162 research outputs found
Using simulation to study service-rate controls to stabilize performance in a single-server queue with time-varying arrival rate
Simulation is used to evaluate the performance of alternative service-rate controls designed to stabilize performance in a queue with time-varying arrival rate, service in order of arrival and unlimited waiting space. Both Markovian and non-Markovian models are considered. Customer service requirements are specified separately from the service rate, which is subject to control. New versions of the inverse method exploiting tables constructed outside the simulation are developed to efficiently generate both the arrival times and service times. The simulation experiments show that a rate-matching service-rate control successfully stabilizes the expected queue length, but not the expected waiting time, while a new square-root service-rate control, based on a assuming that a pointwise-stationary approximation is appropriate, successfully stabilizes the expected waiting time when the arrival rate changes slowly compared to the expected service time.
Rapid Screening for Entry Inhibitors of Highly Pathogenic Viruses under Low-Level Biocontainment
Emerging viruses including Nipah, Hendra, Lujo, and Junin viruses have enormous potential to spread rapidly. Nipah virus, after emerging as a zoonosis, has also evolved the capacity for human-to-human transmission. Most of the diseases caused by these pathogens are untreatable and require high biocontainment conditions. Universal methods for rapidly identifying and screening candidate antivirals are urgently needed. We have developed a modular antiviral platform strategy that relies on simple bioinformatic and genetic information about each pathogen. Central to this platform is the use of envelope glycoprotein cDNAs to establish multi-cycle replication systems under BSL2 conditions for viral pathogens that normally require BSL3 and BSL4 facilities. We generated monoclonal antibodies against Nipah G by cDNA immunization in rats, and we showed that these antibodies neutralize both Nipah and Hendra live viruses. We then used these effective Henipavirus inhibitors to validate our screening strategy. Our proposed strategy should contribute to the response capability for emerging infectious diseases, providing a way to initiate antiviral development immediately upon identifying novel viruses
Petri Nets Validation of Markovian Models of Emergency Department Arrivals
International audienceModeling of hospital’s Emergency Departments (ED) is vital for optimisation of health services offered to patients that shows up at an ED requiring treatments with different level of emergency. In this paper we present a modeling study whose contribution is twofold: first, based on a dataset relative to the ED of an Italian hospital, we derive different kinds of Markovian models capable to reproduce, at different extents, the statistical character of dataset arrivals; second, we validate the derived arrivals model by interfacing it with a Petri net model of the services an ED patient undergoes. The empirical assessment of a few key performance indicators allowed us to validate some of the derived arrival process model, thus confirming that they can be used for predicting the performance of an ED
Gauge-ready formulation of the cosmological kinetic theory in generalized gravity theories
We present cosmological perturbations of kinetic components based on
relativistic Boltzmann equations in the context of generalized gravity
theories. Our general theory considers an arbitrary number of scalar fields
generally coupled with the gravity, an arbitrary number of mutually interacting
hydrodynamic fluids, and components described by the relativistic Boltzmann
equations like massive/massless collisionless particles and the photon with the
accompanying polarizations. We also include direct interactions among fluids
and fields. The background FLRW model includes the general spatial curvature
and the cosmological constant. We consider three different types of
perturbations, and all the scalar-type perturbation equations are arranged in a
gauge-ready form so that one can implement easily the convenient gauge
conditions depending on the situation. In the numerical calculation of the
Boltzmann equations we have implemented four different gauge conditions in a
gauge-ready manner where two of them are new. By comparing solutions solved
separately in different gauge conditions we can naturally check the numerical
accuracy.Comment: 26 pages, 9 figures, revised thoroughly, to appear in Phys. Rev.
