83 research outputs found
Method for Solving State-Path Constrained Optimal Control Problems Using Adaptive Radau Collocation
A new method is developed for accurately approximating the solution to
state-variable inequality path constrained optimal control problems using a
multiple-domain adaptive Legendre-Gauss-Radau collocation method. The method
consists of the following parts. First, a structure detection method is
developed to estimate switch times in the activation and deactivation of
state-variable inequality path constraints. Second, using the detected
structure, the domain is partitioned into multiple-domains where each domain
corresponds to either a constrained or an unconstrained segment. Furthermore,
additional decision variables are introduced in the multiple-domain
formulation, where these additional decision variables represent the switch
times of the detected active state-variable inequality path constraints. Within
a constrained domain, the path constraint is differentiated with respect to the
independent variable until the control appears explicitly, and this derivative
is set to zero along the constrained arc while all preceding derivatives are
set to zero at the start of the constrained arc. The time derivatives of the
active state-variable inequality path constraints are computed using automatic
differentiation and the properties of the chain rule. The method is
demonstrated on two problems, the first being a benchmark optimal control
problem which has a known analytical solution and the second being a
challenging problem from the field of aerospace engineering in which there is
no known analytical solution. When compared against previously developed
adaptive Legendre-Gauss-Radau methods, the results show that the method
developed in this paper is capable of computing accurate solutions to problems
whose solution contain active state-variable inequality path constraints.Comment: 31 pages, 7 figures, 5 table
The pediatric emergency department care experience: A quality measure
To develop and validate a measure of the quality of the pediatric emergency department care experience from the parent perspective. This was a multiphase study conducted at a tertiary-care pediatric health system using qualitative and quantitative methods. A list of candidate questions was developed to measure each of eight dimensions of family-centered pediatric emergency care described in a published framework. This list was evaluated and refined using the Question Appraisal System (QAS-99) followed by cognitive interviewing methods. Remaining questions were field tested using survey methods via telephone interviews with randomly selected parents. Composite scores to measure each of the eight dimensions of family-centered pediatric emergency care were calculated. Reliability was evaluated using measures of internal consistency. Construct validity was evaluated by measuring the association of each question and composite scores with overall satisfaction. A pool of 77 questions was reduced to 51 using QAS-99 criteria. Cognitive interviews with 19 parents resulted in a final list of 24 questions for field testing. With a response rate of 46%, 404 parents participated in the field test. Each individual question exhibited a significant positive association with overall satisfaction. Measures of internal consistency did not support the composite scores based on the initial eight dimensions. An exploratory factor analysis resulted in alternative composite measures that exhibited acceptable reliability and construct validity. This study has resulted in a measure that can be used to inform quality improvement work aimed at improving the pediatric emergency department care experience
Sometimes Sperm Whales (Physeter macrocephalus) Cannot Find Their Way Back to the High Seas: A Multidisciplinary Study on a Mass Stranding
BACKGROUND: Mass strandings of sperm whales (Physeter macrocephalus) remain peculiar and rather unexplained events, which rarely occur in the Mediterranean Sea. Solar cycles and related changes in the geomagnetic field, variations in water temperature and weather conditions, coast geographical features and human activities have been proposed as possible causes. In December 2009, a pod of seven male sperm whales stranded along the Adriatic coast of Southern Italy. This is the sixth instance from 1555 in this basin. METHODOLOGY/PRINCIPAL FINDINGS: Complete necropsies were performed on three whales whose bodies were in good condition, carrying out on sampled tissues histopathology, virology, bacteriology, parasitology, and screening of veins looking for gas emboli. Furthermore, samples for age determination, genetic studies, gastric content evaluation, stable isotopes and toxicology were taken from all the seven specimens. The animals were part of the same group and determined by genetic and photo-identification to be part of the Mediterranean population. Causes of death did not include biological agents, or the "gas and fat embolic syndrome", associated with direct sonar exposure. Environmental pollutant tissue concentrations were relatively high, in particular organochlorinated xenobiotics. Gastric content and morphologic tissue examinations showed a prolonged starvation, which likely caused, at its turn, the mobilization of lipophilic contaminants from the adipose tissue. Chemical compounds subsequently entered the blood circulation and may have impaired immune and nervous functions. CONCLUSIONS/SIGNIFICANCE: A multi-factorial cause underlying this sperm whales' mass stranding is proposed herein based upon the results of postmortem investigations as well as of the detailed analyses of the geographical and historical background. The seven sperm whales took the same "wrong way" into the Adriatic Sea, a potentially dangerous trap for Mediterranean sperm whales. Seismic surveys should be also regarded as potential co-factors, even if no evidence of direct impact has been detected
