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1.
Science ; 381(6656): 427-430, 2023 Jul 28.
Article in English | MEDLINE | ID: mdl-37498998

ABSTRACT

The Hall effect, which originates from the motion of charged particles in magnetic fields, has deep consequences for the description of materials, extending far beyond condensed matter. Understanding such an effect in interacting systems represents a fundamental challenge, even for small magnetic fields. In this work, we used an atomic quantum simulator in which we tracked the motion of ultracold fermions in two-leg ribbons threaded by artificial magnetic fields. Through controllable quench dynamics, we measured the Hall response for a range of synthetic tunneling and atomic interaction strengths. We unveil a universal interaction-independent behavior above an interaction threshold, in agreement with theoretical analyses. The ability to reach hard-to-compute regimes demonstrates the power of quantum simulation to describe strongly correlated topological states of matter.

2.
Nat Commun ; 11(1): 3344, 2020 07 03.
Article in English | MEDLINE | ID: mdl-32620751

ABSTRACT

Diamond Blackfan Anemia (DBA) is a congenital bone marrow failure syndrome associated with ribosomal gene mutations that lead to ribosomal insufficiency. DBA is characterized by anemia, congenital anomalies, and cancer predisposition. Treatment for DBA is associated with significant morbidity. Here, we report the identification of Nemo-like kinase (NLK) as a potential target for DBA therapy. To identify new DBA targets, we screen for small molecules that increase erythroid expansion in mouse models of DBA. This screen identified a compound that inhibits NLK. Chemical and genetic inhibition of NLK increases erythroid expansion in mouse and human progenitors, including bone marrow cells from DBA patients. In DBA models and patient samples, aberrant NLK activation is initiated at the Megakaryocyte/Erythroid Progenitor (MEP) stage of differentiation and is not observed in non-erythroid hematopoietic lineages or healthy erythroblasts. We propose that NLK mediates aberrant erythropoiesis in DBA and is a potential target for therapy.


Subject(s)
Anemia, Diamond-Blackfan/pathology , Hematopoietic Stem Cells/pathology , Protein Serine-Threonine Kinases/metabolism , Anemia, Diamond-Blackfan/diet therapy , Anemia, Diamond-Blackfan/genetics , Animals , Benzamides/pharmacology , Benzamides/therapeutic use , Cell Differentiation/drug effects , Cell Proliferation , Cells, Cultured , Dioxoles/pharmacology , Dioxoles/therapeutic use , Disease Models, Animal , Erythropoiesis/drug effects , Erythropoiesis/genetics , Humans , Mice , Mice, Transgenic , Mutation , Primary Cell Culture , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Protein Serine-Threonine Kinases/antagonists & inhibitors , Protein Serine-Threonine Kinases/genetics , Pyrazoles/pharmacology , Pyrazoles/therapeutic use , Quinolines/pharmacology , Quinolines/therapeutic use , RNA, Small Interfering/metabolism , Ribosomal Proteins/genetics
3.
Phys Rev Lett ; 122(16): 166801, 2019 Apr 26.
Article in English | MEDLINE | ID: mdl-31075039

ABSTRACT

Great efforts are currently devoted to the engineering of topological Bloch bands in ultracold atomic gases. Recent achievements in this direction, together with the possibility of tuning interparticle interactions, suggest that strongly correlated states reminiscent of fractional quantum Hall (FQH) liquids could soon be generated in these systems. In this experimental framework, where transport measurements are limited, identifying unambiguous signatures of FQH-type states constitutes a challenge on its own. Here, we demonstrate that the fractional nature of the quantized Hall conductance, a fundamental characteristic of FQH states, could be detected in ultracold gases through a circular-dichroic measurement, namely, by monitoring the energy absorbed by the atomic cloud upon a circular drive. We validate this approach by comparing the circular-dichroic signal to the many-body Chern number and discuss how such measurements could be performed to distinguish FQH-type states from competing states. Our scheme offers a practical tool for the detection of topologically ordered states in quantum-engineered systems, with potential applications in solid state.

4.
Br J Cancer ; 86(5): 756-60, 2002 Mar 04.
Article in English | MEDLINE | ID: mdl-11875739

ABSTRACT

Structure and expression of the Rad53 homologue CHK2 were studied in vulval neoplasia. We identified the previously described silent polymorphism at codon 84 (A>G at nucleotide 252) in the germ-line of six out of 72, and somatic mutations in two out of 40 cases of vulval squamous cell carcinomas and none of 32 cases of vulval intraepithelial neoplasia. One mutation introduced a premature stop codon in the kinase domain of CHK2, whereas the second resulted in an amino acid substitution in the kinase domain. The two squamous cell carcinomas with mutations in CHK2 also expressed mutant p53. A CpG island was identified close to the putative CHK2 transcriptional start site, but methylation-specific PCR did not detect methylation in any of 40 vulval squamous cell carcinomas, irrespective of human papillomavirus or p53 status. Consistent with this observation, no cancer exhibited loss of CHK2 expression at mRNA or protein level. Taken together, these observations reveal that genetic but not epigenetic changes in CHK2 occur in a small proportion of vulval squamous cell carcinomas.


Subject(s)
Carcinoma, Squamous Cell/genetics , DNA, Neoplasm/genetics , Gene Expression Regulation, Neoplastic , Protein Kinases/biosynthesis , Protein Serine-Threonine Kinases , Vulvar Neoplasms/genetics , Adult , Carcinoma, Squamous Cell/pathology , Checkpoint Kinase 2 , DNA Methylation , DNA Primers , Female , Humans , Papillomaviridae/genetics , Papillomavirus Infections/complications , Papillomavirus Infections/genetics , Polymerase Chain Reaction , Protein Kinases/genetics , RNA, Messenger , Tumor Virus Infections/complications , Tumor Virus Infections/genetics , Vulvar Neoplasms/pathology
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