| 1. |
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| 2. |
- Wiessner, M., et al.
(author)
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Biallelic variants in HPDL cause pure and complicated hereditary spastic paraplegia
- 2021
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In: Brain : a journal of neurology. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 144:5, s. 1422-1434
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Journal article (peer-reviewed)abstract
- Human 4-hydroxyphenylpyruvate dioxygenase-like (HPDL) is a putative iron-containing non-heme oxygenase of unknown specificity and biological significance. We report 25 families containing 34 individuals with neurological disease associated with biallelic HPDL variants. Phenotypes ranged from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spasticity and global developmental delays, sometimes complicated by episodes of neurological and respiratory decompensation. Variants included bona fide pathogenic truncating changes, although most were missense substitutions. Functionality of variants could not be determined directly as the enzymatic specificity of HPDL is unknown; however, when HPDL missense substitutions were introduced into 4-hydroxyphenylpyruvate dioxygenase (HPPD, an HPDL orthologue), they impaired the ability of HPPD to convert 4-hydroxyphenylpyruvate into homogentisate. Moreover, three additional sets of experiments provided evidence for a role of HPDL in the nervous system and further supported its link to neurological disease: (i) HPDL was expressed in the nervous system and expression increased during neural differentiation; (ii) knockdown of zebrafish hpdl led to abnormal motor behaviour, replicating aspects of the human disease; and (iii) HPDL localized to mitochondria, consistent with mitochondrial disease that is often associated with neurological manifestations. Our findings suggest that biallelic HPDL variants cause a syndrome varying from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spastic tetraplegia associated with global developmental delays. © 2021 The Author(s).
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| 3. |
- Donkervoort, S., et al.
(author)
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Pathogenic Variants in the Myosin Chaperone UNC-45B Cause Progressive Myopathy with Eccentric Cores
- 2020
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 107:6, s. 1078-1095
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Journal article (peer-reviewed)abstract
- The myosin-directed chaperone UNC-45B is essential for sarcomeric organization and muscle function from Caenorhabditis elegans to humans. The pathological impact of UNC-45B in muscle disease remained elusive. We report ten individuals with bi-allelic variants in UNC45B who exhibit childhood-onset progressive muscle weakness. We identified a common UNC45B variant that acts as a complex hypomorph splice variant. Purified UNC-45B mutants showed changes in folding and solubility. In situ localization studies further demonstrated reduced expression of mutant UNC-45B in muscle combined with abnormal localization away from the A-band towards the Z-disk of the sarcomere. The physiological relevance of these observations was investigated in C. elegans by transgenic expression of conserved UNC-45 missense variants, which showed impaired myosin binding for one and defective muscle function for three. Together, our results demonstrate that UNC-45B impairment manifests as a chaperonopathy with progressive muscle pathology, which discovers the previously unknown conserved role of UNC-45B in myofibrillar organization.
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| 4. |
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| 5. |
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| 6. |
- Burgunder, J-M, et al.
(author)
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EFNS guidelines for the molecular diagnosis of neurogenetic disorders : motoneuron, peripheral nerve and muscle disorders
- 2011
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In: European Journal of Neurology. - : Wiley-Blackwell. - 1351-5101 .- 1468-1331. ; 18:2, s. 207-E20
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Journal article (peer-reviewed)abstract
- Objectives: These EFNS guidelines on the molecular diagnosis of motoneuron disorders, neuropathies and myopathies are designed to summarize the possibilities and limitations of molecular genetic techniques and to provide diagnostic criteria for deciding when a molecular diagnostic work-up is indicated. Search strategy: To collect data about planning, conditions and performance of molecular diagnosis of these disorders, a literature search in various electronic databases was carried out and original papers, meta-analyses, review papers and guideline recommendations reviewed. Results: The best level of evidence for genetic testing recommendation (B) can be found for the disorders with specific presentations, including familial amyotrophic lateral sclerosis, spinal and bulbar muscular atrophy, Charcot-Marie-Tooth 1A, myotonic dystrophy and Duchenne muscular dystrophy. For a number of less common disorders, a precise description of the phenotype, including the use of immunologic methods in the case of myopathies, is considered as good clinical practice to guide molecular genetic testing. Conclusion: These guidelines are provisional and the future availability of molecular-genetic epidemiological data about the neurogenetic disorders under discussion in this article will allow improved recommendation with an increased level of evidence.
