| 1. |
- Nicolas, Aude, et al.
(författare)
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Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
- 2018
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Ingår i: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 97:6, s. 1268-1283.e6
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Tidskriftsartikel (refereegranskat)abstract
- To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
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| 2. |
- Abara, Precious Ugo, et al.
(författare)
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Spectral Conditions for Stability and Stabilization of Positive Equilibria for a Class of Nonlinear Cooperative Systems
- 2018
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Ingår i: IEEE Transactions on Automatic Control. - : IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. - 0018-9286 .- 1558-2523. ; 63:2, s. 402-417
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Tidskriftsartikel (refereegranskat)abstract
- Nonlinear cooperative systems associated to vector fields that are concave or subhomogeneous describe well interconnected dynamics that are of key interest for communication, biological, economical, and neural network applications. For this class of positive systems, we provide conditions that guarantee existence, uniqueness and stability of strictly positive equilibria. These conditions can be formulated directly in terms of the spectral radius of the Jacobian of the system. If control inputs are available, then it is shown how to use state feedback to stabilize an equilibrium point in the interior of the positive orthant.
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| 3. |
- Fogh, Isabella, et al.
(författare)
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A genome-wide association meta-analysis identifies a novel locus at 17q11.2 associated with sporadic amyotrophic lateral sclerosis
- 2014
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Ingår i: Human Molecular Genetics. - Oxford : Oxford University Press. - 0964-6906 .- 1460-2083. ; 23:8, s. 2220-2231
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Tidskriftsartikel (refereegranskat)abstract
- Identification of mutations at familial loci for amyotrophic lateral sclerosis (ALS) has provided novel insights into the aetiology of this rapidly progressing fatal neurodegenerative disease. However, genome-wide association studies (GWAS) of the more common (90) sporadic form have been less successful with the exception of the replicated locus at 9p21.2. To identify new loci associated with disease susceptibility, we have established the largest association study in ALS to date and undertaken a GWAS meta-analytical study combining 3959 newly genotyped Italian individuals (1982 cases and 1977 controls) collected by SLAGEN (Italian Consortium for the Genetics of ALS) together with samples from Netherlands, USA, UK, Sweden, Belgium, France, Ireland and Italy collected by ALSGEN (the International Consortium on Amyotrophic Lateral Sclerosis Genetics). We analysed a total of 13 225 individuals, 6100 cases and 7125 controls for almost 7 million single-nucleotide polymorphisms (SNPs). We identified a novel locus with genome-wide significance at 17q11.2 (rs34517613 with P 1.11 10(8); OR 0.82) that was validated when combined with genotype data from a replication cohort (P 8.62 10(9); OR 0.833) of 4656 individuals. Furthermore, we confirmed the previously reported association at 9p21.2 (rs3849943 with P 7.69 10(9); OR 1.16). Finally, we estimated the contribution of common variation to heritability of sporadic ALS as 12 using a linear mixed model accounting for all SNPs. Our results provide an insight into the genetic structure of sporadic ALS, confirming that common variation contributes to risk and that sufficiently powered studies can identify novel susceptibility loci.
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| 4. |
- Precious, Ugo Abara, et al.
(författare)
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Existence, uniqueness and stability properties of positive equilibria for a class of nonlinear cooperative systems
- 2015
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Ingår i: Proceedings of 54th IEEE Conference on Decision and Control (CDC). - : Institute of Electrical and Electronics Engineers (IEEE). - 9781479978861 - 9781479978847 - 9781479978854 ; , s. 4406-4411
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Konferensbidrag (refereegranskat)abstract
- We provide conditions that guarantee existence, uniqueness and stability of strictly positive equilibria for nonlinear cooperative systems associated to vector fields that are concave or subhomogeneous. This class of positive systems describes well interconnected dynamics that are of key interest for communication, biological, economical and neural network applications. These conditions can be formulated directly in terms of the spectral radius of the Jacobian of the system, and do not require to use constant inputs to move the equilibrium point from the origin to the interior of the positive orthant.
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| 5. |
- Ugo Abara, Precious, et al.
(författare)
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An infinitesimal characterization of nonlinear contracting interference functions
- 2016
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Ingår i: 2016 IEEE 55th Conference on Decision and Control (CDC). - : IEEE Press. - 9781509018376 - 9781509018444 - 9781509018383 ; , s. 5257-5262
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Konferensbidrag (refereegranskat)abstract
- Contractive interference functions are a subclass of the standard interference functions used in the design and analysis of distributed power control algorithms for wireless networks. Their peculiarity is that for the resulting positive system the existence and global asymptotic stability of a unique positive equilibrium point is guaranteed. In this paper we give an infinitesimal characterization of nonlinear contractiveinterference functions in terms of the spectral radius of the Jacobian linearization at any point in the positive orthant. The condition we obtain, that the spectral radius is always less than 1, extends to the nonlinear case an equivalent property of linear interference functions, and leads to a Jacobian characterization similar to the one commonly used in contraction analysis of nonlinear systems.
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