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"Cooper, N"
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Measuring the Chern number of Hofstadter bands with ultracold bosonic atoms
Chern numbers characterize the quantum Hall effect conductance—non-zero values are associated with topological phases. Previously only spotted in electronic systems, they have now been measured in ultracold atoms subject to artificial gauge fields.
Sixty years ago, Karplus and Luttinger pointed out that quantum particles moving on a lattice could acquire an anomalous transverse velocity in response to a force, providing an explanation for the unusual Hall effect in ferromagnetic metals
1
. A striking manifestation of this transverse transport was then revealed in the quantum Hall effect
2
where the plateaux depicted by the Hall conductivity were attributed to a topological invariant characterizing the Bloch bands: the Chern number
3
. Until now, topological transport associated with non-zero Chern numbers has only been observed in electronic systems
2
,
4
,
5
. Here we use the transverse deflection of an atomic cloud in response to an optical gradient to measure the Chern number of artificially generated Hofstadter bands
6
. These topological bands are very flat and thus constitute good candidates for the realization of fractional Chern insulators
7
. Combining these deflection measurements with the determination of the band populations, we obtain an experimental value for the Chern number of the lowest band
ν
exp
= 0.99(5). This first Chern-number measurement in a non-electronic system is facilitated by an all-optical artificial gauge field scheme, generating uniform flux in optical superlattices.
Journal Article
ماذا يخبئ المستقبل للعالم : رؤى من منظور العلوم الاجتماعية
يبحث هذا الكتاب عن الكيفية التي يمكننا من خلالها النظر بذكاء إلى المستقبل مع الوضع في الاعتبار المقاربات المنهجية المختلفة والمتنوعة التي يتبنها المنتخصصون في استشراق الستقبل وما سيكون عليه من تطورات ومسارات في الحياة البشرية كما يطرق الكتاب عددا من الأسئلة المهمة من قبيل وهي كم سيصبح عدد البشر في المستقبل وما هي أنماط العمل التي ستوجد وكيف ستعمل الحكومات على المستويات الإقليمية والمحلية والعالمية وهل سيبقى التضخم تحت السيطرة.
Book
Membrane-Bound IL-21 Promotes Sustained Ex Vivo Proliferation of Human Natural Killer Cells
NK cells have therapeutic potential for a wide variety of human malignancies. However, because NK cells expand poorly in vitro, have limited life spans in vivo, and represent a small fraction of peripheral white blood cells, obtaining sufficient cell numbers is the major obstacle for NK-cell immunotherapy. Genetically-engineered artificial antigen-presenting cells (aAPCs) expressing membrane-bound IL-15 (mbIL15) have been used to propagate clinical-grade NK cells for human trials of adoptive immunotherapy, but ex vivo proliferation has been limited by telomere shortening. We developed K562-based aAPCs with membrane-bound IL-21 (mbIL21) and assessed their ability to support human NK-cell proliferation. In contrast to mbIL15, mbIL21-expressing aAPCs promoted log-phase NK cell expansion without evidence of senescence for up to 6 weeks of culture. By day 21, parallel expansion of NK cells from 22 donors demonstrated a mean 47,967-fold expansion (median 31,747) when co-cultured with aAPCs expressing mbIL21 compared to 825-fold expansion (median 325) with mbIL15. Despite the significant increase in proliferation, mbIL21-expanded NK cells also showed a significant increase in telomere length compared to freshly obtained NK cells, suggesting a possible mechanism for their sustained proliferation. NK cells expanded with mbIL21 were similar in phenotype and cytotoxicity to those expanded with mbIL15, with retained donor KIR repertoires and high expression of NCRs, CD16, and NKG2D, but had superior cytokine secretion. The mbIL21-expanded NK cells showed increased transcription of the activating receptor CD160, but otherwise had remarkably similar mRNA expression profiles of the 96 genes assessed. mbIL21-expanded NK cells had significant cytotoxicity against all tumor cell lines tested, retained responsiveness to inhibitory KIR ligands, and demonstrated enhanced killing via antibody-dependent cell cytotoxicity. Thus, aAPCs expressing mbIL21 promote improved proliferation of human NK cells with longer telomeres and less senescence, supporting their clinical use in propagating NK cells for adoptive immunotherapy.