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| 7. |
- Burgunder, J-M., et al.
(author)
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Molecular diagnosis of neurogenetic disorders : motoneuron, peripheral nerve and muscle disorders
- 2012. - 2
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In: European handbook of neurological management. - Oxford, UK : Wiley-Blackwell. - 9781444346268 - 9781405185349 ; , s. 97-109
-
Book chapter (peer-reviewed)abstract
- Objectives: The EFNS guidelines on the molecular diagnosis of motoneuron disorders, neuropathies and myopathies are designed to summarize the possibilities and limitations of molecular genetic techniques and to provide diagnostic criteria for deciding when a molecular diagnostic work-up is indicated.Search strategy: To collect data about the planning, conditions and performance of molecular diagnosis of these disorders, a literature search in various electronic databases was carried out and original papers, meta-analyses, review papers and guideline recommendations reviewed.Results: The best level of evidence for genetic testing recommendation (Level B) can be found for the disorders with specific presentations, including familial ALS, spinal and bulbar muscular atrophy, Charcot-Marie-Tooth 1A, myotonic dystrophy and Duchenne muscular dystrophy. For a number of less common disorders a precise description of the phenotype, including the use of immunological methods in the case of myopathies, is considered good clinical practice to guide molecular genetic testing.Conclusion: These guidelines are provisional and the availability of molecular-genetic epidemiological data in the future about the neurogenetic disorders under discussion in the present paper will allow improved recommendation with an increased level of evidence.
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| 8. |
- Kosek, E, et al.
(author)
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Authors' reply
- 2024
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In: LANCET RHEUMATOLOGY. - : Wiley-Blackwell Publishing Inc.. - 2665-9913. ; 131:2, s. 236-237
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Journal article (other academic/artistic)
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| 9. |
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| 10. |
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| 11. |
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| 12. |
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| 13. |
- Nijs, Jo, et al.
(author)
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Nociceptive, neuropathic, or nociplastic low back pain? : The low back pain phenotyping (BACPAP) consortium's international and multidisciplinary consensus recommendations
- 2024
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In: The Lancet Rheumatology. - : Elsevier. - 2665-9913. ; 6:3, s. e178-e188
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Journal article (peer-reviewed)abstract
- The potential to classify low back pain as being characterised by dominant nociceptive, neuropathic, or nociplastic mechanisms is a clinically relevant issue. Preliminary evidence suggests that these low back pain phenotypes might respond differently to treatments; however, more research must be done before making specific recommendations. Accordingly, the low back pain phenotyping (BACPAP) consortium was established as a group of 36 clinicians and researchers from 13 countries (five continents) and 29 institutions, to apply a modified Nominal Group Technique methodology to develop international and multidisciplinary consensus recommendations to provide guidance for identifying the dominant pain phenotype in patients with low back pain, and potentially adapt pain management strategies. The BACPAP consortium's recommendations are also intended to provide direction for future clinical research by building on the established clinical criteria for neuropathic and nociplastic pain. The BACPAP consortium's consensus recommendations are a necessary early step in the process to determine if personalised pain medicine based on pain phenotypes is feasible for low back pain management. Therefore, these recommendations are not ready to be implemented in clinical practice until additional evidence is generated that is specific to these low back pain phenotypes.
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| 14. |
- Ebrahimi-Fakhari, Darius, et al.
