4,171 research outputs found
Use of Marketing Metrics: A Different Point of View
There is a more important problem than developing new marketing metrics. Most packaged-goods manufacturers and other marketers are not getting anywhere near full value from the metrics currently available. In this article, I summarize some data on the underutilization of metrics, hypothesize some reasons for this, and describe some steps to be taken to improve firms’ performance by using metrics more effectively
Recommended from our members
Aortic pulse wave velocity in children with Cushing syndrome: A window into a marker of early cardiovascular disease.
ObjectiveTo investigate early signs of cardiovascular arterial remodelling in paediatric patients with Cushing syndrome (CS) in comparison with normative values from healthy children.Study designThe metrics used to assess cardiac health were from thoracic aorta and carotid MRI. Scans were performed on 18 children with CS (mean: 12.5 ± 3.1 years, range: 6.0-16.8 years, 10 female). Pulse wave velocity (PWV), aortic distensibility (AD) and carotid intima-media thickness (cIMT), well-validated measurements of cardiac compromise, were measured from the images and compared to normative age-matched values where available.ResultsPatients with CS had significantly higher PWV compared to age-adjusted normal median control values (4.0 ± 0.7 m/s vs. 3.4 ± 0.2 m/s, respectively, P = 0.0115). PWV was positively correlated with midnight plasma cortisol (r = 0.56, P = 0.02). Internal and common cIMT were negatively correlated with ascending AD (r = -0.75, P = 0.0022, r = -0.69, P = 0.0068, respectively).ConclusionPulse wave velocity data indicate that paediatric patients with CS have early evidence of cardiovascular remodelling. The results suggest the opportunity for monitoring as these changes begin in childhood
Effect of Interactions on Molecular Fluxes and Fluctuations in the Transport Across Membrane Channels
Transport of molecules across membrane channels is investigated theoretically
using exactly solvable one-dimensional discrete-state stochastic models. An
interaction between molecules and membrane pores is modeled via a set of
binding sites with different energies. It is shown that the interaction
potential strongly influences the particle currents as well as fluctuations in
the number of translocated molecules. For small concentration gradients the
attractive sites lead to largest currents and fluctuations, while the repulsive
interactions yield the largest fluxes and dispersions for large concentration
gradients. Interaction energies that lead to maximal currents and maximal
fluctuations are the same only for locally symmetric potentials, while they
differ for the locally asymmetric potentials. The conditions for the most
optimal translocation transport with maximal current and minimal dispersion are
discussed. It is argued that in this case the interaction strength is
independent of local symmetry of the potential of mean forces. In addition, the
effect of the global asymmetry of the interaction potential is investigated,
and it is shown that it also strongly affects the particle translocation
dynamics. These phenomena can be explained by analyzing the details of the
particle entering and leaving the binding sites in the channel.Comment: submitted to J. Chem. Phy
Effect of Inhomogeneity in Translocation of Polymers through Nanopores
The motion of polymers with inhomogeneous structure through nanopores is
discussed theoretically. Specifically, we consider the translocation dynamics
of polymers consisting of double-stranded and single-stranded blocks. Since
only the single-stranded chain can go through the nanopore the double-stranded
segment has to unzip before the translocation. Utilizing a simple analytical
model, translocation times are calculated explicitly for different polymer
orientations, i.e., when the single-stranded block enters the pore first and
when the double-stranded segment is a leading one. The dependence of the
translocation dynamics on external fields, energy of interaction in the
double-stranded segment, size of the polymer and the fraction of
double-stranded monomers is analyzed. It is found that the order of entrance
into the pore has a significant effect on the translocation dynamics. The
theoretical results are discussed using free-energy landscape arguments.Comment: 12 pages, 5 figures, submitted to J. Chem. Phy
Numerical simulation of conformational variability in biopolymer translocation through wide nanopores
Numerical results on the translocation of long biopolymers through mid-sized
and wide pores are presented. The simulations are based on a novel methodology
which couples molecular motion to a mesoscopic fluid solvent. Thousands of
events of long polymers (up to 8000 monomers) are monitored as they pass
through nanopores. Comparison between the different pore sizes shows that wide
pores can host a larger number of multiple biopolymer segments, as compared to
smaller pores. The simulations provide clear evidence of folding quantization
in the translocation process as the biopolymers undertake multi-folded
configurations, characterized by a well-defined integer number of folds.
