| 1. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 2. |
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| 3. |
- Sampson, Joshua N., et al.
(author)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Journal article (peer-reviewed)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 4. |
- Wang, Zhaoming, et al.
(author)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 5. |
- Ade, Peter, et al.
(author)
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The Simons Observatory : science goals and forecasts
- 2019
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In: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :2
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Journal article (peer-reviewed)abstract
- The Simons Observatory (SO) is a new cosmic microwave background experiment being built on Cerro Toco in Chile, due to begin observations in the early 2020s. We describe the scientific goals of the experiment, motivate the design, and forecast its performance. SO will measure the temperature and polarization anisotropy of the cosmic microwave background in six frequency bands centered at: 27, 39, 93, 145, 225 and 280 GHz. The initial con figuration of SO will have three small-aperture 0.5-m telescopes and one large-aperture 6-m telescope, with a total of 60,000 cryogenic bolometers. Our key science goals are to characterize the primordial perturbations, measure the number of relativistic species and the mass of neutrinos, test for deviations from a cosmological constant, improve our understanding of galaxy evolution, and constrain the duration of reionization. The small aperture telescopes will target the largest angular scales observable from Chile, mapping approximate to 10% of the sky to a white noise level of 2 mu K-arcmin in combined 93 and 145 GHz bands, to measure the primordial tensor-to-scalar ratio, r, at a target level of sigma(r) = 0.003. The large aperture telescope will map approximate to 40% of the sky at arcminute angular resolution to an expected white noise level of 6 mu K-arcmin in combined 93 and 145 GHz bands, overlapping with the majority of the Large Synoptic Survey Telescope sky region and partially with the Dark Energy Spectroscopic Instrument. With up to an order of magnitude lower polarization noise than maps from the Planck satellite, the high-resolution sky maps will constrain cosmological parameters derived from the damping tail, gravitational lensing of the microwave background, the primordial bispectrum, and the thermal and kinematic Sunyaev-Zel'dovich effects, and will aid in delensing the large-angle polarization signal to measure the tensor-to-scalar ratio. The survey will also provide a legacy catalog of 16,000 galaxy clusters and more than 20,000 extragalactic sources.
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| 6. |
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| 7. |
- Anchordoqui, Luis A., et al.
(author)
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The Forward Physics Facility : Sites, experiments, and physics potential
- 2022
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In: Physics reports. - : Elsevier. - 0370-1573 .- 1873-6270. ; 968, s. 1-50
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Journal article (peer-reviewed)abstract
- The Forward Physics Facility (FPF) is a proposal to create a cavern with the space and infrastructure to support a suite of far-forward experiments at the Large Hadron Collider during the High Luminosity era. Located along the beam collision axis and shielded from the interaction point by at least 100 m of concrete and rock, the FPF will house experiments that will detect particles outside the acceptance of the existing large LHC experiments and will observe rare and exotic processes in an extremely low-background environment. In this work, we summarize the current status of plans for the FPF, including recent progress in civil engineering in identifying promising sites for the FPF and the experiments currently envisioned to realize the FPF's physics potential. We then review the many Standard Model and new physics topics that will be advanced by the FPF, including searches for long-lived particles, probes of dark matter and dark sectors, high-statistics studies of TeV neutrinos of all three flavors, aspects of perturbative and non-perturbative QCD, and high-energy astroparticle physics.
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| 8. |
- Ariel, Gil, et al.
(author)
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A multiscale method for stiff ordinary differential equations with resonance
- 2009
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In: Mathematics of Computation. - 0025-5718 .- 1088-6842. ; 78:266, s. 929-956
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Journal article (peer-reviewed)abstract
- A multiscale method for computing the effective behavior of a class of stiff and highly oscillatory ordinary differential equations (ODEs) is presented. The oscillations may be in resonance with one another and thereby generate hidden slow dynamics. The proposed method relies on correctly tracking a set of slow variables whose dynamics is closed up to perturbation, and is sufficient to approximate any variable and functional that are slow under the dynamics of the ODE. This set of variables is detected numerically as a preprocessing step in the numerical methods. Error and complexity estimates are obtained. The advantages of the method is demonstrated with a few examples, including a commonly studied problem of Fermi, Pasta, and Ulam.
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| 9. |
- Ariel, Gil, et al.
(author)
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A reversible multiscale integration method
- 2009
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In: Communications in Mathematical Sciences. - : Duke University Press. - 1539-6746 .- 1945-0796. ; 7:3, s. 595-610
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Journal article (peer-reviewed)abstract
- A multiscale, time reversible method for computing the effective slow behavior of systems of highly oscillatory ordinary differential equations is presented. The proposed method relies on correctly tracking a set of slow variables that is sufficient to approximate any variable and functional that are slow under the dynamics of the system. The algorithm follows the framework of the heterogeneous multiscale method. The notion of time reversibility in the multiple time-scale setting is discussed. The algorithm requires nontrivial matching between the microscopic state variables and the macroscopic slow ones. Numerical examples show the efficiency of the multiscale method and the advantages of time reversibility.
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| 10. |
- Ariel, Gil, et al.
(author)
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Gaussian Beam Decomposition of High Frequency Wave Fields Using Expectation-Maximization
- 2011
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In: Journal of Computational Physics. - : Elsevier. - 0021-9991 .- 1090-2716. ; 230:6, s. 2303-2321
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Journal article (peer-reviewed)abstract
- A new numerical method for approximating highly oscillatory wave fields as a superposition of Gaussian beams is presented. The method estimates the number of beams and their parameters automatically. This is achieved by an expectation–maximization algorithm that fits real, positive Gaussians to the energy of the highly oscillatory wave fields and its Fourier transform. Beam parameters are further refined by an optimization procedure that minimizes the difference between the Gaussian beam superposition and the highly oscillatory wave field in the energy norm.
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| 11. |
- Ariel, Gil, et al.