(author)
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Defining the clinical, molecular and imaging spectrum of adaptor protein complex 4-associated hereditary spastic paraplegia
- 2020
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In: Brain. - OXFORD ENGLAND : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 143:10, s. 2929-2944
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Journal article (peer-reviewed)abstract
- Bi-allelic loss-of-function variants in genes that encode subunits of the adaptor protein complex 4 (AP-4) lead to prototypical yet poorly understood forms of childhood-onset and complex hereditary spastic paraplegia: SPG47 (AP4B1), SPG50 (AP4M1), SPG51 (AP4E1) and SPG52 (AP4S1). Here, we report a detailed cross-sectional analysis of clinical, imaging and molecular data of 156 patients from 101 families. Enrolled patients were of diverse ethnic backgrounds and covered a wide age range (1.0-49.3 years). While the mean age at symptom onset was 0.8 +/- 0.6 years [standard deviation (SD), range 0.2-5.0], the mean age at diagnosis was 10.2 +/- 8.5 years (SD, range 0.1-46.3). We define a set of core features: early-onset developmental delay with delayed motor milestones and significant speech delay (50% non-verbal); intellectual disability in the moderate to severe range; mild hypotonia in infancy followed by spastic diplegia (mean age: 8.4 +/- 5.1 years, SD) and later tetraplegia (mean age: 16.1 +/- 9.8 years, SD); postnatal microcephaly (83%); foot deformities (69%); and epilepsy (66%) that is intractable in a subset. At last follow-up, 36% ambulated with assistance (mean age: 8.9 +/- 6.4 years, SD) and 54% were wheelchair-dependent (mean age: 13.4 +/- 9.8 years, SD). Episodes of stereotypic laughing, possibly consistent with a pseudobulbar affect, were found in 56% of patients. Key features on neuroimaging include a thin corpus callosum (90%), ventriculomegaly (65%) often with colpocephaly, and periventricular white-matter signal abnormalities (68%). Iron deposition and polymicrogyria were found in a subset of patients. AP4B1-associated SPG47 and AP4M1-associated SPG50 accounted for the majority of cases. About two-thirds of patients were born to consanguineous parents, and 82% carried homozygous variants. Over 70 unique variants were present, the majority of which are frameshift or nonsense mutations. To track disease progression across the age spectrum, we defined the relationship between disease severity as measured by several rating scales and disease duration. We found that the presence of epilepsy, which manifested before the age of 3 years in the majority of patients, was associated with worse motor outcomes. Exploring genotype-phenotype correlations, we found that disease severity and major phenotypes were equally distributed among the four subtypes, establishing that SPG47, SPG50, SPG51 and SPG52 share a common phenotype, an 'AP-4 deficiency syndrome'. By delineating the core clinical, imaging, and molecular features of AP-4-associated hereditary spastic paraplegia across the age spectrum our results will facilitate early diagnosis, enable counselling and anticipatory guidance of affected families and help define endpoints for future interventional trials.
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| 15. |
- Miranda, Gisele, et al.
(author)
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Influence of Topology on the Dynamics of in Silico Ecosystems with Non-hierarchical Competition
- 2021
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In: 14th International Conference on Cellular Automata for Research and Industry, ACRI 2020. - Cham : Springer Science and Business Media Deutschland GmbH. ; , s. 113-122
-
Conference paper (peer-reviewed)abstract
- The extinction of ecosystems and the mechanisms that support or limit species coexistence have long been studied by scientists. It has been shown that competition and cyclic dominance among species promote species coexistence, such as in the classic Rock-Paper-Scissors (RPS) game. However, individuals’ mobility and the underlying topology that defines the neighbourhood relations between individuals also play an important role in maintaining biodiversity. Typically, square grids are used for simulating such interactions. However, these constrain the individuals’ spatial degrees of freedom. In this work, we investigate the effect of the underlying topology on the RPS dynamics. For that purpose, we considered networks with varying node degree distributions and generated according to different theoretical models. We analyzed the time to the first extinction and the patchiness of the in silico ecosystem over time. In general, we observed a distinct large effect of the network topology on the RPS dynamics. Moreover, leaving regular networks aside, the probability of extinction is very high for some network models due to their inherent long-range connections. On the other hand, spatial arrangements characterized by nearest neighbors interactions have fewer long-range correlations, which is essential for biodiversity.
