Search

Manipulating terahertz (THz) polarization in an efficient and broadband manner is of great significance to facilitating THz applications, including communications, imaging, defense, and homeland security. In this work, a dispersion compensation scheme is proposed for high‐efficiency and ultra‐broadband THz polarization manipulation using an anisotropic dielectric‐metal hybrid metadevice. The operating bandwidth is broadened by dispersion compensation, where the dielectric grating provides an artificial birefringence with a phase dispersion of positive slope and the metallic grating provides a phase dispersion of negative slope. Experimental results show that the device achieves two ultra‐broadband dispersion compensation, corresponding to the achromatic quarter‐wave plate in the lower frequency band (QWP: 0.5–2.0 THz, PCR >0.95) and the achromatic half‐wave plate in the higher frequency band (HWP: 1.0–2.1 THz, PCR >0.9), respectively. Theoretically, the bandwidth of QWP can be further improved to 2.6 THz by optimizing the grating dispersion, which brings huge application space to cover most of the THz radiation. This hybrid metadevice configuration offers a versatile platform for engineering electromagnetic waves, and the strategy of phase compensation can be generalized to extend the bandwidth of the metadevice in imaging and communications. [ABSTRACT FROM AUTHOR]

Regulation of STAT3 activation is critical for normal and malignant hematopoietic cell proliferation. Here, we have reported that the endogenous transmembrane protein upstream-of-mTORC2 (UT2) negatively regulates activation of STAT3. Specifically, we determined that UT2 interacts directly with GP130 and inhibits phosphorylation of STAT3 on tyrosine 705 ([STAT3.sup.Y705]). This reduces cytokine signaling including IL6 that is implicated in multiple myeloma and other hematopoietic malignancies. Modulation of UT2 resulted in inverse effects on animal survival in myeloma models. Samples from multiple myeloma patients also revealed a decreased copy number of UT2 and decreased expression of UT2 in genomic and transcriptomic analyses, respectively. Together, these studies identify a transmembrane protein that functions to negatively regulate cytokine signaling through GP130 and p[STAT3.sup.Y705] and is molecularly and mechanistically distinct from the suppressors of cytokine signaling (SOCS) family of genes. Moreover, this work provides evidence that perturbations of this activation-dampening molecule participate in hematologic malignancies and may serve as a key determinant of multiple myeloma pathophysiology. UT2 is a negative regulator shared across STAT3 and mTORC2 signaling cascades, functioning as a tumor suppressor in hematologic malignancies driven by those pathways., Introduction We identified UT2 as a transmembrane molecule altered in leukemic cells that emerged from an animal model with modifications in specific BM stromal cells (1). Hypothesizing that the genes [...]

Autoreactive B cells are regulated in the BM during development through mechanisms, including editing of the B cell receptor (BCR), clonal deletion, and anergy. Peripheral B cell tolerance is also important for protection from autoimmune damage, although the mechanisms are less well defined. Here we demonstrated, using a mouse model of SLE-like serology, that during an autoimmune response, RAG was reinduced in antigen-activated early memory or preplasma B cells. Expression of RAG was specific to antigen-reactive B cells, required the function of the IL-7 receptor (IL-7R), and contributed to maintenance of humoral tolerance. We also showed that soluble antigen could diminish a non-autoreactive antibody response through induction of BCR revision. These data suggest that tolerance induction operates in B cells at a postactivation checkpoint and that BCR revision helps regulate autoreactivity generated during an ongoing immune response., Introduction During B lymphocyte development in the BM, immature B cells expressing self-reactive antigen receptors are tolerized by a variety of mechanisms. Prominent among these are clonal deletion, which purges [...]

Azoospermia patients who carry a monogenetic mutation that causes meiotic arrest may have their biological child through genetic correction in spermatogonial stem cells (SSCs). However, such therapy for infertility has not been experimentally investigated yet. In this study, a mouse model with an X-linked testis-expressed 11 (TEX11) mutation (Tex11PM/Y) identified in azoospermia patients exhibited meiotic arrest due to aberrant chromosome segregation. Tex11PM/Y SSCs could be isolated and expanded in vitro normally, and the mutation was corrected by clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated endonuclease 9 (Cas9), leading to the generation of repaired SSC lines. Whole-genome sequencing demonstrated that the mutation rate in repaired SSCs is comparable with that of autonomous mutation in untreated Tex11PM/Y SSCs, and no predicted off-target sites are modified. Repaired SSCs could restore spermatogenesis in infertile males and give rise to fertile offspring at a high efficiency. In summary, our study establishes a paradigm for the treatment of male azoospermia by combining in vitro expansion of SSCs and gene therapy. [ABSTRACT FROM AUTHOR]

Cancer survivors have recovered from a brush with death, but their battle is often not over. The rigors of their initial bout with the disease predispose them to a second [...]