155 research outputs found
On the waiting time of arriving aircrafts and the capacity of airports with one or two runways
In this paper we examine a model for the landing procedure of aircrafts at an airport. The characteristic feature here is that due to air turbulence the safety distance between two landing aircrafts depends on the types of these two machines. Hence, an eficient routing of the aircraft to two runways may reduce their waiting time.
First, we use M/SM/1 queues (with dependent service times) to model a single runway. We give the stability condition and a formula for the average waiting time of the aircrafts. Moreover, we derive easy to compute bounds on the waiting times by comparison to simpler queuing systems. In particular we study the effect of neglecting the dependency of the service times when using M/G/1-models.
We then consider the case of two runways with a number of heuristic routing strategies such as coin flipping, type splitting, Round Robin and variants of the join-the-least-load rule. These strategies are analyzed and compared numerically with respect to the average delay they cause.
It turns out that a certain modication of join-the-least-load gives the best results
Routing of airplanes to two runways: monotonicity of optimal controls
We consider the problem of routing incoming airplanes to two runways of an airport. Due to air turbulence, the necessary separation time between two successive landing operations depends on the types of the airplanes. When viewed as a queueing problem, this means that we have dependent service times. The aim is to minimise waiting times of aircrafts. We consider here a model where arrivals form a stochastic process and where the decision maker does not know anything about future arrivals. We formulate this as a problem of stochastic dynamic programming and investigate monotonicity of optimal routing strategies with respect e.g. to the workload of the runways. We show that an optimal strategy is monotone (i.e. of switching type) only in a restricted case where decisions depend on the state of the runways only and not on the type of the arriving aircraft. Surprisingly, in the more realistic case where this type is also known to the decision maker, monotonicity need not hold
Chitosan Nanocomplexes for the Delivery of ENaC Antisense Oligonucleotides to Airway Epithelial Cells
Nanoscale drug delivery systems exhibit a broad range of applications and promising treatment possibilities for various medical conditions. Nanomedicine is of great interest, particularly for rare diseases still lacking a curative treatment such as cystic fibrosis (CF). CF is defined by a lack of Cl− secretion through the cystic fibrosis transmembrane conductance regulator (CFTR) and an increased Na+ absorption mediated by the epithelial sodium channel (ENaC). The imbalanced ion and water transport leads to pathological changes in many organs, particularly in the lung. We developed a non-viral delivery system based on the natural aminopolysaccharide chitosan (CS) for the transport of antisense oligonucleotides (ASO) against ENaC to specifically address Na+ hyperabsorption. CS–ASO electrostatic self-assembled nanocomplexes were formed at varying positive/negative (P/N) charge ratios and characterized for their physicochemical properties. Most promising nanocomplexes (P/N 90) displayed an average size of ~150 nm and a zeta potential of ~+30 mV. Successful uptake of the nanocomplexes by the human airway epithelial cell line NCI-H441 was confirmed by fluorescence microscopy. Functional Ussing chamber measurements of transfected NCI-H441 cells showed significantly decreased Na+ currents, indicating successful downregulation of ENaC. The results obtained confirm the promising characteristics of CS as a non-viral and non-toxic delivery system and demonstrate the encouraging possibility to target ENaC with ASOs to treat abnormal ion transport in CF
The histone chaperones Vps75 and Nap1 form ring-like, tetrameric structures in solution
NAP-1 fold histone chaperones play an important role in escorting histones to and from sites of nucleosome assembly and disassembly. The two NAP-1 fold histone chaperones in budding yeast, Vps75 and Nap1, have previously been crystalized in a characteristic homodimeric conformation. In this study, a combination of small angle X-ray scattering, multi angle light scattering and pulsed electron–electron double resonance approaches were used to show that both Vps75 and Nap1 adopt ring-shaped tetrameric conformations in solution. This suggests that the formation of homotetramers is a common feature of NAP-1 fold histone chaperones. The tetramerisation of NAP-1 fold histone chaperones may act to shield acidic surfaces in the absence of histone cargo thus providing a ‘self-chaperoning’ type mechanism
Capsaicin-Loaded Chitosan Nanocapsules for wtCFTR-mRNA Delivery to a Cystic Fibrosis Cell Line
