56 research outputs found
Excitonic Bound State in the Extended Anderson Model with c-f Coulomb Interaction
The Anderson model with the Coulomb interaction between the local and
conduction electrons is studied in the semiconducting phase. Based on a
perturbation theory from the atomic limit, leading contributions for the c-f
Coulomb interaction are incorporated as a vertex correction to hybridization.
An analytical solution shows that the effective attraction in the intermediate
states leads to a bound state localized at the local electron site.
Self-consistent equations are constructed as an extension of the non-crossing
approximation (NCA) to include the vertex part yielding the bound state. A
numerical calculation demonstrates the excitonic bound state inside the
semiconducting gap for single-particle excitations, and a discontinuity at the
gap edge for magnetic excitations.Comment: 15 pages, 20 figures, submitted to J. Phys. Soc. Jp
Resistivity, Hall effect and Shubnikov-de Haas oscillations in CeNiSn
The resistivity and Hall effect in CeNiSn are measured at temperatures down
to 35 mK and in magnetic fields up to 20 T with the current applied along the
{\it b} axis. The resistivity at zero field exhibits quadratic temperature
dependence below 0.16 K with a huge coefficient of the term (54
cm/K). The resistivity as a function of field shows an
anomalous maximum and dip, the positions of which vary with field directions.
Shubnikov-de Haas (SdH) oscillations with a frequency {\it F} of 100 T
are observed for a wide range of field directions in the {\it ac} and {\it bc}
planes, and the quasiparticle mass is determined to be 10-20 {\it m}.
The carrier density is estimated to be electron/Ce. In a narrow
range of field directions in the {\it ac} plane, where the
magnetoresistance-dip anomaly manifests itself clearer than in other field
directions, a higher-frequency () SdH oscillation is
found at high fields above the anomaly. This observation is discussed in terms
of possible field-induced changes in the electronic structure.Comment: 15 pages, 5 figures, to appear in Phys. Rev. B (15 Sept. 2002 issue
Clustered mutations in the GRIK2 kainate receptor subunit gene underlie diverse neurodevelopmental disorders
Kainate receptors (KARs) are glutamate-gated cation channels with diverse roles in the central nervous system. Bi-allelic loss of function of the KAR-encoding gene GRIK2 causes a nonsyndromic neurodevelopmental disorder (NDD) with intellectual disability and developmental delay as core features. The extent to which mono-allelic variants in GRIK2 also underlie NDDs is less understood because only a single individual has been reported previously. Here, we describe an additional eleven individuals with heterozygous de novo variants in GRIK2 causative for neurodevelopmental deficits that include intellectual disability. Five children harbored recurrent de novo variants (three encoding p.Thr660Lys and two p.Thr660Arg), and four children and one adult were homozygous for a previously reported variant (c.1969G>A [p.Ala657Thr]). Individuals with shared variants had some overlapping behavioral and neurological dysfunction, suggesting that the GRIK2 variants are likely pathogenic. Analogous mutations introduced into recombinant GluK2 KAR subunits at sites within the M3 transmembrane domain (encoding p.Ala657Thr, p.Thr660Lys, and p.Thr660Arg) and the M3-S2 linker domain (encoding p.Ile668Thr) had complex effects on functional properties and membrane localization of homomeric and heteromeric KARs. Both p.Thr660Lys and p.Thr660Arg mutant KARs exhibited markedly slowed gating kinetics, similar to p.Ala657Thr-containing receptors. Moreover, we observed emerging genotype-phenotype correlations, including the presence of severe epilepsy in individuals with the p.Thr660Lys variant and hypomyelination in individuals with either the p.Thr660Lys or p.Thr660Arg variant. Collectively, these results demonstrate that human GRIK2 variants predicted to alter channel function are causative for early childhood development disorders and further emphasize the importance of clarifying the role of KARs in early nervous system development.Genetics of disease, diagnosis and treatmen
More than smell - COVID-19 is associated with severe impairment of smell, taste, and chemesthesis
Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments, such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, and generally lacked quantitative measurements. Here, we report the development, implementation, and initial results of a multilingual, international questionnaire to assess self-reported quantity and quality of perception in 3 distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, and 8 others, aged 19-79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste, and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change ñ100) revealed a mean reduction of smell (-79.7 ñ 28.7, mean ñ standard deviation), taste (-69.0 ñ 32.6), and chemesthetic (-37.3 ñ 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell but also affects taste and chemesthesis. The multimodal impact of COVID-19 and the lack of perceived nasal obstruction suggest that severe acute respiratory syndrome coronavirus strain 2 (SARS-CoV-2) infection may disrupt sensory-neural mechanisms. é 2020 The Author(s) 2020. Published by Oxford University Press. All rights reserved
