High-impedance surface acoustic wave resonators

Because of their small size, low loss, and compatibility with magnetic fields and elevated temperatures, surface acoustic wave resonators hold significant potential as future quantum interconnects. Here, we design, fabricate, and characterize GHz-frequency surface acoustic wave resonators with the potential for strong capacitive coupling to nanoscale solid-state quantum systems, including semiconductor quantum dots. Strong capacitive coupling to such systems requires a large characteristic impedance, and the resonators we fabricate have impedance values above 100 $\Omega$. We achieve such high impedance values by tightly confining a Gaussian acoustic mode. At the same time, the resonators also have low loss, with quality factors of several thousand at millikelvin temperatures. These high-impedance resonators are expected to exhibit large vacuum electric-field fluctuations and have the potential for strong coupling to a variety of solid-state quantum systems

SHARPIN Is Essential for Cytokine Production, NF-κB Signaling, and Induction of Th1 Differentiation by Dendritic Cells

Spontaneous mutations of the Sharpin (SHANK-associated RH domain-interacting protein, other aliases: Rbckl1, Sipl1) gene in mice result in systemic inflammation that is characterized by chronic proliferative dermatitis and dysregulated secretion of T helper1 (Th1) and Th2 cytokines. The cellular and molecular mechanisms underlying this inflammatory phenotype remain elusive. Dendritic cells may contribute to the initiation and progression of the phenotype of SHARPIN-deficient mice because of their pivotal role in innate and adaptive immunity. Here we show by flow cytometry that SHARPIN- deficiency did not alter the distribution of different DC subtypes in the spleen. In response to TOLL-like receptor (TLR) agonists LPS and poly I:C, cultured bone marrow-derived dendritic cells (BMDC) from WT and mutant mice exhibited similar increases in expression of co-stimulatory molecules CD40, CD80, and CD86. However, stimulated SHARPIN-deficient BMDC had reduced transcription and secretion of pro-inflammatory mediators IL6, IL12P70, GMCSF, and nitric oxide. Mutant BMDC had defective activation of NF-κB signaling, whereas the MAPK1/3 (ERK1/2) and MAPK11/12/13/14 (p38 MAP kinase isoforms) and TBK1 signaling pathways were intact. A mixed lymphocyte reaction showed that mutant BMDC only induced a weak Th1 immune response but stimulated increased Th2 cytokine production from allogeneic naïve CD4+ T cells. In conclusion, loss of Sharpin in mice significantly affects the immune function of DC and this may partially account for the systemic inflammation and Th2-biased immune response

Chronic Proliferative Dermatitis in Sharpin Null Mice: Development of an Autoinflammatory Disease in the Absence of B and T Lymphocytes and IL4/IL13 Signaling.

SHARPIN is a key regulator of NFKB and integrin signaling. Mice lacking Sharpin develop a phenotype known as chronic proliferative dermatitis (CPDM), typified by progressive epidermal hyperplasia, apoptosis of keratinocytes, cutaneous and systemic eosinophilic inflammation, and hypoplasia of secondary lymphoid organs. Rag1−/− mice, which lack mature B and T cells, were crossed with Sharpin−/− mice to examine the role of lymphocytes in CDPM. Although inflammation in the lungs, liver, and joints was reduced in these double mutant mice, dermatitis was not reduced in the absence of functional lymphocytes, suggesting that lymphocytes are not primary drivers of the inflammation in the skin. Type 2 cytokine expression is increased in CPDM. In an attempt to reduce this aspect of the phenotype, Il4ra−/− mice, unresponsive to both IL4 and IL13, were crossed with Sharpin−/− mice. Double homozygous Sharpin−/−, Il4ra−/−mice developed an exacerbated granulocytic dermatitis, acute system inflammation, as well as hepatic necrosis and mineralization. High expression of CHI3L4, normally seen in CPDM skin, was abolished in Sharpin−/−, Il4ra−/− double mutant mice indicating the crucial role of IL4 and IL13 in the expression of this protein. Cutaneous eosinophilia persisted in Sharpin−/−, Il4ra−/−mice, although expression of Il5 mRNA was reduced and the expression of Ccl11 and Ccl24was completely abolished. TSLP and IL33 were both increased in the skin of Sharpin−/− mice and this was maintained in Sharpin−/−, Il4ra−/− mice suggesting a role for TSLP and IL33 in the eosinophilic dermatitis in SHARPIN-deficient mice. These studies indicate that cutaneous inflammation in SHARPIN-deficient mice is autoinflammatory in nature developing independently of B and T lymphocytes, while the systemic inflammation seen in CPDM has a strong lymphocyte-dependent component. Both the cutaneous and systemic inflammation is enhanced by loss of IL4 and IL13 signaling indicating that these cytokines normally play an anti-inflammatory role in SHARPIN-deficient mice