(author)
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Numerical multiscale methods for coupled oscillators
- 2009
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In: Multiscale Modeling & simulation. - : Society for Industrial & Applied Mathematics (SIAM). - 1540-3459 .- 1540-3467. ; 7:3, s. 1387-1404
-
Journal article (peer-reviewed)abstract
- A multiscale method for computing the effective slow behavior of a system of weakly coupled nonlinear planar oscillators is presented. The oscillators may be either in the form of a periodic solution or a stable limit cycle. Furthermore, the oscillators may be in resonance with one another and thereby generate some hidden slow dynamics. The proposed method relies on correctly tracking a set of slow variables that is sufficient to approximate any variable and functional that are slow under the dynamics of the ordinary differential equation. The technique is more efficient than existing methods, and its advantages are demonstrated with examples. The algorithm follows the framework of the heterogeneous multiscale method.
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| 12. |
- Ariel, G., et al.
(author)
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Parareal multiscale methods for highly oscillatory dynamical systems
- 2016
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In: SIAM Journal on Scientific Computing. - : Society for Industrial and Applied Mathematics Publications. - 1064-8275 .- 1095-7197. ; 38:6, s. A3540-A3564
-
Journal article (peer-reviewed)abstract
- We introduce a new strategy for coupling the parallel in time (parareal) iterative methodology with multiscale integrators. Following the parareal framework, the algorithm computes a low-cost approximation of all slow variables in the system using an appropriate multiscale integrator, which is refined using parallel fine scale integrations. Convergence is obtained using an alignment algorithm for fast phase-like variables. The method may be used either to enhance the accuracy and range of applicability of the multiscale method in approximating only the slow variables, or to resolve all the state variables. The numerical scheme does not require that the system is split into slow and fast coordinates. Moreover, the dynamics may involve hidden slow variables, for example, due to resonances. We propose an alignment algorithm for almost-periodic solutions, in which case convergence of the parareal iterations is proved. The applicability of the method is demonstrated in numerical examples.
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| 13. |
- Atle, Andreas, 1972-
(author)
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Approximations of Integral Equations for WaveScattering
- 2006
-
Doctoral thesis (other academic/artistic)abstract
- Wave scattering is the phenomenon in which a wave field interacts with physical objects. An incoming wave is scattered at the surface of the object and a scattered wave is produced. Common practical cases are acoustic, electromagnetic and elastic wave scattering. The numerical simulation of the scattering process is important, for example, in noise control, antenna design, prediction of radar cross sections and nondestructive testing.Important classes of numerical methods for accurate simulation of scattering are based on integral representations of the wave fields and theses representations require the knowledge of potentials on the surfaces of the scattering objects. The potential is typically computed by a numerical approximation of an integral equation that is defined on the surface. We first develop such numerical methods in time domain for the scalar wave equation. The efficiency of the techniques are improved by analytic quadrature and in some cases by local approximation of the potential.Most scattering simulations are done for harmonic or single frequency waves. In the electromagnetic case the corresponding integral equation method is called the method of moments. This numerical approximation is computationally very costly for high frequency waves. A simplification is suggested by physical optics, which directly gives an approximation of the potential without the solution of an integral equation. Physical optics is however only accurate for very high frequencies.In this thesis we improve the accuracy in the physical optics approximation of scalar waves by basing the computation of the potential on the theory of radiation boundary conditions. This theory describes the local coupling of derivatives in the wave field and if it is applied at the surface of the scattering object it generates an expression for the unknown potential. The full wave field is then computed as for other integral equation methods.The new numerical techniques are analyzed mathematically and their efficiency is established in a sequence of numerical experiments. The new on surface radiation conditions give, for example, substantial improvement in the estimation of the scattered waves in the acoustic case. This numerical experiment corresponds to radar cross-section estimation in the electromagnetic case.
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| 14. |
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| 15. |
- Chen, C., et al.
(author)
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An implicit boundary integral method for interfaces evolving by Mullins-Sekerka dynamics
- 2017
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In: Springer Proceedings in Mathematics and Statistics. - Cham : Springer New York LLC. - 9783319667621 ; , s. 1-21
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Conference paper (peer-reviewed)abstract
- We present an algorithm for computing the nonlinear interface dynamics of the Mullins-Sekerka model for interfaces that are defined implicitly (e.g. by a level set function) using integral equations. The computation of the dynamics involves solving Laplace’s equation with Dirichlet boundary conditions on multiply connected and unbounded domains and propagating the interface using a normal velocity obtained from the solution of the PDE at each time step. Our method is based on a simple formulation for implicit interfaces, which rewrites boundary integrals as volume integrals over the entire space. The resulting algorithm thus inherits the benefits of both level set methods and boundary integral methods to simulate the nonlocal front propagation problem with possible topological changes. We present numerical results in both two and three dimensions to demonstrate the effectiveness of the algorithm.
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| 16. |
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| 17. |
- Chen, Hao Yu, et al.
(author)
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Association of FADS1/2 Locus Variants and Polyunsaturated Fatty Acids With Aortic Stenosis
- 2020
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In: JAMA cardiology. - : American Medical Association (AMA). - 2380-6583 .- 2380-6591. ; 5:6, s. 694-702
-
Journal article (peer-reviewed)abstract
- Importance: Aortic stenosis (AS) has no approved medical treatment. Identifying etiological pathways for AS could identify pharmacological targets.Objective: To identify novel genetic loci and pathways associated with AS.Design, Setting, and Participants: This genome-wide association study used a case-control design to evaluate 44 703 participants (3469 cases of AS) of self-reported European ancestry from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort (from January 1, 1996, to December 31, 2015). Replication was performed in 7 other cohorts totaling 256 926 participants (5926 cases of AS), with additional analyses performed in 6942 participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Follow-up biomarker analyses with aortic valve calcium (AVC) were also performed. Data were analyzed from May 1, 2017, to December 5, 2019.Exposures: Genetic variants (615 643 variants) and polyunsaturated fatty acids (ω-6 and ω-3) measured in blood samples.Main Outcomes and Measures: Aortic stenosis and aortic valve replacement defined by electronic health records, surgical records, or echocardiography and the presence of AVC measured by computed tomography.Results: The mean (SD) age of the 44 703 GERA participants was 69.7 (8.4) years, and 22 019 (49.3%) were men. The rs174547 variant at the FADS1/2 locus was associated with AS (odds ratio [OR] per C allele, 0.88; 95% CI, 0.83-0.93; P = 3.0 × 10-6), with genome-wide significance after meta-analysis with 7 replication cohorts totaling 312 118 individuals (9395 cases of AS) (OR, 0.91; 95% CI, 0.88-0.94; P = 2.5 × 10-8). A consistent association with AVC was also observed (OR, 0.91; 95% CI, 0.83-0.99; P = .03). A higher ratio of arachidonic acid to linoleic acid was associated with AVC (OR per SD of the natural logarithm, 1.19; 95% CI, 1.09-1.30; P = 6.6 × 10-5). In mendelian randomization, increased FADS1 liver expression and arachidonic acid were associated with AS (OR per unit of normalized expression, 1.31 [95% CI, 1.17-1.48; P = 7.4 × 10-6]; OR per 5-percentage point increase in arachidonic acid for AVC, 1.23 [95% CI, 1.01-1.49; P = .04]; OR per 5-percentage point increase in arachidonic acid for AS, 1.08 [95% CI, 1.04-1.13; P = 4.1 × 10-4]).Conclusions and Relevance: Variation at the FADS1/2 locus was associated with AS and AVC. Findings from biomarker measurements and mendelian randomization appear to link ω-6 fatty acid biosynthesis to AS, which may represent a therapeutic target.