Cystic fibrosis (CF), a lethal hereditary disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene coding for an epithelial chloride channel, is characterized by an imbalanced homeostasis of ion and water transports in secretory epithelia. As the disease is single-gene based, transcript therapy using therapeutic mRNA is a promising concept of treatment in order to correct many aspects of the fatal pathology on a cellular level. Hence, we developed chitosan nanocapsules surface-loaded with wtCFTR-mRNA to restore CFTR function. Furthermore, we loaded the nanocapsules with capsaicin, aiming to enhance the overall efficiency of transcript therapy by reducing sodium hyperabsorption by the epithelial sodium channel (ENaC). Dynamic light scattering with non-invasive back scattering (DLS-NIBS) revealed nanocapsules with an average hydrodynamic diameter of ~200 nm and a Zeta potential of ~+60 mV. The results of DLS-NIBS measurements were confirmed by asymmetric flow field-flow fractionation (AF4) with multidetection, while transmission electron microscopy (TEM) images confirmed the spherical morphology and size range. After stability measurements showed that the nanocapsules were highly stable in cell culture transfection medium, and cytotoxicity was ruled out, transfection experiments were performed with the CF cell line CFBE41o-. Finally, transepithelial measurements with a new state-of-the-art Ussing chamber confirmed successfully restored CFTR function in transfected cells. This study demonstrates that CS nanocapsules as a natural and non-toxic delivery system for mRNA to target cells could effectively replace risky vectors for gene delivery. The nanocapsules are not only suitable as a transcript therapy for treatment of CF, but open aspiring possibilities for safe gene delivery in general
Radio pulsar populations
The goal of this article is to summarize the current state of play in the
field of radio pulsar statistics. Simply put, from the observed sample of
objects from a variety of surveys with different telescopes, we wish to infer
the properties of the underlying sample and to connect these with other
astrophysical populations (for example supernova remnants or X-ray binaries).
The main problem we need to tackle is the fact that, like many areas of
science, the observed populations are often heavily biased by a variety of
selection effects. After a review of the main effects relevant to radio
pulsars, I discuss techniques to correct for them and summarize some of the
most recent results. Perhaps the main point I would like to make in this
article is that current models to describe the population are far from complete
and often suffer from strong covariances between input parameters. That said,
there are a number of very interesting conclusions that can be made concerning
the evolution of neutron stars based on current data. While the focus of this
review will be on the population of isolated Galactic pulsars, I will also
briefly comment on millisecond and binary pulsars as well as the pulsar content
of globular clusters and the Magellanic Clouds.Comment: 16 pages, 6 figures, to appear in Proceedings of ICREA Workshop on
The High-Energy Emission from Pulsars and their Systems, Sant Cugat, Spain,
2010 April 12-16 (Springer
Random field sampling for a simplified model of melt-blowing considering turbulent velocity fluctuations
In melt-blowing very thin liquid fiber jets are spun due to high-velocity air
streams. In literature there is a clear, unsolved discrepancy between the
measured and computed jet attenuation. In this paper we will verify numerically
that the turbulent velocity fluctuations causing a random aerodynamic drag on
the fiber jets -- that has been neglected so far -- are the crucial effect to
close this gap. For this purpose, we model the velocity fluctuations as vector
Gaussian random fields on top of a k-epsilon turbulence description and develop
an efficient sampling procedure. Taking advantage of the special covariance
structure the effort of the sampling is linear in the discretization and makes
the realization possible
Interaction patterns of methoprene-tolerant and germ cell-expressed Drosophila JH receptors suggest significant differences in their functioning
Methoprene-tolerant (Met) and germ cell-expressed (Gce) proteins were shown to be juvenile hormone (JH) receptors of Drosophila melanogaster with partially redundant functions. We raised the question of where the functional differentiation of paralogs comes from. Therefore, we tested Met and Gce interaction patterns with selected partners. In this study, we showed the ability of Gce and its C-terminus (GceC) to interact with 14-3-3 in the absence of JH. In contrast, Met or Met C-terminus (MetC) interactions with 14-3-3 were not observed. We also performed a detailed structural analysis of Met/Gce interactions with the nuclear receptor fushi tarazu factor-1 (Ftz-F1) ligand-binding domain. We showed that GceC comprising an Ftz-F1-binding site and full-length protein interacts with Ftz-F1. In contrast to Gce, only MetC (not full-length Met) can interact with Ftz-F1 in the absence of JH. We propose that the described differences result from the distinct tertiary structure and accessibility of binding sites in the full-length Met/Gce. Moreover, we hypothesize that each interacting partner can force disordered MetC and GceC to change the structure in a partner-specific manner. The observed interactions seem to determine the subcellular localization of Met/Gce by forcing their translocation between the nucleus and the cytoplasm, which may affect the activity of the proteins. The presented differences between Met and Gce can be crucial for their functional differentiation during D. melanogaster development and indicate Gce as a more universal and more active paralog. It is consistent with the theory indicating gce as an ancestor gene