The Genomic Signature of Crop-Wild Introgression in Maize
The evolutionary significance of hybridization and subsequent introgression
has long been appreciated, but evaluation of the genome-wide effects of these
phenomena has only recently become possible. Crop-wild study systems represent
ideal opportunities to examine evolution through hybridization. For example,
maize and the conspecific wild teosinte Zea mays ssp. mexicana, (hereafter,
mexicana) are known to hybridize in the fields of highland Mexico. Despite
widespread evidence of gene flow, maize and mexicana maintain distinct
morphologies and have done so in sympatry for thousands of years. Neither the
genomic extent nor the evolutionary importance of introgression between these
taxa is understood. In this study we assessed patterns of genome-wide
introgression based on 39,029 single nucleotide polymorphisms genotyped in 189
individuals from nine sympatric maize-mexicana populations and reference
allopatric populations. While portions of the maize and mexicana genomes were
particularly resistant to introgression (notably near known
cross-incompatibility and domestication loci), we detected widespread evidence
for introgression in both directions of gene flow. Through further
characterization of these regions and preliminary growth chamber experiments,
we found evidence suggestive of the incorporation of adaptive mexicana alleles
into maize during its expansion to the highlands of central Mexico. In
contrast, very little evidence was found for adaptive introgression from maize
to mexicana. The methods we have applied here can be replicated widely, and
such analyses have the potential to greatly informing our understanding of
evolution through introgressive hybridization. Crop species, due to their
exceptional genomic resources and frequent histories of spread into sympatry
with relatives, should be particularly influential in these studies
Cosmological Tests of Gravity
Modifications of general relativity provide an alternative explanation to
dark energy for the observed acceleration of the universe. We review recent
developments in modified gravity theories, focusing on higher dimensional
approaches and chameleon/f(R) theories. We classify these models in terms of
the screening mechanisms that enable such theories to approach general
relativity on small scales (and thus satisfy solar system constraints). We
describe general features of the modified Friedman equation in such theories.
The second half of this review describes experimental tests of gravity in
light of the new theoretical approaches. We summarize the high precision tests
of gravity on laboratory and solar system scales. We describe in some detail
tests on astrophysical scales ranging from ~kpc (galaxy scales) to ~Gpc
(large-scale structure). These tests rely on the growth and inter-relationship
of perturbations in the metric potentials, density and velocity fields which
can be measured using gravitational lensing, galaxy cluster abundances, galaxy
clustering and the Integrated Sachs-Wolfe effect. A robust way to interpret
observations is by constraining effective parameters, such as the ratio of the
two metric potentials. Currently tests of gravity on astrophysical scales are
in the early stages --- we summarize these tests and discuss the interesting
prospects for new tests in the coming decade.Comment: Invited review for Annals of Physics; 58 pages, 8 figures
Association and Linkage Analysis of Aluminum Tolerance Genes in Maize
Aluminum (Al) toxicity is a major worldwide constraint to crop productivity on acidic soils. Al becomes soluble at low pH, inhibiting root growth and severely reducing yields. Maize is an important staple food and commodity crop in acidic soil regions, especially in South America and Africa where these soils are very common. Al exclusion and intracellular tolerance have been suggested as two important mechanisms for Al tolerance in maize, but little is known about the underlying genetics. linkage populations with approximately 200 individuals each were used to study genetic variation in this complex trait. Al tolerance was measured as net root growth in nutrient solution under Al stress, which exhibited a wide range of variation between lines. Comparative and physiological genomics-based approaches were used to select 21 candidate genes for evaluation by association analysis.). These four candidate genes are high priority subjects for follow-up biochemical and physiological studies on the mechanisms of Al tolerance in maize. Immediately, elite haplotype-specific molecular markers can be developed for these four genes and used for efficient marker-assisted selection of superior alleles in Al tolerance maize breeding programs
NCAM (CD56) Expression in keratin-producing odontogenic cysts: aberrant expression in KCOT