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| 18. |
- Chu, J., et al.
(author)
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Volumetric variational principles for a class of partial differential equations defined on surfaces and curves : In memory of Heinz-Otto Kreiss
- 2018
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In: Research in Mathematical Sciences. - : Springer. - 2522-0144 .- 2197-9847. ; 5:2
-
Journal article (peer-reviewed)abstract
- In this paper, we propose simple numerical algorithms for partial differential equations (PDEs) defined on closed, smooth surfaces (or curves). In particular, we consider PDEs that originate from variational principles defined on the surfaces; these include Laplace–Beltrami equations and surface wave equations. The approach is to systematically formulate extensions of the variational integrals and derive the Euler–Lagrange equations of the extended problem, including the boundary conditions that can be easily discretized on uniform Cartesian grids or adaptive meshes. In our approach, the surfaces are defined implicitly by the distance functions or by the closest point mapping. As such extensions are not unique, we investigate how a class of simple extensions can influence the resulting PDEs. In particular, we reduce the surface PDEs to model problems defined on a periodic strip and the corresponding boundary conditions and use classical Fourier and Laplace transform methods to study the well-posedness of the resulting problems. For elliptic and parabolic problems, our boundary closure mostly yields stable algorithms to solve nonlinear surface PDEs. For hyperbolic problems, the proposed boundary closure is unstable in general, but the instability can be easily controlled by either adding a higher-order regularization term or by periodically but infrequently “reinitializing” the computed solutions. Some numerical examples for each representative surface PDEs are presented.
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| 19. |
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| 20. |
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| 21. |
- Engquist, Bjoern, et al.
(author)
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Fast sweeping methods for hyperbolic systems of conservation laws at steady state II
- 2015
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In: Journal of Computational Physics. - : Elsevier BV. - 0021-9991 .- 1090-2716. ; 286, s. 70-86
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Journal article (peer-reviewed)abstract
- The idea of using fast sweeping methods for solving stationary systems of conservation laws has previously been proposed for efficiently computing solutions with sharp shocks. We further develop these methods to allow for a more challenging class of problems including problems with sonic points, shocks originating in the interior of the domain, rarefaction waves, and two-dimensional systems. We show that fast sweeping methods can produce higher-order accuracy. Computational results validate the claims of accuracy, sharp shock curves, and optimal computational efficiency.
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| 22. |
- Figueiredo, I. N., et al.
(author)
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Colonic Polyp Identification Using Pareto Depth Anomaly Detection Algorithm
- 2019
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In: Lecture Notes in Computational Vision and Biomechanics. - Cham : Springer Netherlands. ; , s. 3-11
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Conference paper (peer-reviewed)abstract
- Colon cancer prevention, diagnosis, and prognosis are directly related to the identification of colonic polyps, in colonoscopy video sequences. In addition, diagnosing colon cancer in the early stages improves significantly the chance of surviving and effective treatment. Due to the large number of images that come from colonoscopy, the identification of polyps needs to be automated for effciency. In this paper, we propose a strategy for automatic polyp recognition, based on a recent multi-objective anomaly detection concept, which itself is based on Pareto Depth Analysis (PDA). Clinically, in medical images, polyps are diagnosed based on a few criteria, such as texture, shape and color. Few works use multi-criteria classification in a systematic way for polyp detection. In the present paper we use a PDA approach, to act as a binary classifier for the identification of colonic polyps. The results obtained in a medical dataset, of conventional colonoscopy images, consisting of short videos from 34 different patients, and 34 different polyps, with a total of 1360 different polyp frames, confirm that the proposed method clearly outperforms the single performance of each criterion.
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| 23. |
- Figueiredo, Isabel N., et al.
(author)
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Dissimilarity Measure of Consecutive Frames in Wireless Capsule Endoscopy Videos : a way of searching for abnormalities
- 2017
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In: 2017 IEEE 30TH INTERNATIONAL SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS (CBMS). - : IEEE. - 9781538617106 ; , s. 702-707
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Conference paper (peer-reviewed)abstract
- In a previous work we have shown that the curve representing the dissimilarity measure between consecutive frames of a wireless capsule endoscopic video of the small bowel, obtained by means of an image registration method, can be regarded as a rough indicator of the speed of the capsule, and simultaneously, it is also a valuable auxiliary medical tool. In effect, this curve enables a global and fast interpretation of the video, in the sense that it clearly divides the video frames into two main categories: consecutive frames with similar content, which correspond to low values in the curve, and consecutive frames displaying abrupt changes in the image content, which are depicted by peaks, i.e. high values, in the curve. As the main goal of a wireless capsule video examination consists in searching for abnormal features in the images, the purpose of the present work is to analyse whether this curve can also be used to search, quickly, for abnormalities. The experiments performed focus on bleeding identification in small bowel images.
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| 24. |
- Figueiredo, Isabel N., et al.