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| 16. |
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| 17. |
- Bossert, J., et al.
(author)
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Study of the tribological performance of a halogen-free pure lubricant in a steel-steel contact
- 2018
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In: Proceedings of Asia international conference on tribology 2018 (ASIATRIB 2018). - : MALAYSIAN TRIBOLOGY SOC-MYTRIBOS. - 9789671362525 ; , s. 309-310
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Conference paper (peer-reviewed)abstract
- The consumption of materials is too high due to the short lifetime of these. The necessity to use an efficient and "green" lubricant grow more and more. In the present study, a halogen-free lubricant was used in a steel-steel contact and the friction and wear were measured. The work was performed to analyze the protective tribofilm formed between the two moving parts. The experiments show a lower friction and wear when the new lubricant is used than with a conventional base oil. The XPS analysis confirms the low friction especially because of the presence of specific compounds in the tribolayer. Further analysis will be performed in a future work to confirm the chemical composition of the thin film.
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| 18. |
- Buffolo, M., et al.
(author)
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Modeling of the Optical and Electrical Degradation of 845 nm VCSILs
- 2023
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In: 2023 Conference on Lasers and Electro-Optics, CLEO 2023.
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Conference paper (peer-reviewed)abstract
- Optical and electrical degradation of novel micro-transfer-printed VCSILs is investigated. Modeling of experimental data suggests that the main degradation mechanism is represented by the relocation of impurities, originating from the p-side, toward the active region.
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| 19. |
- Caut, Alexander, 1994, et al.
(author)
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Angled Flip-Chip Integration of VCSELs on Silicon Photonic Integrated Circuits
- 2022
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In: Journal of Lightwave Technology. - 0733-8724 .- 1558-2213. ; 40:15, s. 5190-5200
-
Journal article (peer-reviewed)abstract
- An investigation of angled flip-chip integration of a singlemode 850 nm vertical-cavity surface-emitting laser (VCSEL) on a silicon nitride photonic integrated circuit (PIC) is presented. Using numerical FDTD simulations, we consider the conditions under which the VCSEL can be integrated at an angle over a grating coupler with high coupling efficiency and low optical feedback. With both coupling efficiency and feedback decreasing with increasing angle, there is a trade-off. With co-directional coupling, first-order diffraction loss sets in at a critical angle, which further reduces the coupling efficiency. No such critical angle exists for contra-directional coupling. We also experimentally demonstrate angled flip-chip integration of GaAs-based 850 nm single transverse and polarization mode VCSELs over grating couplers on a silicon-nitride PIC. At the output grating coupler, light is either collected by an optical fiber or converted to a photocurrent using a flip-chip integrated GaAs-based photodetector. The latter forms an on-PIC optical link. We measured an insertion loss of 21.9, 17.6 and 20.1 dB with a singlemode fiber, multimode fiber and photodetector over the output grating coupler, respectively.
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| 20. |
- De Baets, K., et al.
(author)
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Tectonic blocks and molecular clocks
- 2016
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In: Philosophical Transactions of the Royal Society B-Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 371:1699
-
Journal article (peer-reviewed)abstract
- Evolutionary timescales have mainly used fossils for calibrating molecular clocks, though fossils only really provide minimum clade age constraints. In their place, phylogenetic trees can be calibrated by precisely dated geological events that have shaped biogeography. However, tectonic episodes are protracted, their role in vicariance is rarely justified, the biogeography of living clades and their antecedents may differ, and the impact of such events is contingent on ecology. Biogeographic calibrations are no panacea for the shortcomings of fossil calibrations, but their associated uncertainties can be accommodated. We provide examples of how biogeographic calibrations based on geological data can be established for the fragmentation of the Pangaean supercontinent: (i) for the uplift of the Isthmus of Panama, (ii) the separation of New Zealand from Gondwana, and (iii) for the opening of the Atlantic Ocean. Biogeographic and fossil calibrations are complementary, not competing, approaches to constraining molecular clock analyses, providing alternative constraints on the age of clades that are vital to avoiding circularity in investigating the role of biogeographic mechanisms in shaping modern biodiversity. This article is part of the themed issue 'Dating species divergences using rocks and clocks'.
