Funnel Models Research Articles

Strategic Marketing Funnel Models in Healthcare: The Role of Healthcare Professionals and Patients in the Referral Paths and the Consumerization of Healthcare Industry

Strategic Marketing Funnel Models in Healthcare: The Role of Healthcare Professionals and Patients in the Referral Paths and the Consumerization of Healthcare Industry

Differences and Similarities between Front-of-Pack Nutrition Labels in Europe: A Comparison of Functional and Visual Aspects.

Many different front-of-pack (FOP) nutrition labels have been introduced worldwide. To continue the debate on the most effective FOP labels for increased consumer health, full comprehension of their visual and functional features is relevant. This paper compares and provides an overview of all FOP labels currently in practice or in preparation in Europe, by means of the visually oriented Funnel Model. The Funnel Models were completed in collaboration with the respective FOP labelling initiatives. In total, six positive FOP labels, two mixed FOP labels and one negative FOP label were compared. There are multiple similarities and differences between the FOP labels, with each FOP label being characterised by a unique set of criteria and methodological approach. This Funnel Model comparison provides the knowledge to ultimately find more common ground for all stakeholders involved in the FOP labelling debate. Importantly, implementation and evaluation activities carried out by FOP labelling organisations are crucial success factors for FOP labels in practice. We conclude that more attention should be paid to methodological differences between FOP labels and recommend that the current comparison is expanded to a global level and periodically updated, as the variety of FOP labels in the global marketplace is changing constantly.

Mechanism of water inrush and quicksand movement induced by a borehole and measures for prevention and remediation

In coal mining, a poorly sealed borehole is one of the channels that can lead to an inrush of water and quicksand movement, seriously compromising the safety of the coal mine. In this paper, we used the water inrush and quicksand incident at Longde Coal Mine as an example in order to investigate the mechanism of water inrush and quicksand movement induced by a borehole, as well as to develop measures for the prevention and remediation of such problems. Two sand funnel models and a water inrush outlet model are introduced from which to calculate the flow of the water and quicksand; a comparison of the two shows that the flow predicted by the water inrush outlet model is more consistent with observations from the accident than the sand funnel models. Based on the water inrush outlet model, the aquifer thickness and borehole diameter are the two key factors affecting the flow. The aquifer channel is inferred as tubular, with its diameter gradually decreasing from ground surface to underground, and a time-dependent surface subsidence model is constructed. Finally, we develop a prevention method, “Prior to mining development, borehole should be investigated and plugged for prevention,” and propose a remediation method, “Changing the pipeline flow into fracture flow, followed by changing the fracture flow into pore flow, and finally grouting and plugging.”

Smoothing Protein Energy Landscapes by Integrating Folding Models with Structure Prediction

Decades of work has investigated the energy landscapes of simple protein models, but what do the landscapes of real, large, atomically detailed proteins look like? We explore an approach to this problem that systematically extracts simple funnel models of actual proteins using ensembles of structure predictions and physics-based atomic force fields and sampling. Central to our effort are calculations of a quantity called the relative entropy, which quantifies the extent to which a given set of structure decoys and a putative native structure can be projected onto a theoretical funnel description. We examine 86 structure prediction targets and one coupled folding-binding system, and find that in a majority of cases the relative entropy robustly signals which structures are nearest to native (i.e., which appear to lie closest to a funnel bottom). Importantly, the landscape model improves substantially upon purely energetic measures in scoring decoys. Our results suggest that physics-based models—including both folding theories and all-atom force fields—may be successfully integrated with structure prediction efforts. Conversely, detailed predictions of structures and the relative entropy approach enable one to extract coarse topographic features of protein landscapes that may enhance the development and application of simpler folding models.

How general is the nucleation-condensation mechanism?

We investigate the structures of the major folding transition states of nine proteins by correlation of published Phi-values with inter-residue contact maps. Combined with previous studies on six proteins, the analysis suggests that at least 10 of the 15 small globular proteins fold via a nucleation-condensation mechanism with a concurrent build-up of secondary and tertiary structure contacts, but a structural consolidation that is clearly nonuniformly distributed over the molecule and most intense in a single structural region suggesting the occurrence of a single folding nucleus. However, on average helix- and sheet-forming residues show somewhat larger Phi-values in the major transition state, suggesting that secondary structure formation is one important driving force in the nucleation-condensation in many proteins and that secondary-structure forming residues tend to be more prominent in folding nuclei. We synthesize the combined information on these 10 of 15 proteins into a unified nucleation-condensation mechanism which also accounts for effects described by the framework, hydrophobic collapse, zipper, and funnel models.