(author)
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Fast colonic polyp detection using a Hamilton-Jacobi approach to non-dominated sorting
- 2020
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In: Biomedical Signal Processing and Control. - : Elsevier. - 1746-8094 .- 1746-8108. ; 61
-
Journal article (peer-reviewed)abstract
- This paper describes a novel method for fast colonic polyp detection in colonoscopy images. Firstly, polyp detection is formulated as a similarity-based anomaly detection method, which formally involves non-dominated sorting based on multiple objectives. The chosen objectives rely on the main physical and visible differences, observed in colonoscopy images, between regions containing colonic polyps and the surrounding normal mucosa. These differences are defined primarily according to the contrast in shape, texture, and color. Secondly, as non-dominated sorting is of combinatorial nature and is costly to compute, it is replaced by a fast algorithm that approximates the sorting in the continuum limit. The fast algorithm involves numerical solutions to a particular Hamilton-Jacobi equation. The proposed similarity-based anomaly detection is thus reformulated into a fast polyp detection method. Several experiments were conducted with a proprietary medical data set, containing 1640 instances of 41 different polyps. The results show that the proposed Hamilton-Jacobi approach to non-dominated sorting speeds up the non-dominated sorting procedure, by more than 500%, and, when compared with other existing methods, it is also faster without lost of accuracy. Moreover, the tests conducted for streaming data, reveal an outstanding performance, in terms of sensitivity and specificity, as well as, a fast auto-adaptability, which demonstrate the power of the proposed approach towards a real-time and automatic detection, undoubtedly beneficial for clinical practice.
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| 25. |
- Figueiredo, Isabel N., et al.
(author)
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Unsupervised segmentation of colonic polyps in narrow-band imaging data based on manifold representation of images and Wasserstein distance
- 2019
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In: Biomedical Signal Processing and Control. - : ELSEVIER SCI LTD. - 1746-8094 .- 1746-8108. ; 53
-
Journal article (peer-reviewed)abstract
- Colorectal cancer (CRC) is one of the most common cancers worldwide and after a certain age (>= 50) regular colonoscopy examination for CRC screening is highly recommended. One of the most prominent precursors of CRC are abnormal growths known as polyps. If a polyp is detected during colonoscopy examination the endoscopist needs to decide whether the polyp should be discarded, removed, or biopsied for further examination. However, the last two options involve some risks for the patient, while not all the polyps are precancerous. On the other hand, discarding a polyp has the risk of failing to detect CRC. We propose an automatic and unsupervised method for the segmentation of colonic polyps for in vivo Narrow-Band-Imaging (NBI) data. Polyp segmentation is a crucial step towards an automatic real-time polyp classification system, that could help the endoscopist in the diagnosis of CRC. The proposed method is a histogram based two-phase segmentation model, involving the Wasserstein distance. These histograms incorporate fused information about suitable image descriptors, namely semi-local texture, geometry and color. To test the proposed segmentation methodology we use a dataset consisting of 86 NBI polyp frames: the 83% sensitivity, 95% specificity, and 93% accuracy suggest a better performance compared to the results obtained with other methods.
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| 26. |
- Frank, Matthias, et al.
(author)
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Femtosecond X-ray diffraction from two-dimensional protein crystals
- 2014
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In: IUCrJ. - 2052-2525. ; 1:2, s. 95-100
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Journal article (peer-reviewed)abstract
- X-ray diffraction patterns from two-dimensional (2-D) protein crystals obtained using femtosecond X-ray pulses from an X-ray free-electron laser (XFEL) are presented. To date, it has not been possible to acquire transmission X-ray diffraction patterns from individual 2-D protein crystals due to radiation damage. However, the intense and ultrafast pulses generated by an XFEL permit a new method of collecting diffraction data before the sample is destroyed. Utilizing a diffract-before-destroy approach at the Linac Coherent Light Source, Bragg diffraction was acquired to better than 8.5 Å resolution for two different 2-D protein crystal samples each less than 10 nm thick and maintained at room temperature. These proof-of-principle results show promise for structural analysis of both soluble and membrane proteins arranged as 2-D crystals without requiring cryogenic conditions or the formation of three-dimensional crystals.
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| 27. |
- Gruhl, T., et al.
(author)
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Ultrafast structural changes direct the first molecular events of vision
- 2023
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 615, s. 939-944
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Journal article (peer-reviewed)abstract
- Vision is initiated by the rhodopsin family of light-sensitive G protein-coupled receptors (GPCRs)(1). A photon is absorbed by the 11-cis retinal chromophore of rhodopsin, which isomerizes within 200 femtoseconds to the all-trans conformation(2), thereby initiating the cellular signal transduction processes that ultimately lead to vision. However, the intramolecular mechanism by which the photoactivated retinal induces the activation events inside rhodopsin remains experimentally unclear. Here we use ultrafast time-resolved crystallography at room temperature(3) to determine how an isomerized twisted all-trans retinal stores the photon energy that is required to initiate the protein conformational changes associated with the formation of the G protein-binding signalling state. The distorted retinal at a 1-ps time delay after photoactivation has pulled away from half of its numerous interactions with its binding pocket, and the excess of the photon energy is released through an anisotropic protein breathing motion in the direction of the extracellular space. Notably, the very early structural motions in the protein side chains of rhodopsin appear in regions that are involved in later stages of the conserved class A GPCR activation mechanism. Our study sheds light on the earliest stages of vision in vertebrates and points to fundamental aspects of the molecular mechanisms of agonist-mediated GPCR activation.
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| 28. |
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| 29. |
- Holmes, Michael V., et al.