Multiancestry analysis of the HLA locus in Alzheimerâs and Parkinsonâs diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes
Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinsonâs disease (PD) and Alzheimerâs disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased AÎČ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues
Narcolepsieâ: une maladie auto-immune affectant un peptide de lâĂ©veil liĂ©e Ă un mimĂ©tisme molĂ©culaire avec des Ă©pitopes du virus de la grippe
La narcolepsie et la cataplexie sont dĂ©crites pour la premiĂšre fois Ă la fin du XIXeâsiĂšcle en Allemagne et en France. La prĂ©valence de la maladie est Ă©tablie Ă 0,05â% et un modĂšle canin est dĂ©couvert dans les annĂ©esâ1970. En 1983, une Ă©tude japonaise rĂ©vĂšle que les patients narcoleptiques sont porteurs dâun marqueur gĂ©nĂ©tique unique, lâantigĂšne leucocytaireâHLA-DR2, suggĂ©rant lâauto-immunitĂ© comme cause de la maladie. Il faudra attendre 1992 pour quâil soit montrĂ©, grĂące Ă une Ă©tude chez des patients afro-amĂ©ricains, que DQ0602, un autre gĂšne HLA, est la vĂ©ritable cause de cette association. Des Ă©tudes pharmacologiques conduites sur le modĂšle canin Ă©tablissent que la stimulation dopaminergique est le mode dâaction des stimulants sur lâĂ©veil, tandis que les antidĂ©presseurs suppriment la cataplexie en inhibant la recapture adrĂ©nergique. Aucune association HLA nâest cependant mise en Ă©vidence chez les chiens, suggĂ©rant une cause distincte de la maladie humaine. Une Ă©tude de liaison gĂ©nĂ©tique chez les chiens, initiĂ©e en 1988, rĂ©vĂšle en 1999 que la narcolepsie canine est causĂ©e par des mutations du rĂ©cepteurâ2 de lâhypocrĂ©tine (orexine). En 2000, lâhypocrĂ©tine-1/orexineâA est mesurĂ©e dans le liquide cĂ©phalo-rachidien (LCR) et on dĂ©couvre quâelle est indĂ©tectable chez la plupart des patients narcoleptiques, Ă©tablissant quâun dĂ©ficit hypocrĂ©tinergique est la cause de la narcolepsie humaine. La diminution de lâhypocrĂ©tine-1 dans le LCR, secondaire Ă la perte des 70â000âneurones hypothalamiques produisant lâhypocrĂ©tine, est dĂ©montrĂ©e, ce qui, avec lâassociation au locus HLA, suggĂšre quâune destruction immunitaire de ces cellules est la cause de la maladie. Dâautres Ă©tudes gĂ©nĂ©tiques, notamment dâassociation Ă lâĂ©chelle du gĂ©nome (GWAS), rĂ©vĂšlent lâexistence de nombreux facteurs gĂ©nĂ©tiques prĂ©disposant Ă la narcolepsie, la plupart Ă©tant Ă©galement impliquĂ©s dans dâautres maladies auto-immunes. Une association forte et unique avec les loci des rĂ©cepteurs lymphocytairesâT (TCR) alpha et bĂȘta est aussi observĂ©e, suggĂ©rant un rĂŽle prĂ©pondĂ©rant des lymphocytesâT. En dĂ©pit de nombreux efforts, toutes les tentatives visant Ă dĂ©montrer la prĂ©sence dâauto-anticorps contre les cellules Ă hypocrĂ©tine dans la narcolepsie Ă©chouent, et la cause auto-immune prĂ©sumĂ©e de cette maladie reste Ă lâĂ©tat dâhypothĂšse. Ă la suite de la grippe pandĂ©mique influenzaâAâpH1N1 en 2009, de nombreux cas de narcolepsie apparaissent, suggĂ©rant un mimĂ©tisme molĂ©culaire avec le virus de la grippe qui pourrait dĂ©clencher la maladie auto-immune. Cette hypothĂšse est confirmĂ©e par un criblage peptidique montrant une plus grande rĂ©activitĂ© des lymphocytesâTâCD4+ Ă un segment spĂ©cifique de lâhypocrĂ©tine (HCRTNH2) et une rĂ©activitĂ© croisĂ©e des TCR correspondants Ă un segment dâhĂ©magglutinine de pH1N1 qui partage une homologie avec HCRTNH2. De façon remarquable, le TCR le plus frĂ©quent dans la population et qui reconnaĂźt ces antigĂšnes contient des sĂ©quences TRAJ24 ou TRVB4-2, segments modulĂ©s par des polymorphismes gĂ©nĂ©tiques associĂ©s Ă la narcolepsie dans les Ă©tudes GWAS. Il est probable que les lymphocytesâTâCD4+ autorĂ©actifs avec HCRTNH2 recrutent par la suite des lymphocytesâTâCD8+ qui dĂ©truisent les cellules Ă hypocrĂ©tine. On peut sâattendre Ă ce que dâautres sĂ©quences mimiques grippales inconnues soient dĂ©couvertes prochainement puisque la narcolepsie existait avant 2009. Ces dĂ©couvertes dĂ©montrent enfin la cause auto-immune de la narcolepsie. Les travaux menĂ©s au cours des annĂ©es sur la narcolepsie offrent une perspective unique sur la conduite de la recherche sur lâĂ©tiopathogĂ©nie dâune maladie bien identifiĂ©e
Observation of an electronic singlet ground state in Au171 Yb
International audienc
Nuclear-induced resistivity drop in the Kondo alloy Au-171 Yb
The electrical resistivities of monoisotopic dilute alloys of Au- 171Yb and Au-174Yb have been measured down to 18 mK. A resistivity drop is observed in Au-171Yb, below 90 mK. This effect is shown to result from the magnetic hyperfine coupling in 171Yb which splits the electro-nuclear levels into a singlet ground state and a triplet excited state. A simple model is proposed which accounts for the experimental results.La résistivité électrique d'alliages dilués monoisotopiques d'Au- 171Yb et de Au-174Yb a été mesurée jusqu'à 18 mK. Dans l'Au-171Yb, on observe une chute de résistivité en dessous de 90 mK. On montre que cet effet résulte du couplage hyperfin magnétique dans l'171Yb qui lÚve la dégénérescence des niveaux électronucléaires en produisant un état fondamental singulet et un état excité triplet. On propose un modÚle simple qui rend compte des résultats expérimentaux
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