Background: Keratin-producing odontogenic cysts (KPOCs) are a group of cystic lesions that are often aggressive, with high rates of recurrence and multifocality. KPOCs included orthokeratinised odontogenic cyst (OOC) and parakeratotic odontogenic cysts, which are now considered true tumours denominated keratocystic odontogenic tumours (KCOTs). GLUT1 is a protein transporter that is involved in the active uptake of glucose across cell membranes and that is overexpressed in tumours in close correlation with the proliferation rate and positron emission tomography (PET) imaging results. Methods: A series of 58 keratin-producing odontogenic cysts was evaluated histologically and immunohistochemically in terms of GLUT1 expression. Different data were correlated using the beta regression model in relation to histological type and immunohistochemical expression of GLUT1, which was quantified using two different morphological methods. Results: KPOC cases comprised 12 OOCs and 46 KCOTs, the latter corresponding to 6 syndromic and 40 sporadic KCOTs. GLUT1 expression was very low in OOC cases compared with KCOT cases, with statistical significant differences when quantification was considered. Different GLUT1 localisation patterns were revealed by immunostaining, with the parabasal cells showing higher reactivity in KCOTs. However, among KCOTs cases, GLUT1 expression was unable to establish differences between syndromic and sporadic cases. Conclusions: GLUT1 expression differentiated between OOC and KCOT cases, with significantly higher expression in KCOTs, but did not differentiate between syndromic and sporadic KCOT cases. However, given the structural characteristics of KCOTs, we hypothesised that PET imaging methodology is probably not a useful diagnostic tool for KCOTs. Further studies of GLUT1 expression and PET examination in KCOT series are needed to confirm this last hypothesis. Keywords: Glucose transporter protein, Immunohistochemistry, Keratin-producing odontogenic cyst, Keratocystic odontogenic tumour, Orthokeratinised odontogenic cyst, Positron emission tomograph
Modified Gravity and Cosmology
In this review we present a thoroughly comprehensive survey of recent work on
modified theories of gravity and their cosmological consequences. Amongst other
things, we cover General Relativity, Scalar-Tensor, Einstein-Aether, and
Bimetric theories, as well as TeVeS, f(R), general higher-order theories,
Horava-Lifschitz gravity, Galileons, Ghost Condensates, and models of extra
dimensions including Kaluza-Klein, Randall-Sundrum, DGP, and higher
co-dimension braneworlds. We also review attempts to construct a Parameterised
Post-Friedmannian formalism, that can be used to constrain deviations from
General Relativity in cosmology, and that is suitable for comparison with data
on the largest scales. These subjects have been intensively studied over the
past decade, largely motivated by rapid progress in the field of observational
cosmology that now allows, for the first time, precision tests of fundamental
physics on the scale of the observable Universe. The purpose of this review is
to provide a reference tool for researchers and students in cosmology and
gravitational physics, as well as a self-contained, comprehensive and
up-to-date introduction to the subject as a whole.Comment: 312 pages, 15 figure
Single domain antibody multimers confer protection against rabies infection
Post-exposure prophylactic (PEP) neutralizing antibodies against Rabies are the most effective way to prevent infection-related fatality. The outer envelope glycoprotein of the Rabies virus (RABV) is the most significant surface antigen for generating virus-neutralizing antibodies. The small size and uncompromised functional specificity of single domain antibodies (sdAbs) can be exploited in the fields of experimental therapeutic applications for infectious diseases through formatting flexibilities to increase their avidity towards target antigens. In this study, we used phage display technique to select and identify sdAbs that were specific for the RABV glycoprotein from a naïve llama-derived antibody library. To increase their neutralizing potencies, the sdAbs were fused with a coiled-coil peptide derived from the human cartilage oligomeric matrix protein (COMP48) to form homogenous pentavalent multimers, known as combodies. Compared to monovalent sdAbs, the combodies, namely 26424 and 26434, exhibited high avidity and were able to neutralize 85-fold higher input of RABV (CVS-11 strain) pseudotypes in vitro, as a result of multimerization, while retaining their specificities for target antigen. 26424 and 26434 were capable of neutralizing CVS-11 pseudotypes in vitro by 90–95% as compared to human rabies immunoglobulin (HRIG), currently used for PEP in Rabies. The multimeric sdAbs were also demonstrated to be partially protective for mice that were infected with lethal doses of rabies virus in vivo. The results demonstrate that the combodies could be valuable tools in understanding viral mechanisms, diagnosis and possible anti-viral candidate for RABV infection
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