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| 21. |
- De Baets, L., et al.
(author)
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The interplay between symptoms of insomnia and pain in people with osteoarthritis: A narrative review of the current evidence
- 2023
-
In: Sleep Medicine Reviews. - 1087-0792. ; 70
-
Research review (peer-reviewed)abstract
- Osteoarthritis (OA) is a leading cause of disability worldwide and clinical pain is the major symptom of OA. This clinical OA-related pain is firmly associated with symptoms of insomnia, which are reported in up to 81% of people with OA. Since understanding the association between both symptoms is critical for their appropriate management, this narrative review synthesizes the existing evidence in people with OA on i) the mechanisms underlying the association between insomnia symptoms and clinical OA-related pain, and ii) the effectiveness of conservative non-pharmacological treatments on insomnia symptoms and clinical OA-related pain. The evidence available identifies depressive symptoms, pain catastrophizing and pain self-efficacy as mechanisms partially explaining the cross-sectional association between insomnia symptoms and pain in people with OA. Furthermore, in comparison to treatments without a specific insomnia intervention, the ones including an insomnia intervention appear more effective for improving insomnia symptoms, but not for reducing clinical OA-related pain. However, at a withinperson level, treatment-related positive effects on insomnia symptoms are associated with a longterm pain reduction. Future longitudinal prospective studies offering fundamental insights into neurobiological and psychosocial mechanisms explaining the association between insomnia symptoms and clinical OA-related pain will enable the development of effective treatments targeting both symptoms.
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| 22. |
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| 23. |
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| 24. |
- Gobeyn, Sacha, et al.
(author)
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Impact of the timing of a SAR image acquisition on the calibration of a flood inundation model
- 2017
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In: Advances in Water Resources. - : ELSEVIER SCI LTD. - 0309-1708 .- 1872-9657. ; 100, s. 126-138
-
Journal article (peer-reviewed)abstract
- Synthetic Aperture Radar (SAR) data have proven to be a very useful source of information for the calibration of flood inundation models. Previous studies have focused on assigning uncertainties to SAR images in order to improve flood forecast systems (e.g. Giustarini et al. (2015) and Stephens et al. (2012)). This paper investigates whether the timing of a SAR acquisition of a flood has an important impact on the calibration of a flood inundation model. As no suitable time series of SAR data exists, we generate a sequence of consistent SAR images through the use of a synthetic framework. This framework uses two available ERS-2 SAR images of the study area, one taken during the flood event of interest, the second taken during a dry reference period. The obtained synthetic observations at different points in time during the flood event are used to calibrate the flood inundation model. The results of this study indicate that the uncertainty of the roughness parameters is lower when the model is calibrated with an image taken before rather than during or after the flood peak. The results also show that the error on the modelled extent is much lower when the model is calibrated with a pre-flood peak image than when calibrated with a near-flood peak or a post-flood peak image. It is concluded that the timing of the SAR image acquisition of the flood has a clear impact on the model calibration and consequently on the precision of the predicted flood extent.
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| 25. |
- Haglund, Erik, 1985, et al.
(author)
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High-power single transverse and polarization mode VCSEL for silicon photonics integration
- 2019
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In: Optics Express. - 1094-4087 .- 1094-4087. ; 27:13, s. 18892-18899
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Journal article (peer-reviewed)abstract
- © 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement. We demonstrate a 6.5 mW single transverse and polarization mode GaAs-based oxide-confined VCSEL at 850 nm. High power is enabled by a relatively large oxide aperture and an epitaxial design for low resistance, low optical loss, and high slope efficiency VCSELs. With the oxide aperture supporting multiple polarization unrestrained transverse modes, single transverse and polarization mode operation is achieved by a transverse and polarization mode filter etched into the surface of the VCSEL. While the VCSEL is specifically designed for light source integration on a silicon photonic integrated circuit, its performance in terms of power, spectral purity, polarization, and beam properties are of great interest for a large range of applications.