Accordingly, the translocation time is no longer represented by a
single-exponent power law dependence on the length, as it is the case for
single-file translocation through narrow pores. The folding quantization
increases with the biopolymer length, while the rate of translocated beads at
each time step is linearly correlated to the number of resident beads in the
pore. Finally, analysis of the statistics over the translocation work unravels
the importance of the hydrodynamic interactions in the process.Comment: 10 pages, 6 figures, to appear in J. Stat. (2009
Models of dynamic extraction of lipid tethers from cell membranes
When a ligand that is bound to an integral membrane receptor is pulled, the
membrane and the underlying cytoskeleton can deform before either the membrane
delaminates from the cytoskeleton or the ligand detaches from the receptor. If
the membrane delaminates from the cytoskeleton, it may be further extruded and
form a membrane tether. We develop a phenomenological model for this processes
by assuming that deformations obey Hooke's law up to a critical force at which
the cell membrane locally detaches from the cytoskeleton and a membrane tether
forms. We compute the probability of tether formation and show that they can be
extruded only within an intermediate range of force loading rates and pulling
velocities. The mean tether length that arises at the moment of ligand
detachment is computed as are the force loading rates and pulling velocities
that yield the longest tethers.Comment: 16 pages, 7 figure
A novel method for measuring the bending rigidity of model lipid membranes by simulating tethers
The tensile force along a cylindrical lipid bilayer tube is proportional to
the membrane's bending modulus and inversely proportional to the tube radius.
We show that this relation, which is experimentally exploited to measure
bending rigidities, can be applied with even greater ease in computer
simulations. Using a coarse-grained bilayer model we efficiently obtain bending
rigidities that compare very well with complementary measurements based on an
analysis of thermal undulation modes. We furthermore illustrate that no
deviations from simple quadratic continuum theory occur up to a radius of
curvature comparable to the bilayer thickness.Comment: 7 pages, 5 figures, 1 tabl
Protein search for multiple targets on DNA
Protein-DNA interactions are crucial for all biological processes. One of the
most important fundamental aspects of these interactions is the process of
protein searching and recognizing specific binding sites on DNA. A large number
of experimental and theoretical investigations have been devoted to uncovering
the molecular description of these phenomena, but many aspects of the
mechanisms of protein search for the targets on DNA remain not well understood.
One of the most intriguing problems is the role of multiple targets in protein
search dynamics. Using a recently developed theoretical framework we analyze
this question in detail. Our method is based on a discrete-state stochastic
approach that takes into account most relevant physical-chemical processes and
leads to fully analytical description of all dynamic properties. Specifically,
systems with two and three targets have been explicitly investigated. It is
found that multiple targets in most cases accelerate the search in comparison
with a single target situation. However, the acceleration is not always
proportional to the number of targets. Surprisingly, there are even situations
when it takes longer to find one of the multiple targets in comparison with the
single target. It depends on the spatial position of the targets, distances
between them, average scanning lengths of protein molecules on DNA, and the
total DNA lengths. Physical-chemical explanations of observed results are
presented. Our predictions are compared with experimental observations as well
as with results from a continuum theory for the protein search. Extensive Monte
Carlo computer simulations fully support our theoretical calculations
Recent advances in experimental techniques to probe fast excited-state dynamics in biological molecules in the gas phase : dynamics in nucleotides, amino acids and beyond
In many chemical reactions, an activation barrier must be overcome before a chemical transformation can occur. As such, understanding the behaviour of molecules in energetically excited states is critical to understanding the chemical changes that these molecules undergo. Among the most prominent reactions for mankind to understand are chemical changes that occur in our own biological molecules. A notable example is the focus towards understanding the interaction of DNA with ultraviolet radiation and the subsequent chemical changes. However, the interaction of radiation with large biological structures is highly complex, and thus the photochemistry of these systems as a whole is poorly understood. Studying the gas-phase spectroscopy and ultrafast dynamics of the building blocks of these more complex biomolecules offers the tantalizing prospect of providing a scientifically intuitive bottom-up approach, beginning with the study of the subunits of large polymeric biomolecules and monitoring the evolution in photochemistry as the complexity of the molecules is increased. While highly attractive, one of the main challenges of this approach is in transferring large, and in many cases, thermally labile molecules into vacuum. This review discusses the recent advances in cutting-edge experimental methodologies, emerging as excellent candidates for progressing this bottom-up approach
- …