Journal Article
Challenges in the diagnosis of neurofibromatosis type 1 (NF1) in young children facilitated by means of revised diagnostic criteria including genetic testing for pathogenic NF1 gene variants
Neurofibromatosis type 1 (NF1) is the most frequent disorder associated with multiple café-au-lait macules (CALM) which may either be present at birth or appear during the first year of life. Other NF1-associated features such as skin-fold freckling and Lisch nodules occur later during childhood whereas dermal neurofibromas are rare in young children and usually only arise during early adulthood. The NIH clinical diagnostic criteria for NF1, established in 1988, include the most common NF1-associated features. Since many of these features are age-dependent, arriving at a definitive diagnosis of NF1 by employing these criteria may not be possible in infancy if CALM are the only clinical feature evident. Indeed, approximately 46% of patients who are diagnosed with NF1 later in life do not meet the NIH diagnostic criteria by the age of 1 year. Further, the 1988 diagnostic criteria for NF1 are not specific enough to distinguish NF1 from other related disorders such as Legius syndrome. In this review, we outline the challenges faced in diagnosing NF1 in young children, and evaluate the utility of the recently revised (2021) diagnostic criteria for NF1, which include the presence of pathogenic variants in the NF1 gene and choroidal anomalies, for achieving an early and accurate diagnosis.
Journal Article
The Human Gene Mutation Database: towards a comprehensive repository of inherited mutation data for medical research, genetic diagnosis and next-generation sequencing studies
The Human Gene Mutation Database (HGMD
®
) constitutes a comprehensive collection of published germline mutations in nuclear genes that underlie, or are closely associated with human inherited disease. At the time of writing (March 2017), the database contained in excess of 203,000 different gene lesions identified in over 8000 genes manually curated from over 2600 journals. With new mutation entries currently accumulating at a rate exceeding 17,000 per annum, HGMD represents de facto the central unified gene/disease-oriented repository of heritable mutations causing human genetic disease used worldwide by researchers, clinicians, diagnostic laboratories and genetic counsellors, and is an essential tool for the annotation of next-generation sequencing data. The public version of HGMD (
http://www.hgmd.org
) is freely available to registered users from academic institutions and non-profit organisations whilst the subscription version (HGMD Professional) is available to academic, clinical and commercial users under license via QIAGEN Inc.
Journal Article
The Human Gene Mutation Database (HGMD®): optimizing its use in a clinical diagnostic or research setting
The Human Gene Mutation Database (HGMD®) constitutes a comprehensive collection of published germline mutations in nuclear genes that are thought to underlie, or are closely associated with human inherited disease. At the time of writing (June 2020), the database contains in excess of 289,000 different gene lesions identified in over 11,100 genes manually curated from 72,987 articles published in over 3100 peer-reviewed journals. There are primarily two main groups of users who utilise HGMD on a regular basis; research scientists and clinical diagnosticians. This review aims to highlight how to make the most out of HGMD data in each setting.
Journal Article
M-CAP eliminates a majority of variants of uncertain significance in clinical exomes at high sensitivity
Gill Bejerano and colleagues present M-CAP, a classifier that estimates variant pathogenicity in clinical exome data sets. They show that M-CAP outperforms other existing methods at all thresholds and correctly dismisses 60% of rare missense variants of uncertain significance at 95% sensitivity.
Variant pathogenicity classifiers such as SIFT, PolyPhen-2, CADD, and MetaLR assist in interpretation of the hundreds of rare, missense variants in the typical patient genome by deprioritizing some variants as likely benign. These widely used methods misclassify 26 to 38% of known pathogenic mutations, which could lead to missed diagnoses if the classifiers are trusted as definitive in a clinical setting. We developed M-CAP, a clinical pathogenicity classifier that outperforms existing methods at all thresholds and correctly dismisses 60% of rare, missense variants of uncertain significance in a typical genome at 95% sensitivity.
Journal Article