Which chronic diseases and disease combinations are specific to multimorbidity in the elderly? Results of a claims data based cross-sectional study in Germany
<p>Abstract</p> <p>Background</p> <p>Growing interest in multimorbidity is observable in industrialized countries. For Germany, the increasing attention still goes still hand in hand with a small number of studies on multimorbidity. The authors report the first results of a cross-sectional study on a large sample of policy holders (n = 123,224) of a statutory health insurance company operating nationwide. This is the first comprehensive study addressing multimorbidity on the basis of German claims data. The main research question was to find out which chronic diseases and disease combinations are specific to multimorbidity in the elderly.</p> <p>Methods</p> <p>The study is based on the claims data of all insured policy holders aged 65 and older (n = 123,224). Adjustment for age and gender was performed for the German population in 2004. A person was defined as multimorbid if she/he had at least 3 diagnoses out of a list of 46 chronic conditions in three or more quarters within the one-year observation period. Prevalences and risk-ratios were calculated for the multimorbid and non-multimorbid samples in order to identify diagnoses more specific to multimorbidity and to detect excess prevalences of multimorbidity patterns.</p> <p>Results</p> <p>62% of the sample was multimorbid. Women in general and patients receiving statutory nursing care due to disability are overrepresented in the multimorbid sample. Out of the possible 15,180 combinations of three chronic conditions, 15,024 (99%) were found in the database. Regardless of this wide variety of combinations, the most prevalent individual chronic conditions do also dominate the combinations: Triads of the six most prevalent individual chronic conditions (hypertension, lipid metabolism disorders, chronic low back pain, diabetes mellitus, osteoarthritis and chronic ischemic heart disease) span the disease spectrum of 42% of the multimorbid sample. Gender differences were minor. Observed-to-expected ratios were highest when purine/pyrimidine metabolism disorders/gout and osteoarthritis were part of the multimorbidity patterns.</p> <p>Conclusions</p> <p>The above list of dominating chronic conditions and their combinations could present a pragmatic start for the development of needed guidelines related to multimorbidity.</p
On the pulse--width statistics in radio pulsars. I. Importance of the interpulse emission
We performed Monte Carlo simulations of different properties of pulsar radio
emission, such as: pulsar periods, pulse-widths, inclination angles and rates
of occurrence of interpulse emission (IP). We used recently available large
data sets of the pulsar periods P, the pulse profile widths W and the magnetic
inclination angle alpha. We also compiled the largest ever database of pulsars
with interpulse emission, divided into the double-pole (DP-IP) and the
single-pole (SP-IP) cases. Their distribution on the P - Pdot diagram strongly
suggests a secular alignment of the magnetic axis from the originally random
orientation. We derived possible parent distribution functions of important
pulsar parameters by means of the Kolmogorov-Smirnov significance test using
the available data sets (P, W, alpha and IP), different models of pulsar radio
beam rho = rho(P) as well as different trial distribution functions of pulsar
period and the inclination angles. The best suited parent period distribution
function is the log-normal distribution, although the gamma function
distribution cannot be excluded. The strongest constraint on derived model
distribution functions was the requirement that the numbers of interpulses were
exactly (within 1sigma errors) at the observed level of occurrences. We found
that a suitable model distribution function for the inclination angle is the
complicated trigonometric function which has two local maxima, one near 0 deg
and the other near 90 deg. The former and the latter implies the right rates of
IP occurrence. It is very unlikely that the pulsar beam deviates significantly
from the circular cross-section. We found that the upper limit for the average
beaming factor fb describing a fraction of the full sphere (called also beaming
fraction) covered by a pulsar beam is about 10%. This implies that the number
of the neutron stars in the Galaxy might be underestimated.Comment: 35 pages, 18 figure
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