| 11. |
- Ebrahimi-Fakhari, Darius, et al.
(författare)
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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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Ingår i: Brain. - OXFORD ENGLAND : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 143:10, s. 2929-2944
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Tidskriftsartikel (refereegranskat)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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| 12. |
- Yaneva, A., et al.
(författare)
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FAST-TIMING MEASUREMENT IN 96Pd: IMPROVED ACCURACY FOR THE LIFETIME OF THE 4+1 STATE
- 2023
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Ingår i: Acta Physica Polonica B, Proceedings Supplement. - : Jagiellonian University. - 1899-2358 .- 2082-7865. ; , s. 1-1
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Konferensbidrag (refereegranskat)abstract
- Direct lifetime measurements via γ–γ coincidences using the FATIMA fast-timing LaBr3(Ce) array were performed for the excited states below previously reported isomers. In the N = 50 semi-magic 96Pd nucleus, lifetimes below the Iπ = 8+ seniority isomer were addressed as a benchmark for further analysis. The results for the Iπ = 2+ and 4+ states confirm the published values. Increased accuracy for the lifetime value was achieved for the 4+ state.
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| 17. |
- Kovyrshin, Arseny, et al.
(författare)
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Nonadiabatic Nuclear-Electron Dynamics: A Quantum Computing Approach
- 2023
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Ingår i: Journal of Physical Chemistry Letters. - 1948-7185. ; 14:31, s. 7065-7072
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Tidskriftsartikel (refereegranskat)abstract
- Coupled quantum electron-nuclear dynamics is oftenassociatedwith the Born-Huang expansion of the molecular wave functionand the appearance of nonadiabatic effects as a perturbation. On theother hand, native multicomponent representations of electrons andnuclei also exist, which do not rely on any a priori approximation.However, their implementation is hampered by prohibitive scaling.Consequently, quantum computers offer a unique opportunity for extendingtheir use to larger systems. Here, we propose a quantum algorithmfor simulating the time-evolution of molecular systems and apply itto proton transfer dynamics in malonaldehyde, described as a rigidscaffold. The proposed quantum algorithm can be easily generalizedto include the explicit dynamics of the classically described molecularscaffold. We show how entanglement between electronic and nucleardegrees of freedom can persist over long times if electrons do notfollow the nuclear displacement adiabatically. The proposed quantumalgorithm may become a valid candidate for the study of such phenomenawhen sufficiently powerful quantum computers become available.
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| 19. |
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| 20. |
- Nykänen, Anton, et al.
(författare)
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Toward Accurate Post-Born-Oppenheimer Molecular Simulations on Quantum Computers: An Adaptive Variational Eigensolver with Nuclear-Electronic Frozen Natural Orbitals
- 2023
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Ingår i: Journal of Chemical Theory and Computation. - 1549-9626 .- 1549-9618. ; 19:24, s. 9269-9277
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Tidskriftsartikel (refereegranskat)abstract
- Nuclear quantum effects such as zero-point energy and hydrogen tunneling play a central role in many biological and chemical processes. The nuclear-electronic orbital (NEO) approach captures these effects by treating selected nuclei quantum mechanically on the same footing as electrons. On classical computers, the resources required for an exact solution of NEO-based models grow exponentially with system size. By contrast, quantum computers offer a means of solving this problem with polynomial scaling. However, due to the limitations of current quantum devices, NEO simulations are confined to the smallest systems described by minimal basis sets, whereas realistic simulations beyond the Born-Oppenheimer approximation require more sophisticated basis sets. For this purpose, we herein extend a hardware-efficient ADAPT-VQE method to the NEO framework in the frozen natural orbital (FNO) basis. We demonstrate on H2 and D2 molecules that the NEO-FNO-ADAPT-VQE method reduces the CNOT count by several orders of magnitude relative to the NEO unitary coupled cluster method with singles and doubles while maintaining the desired accuracy. This extreme reduction in the CNOT gate count is sufficient to permit practical computations employing the NEO method─an important step toward accurate simulations involving nonclassical nuclei and non-Born-Oppenheimer effects on near-term quantum devices. We further show that the method can capture isotope effects, and we demonstrate that inclusion of correlation energy systematically improves the prediction of difference in the zero-point energy (ΔZPE) between isotopes.
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