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| 26. |
- Haglund, Erik, 1985, et al.
(author)
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Vertical-Cavity Silicon-Integrated Lasers by Bonding and Transfer Printing
- 2018
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In: Conference Digest - IEEE International Semiconductor Laser Conference. - 0899-9406. ; 2018-September, s. 241-242
-
Conference paper (peer-reviewed)abstract
- We present the design and performance of the first current-driven hybrid-vertical-cavity silicon-integrated laser with in-plane waveguide emission. We also show results from preliminary work on transfer printing for large-scale integration of such light sources on silicon photonic integrated circuits.
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| 27. |
- Juneja, M, et al.
(author)
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PFN2 and GAMT as common molecular determinants of axonal Charcot-Marie-Tooth disease
- 2018
-
In: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 89:8, s. 870-878
-
Journal article (peer-reviewed)abstract
- Charcot-Marie-Tooth type 2 (CMT2) neuropathy is characterised by a vast clinical and genetic heterogeneity complicating its diagnosis and therapeutic intervention. Identification of molecular signatures that are common to multiple CMT2 subtypes can aid in developing therapeutic strategies and measuring disease outcomes.MethodsA proteomics-based approach was performed on lymphoblasts from CMT2 patients genetically diagnosed with different gene mutations to identify differentially regulated proteins. The candidate proteins were validated through real-time quantitative PCR and western blotting on lymphoblast samples of patients and controls, motor neurons differentiated from patient-derived induced pluripotent stem cells (iPSCs) and sciatic nerves of CMT2 mouse models.ResultsProteomic profiling of patient lymphoblasts resulted in the identification of profilin 2 (PFN2) and guanidinoacetate methyltransferase (GAMT) as commonly downregulated proteins in different genotypes compared with healthy controls. This decrease was also observed at the transcriptional level on screening 43 CMT2 patients and 22 controls, respectively. A progressive decrease in PFN2 expression with age was observed in patients, while in healthy controls its expression increased with age. Reduced PFN2 expression was also observed in motor neurons differentiated from CMT2 patient-derived iPSCs and sciatic nerves of CMT2 mice when compared with controls. However, no change in GAMT levels was observed in motor neurons and CMT2 mouse-derived sciatic nerves.ConclusionsWe unveil PFN2 and GAMT as molecular determinants of CMT2 with possible indications of the role of PFN2 in the pathogenesis and disease progression. This is the first study describing biomarkers that can boost the development of therapeutic strategies targeting a wider spectrum of CMT2 patients.
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| 28. |
- Nijs, Jo, et al.
(author)
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Nociplastic Pain Criteria or Recognition of Central Sensitization? Pain Phenotyping in the Past, Present and Future
- 2021
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In: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 10:15
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Journal article (peer-reviewed)abstract
- Recently, the International Association for the Study of Pain (IASP) released clinical criteria and a grading system for nociplastic pain affecting the musculoskeletal system. These criteria replaced the 2014 clinical criteria for predominant central sensitization (CS) pain and accounted for clinicians' need to identify (early) and correctly classify patients having chronic pain according to the pain phenotype. Still, clinicians and researchers can become confused by the multitude of terms and the variety of clinical criteria available. Therefore, this paper aims at (1) providing an overview of what preceded the IASP criteria for nociplastic pain ('the past'); (2) explaining the new IASP criteria for nociplastic pain in comparison with the 2014 clinical criteria for predominant CS pain ('the present'); and (3) highlighting key areas for future implementation and research work in this area ('the future'). It is explained that the 2021 IASP clinical criteria for nociplastic pain are in line with the 2014 clinical criteria for predominant CS pain but are more robust, comprehensive, better developed and hold more potential. Therefore, the 2021 IASP clinical criteria for nociplastic pain are important steps towards precision pain medicine, yet studies examining the clinimetric and psychometric properties of the criteria are urgently needed.
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| 29. |
- Oldfors Hedberg, Carola, 1969, et al.