(author)
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Mendelian randomization of blood lipids for coronary heart disease
- 2015
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In: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 36:9, s. 539-539
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Journal article (peer-reviewed)abstract
- Aims To investigate the causal role of high-density lipoprotein cholesterol (HDL-C) and triglycerides in coronary heart disease (CHD) using multiple instrumental variables for Mendelian randomization. Methods and results We developed weighted allele scores based on single nucleotide polymorphisms (SNPs) with established associations with HDL-C, triglycerides, and low-density lipoprotein cholesterol (LDL-C). For each trait, we constructed two scores. The first was unrestricted, including all independent SNPs associated with the lipid trait identified from a priormeta-analysis (threshold P < 2 x 10(-6)); and the second a restricted score, filtered to remove any SNPs also associated with either of the other two lipid traits at P <= 0.01. Mendelian randomization meta-analyses were conducted in 17 studies including 62,199 participants and 12,099 CHD events. Both the unrestricted and restricted allele scores for LDL-C (42 and 19 SNPs, respectively) associated with CHD. For HDL-C, the unrestrictedallele score (48SNPs) was associated with CHD(OR: 0.53; 95% CI: 0.40, 0.70), per 1 mmol/L higher HDL-C, but neither the restricted allele score (19 SNPs; OR: 0.91; 95% CI: 0.42, 1.98) nor the unrestricted HDL-C allele score adjusted for triglycerides, LDL-C, or statin use (OR: 0.81; 95% CI: 0.44, 1.46) showed a robust association. For triglycerides, the unrestricted allele score (67 SNPs) and the restricted allele score (27 SNPs) were both associated with CHD (OR: 1.62; 95% CI: 1.24, 2.11 and 1.61; 95% CI: 1.00, 2.59, respectively) per 1-log unit increment. However, the unrestricted triglyceride score adjusted for HDL-C, LDL-C, and statin use gave an OR for CHD of 1.01 (95% CI: 0.59, 1.75). Conclusion The genetic findings support a causal effect of triglycerides on CHD risk, but a causal role for HDL-C, though possible, remains less certain.
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| 30. |
- Izzo, Federico, et al.
(author)
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Convergence of a class of high order corrected trapezoidal rules
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Other publication (other academic/artistic)abstract
- We present convergence theory for corrected quadrature rules on uniform Cartesian grids for functions with a point singularity. We begin by deriving an error estimate for the punctured trapezoidal rule, and then derive error expansions. We define the corrected trapezoidal rules, based on the punctured trapezoidal rule, where the weights for the nodes close to the singularity are judiciously corrected based on these expansions. Then we define the composite corrected trapezoidal rules for a larger family of functions using series expansions around the point singularity and applying corrected trapezoidal rules appropriately. We prove that we can achieve high order accuracy by using a sufficient number of correction nodes around the point singularity and of expansion terms.
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| 31. |
- Izzo, Federico, et al.
(author)
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Corrected Trapezoidal Rule-IBIM for linearized Poisson-Boltzmann equation
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Other publication (other academic/artistic)abstract
- In this paper, we solve the linearized Poisson-Boltzmann equation, used to model the electric potential of macromolecules in a solvent. We derive a corrected trapezoidal rule with improved accuracy for a boundary integral formulation of the linearized Poisson-Boltzmann equation. More specifically, in contrast to the typical boundary integral formulations, the corrected trapezoidal rule is applied to integrate a system of compacted supported singular integrals using uniform Cartesian grids in R3, without explicit surface parameterization. A Krylov method, accelerated by a fast multipole method, is used to invert the resulting linear system. We study the efficacy of the proposed method, and compare it to an existing, lower order method. We then apply the method to the computation of electrostatic potential of macromolecules immersed in solvent. The solvent excluded surfaces, defined by a common approach, are merely piecewise smooth, and we study the effectiveness of the method for such surfaces.
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| 32. |
- Izzo, Federico, et al.
(author)
-
Corrected trapezoidal rules for singular implicit boundary integrals
- 2022
-
In: Journal of Computational Physics. - : Elsevier BV. - 0021-9991 .- 1090-2716. ; 461, s. 111193-
-
Journal article (peer-reviewed)abstract
- We present new higher-order quadratures for a family of boundary integral operators re derived using the approach introduced in Kublik et al. (2013) [7]. In this formulation, a boundary integral over a smooth, closed hypersurface is transformed into an equivalent volume integral defined in a sufficiently thin tubular neighborhood of the surface. The volumetric formulation makes it possible to use the simple trapezoidal rule on uniform Cartesian grids and relieves the need to use parameterization for developing quadrature. Consequently, typical point singularities in a layer potential extend along the surface's normal lines. We propose new higher-order corrections to the trapezoidal rule on the grid nodes around the singularities. This correction is based on local decompositions of the singularity and is dependent on the angle of approach to the singularity relative to the surface's principal curvature directions. The proposed decomposition, combined with the volumetric formulation, leads to a special quadrature error cancellation.
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| 33. |
- Izzo, Federico, et al.
(author)
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High order corrected trapezoidal rules for a class of singular integrals
-
Other publication (other academic/artistic)abstract
- We present a family of high order trapezoidal rule-based quadratures for a class of singular integrals, where the integrand has a point singularity. The singular part of the integrand is expanded in a Taylor series involving terms of increasing smoothness. The quadratures are based on the trapezoidal rule, with the quadrature weights for Cartesian nodes close to the singularity judiciously corrected based on the expansion. High order accuracy can be achieved by utilizing a sufficient number of correction nodes around the singularity to approximate the terms in the series expansion. The derived quadratures are applied to the Implicit Boundary Integral formulation of surface integrals involving the Laplace layer kernels.
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| 34. |
- Izzo, Federico, et al.
(author)
-
High-order corrected trapezoidal rules for a class of singular integrals
- 2023
-
In: Advances in Computational Mathematics. - : Springer Nature. - 1019-7168 .- 1572-9044. ; 49:4
-
Journal article (peer-reviewed)abstract
- We present a family of high-order trapezoidal rule-based quadratures for a class of singular integrals, where the integrand has a point singularity. The singular part of the integrand is expanded in a Taylor series involving terms of increasing smoothness. The quadratures are based on the trapezoidal rule, with the quadrature weights for Cartesian nodes close to the singularity judiciously corrected based on the expansion. High-order accuracy can be achieved by utilizing a sufficient number of correction nodes around the singularity to approximate the terms in the series expansion. The derived quadratures are applied to the implicit boundary integral formulation of surface integrals involving the Laplace layer kernels.
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| 35. |
- Kilpelainen, TO, et al.
(author)
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Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity
- 2019
-
In: Nature communications. - London : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 376-
-
Journal article (peer-reviewed)abstract
- Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.
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| 36. |
- Kristanl, Matej, et al.