Implausibility of Hydrostatic Funnels Constituting the Sun’s Upper Transition Region

Over the past thirty years, two bodies of literature have developed in parallel presenting mutually exclusive views of the Sun’s upper transition region. One model holds that the Sun’s upper-transition-region plasmas are confined primarily in hydrostatic funnels with a substantial backheating component. The other model holds that discrete structures, which are effectively isolated from the corona, predominate in the Sun’s upper transition region. Purveyors of the latter position have recently begun to present near-resolved observations of discrete structures. The funnel scenario, in contrast, has only been addressed by modeling unresolved upper transition region emission. To address this paradox we have constructed hydrostatic funnel models and tested them against a wider set of solar observations than previously performed. We reproduce the results of the previous analyses, yet find that the hydrostatic funnels are unable to self-consistently match the wider set of observations against which we test the models. We show that it is not possible for a class of funnels having peak temperatures in the transition region or in the corona to match the observations. We conclude that it is implausible that a class of hydrostatic funnels constitutes the dominant emitting component of the Sun’s upper-transition-region plasmas as has been suggested.

Stretched versus compressed exponential kinetics in α-helix folding

In a recent paper (J. Bredenbeck, J. Helbing, J.R. Kumita, G.A. Woolley, P. Hamm, α-helix formation in a photoswitchable peptide tracked from picoseconds to microseconds by time resolved IR spectroscopy, Proc. Natl. Acad. Sci USA 102 (2005) 2379), we have investigated the folding of a photo-switchable α-helix with a kinetics that could be fit by a stretched exponential function exp(−( t/ τ) β ). The stretching factor β became smaller as the temperature was lowered, a result which has been interpreted in terms of activated diffusion on a rugged energy surface. In the present paper, we discuss under which conditions diffusion problems occur with stretched exponential kinetics ( β < 1) and under which compressed exponential kinetics is obtained ( β > 1). We show that diffusion problems do have a strong tendency to yield stretched exponential kinetics, yet, that there are conditions (strong perturbation from equilibrium, performing the experiment in the folding direction) under which compressed exponential kinetics would be expected instead. We discuss the kinetics on free energy surfaces predicted by simple initiation-propagation models (zipper models) of α-helix folding, as well as by folding funnel models. We show that our recent experiment has been performed under condition for which models with strong downhill driving force, such as the zipper model, would predict compressed, rather than stretched exponential kinetics, in disagreement with the experimental observation. We therefore propose that the free energy surface along a reaction coordinate that governs the folding kinetics must be relatively flat and has a shape similar to a 1D golf course. We discuss how this conclusion can be unified with the thermodynamically well established zipper model by introducing an additional kinetic reaction coordinate.

Application of the Gauss theorem to the study of silicic calderas: The calderas of La Primavera, Los Azufres, and Los Humeros (Mexico)

We explored applications (including limitations) of Gauss's theorem to the study of silicic calderas. First it enables us to determine the mass deficiency from calderas. Mass deficiency itself has also other potential applications. It enables to make qualitative comparisons between calderas. We can use the mass deficiency to test, in a quick way and as a preliminary step to a formal gravity inversion, for the feasibility of caldera types of simple geometry (i.e., piston subsidence and funnel models). This application can be done in a straightforward way, once the mass deficiency has been determined. For this purpose the mass deficiency is converted to the volume of material missing at the caldera. Subsequently, for example, this volume and the respective caldera diameter enable us to estimate the height of the cylinder fitting the piston subsidence model. If the obtained parameters are congruent with the known geology and geophysical information then the model may be considered further in the inversion of the gravity data for the detailed structure. Other simple models (i.e., the funnel model) can also be analyzed in this way. In particular, when working with a piston subsidence caldera type, the Gauss theorem enables us to estimate the caldera collapse (very difficult to obtain based on geologic information alone). These possible uses of Gauss's theorem are illustrated with the calderas of La Primavera, Los Azufres, and Los Humeros caldera (Mexico). The obtained mass deficiency from these calderas follow the linear mass deficiency–diameter trend observed for other calderas. In particular, because of their diameters and mass deficiencies, La Primavera and Krakatau calderas can be considered equiparable. This comparison is of the most importance considering that La Primavera is located in the neighbourhood of a metropolis (Guadalajara City). Since geophysical studies have already established a piston subsidence model for these calderas, we assessed Gauss's theorem used to estimate their collapses. The respective estimated subsidences for La Primavera (600 m), Los Humeros (500 m), and Los Azufres calderas (800 and 1200 m, respectively) are supported by borehole data. These relatively small subsidences, in relation to many calderas in western US, can be explained by the presence of cylindrical to sub-spherical magma chambers (of smaller size than those underlying the western US calderas—of Yellowstone, Valles, and Long Valley for example) in an epicontinental setting of young Quaternary rocks (against Precambrian cratonic basement in western US). A reassessment of all the available geological and geophysical information was also done. In particular, the caldera limits were checked and corrected when necessary based on available 2-D gravity modeling, gravity gradients, and the location of the volcanic vents. Regional tectonic lineaments might explain many of the particular details of their structures. La Primavera caldera might have formed through a piecemeal subsidence (controlled by the pre-caldera tectonics); Los Humeros caldera is an example of a caldera that evolved by incremental growth (as the Vulsiniani calderas in Italy). The Los Azufres caldera comprises two contiguous calderas emplaced in a regional tectonic depression.

