XR-RF Imaging Enabled by Software-Defined Metasurfaces and Machine Learning: Foundational Vision, Technologies and Challenges

We present a new approach to Extended Reality (XR), denoted as iCOPYWAVES, which seeks to offer naturally low-latency operation and cost-effectiveness, overcoming the critical scalability issues faced by existing solutions. iCOPYWAVES is enabled by emerging PWEs, a recently proposed technology in wireless communications. Empowered by intelligent (meta)surfaces, PWEs transform the wave propagation phenomenon into a software-defined process. We leverage PWEs to i) create, and then ii) selectively copy the scattered RF wavefront of an object from one location in space to another, where a machine learning module, accelerated by FPGAs, translates it to visual input for an XR headset using PWEdriven, RF imaging principles (XR-RF). This makes for an XR system whose operation is bounded in the physical layer and, hence, has the prospects for minimal end-to-end latency. Over large distances, RF-to-fiber/fiber-to-RF is employed to provide intermediate connectivity. The paper provides a tutorial on the iCOPYWAVES system architecture and workflow. A proof-of-concept implementation via simulations is provided, demonstrating the reconstruction of challenging objects in iCOPYWAVES produced computer graphics

Efficient liver gene transfer with foamy virus vectors

Liver gene transfer offers hope for the correction of genetic and acquired disorders. Efficient gene transfer in large animals can be obtained with hydrodynamic gene transfer (HGT), a method that can achieve sufficient levels of gene delivery. To test the relative efficiency between plasmid versus foamy virus (FV) vector-based liver gene transfer efficiency, we applied HGT in 4 juvenile pigs, using the same plasmid backbone, either naked or coated as a FV vector particle. Gene transfer efficiency and persistence of expression was assayed by PCR and real-time PCR, respectively, at 1 week and at 1 month after the infusions. HGT was tolerated well and no adverse reactions were observed. Plasmid injections resulted in no detectable DNA sequences at 1 week. At the 1 month time point, 2/15 liver sections analyzed were positive for the presence of plasmid DNA. When FV vectors were infused under identical conditions, 18/28 (64.3%) of the liver samples were positive for the presence of vector sequences, and the expression levels reached 29.7 and 15.6% of the endogenous GAPDH levels in the injected and the adjacent liver lobes. Our results indicate that medium-term therapeutic levels of gene expression can be obtained with FV vectors, an effect that can be attributed to the potential of the HGT procedure and to the natural affinity of FV vectors for hepatocytes

Correction: Hippocampal neural stem cells and microglia response to experimental inflammatory bowel disease (IBD) (Molecular Psychiatry, (2021), 26, 4, (1248-1263), 10.1038/s41380-020-0651-6)

An amendment to this paper has been published and can be accessed via a link at the top of the paper. © 2020, Springer Nature Limited

TFEB signaling attenuates NLRP3-driven inflammatory responses in severe asthma

Background: NLRP3-driven inflammatory responses by circulating and lung-resident monocytes are critical drivers of asthma pathogenesis. Autophagy restrains NLRP3-induced monocyte activation in asthma models. Yet, the effects of autophagy and its master regulator, transcription factor EB (TFEB), on monocyte responses in human asthma remain unexplored. Here, we investigated whether activation of autophagy and TFEB signaling suppress inflammatory monocyte responses in asthmatic individuals. Methods: Peripheral blood CD14+ monocytes from asthmatic patients (n = 83) and healthy controls (n = 46) were stimulated with LPS/ATP to induce NLRP3 activation with or without the autophagy inducer, rapamycin. ASC specks, caspase-1 activation, IL-1β and IL-18 levels, mitochondrial function, ROS release, and mTORC1 signaling were examined. Autophagy was evaluated by LC3 puncta formation, p62/SQSTM1 degradation and TFEB activation. In a severe asthma (SA) model, we investigated the role of NLRP3 signaling using Nlrp3−/− mice and/or MCC950 administration, and the effects of TFEB activation using myeloid-specific TFEB-overexpressing mice or administration of the TFEB activator, trehalose. Results: We observed increased NLRP3 inflammasome activation, concomitant with impaired autophagy in circulating monocytes that correlated with asthma severity. SA patients also exhibited mitochondrial dysfunction and ROS accumulation. Autophagy failed to inhibit NLRP3-driven monocyte responses, due to defective TFEB activation and excessive mTORC1 signaling. NLRP3 blockade restrained inflammatory cytokine release and linked airway disease. TFEB activation restored impaired autophagy, attenuated NLRP3-driven pulmonary inflammation, and ameliorated SA phenotype. Conclusions: Our studies uncover a crucial role for TFEB-mediated reprogramming of monocyte inflammatory responses, raising the prospect that this pathway can be therapeutically harnessed for the management of SA. © 2022 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd

Comparative analysis of FV vectors with human alpha- or beta-globin gene regulatory elements for the correction of beta-thalassemia

beta-Globin locus control region (LCR) sequences have been widely used for the regulated expression of the human beta-globin gene in therapeutic viral vectors. In this study, we compare the expression of the human beta-globin gene from either the HS2/HS3 beta-globin LCR or the HS40 regulatory element from the alpha-globin locus in the context of foamy virus (FV) vectors for the genetic correction of beta-thalassemia. Both regulatory elements expressed comparable levels of human beta-globin in a murine erythroleukemic line, whereas in murine hematopoietic stem cells the HS40.beta vector proved more efficient in beta-globin expression and correction of the beta-thalassemia phenotype. Following transplantation in the Hbb(th3/+) mouse model, the expression efficiency by the two vectors was similar, whereas the HS40.beta vector achieved relatively more stable transgene expression. In addition, in an ex vivo assay using CD34+ cells from thalassemic patients, both vectors achieved significant human beta-globin expression and restoration of the thalassemic phenotype as evidenced by enhanced erythropoiesis and decreased apoptosis. Our data suggest that FV vectors with the alpha-globin HS40 element can be used as alternative but equally efficient vehicles for human beta-globin gene expression for the genetic correction of beta-thalassemia. Gene Therapy (2012) 19, 303-311; doi:10.1038/gt.2011.98; published online 7 July 201