(author)
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The Seventh Visual Object Tracking VOT2019 Challenge Results
- 2019
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In: 2019 IEEE/CVF INTERNATIONAL CONFERENCE ON COMPUTER VISION WORKSHOPS (ICCVW). - : IEEE COMPUTER SOC. - 9781728150239 ; , s. 2206-2241
-
Conference paper (peer-reviewed)abstract
- The Visual Object Tracking challenge VOT2019 is the seventh annual tracker benchmarking activity organized by the VOT initiative. Results of 81 trackers are presented; many are state-of-the-art trackers published at major computer vision conferences or in journals in the recent years. The evaluation included the standard VOT and other popular methodologies for short-term tracking analysis as well as the standard VOT methodology for long-term tracking analysis. The VOT2019 challenge was composed of five challenges focusing on different tracking domains: (i) VOT-ST2019 challenge focused on short-term tracking in RGB, (ii) VOT-RT2019 challenge focused on "real-time" short-term tracking in RGB, (iii) VOT-LT2019 focused on long-term tracking namely coping with target disappearance and reappearance. Two new challenges have been introduced: (iv) VOT-RGBT2019 challenge focused on short-term tracking in RGB and thermal imagery and (v) VOT-RGBD2019 challenge focused on long-term tracking in RGB and depth imagery. The VOT-ST2019, VOT-RT2019 and VOT-LT2019 datasets were refreshed while new datasets were introduced for VOT-RGBT2019 and VOT-RGBD2019. The VOT toolkit has been updated to support both standard short-term, long-term tracking and tracking with multi-channel imagery. Performance of the tested trackers typically by far exceeds standard baselines. The source code for most of the trackers is publicly available from the VOT page. The dataset, the evaluation kit and the results are publicly available at the challenge website(1).
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| 37. |
- Kublik, Catherine, et al.
(author)
-
An extrapolative approach to integration over hypersurfaces in the level set framework
- 2018
-
In: Mathematics of Computation. - : American Mathematical Society (AMS). - 0025-5718 .- 1088-6842. ; 87:313, s. 2365-2392
-
Journal article (peer-reviewed)abstract
- We provide a new approach for computing integrals over hypersurfaces in the level set framework. The method is based on the discretization (via simple Riemann sums) of the classical formulation used in the level set framework, with the choice of specific kernels supported on a tubular neighborhood around the interface to approximate the Dirac delta function. The novelty lies in the choice of kernels, specifically its number of vanishing moments, which enables accurate computations of integrals over a class of closed, continuous, piecewise smooth, curves or surfaces; e.g., curves in two dimensions that contain a finite number of corners. We prove that for smooth interfaces, if the kernel has enough vanishing moments (related to the dimension of the embedding space), the analytical integral formulation coincides exactly with the integral one wishes to calculate. For curves with corners and cusps, the formulation is not exact but we provide an analytical result relating the severity of the corner or cusp with the width of the tubular neighborhood. We show numerical examples demonstrating the capability of the approach, especially for integrating over piecewise smooth interfaces and for computing integrals where the integrand is only Lipschitz continuous or has an integrable singularity.
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| 38. |
- Kublik, C., et al.
(author)
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Integration over curves and surfaces defined by the closest point mapping
- 2016
-
In: Research in Mathematical Sciences. - : Springer International Publishing. - 2522-0144 .- 2197-9847. ; 3:1
-
Journal article (peer-reviewed)abstract
- We propose a new formulation for integrating over smooth curves and surfaces that are described by their closest point mappings. Our method is designed for curves and surfaces that are not defined by any explicit parameterization and is intended to be used in combination with level set techniques. However, contrary to the common practice with level set methods, the volume integrals derived from our formulation coincide exactly with the surface or line integrals that one wishes to compute. We study various aspects of this formulation and provide a geometric interpretation of this formulation in terms of the singular values of the Jacobian matrix of the closest point mapping. Additionally, we extend the formulation—initially derived to integrate over manifolds of codimension one—to include integration along curves in three dimensions. Some numerical examples using very simple discretizations are presented to demonstrate the efficacy of the formulation.
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| 39. |
- Liti, Gianni, et al.
(author)
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Population genomics of domestic and wild yeasts.
- 2009
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 458:7236, s. 337-41
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Journal article (peer-reviewed)abstract
- Since the completion of the genome sequence of Saccharomyces cerevisiae in 1996 (refs 1, 2), there has been a large increase in complete genome sequences, accompanied by great advances in our understanding of genome evolution. Although little is known about the natural and life histories of yeasts in the wild, there are an increasing number of studies looking at ecological and geographic distributions, population structure and sexual versus asexual reproduction. Less well understood at the whole genome level are the evolutionary processes acting within populations and species that lead to adaptation to different environments, phenotypic differences and reproductive isolation. Here we present one- to fourfold or more coverage of the genome sequences of over seventy isolates of the baker's yeast S. cerevisiae and its closest relative, Saccharomyces paradoxus. We examine variation in gene content, single nucleotide polymorphisms, nucleotide insertions and deletions, copy numbers and transposable elements. We find that phenotypic variation broadly correlates with global genome-wide phylogenetic relationships. S. paradoxus populations are well delineated along geographic boundaries, whereas the variation among worldwide S. cerevisiae isolates shows less differentiation and is comparable to a single S. paradoxus population. Rather than one or two domestication events leading to the extant baker's yeasts, the population structure of S. cerevisiae consists of a few well-defined, geographically isolated lineages and many different mosaics of these lineages, supporting the idea that human influence provided the opportunity for cross-breeding and production of new combinations of pre-existing variations.
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| 40. |
- Mahajan, Anubha, et al.
(author)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
-
In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
-
Journal article (peer-reviewed)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 41. |
- Marcano, Alejandro I., et al.