The Solar Chromosphere/Corona Interface. I. Far‐Ultraviolet to Extreme‐Ultraviolet Observations and Modeling of Unresolved Coronal Funnels

A coronal funnel model, developed by D. Rabin, was tested against a calibrated spectroheliogram recorded in the 170-1 75 A bandpass. This image was recorded on board a sounding-rocket experiment flown on 1994 November 3, called the Multi-Spectral Solar Telescope Array II (MSSTA II). MSSTA, a joint project of Stanford University, the NASA Marshall Space Flight Center, and the Lawrence Livermore National Laboratory' is an observing platform composed of a set of normal-incidence, multilayer-coated optics designed to obtain narrow-bandpass, high-resolution images (1 sec.- 3 sec.) at selected far-ultraviolet (FUV), extreme-ultraviolet (EUV), and soft X-ray wavelengths (44-1550 A). Using full disk images centered at 1550 A (C IV) and 173 A (Fe IX/X), the funnel model, which is based on coronal back-heating, was tested against the data incorporating observed constraints on global coverage and measured flux. Found was a class of funnel models that could account for the quiescent, globally diffuse and unresolved emission seen in the 171-175 A bandpass, where the funnels are assumed to be rooted in the C IV supergranular network. These models, when incorporated with the CHIANTI spectral code, suggest that this emission is mostly of upper transition region origin and primarily composed of Fe IX plasma. The funnels are found to have constrictions, Gamma approx. 6-20, which is in good agreement with the observations. Further, the fitted models simultaneously satisfy global areal constraints seen in both images; namely,that a global network of funnels must cover approx. 700 - 95% of the total solar surface area seen in the 171-175 A image, and a 5% of the disk area seen in the 1550 A bandpass. These findings support the configuration of the EUV magnetic network as suggested by Reeves et al. and put forth in more detail by Gabriel. Furthermore, the models are in good agreement with differential emission measure estimates made of the transition region by J. C. Raymond & J. G. Doyle for temperatures 250,000 K less than or = T less than or = 650,000 K, based on full-disk observations made on board Skylab.

Fast-folding protein kinetics, hidden intermediates, and the sequential stabilization model.

Do two-state proteins fold by pathways or funnels? Native-state hydrogen exchange experiments show discrete nonnative structures in equilibrium with the native state. These could be called hidden intermediates (HI) because their populations are small at equilibrium, and they are not detected in kinetic experiments. HIs have been invoked as disproof of funnel models, because funnel pictures appear to indicate (1) no specific sequences of events in folding; (2) a continuum, rather than a discrete ladder, of structures; and (3) smooth landscapes. In the present study, we solve the exact dynamics of a simple model. We find, instead, that the present microscopic model is indeed consistent with HIs and transition states, but such states occur in parallel, rather than along the single pathway predicted by the sequential stabilization model. At the microscopic level, we observe a huge multiplicity of trajectories. But at the macroscopic level, we observe two pathways of specific sequences of events that are relatively traditional except that they are in parallel, so there is not a single reaction coordinate. Using singular value decomposition, we show an accurate representation of the shapes of the model energy landscapes. They are highly complex funnels.

X-ray spectra and light curves of accreting magnetic degenerate dwarfs

We report detailed calculations of the X-ray spectra and X-ray light curves of accreting magnetic 1 M/sub sun/ degenerate dwarfs. We use accretion funnel models in which plasma flows toward the dwarf along dipole magnetic field lines and accretes onto a small cap at the dwarf's magnetic pole of area 4..pi..R/sup 2//sub asterisk/ f, where R/sub asterisk/ is the stellar radius and f<<1. Above the dwarf's surface, the plasma forms a radiating shock which produces the X-rays. We find that the X-ray spectra of weakly magnetic degenerate dwarfs are qualitatively similar to the spectra of nonmagnetic dwarfs. However, because the optical depth perpendicular to the field lines in the funnel is less than the optical depth parallel to the field lines, the majority of the X-rays escape in directions perpendicular to the field lines. This has two effects: (1) For magnetic and nonmagnetic models with equivalent accretion rates per square centimeter, i.e., equal ''effective luminosities'' L/sub f/(equivalent L/f), the emergent photons in the magnetic case suffer fewer scatterings than those in the nonmagnetic case and thus show less energy degradation. (2) The beaming of the photons into directions perpendicular to the field lines leads to X-ray light curves which exhibitmore » a wide range of behaviors. The shapes of the light curves are sensitive to f and L/sub f/, to the inclination of the magnetic field axis to the dwarf's rotation axis, and to the viewing angle of the dwarf. Thus, observed X-ray light curves can be used to constrain the physical characteristics and geometry of the accreting degenerate dwarf.« less