| 2. |
- Oikonomou, Vasileios, et al.
(författare)
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The Role of Interferon-γ in Autoimmune Polyendocrine Syndrome Type 1.
- 2024
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Ingår i: The New England journal of medicine. - 1533-4406. ; 390:20, s. 1873-1884
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune polyendocrine syndrome type 1 (APS-1) is a life-threatening, autosomal recessive syndrome caused by autoimmune regulator (AIRE) deficiency. In APS-1, self-reactive T cells escape thymic negative selection, infiltrate organs, and drive autoimmune injury. The effector mechanisms governing T-cell-mediated damage in APS-1 remain poorly understood.We examined whether APS-1 could be classified as a disease mediated by interferon-γ. We first assessed patients with APS-1 who were participating in a prospective natural history study and evaluated mRNA and protein expression in blood and tissues. We then examined the pathogenic role of interferon-γ using Aire-/-Ifng-/- mice and Aire-/- mice treated with the Janus kinase (JAK) inhibitor ruxolitinib. On the basis of our findings, we used ruxolitinib to treat five patients with APS-1 and assessed clinical, immunologic, histologic, transcriptional, and autoantibody responses.Patients with APS-1 had enhanced interferon-γ responses in blood and in all examined autoimmunity-affected tissues. Aire-/- mice had selectively increased interferon-γ production by T cells and enhanced interferon-γ, phosphorylated signal transducer and activator of transcription 1 (pSTAT1), and CXCL9 signals in multiple organs. Ifng ablation or ruxolitinib-induced JAK-STAT blockade in Aire-/- mice normalized interferon-γ responses and averted T-cell infiltration and damage in organs. Ruxolitinib treatment of five patients with APS-1 led to decreased levels of T-cell-derived interferon-γ, normalized interferon-γ and CXCL9 levels, and remission of alopecia, oral candidiasis, nail dystrophy, gastritis, enteritis, arthritis, Sjögren's-like syndrome, urticaria, and thyroiditis. No serious adverse effects from ruxolitinib were identified in these patients.Our findings indicate that APS-1, which is caused by AIRE deficiency, is characterized by excessive, multiorgan interferon-γ-mediated responses. JAK inhibition with ruxolitinib in five patients showed promising results. (Funded by the National Institute of Allergy and Infectious Diseases and others.).
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| 3. |
- Jalai Jafari, Behdad, 1965, et al.
(författare)
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Detection of On-Chip Generated Weak Microwave Radiation Using Superconducting Normal-Metal SET
- 2016
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Ingår i: Applied Sciences (Switzerland). - : MDPI AG. - 2076-3417. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- The present work addresses quantum interaction phenomena of microwave radiation with a single-electron tunneling system. For this study, an integrated circuit is implemented, combining on the same chip a Josephson junction (Al/AlO /Al) oscillator and a single-electron transistor (SET) with the superconducting island (Al) and normal-conducting leads (AuPd). The transistor is demonstrated to operate as a very sensitive photon detector, sensing down to a few tens of photons per second in the microwave frequency range around 100 GHz. On the other hand, the Josephson oscillator, realized as a two-junction SQUID and coupled to the detector via a coplanar transmission line (Al), is shown to provide a tunable source of microwave radiation: controllable variations in power or in frequency were accompanied by significant changes in the detector output, when applying magnetic flux or adjusting the voltage across the SQUID, respectively. It was also shown that the effect of substrate-mediated phonons, generated by our microwave source, on the detector output was negligibly small.
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