171Asp variant additionally displayed decreased PTPA protein stability. Crucially, expression of both variants was associated with decreased PP2A complex levels and impaired PP2A phosphatase activation. PTPA orthologue knock-down in Drosophila neurons induced a significant impairment of locomotion in the climbing test. This defect was age-dependent and fully reversed by L-DOPA treatment. We conclude that bi-allelic missense PTPA variants associated with impaired activation of the PP2A phosphatase cause autosomal recessive early-onset parkinsonism with intellectual disability. Our findings might also provide new insights for understanding the role of the PP2A complex in the pathogenesis of more common forms of neurodegeneration.</p
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