| 1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)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. |
- Thompson, Paul M., et al.
(författare)
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The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
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Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
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Tidskriftsartikel (refereegranskat)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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| 3. |
- Joshi, Peter K, et al.
(författare)
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Directional dominance on stature and cognition in diverse human populations
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462
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Tidskriftsartikel (refereegranskat)abstract
- Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
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| 4. |
- Dam, Hai Huyen, et al.
(författare)
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Iterative Method for the Design of DFT Filter Bank
- 2004
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Ingår i: IEEE transactions on circuits and systems. 2, Analog and digital signal processing (Print). - : IEEE, USA. - 1057-7130 .- 1558-125X. ; 51:11, s. 581-6
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Tidskriftsartikel (refereegranskat)abstract
- Multi-rate adaptive filters have numerous advantages such as low computational load, fast convergence and parallelism in the adaptation. Drawbacks when using multi-rate processing are mainly related to aliasing and reconstruction effects. These effects can be minimized by introducing appropriate problem formulation and employing sophisticated optimization techniques. In this paper, we propose a formulation for the design of filter bank which controls the distortion level for each frequency component directly and minimizes the inband aliasing and the residual aliasing between different subbands. The advantage of this problem formulation is that the distortion level can be weighted for each frequency depending on the particular practical application. A new iterative algorithm is proposed to optimize simultaneously over both the analysis and the synthesis filter banks. This algorithm is shown to have a unique solution for each iteration. For a fixed distortion level, the proposed algorithm yields a significant reduction in both the inband aliasing and the residual aliasing levels compared to existing methods applied to the numerical examples.
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| 5. |
- Fundin, Per, et al.
(författare)
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Minimal Aliasing Subband System Identification
- 2001
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Konferensbidrag (refereegranskat)abstract
- Subband adaptive filters have been proposed to avoid the drawbacks of slow convergence and high computational complexity associated with time domain adaptive filters. While the computational complexity is reduced, other undesired properties, such as signal delays and signal aliasing, are introduced. Aliasing effects may result in loss of perception in speech applications. A method for the design of oversampled filter banks is proposed to reduce these effects. The design method aims at reducing the inband aliasing as well as the reconstruction aliasing for the reason of achieving robustness when weighting in the subbands alters the subband signal phase and magnitude.
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| 6. |
- Grbic, Nedelko, et al.
(författare)
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Design of Oversampled Uniform DFT Filter Banks with Reduced Inband Aliasing and Delay Constraints
- 2001
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Konferensbidrag (refereegranskat)abstract
- Subband adaptive filters have been proposed to avoid the drawbacks of slow convergence and high computational complexity associated with time domain adaptive filters. Subband processing introduces transmission delays caused by the filter bank and signal degradations due to aliasing effects. One efficient way to reduce the aliasing effects is to allow a higher sample rate than critically needed in the subbands and thus reduce subband signal degradation. We suggest a design method, for a uniform DFT filter bank with any over sampling factor, where the total filter bank group delay may be specified, and where the aliasing and magnitude/phase distortions are minimized.
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| 7. |
- Haan, Jan Mark de
(författare)
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Convergence and Complexity Analysis of Delayless Subband Adaptive Filters
- 2004
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Subband adaptive filters have been proposed to circumvent the drawbacks of slow convergence and high computational complexity associated with time domain adaptive filters. Subband processing introduces transmission delays and signal degradations due to aliasing effects. In order to overcome the transmission delays, delayless adaptive filtering has been introduced where the coefficient adaptation is performed in the subband domain while signal filtering is performed in fullband. In this paper convergence behavior and computational complexity of two different types of delayless adaptive filters are considered. Both open loop and closed loop configurations are studied. The theoretical results are compared with simulations of algorithms in a system identification scenario.
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| 8. |
- Haan, Jan Mark de, et al.
(författare)
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Design and Evaluation of Nonuniform DFT Filter Banks in Subband Microphone Arrays
- 2002
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Konferensbidrag (refereegranskat)abstract
- This paper presents a method for the design of nonuniform DFT filter banks for subband beamforming. Filter banks designed with the method are evaluated in subband beamforming in a real-world microphone array application. Different source positions in array applications give rise to different signal delays, which means that adaptive beamformers in the subbands alter the phase information of the subband signals in order to extract the source from a noisy background. Phase alterations in the subbands lead to signal degradations when perfect reconstruction filter banks are used for the subband decomposition and reconstruction. The objective of the proposed design is to minimize the magnitude of all aliasing components individually, such that aliasing distortion is minimized although phase alterations occur in the subbands. The proposed method is evaluated in a car hands-free mobile telephony environment with real speech signals and the results show that the performance can be increased by several decibel when using nonuniform filter banks instead of uniform filterbanks while maintaining the length of the subband filters.
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| 9. |
- Haan, Jan Mark de, et al.
(författare)
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Design of Nonuniform Filter Banks with Frequency Domain Criteria
- 2004
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This paper presents methods for the design of nonuniform filter banks. The filter bank structure is obtained from an uniformly modulated filter bank by using an allpass transform which has a lossless frequency function and a nonlinear phase function. The proposed design methods include linear and quadratic frequency domain criteria and linear constraints. Considered applications are subband adaptive filtering and subband coding. Analysis filter banks and synthesis filter banks are designed in two subsequent stages, and design objectives include minimization of subband aliasing as well as reconstruction output residual aliasing components on an individual basis. This way to formulate design objectives is appropriate for filter banks used in subband adaptive filtering. Other design objectives are to optimize the overall filter bank response for low amplitude and phase distortion. Designs with phase compensation for linear phase overall response are included. Examples are included of filter banks with increasing bandwidth.
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| 10. |
- Haan, Jan Mark de, et al.
(författare)
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Design of oversampled uniform dft filter banks with delay specification using quadratic optimization
- 2001
-
Konferensbidrag (refereegranskat)abstract
- Subband adaptive filters have been proposed to avoid the drawbacks of slow convergence and high computational complexity associated with time domain adaptive filters. Subband processing introduces transmission delays caused by the filter bank and signal degradations due to aliasing effects. One efficient way to reduce the aliasing effects is to allow a higher sample rate than critically needed in the subbands and thus reduce subband signal degradation. We suggest a design method, for uniform DFT filter banks with any oversampling factor, where the total filter bank group delay may be specified, and where the aliasing and magnitude/phase distortions are minimized.
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