(author)
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Functional characterization of GYG1 variants in two patients with myopathy and glycogenin-1 deficiency
- 2019
-
In: Neuromuscular Disorders. - : Elsevier BV. - 0960-8966. ; 29:12, s. 951-960
-
Journal article (peer-reviewed)abstract
- Glycogen storage disease XV is caused by variants in the glycogenin-1 gene, GYG1, and presents as a predominant skeletal myopathy or cardiomyopathy. We describe two patients with late-onset myopathy anti biallelic GYG1 variants. In patient 1, the novel c.144-2A>G splice acceptor variant and the novel frameshift variant c.631delG (p.Va1211Cysfs(star)30) were identified, and in patient 2, the previously described c.304G>C (p.Asp102His) and c.487deLG (p.Asp163Thrfs(star)5) variants were found. Protein analysis showed total absence of glycogenin-1 expression in patient 1, whereas in patient 2 there was reduced expression of glycogenin-1, with the residual protein being non-functional. Both patients showed glycogen and polyglucosan storage in their muscle fibers, as revealed by PAS staining and electron microscopy. Age at onset of the myopathy phenotype was 53 years and 70 years respectively, with the selective pattern of muscle involvement on MRI corroborating the pattern of weakness. Cardiac evaluation of patient 1 and 2 did not show any specific abnormalities linked to the glycogenin-1 deficiency. In patient 2, who was shown to express the p.Asp102His mutated glycogenin-1, cardiac evaluation was still normal at age 77 years. This contrasts with the association of the p.Asp102His variant in homozygosity with a severe cardiomyopathy in several cases with an onset age between 30 and 50 years. This finding might indicate that the level of p.Asp102His mutated glycogenin-1 determines if a patient will develop a cardiomyopathy. (C) 2019 Elsevier B.V. All rights reserved.
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| 30. |
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| 31. |
- Zenari, M., et al.
(author)
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Addressing the electrical degradation of 845 nm micro-transfer printed VCSILs through TCAD simulations
- 2023
-
In: Proceedings of the International Conference on Numerical Simulation of Optoelectronic Devices, NUSOD. - 2158-3234. ; 2023-September, s. 91-92
-
Conference paper (peer-reviewed)abstract
- In this work we present the electrical modeling of novel 845 nm vertical-cavity silicon-integrated lasers (VCSILs) for silicon photonics (SiPh). We tested the reliability of the devices by submitting them to high current stress, corresponding to ≈ 20xIth, to observe the degradation as a function of time. During the stress experiment, we monitored the electrical characteristics at regular intervals and we observed two separate degradation phenomena: the series resistance increment and the lowering of the turn-on voltage. Thanks to a Poisson-drift diffusion simulator we simulated the I-V characteristics and the band diagrams to interpret the degradation phenomena. The results of the simulations confirmed that the electrical degradation can be caused by the diffusion of compensation impurities originating from the p-contact layers. The same mechanism was also responsible of the optical degradation of the devices.
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| 32. |
- Zenari, M., et al.
(author)
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Analysis of defect-related optical degradation of VCSILs for photonic integrated circuits
- 2023
-
In: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 12439
-
Conference paper (peer-reviewed)abstract
- Laser diodes are of paramount importance for on-chip telecommunications applications, and a wide range of sensing devices that require near-infrared sources. In this work, the devices under test are vertical-cavity silicon-integrated lasers (VCSILs) designed for operation at 845 nm in photonic integrated circuits (PICs). We focus on the analysis of the degradation of the optical performance during aging. To investigate the reliability of the devices, we carried out several stress tests at constant current, ranging from 3.5 mA to 4.5 mA representing a highly accelerated stress condition. We observed two different degradation modes. In the first part of the experiments, the samples exhibited a worsening of the threshold current, but the sub-threshold emission was unaffected by degradation. We associated this behavior to the diffusion of impurities that, from the p-contact, were crossing the upper mirror implying a worsening of the DBR optical absorption. In the second stage of the stress test, the devices showed a higher degradation rate of the threshold current, whose variation was found to be linearly correlated to the worsening of the sub-threshold emission. We related this second degradation mode to the migration of the same impurities degrading the top DBR that, when reaching the active region of the laser, induced an increase in the non-radiative recombination rate. In addition to that, we related the two degradation modes to the change in series resistance, which was ascribed to the resistivity increment of the top DBR first and of oxide aperture afterwards.