(author)
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Income change after cruciate ligament injury - A population-based study
- 2019
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In: Knee (Oxford). - : Elsevier BV. - 0968-0160 .- 1873-5800. ; 26:3, s. 603-611
-
Journal article (peer-reviewed)abstract
- Objectives: To investigate the association between choice of treatment and patients' income after cruciate ligament (CL) injury and assess the effect of different covariates such as sex, age, comorbidities and type of work.Methods: This entire-population cohort study in Sweden included working patients with a diagnosed CL injury between 2002 and 2005, identified in The National Swedish Patient Register (n = 13,662). The exposure was the treatment choice (operative or non-operative treatment). The main outcome measure was average yearly income five years after CL diagnosis, adjusted for the following covariates: sex, age, comorbidities, type of work, region, calendar year, education and income.Results: Relative to non-operative treatment, operative treatment was associated with greater average yearly incomes (nine to 15%) after injury among patients between 20 and 50 years, patients with partial university education, patients living in large cities and patients with one comorbidity, despite no overall significant association in the national cohort. Delayed operative treatment (>1 year) had no significant association with income change, whereas early operative treatment (<1 year) was associated with higher average yearly incomes (11 to 16%) among females, patients between 20 and 50 years, patients living in large cities and patients with one comorbidity.Conclusions: In a broad sense, treatment choice was not associated with changes in income five years after CL injuries among patients in the workforce, however earlier operative treatment was associated with higher average incomes among patients with ages between 20 and 50, females, living in large cities, with one comorbidity and with a high level of education.
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| 42. |
- Nguyen, H., et al.
(author)
-
A stable parareal-like method for the second order wave equation
- 2020
-
In: Journal of Computational Physics. - : Academic Press. - 0021-9991 .- 1090-2716. ; 405
-
Journal article (peer-reviewed)abstract
- A new parallel-in-time iterative method is proposed for solving the homogeneous second-order wave equation. The new method involves a coarse scale propagator, allowing for larger time steps, and a fine scale propagator which fully resolves the medium using finer spatial grid and uses shorter time steps. The fine scale propagator is run in parallel for short time intervals. The two propagators are coupled in an iterative way that resembles the standard parareal method [24]. We present a data-driven strategy in which the computed data gathered from each iteration are re-used to stabilize the coupling by minimizing the wave energy residual of the fine and coarse propagated solutions. Several examples, including a wave speed with discontinuities, are provided to demonstrate the effectiveness of the proposed method.
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| 43. |
- Nordenvall, Richard, et al.
(author)
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The Effect of Socioeconomic Status on the Choice of Treatment for Patients With Cruciate Ligament Injuries in the Knee : A Population-Based Cohort Study
- 2017
-
In: American Journal of Sports Medicine. - : SAGE Publications. - 0363-5465 .- 1552-3365. ; 45:3, s. 535-540
-
Journal article (peer-reviewed)abstract
- Background:The socioeconomic status (SES) of patients has been widely recognized as playing an important role in many health-related conditions, including orthopaedic conditions, in which a higher SES has been associated with a higher utilization of more advanced medical treatments such as drugs, diagnostics, and surgery. However, the association between SES and cruciate ligament surgery has not been thoroughly investigated.Purpose:To evaluate the association between SES and choice of treatment in patients with a cruciate ligament injury.Study Design:Cohort study; Level of evidence, 3.Methods:All Swedish patients with a diagnosed cruciate ligament injury between 1987 and 2010 were identified from the Swedish National Patient Register (N = 98,349). The Longitudinal Integration Database for Health Insurance and Labor Market Studies (LISA) provided information on household income and highest achieved educational level, which were used as socioeconomic indices. The exposure was the SES of patients as determined by the household income and educational level, and the main outcome measure was treatment choice (surgical reconstruction vs nonoperative treatment). Poisson regression models estimated the association.Results:A total of 52,566 patients were included in the study; of these, 20,660 (39%) were treated operatively. Patients in the highest quartile of household income had a significantly higher likelihood of undergoing surgery than those in the lowest quartile (relative risk [RR], 1.16; 95% CI, 1.11-1.20). Patients classified as highly educated had a significantly increased likelihood of being treated operatively compared with those with a low education (RR, 1.29; 95% CI, 1.19-1.39).Conclusion:This study provides a population-based validation that having a higher SES as determined by the household income and/or level of education increases the likelihood of undergoing operative treatment after a cruciate ligament injury.Clinical Relevance:All Swedish citizens are entitled by law to the same quality of health care; therefore, unmotivated differences in treatment between different socioeconomic groups are to be seen as a challenge. It is important to evaluate the specific mechanisms by which the patient's SES influences the decision of whether to treat a cruciate ligament injury operatively.
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| 44. |
- Ohtsuka, T., et al.
(author)
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A Level Set Approach Reflecting Sheet Structure with Single Auxiliary Function for Evolving Spirals on Crystal Surfaces
- 2015
-
In: Journal of Scientific Computing. - : Springer Science and Business Media LLC. - 0885-7474 .- 1573-7691. ; 62:3, s. 831-874
-
Journal article (peer-reviewed)abstract
- We introduce a new level set method to simulate motion of spirals in a crystal surface governed by an eikonal-curvature flow equation. Our formulation allows collision of several spirals and different strength (different modulus of Burgers vectors) of screw dislocation centers. We represent a set of spirals by a level set of a single auxiliary function u minus a pre-determined multi-valued sheet structure function theta, which reflects the strength of spirals (screw dislocation centers). The level set equation used in our method for u - theta is the same as that of the eikonal-curvature flow equation. The multi-valued nature of the sheet structure function is only invoked when preparing the initial auxiliary function, which is nontrivial, and in the final step when extracting information such as the height of the spiral steps. Our simulation enables us not only to reproduce all speculations on spirals in a classical paper by Burton et al. (Philos Trans R Soc Lond Ser A Math Phys Sci 243, 299-358, 1951) but also to find several new phenomena.
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| 45. |
- Ohtsuka, T., et al.
(author)
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Growth Rate of Crystal Surfaces with Several Dislocation Centers
- 2018
-
In: Crystal Growth & Design. - : American Chemical Society (ACS). - 1528-7483 .- 1528-7505. ; 18:3, s. 1917-1929
-
Journal article (peer-reviewed)abstract
- We studied analytically and numerically the growth rate of a crystal surface growing by several screw dislocations. We observed some discrepancy between the growth rates computed by our level set method (J. Sci. Comput. 2015, 62.
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| 46. |
- Ossenkoppele, Rik, et al.