Alterations in voltage-sensing of the mitochondrial permeability transition pore in ANT1-deficient cells
The probability of mitochondrial permeability transition (mPT) pore opening is inversely related to the magnitude of the proton electrochemical gradient. The module conferring sensitivity of the pore to this gradient has not been identified. We investigated mPT's voltage-sensing properties elicited by calcimycin or H2O2 in human fibroblasts exhibiting partial or complete lack of ANT1 and in C2C12 myotubes with knocked-down ANT1 expression. mPT onset was assessed by measuring in situ mitochondrial volume using the 'thinness ratio' and the 'cobalt-calcein' technique. De-energization hastened calcimycin-induced swelling in control and partially-expressing ANT1 fibroblasts, but not in cells lacking ANT1, despite greater losses of mitochondrial membrane potential. Matrix Ca(2+) levels measured by X-rhod-1 or mitochondrially-targeted ratiometric biosensor 4mtD3cpv, or ADP-ATP exchange rates did not differ among cell types. ANT1-null fibroblasts were also resistant to H2O2-induced mitochondrial swelling. Permeabilized C2C12 myotubes with knocked-down ANT1 exhibited higher calcium uptake capacity and voltage-thresholds of mPT opening inferred from cytochrome c release, but intact cells showed no differences in calcimycin-induced onset of mPT, irrespective of energization and ANT1 expression, albeit the number of cells undergoing mPT increased less significantly upon chemically-induced hypoxia than control cells. We conclude that ANT1 confers sensitivity of the pore to the electrochemical gradient
Alterations in voltage-sensing of the mitochondrial permeability transition pore in ANT1-deficient cells
The probability of mitochondrial permeability transition (mPT) pore opening is inversely related to the magnitude of the proton electrochemical gradient. The module conferring sensitivity of the pore to this gradient has not been identified. We investigated mPT's voltage-sensing properties elicited by calcimycin or H2O2 in human fibroblasts exhibiting partial or complete lack of ANT1 and in C2C12 myotubes with knocked-down ANT1 expression. mPT onset was assessed by measuring in situ mitochondrial volume using the 'thinness ratio' and the 'cobalt-calcein' technique. De-energization hastened calcimycin-induced swelling in control and partially-expressing ANT1 fibroblasts, but not in cells lacking ANT1, despite greater losses of mitochondrial membrane potential. Matrix Ca(2+) levels measured by X-rhod-1 or mitochondrially-targeted ratiometric biosensor 4mtD3cpv, or ADP-ATP exchange rates did not differ among cell types. ANT1-null fibroblasts were also resistant to H2O2-induced mitochondrial swelling. Permeabilized C2C12 myotubes with knocked-down ANT1 exhibited higher calcium uptake capacity and voltage-thresholds of mPT opening inferred from cytochrome c release, but intact cells showed no differences in calcimycin-induced onset of mPT, irrespective of energization and ANT1 expression, albeit the number of cells undergoing mPT increased less significantly upon chemically-induced hypoxia than control cells. We conclude that ANT1 confers sensitivity of the pore to the electrochemical gradient
Bidirectional fluxes of spermine across the mitochondrial membrane.
The polyamine spermine is transported into the
mitochondrial matrix by an electrophoretic mechanism
having as driving force the negative electrical membrane
potential (DW). The presence of phosphate increases
spermine uptake by reducingDpH and enhancingDW. The
transport system is a specific uniporter constituted by a
protein channel exhibiting two asymmetric energy barriers
with the spermine binding site located in the energy well
between the two barriers. Although spermine transport is
electrophoretic in origin, its accumulation does not follow
the Nernst equation for the presence of an efflux pathway.
Spermine efflux may be induced by different agents, such as
FCCP, antimycin A and mersalyl, able to completely or
partially reduce theDWvalue and, consequently, suppress
or weaken the force necessary to maintain spermine in the
matrix. However this efflux may also take place in normal
conditions when the electrophoretic accumulation of the
polycationic polyamine induces a sufficient drop inDWable
to trigger the efflux pathway. The release of the polyamine
is most probably electroneutral in origin and can take place
in exchange with protons or in symport with phosphate
anion. The activity of both the uptake and efflux pathways
induces a continuous cycling of spermine across the mitochondrial membrane, the rate of which may be prominent in imposing the concentrations of spermine in the inner and
outer compartment. Thus, this event has a significant role on
mitochondrial permeability transition modulation and consequently on the triggering of intrinsic apoptosis
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