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| 33. |
- Zenari, M., et al.
(author)
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Impact of the oxide aperture width on the degradation of 845 nm VCSELs for silicon photonics
- 2024
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In: IEEE Journal of Selected Topics in Quantum Electronics. - 1558-4542 .- 1077-260X. ; In Press
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Journal article (peer-reviewed)abstract
- For the first time, we analyzed the degradation as a function of the oxide aperture in 845 nm VCSELs designed for silicon photonics (SiPh) applications. First, we evaluated the optical degradation of the devices by collecting EL images during a constant current stress. The experimental results showed an increased spreading of the optical beam of the VCSEL with increasing ageing time. Based on numerical simulations, we demonstrated that the electrical degradation (increase in series resistance) is responsible a larger current spreading which, in turn, increases the FWHM (full width half maximum) of the optical beam. We further evaluated the series resistance variation by aging four lasers with different oxide apertures. The results of this set of experiments showed that the electrical degradation is stronger as the oxide aperture is smaller, and mostly depends on the contribution of the top DBR resistance. Thanks to our analysis we proved that the use of a larger aperture can result in a better device reliability.
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| 34. |
- Zenari, M., et al.
(author)
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Modeling the Electrical Degradation of Micro-Transfer Printed 845 nm VCSILs for Silicon Photonics
- 2024
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In: IEEE Transactions on Electron Devices. - 1557-9646 .- 0018-9383. ; 71:2, s. 1131-1138
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Journal article (peer-reviewed)abstract
- This article deals for the first time with the electrical degradation of novel 845 nm vertical-cavity silicon-integrated lasers (VCSILs) for silicon photonics (SiPh). We analyzed the reliability of these devices by submitting them to high current stress. The experimental results showed that stress induced: 1) a significant increase in the series resistance, occurring in two separated time-windows and 2) a lowering of the turn-on voltage. To understand the origin of such degradation phenomena, we simulated the $\textit{I}$ - $\textit{V}$ characteristics and the band diagrams by a Poisson-drift-diffusion simulator. We demonstrated that the degradation was caused by the diffusion of mobile species capable of compensating the p-type doping. The diffusing species are expected to migrate from the p-contact region in the top distributed Bragg reflector (DBR) towards the active layers.
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| 35. |
- Zenari, M., et al.
(author)
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Understanding the optical degradation of 845nm micro-transfer-printed VCSILs for photonic integrated circuits
- 2023
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In: IEEE Journal of Quantum Electronics. - 0018-9197 .- 1558-1713. ; 59:4
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Journal article (peer-reviewed)abstract
- For the first time we investigate the optical degradation of vertical-cavity silicon-integrated lasers (VCSILs) designed for operation at 845 nm in photonic integrated circuits (PICs). The study is based on the combined electro-optical characterization of VCSIL, submitted to constant-current stress tests at different current levels. The original results obtained within the manuscript indicate that degradation is related to the diffusion of impurities. Remarkably, depending on the region through which these impurities are migrating, the diffusion process affects device characteristics in different ways. During Phase 1 (Ph1), compensating impurities originating from the metal-semiconductor contact cross the top DBR, thus degrading mirror reflectivity, which is rarely observed in the literature, and leading to an increase in the threshold current of the device. As the impurities start reaching the active region we observe the onset of Phase 2 (Ph2), during which both threshold current and sub-threshold slope worsen, due to the increase of the Shockley-Read-Hall recombination rate. This phase is also characterized by a measurable increase in series resistance, which is ascribed to a change in the resistance of the oxide aperture. The identification of the root cause of physical degradation represents a fundamental step for future lifetime improvement of these novel optical sources, which are set to replace conventional solid-state sources in the 0.85 μm communication window.
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