(author)
-
Distinct tau PET patterns in atrophy-defined subtypes of Alzheimer's disease
- 2020
-
In: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 16:2, s. 335-344
-
Journal article (peer-reviewed)abstract
- Introduction: Differential patterns of brain atrophy on structural magnetic resonance imaging (MRI) revealed four reproducible subtypes of Alzheimer's disease (AD): (1) “typical”, (2) “limbic-predominant”, (3) “hippocampal-sparing”, and (4) “mild atrophy”. We examined the neurobiological characteristics and clinical progression of these atrophy-defined subtypes. Methods: The four subtypes were replicated using a clustering method on MRI data in 260 amyloid-β–positive patients with mild cognitive impairment or AD dementia, and we subsequently tested whether the subtypes differed on [18F]flortaucipir (tau) positron emission tomography, white matter hyperintensity burden, and rate of global cognitive decline. Results: Voxel-wise and region-of-interest analyses revealed the greatest neocortical tau load in hippocampal-sparing (frontoparietal-predominant) and typical (temporal-predominant) patients, while limbic-predominant patients showed particularly high entorhinal tau. Typical patients with AD had the most pronounced white matter hyperintensity load, and hippocampal-sparing patients showed the most rapid global cognitive decline. Discussion: Our data suggest that structural MRI can be used to identify biologically and clinically meaningful subtypes of AD.
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| 47. |
- Rabideau Childers, Richard A., et al.
(author)
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A hypothesis for robust polarization vision : an example from the Australian imperial blue butterfly, Jalmenus evagoras
- 2023
-
In: Journal of Experimental Biology. - : The Company of Biologists. - 0022-0949 .- 1477-9145. ; 226:7
-
Journal article (peer-reviewed)abstract
- The Australian lycaenid butterfly Jalmenus evagoras has iridescent wings that are sexually dimorphic, spectrally and in their degree of polarization, suggesting that these properties are likely to be important in mate recognition. We first describe the results of a field experiment showing that free-flying individuals of J. evagoras discriminate between visual stimuli that vary in polarization content in blue wavelengths but not in others. We then present detailed reflectance spectrophotometry measurements of the polarization content of male and female wings, showing that female wings exhibit blue-shifted reflectance, with a lower degree of polarization relative to male wings. Finally, we describe a novel method for measuring alignment of ommatidial arrays: by measuring variation of depolarized eyeshine intensity from patches of ommatidia as a function of eye rotation, we show that (a) individual rhabdoms contain mutually perpendicular microvilli; (b) many rhabdoms in the array have their microvilli misaligned with respect to neighboring rhabdoms by as much as 45 deg; and (c) the misaligned ommatidia are useful for robust polarization detection. By mapping the distribution of the ommatidial misalignments in eye patches of J. evagoras, we show that males and females exhibit differences in the extent to which ommatidia are aligned. Both the number of misaligned ommatidia suitable for robust polarization detection and the number of aligned ommatidia suitable for edge detection vary with respect to both sex and eye patch elevation. Thus, J. evagoras exhibits finely tuned ommatidial arrays suitable for perception of polarized signals, likely to match sex-specific life history differences in the utility of polarized signals.
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| 48. |
- Rojas, Julio C, et al.
(author)
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Plasma neurofilament light chain predicts progression in progressive supranuclear palsy.
- 2016
-
In: Annals of clinical and translational neurology. - : Wiley. - 2328-9503. ; 3:3, s. 216-25
-
Journal article (peer-reviewed)abstract
- Blood-based biomarkers for neurodegenerative conditions could improve diagnosis and treatment development. Neurofilament light chain (NfL), a marker of axonal injury, is elevated in cerebrospinal fluid (CSF) of patients with progressive supranuclear palsy (PSP). The goal of this study was to determine the diagnostic and prognostic value of plasma NfL in patients with PSP.
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| 49. |
- Schutzer, Steven E., et al.
(author)
-
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and fibromyalgia are indistinguishable by their cerebrospinal fluid proteomes
- 2022
-
In: bioRxiv Neurology. - : Cold Spring Harbor Laboratory Press (CSHL).
-
Journal article (other academic/artistic)abstract
- Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and fibromyalgia have overlapping neurologic symptoms particularly disabling fatigue. This has given rise to the question whether they are distinct central nervous system (CNS) entities or is one an extension of the other. To investigate this, we used unbiased quantitative mass spectrometry-based proteomics to examine the most proximal fluid to the brain, cerebrospinal fluid (CSF). This was to ascertain if the proteome profile of one was the same or different from the other. We examined two separate groups of ME/CFS, one with (n=15) and one without (n=15) fibromyalgia. We quantified a total of 2,083 proteins using immunoaffinity depletion, tandem mass tag isobaric labeling and offline two-dimensional liquid chromatography coupled to tandem mass spectrometry, including 1,789 that were quantified in all the CSF samples. ANOVA analysis did not yield any proteins with an adjusted p-value < 0.05. This supports the notion that ME/CFS and fibromyalgia as currently defined are not distinct entities.
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| 50. |
- Schutzer, Steven E., et al.
(author)
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Myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia are indistinguishable by their cerebrospinal fluid proteomes
- 2023
-
In: Annals of Medicine. - : Taylor & Francis. - 0785-3890 .- 1365-2060. ; 55:1
-
Journal article (peer-reviewed)abstract
- Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and fibromyalgia have overlapping neurologic symptoms particularly disabling fatigue. This has given rise to the question whether they are distinct central nervous system (CNS) entities or is one an extension of the other.Material and methods: To investigate this, we used unbiased quantitative mass spectrometry-based proteomics to examine the most proximal fluid to the brain, cerebrospinal fluid (CSF). This was to ascertain if the proteome profile of one was the same or different from the other. We examined two separate groups of ME/CFS, one with (n = 15) and one without (n = 15) fibromyalgia.Results: We quantified a total of 2083 proteins using immunoaffinity depletion, tandem mass tag isobaric labelling and offline two-dimensional liquid chromatography coupled to tandem mass spectrometry, including 1789 that were quantified in all the CSF samples. ANOVA analysis did not yield any proteins with an adjusted p value <.05.Conclusion: This supports the notion that ME/CFS and fibromyalgia as currently defined are not distinct entities.
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