Long-range dipole-dipole exchange-induced atomic grating

We propose a theoretical scheme for dipole exchange-induced grating (DEIG) based on a hybrid system consisting of ultra-cold Rubidium ($^{87}$Rb) atomic ensemble and movable Rydberg spin atoms. The optical response of the grating appears as a superposition of three- and four-level configurations, similar to the cooperative optical nonlinear effect caused by the dipole blockade effect. However, such Rydberg atomic grating uniquely responds to the spatial positions of spin atoms, offering a novel approach to dynamically control electromagnetically induced gratings (EIG) except for input probe intensity

Geometrical Model for Non-Zero theta_13

Based on Friedberg and Lee's geometric picture by which the tribimaximal Pontecorvo-Maki-Nakawaga-Sakata leptonic mixing matrix is constructed, namely, corresponding mixing angles correspond to the geometric angles among the sides of a cube. We suggest that the three realistic mixing angles, which slightly deviate from the values determined for the cube, are due to a viable deformation from the perfectly cubic shape. Taking the best-fitted results of $\theta_{12}$ and $\theta_{23}$ as inputs, we determine the central value of $\sin^22\theta_{13}$ should be 0.0238, with a relatively large error tolerance; this value lies in the range of measurement precision of the Daya Bay experiment and is consistent with recent results from the T2K Collaboration.Comment: 14 pages, 7 figures. Published version in Phys. Rev.

Tissue-specific Genome Editing in vivo by MicroRNA-repressible Anti-CRISPR Proteins [preprint]

CRISPR-Cas systems are bacterial adaptive immune pathways that have revolutionized biotechnology and biomedical applications. Despite the potential for human therapeutic development, there are many hurdles that must be overcome before its use in clinical settings. Some clinical safety concerns arise from persistent activity of Cas9 after the desired editing is complete, or from editing activity in unintended cell types or tissues upon in vivo delivery [e.g. by adeno-associated viruses (AAV)]. Although tissue-specific promoters and serotypes with tissue tropisms can be used, suitably compact promoters are not always available for desired cell types, and AAV tissue tropisms are not absolute. To reinforce tissue-specific editing, we exploited anti-CRISPR proteins (Acrs), which are proteins evolved as countermeasures against CRISPR immunity. To inhibit Cas9 in all ancillary tissues without compromising editing in the target tissue, we established a flexible platform in which an Acr transgene is repressed by endogenous, tissue-specific microRNAs (miRNAs). We demonstrate that miRNAs regulate the expression of an Acr transgene bearing miRNA-binding sites in its 3’ UTR, and control subsequent genome editing outcomes in a cell-type specific manner. We also show that the strategy is applicable to multiple Cas9 orthologs and their respective Acrs. Furthermore, we demonstrate that in vivo delivery of Cas9 and Acrs that are targeted for repression by liver-specific miR-122 allow editing in the liver while Acrs devoid of miRNA regulation prevent Cas9 activity. This strategy provides additional safeguards against off-tissue genome editing by confining Cas9 activity to selected cell types

Tissue-restricted genome editing in vivo specified by microRNA-repressible anti-CRISPR proteins

CRISPR-Cas systems are bacterial adaptive immune pathways that have revolutionized biotechnology and biomedical applications. Despite the potential for human therapeutic development, there are many hurdles that must be overcome before its use in clinical settings. Some clinical safety concerns arise from editing activity in unintended cell types or tissues upon in vivo delivery (e.g., by adeno-associated virus (AAV) vectors). Although tissue-specific promoters and serotypes with tissue tropisms can be used, suitably compact promoters are not always available for desired cell types, and AAV tissue tropism specificities are not absolute. To reinforce tissue-specific editing, we exploited anti-CRISPR proteins (Acrs) that have evolved as natural countermeasures against CRISPR immunity. To inhibit Cas9 in all ancillary tissues without compromising editing in the target tissue, we established a flexible platform in which an Acr transgene is repressed by endogenous, tissue-specific microRNAs (miRNAs). We demonstrate that miRNAs regulate the expression of an Acr transgene bearing miRNA-binding sites in its 3\u27-UTR and control subsequent genome editing outcomes in a cell-type specific manner. We also show that the strategy is applicable to multiple Cas9 orthologs and their respective anti-CRISPRs. Furthermore, we validate this approach in vivo by demonstrating that AAV9 delivery of Nme2Cas9, along with an AcrIIC3 Nme construct that is targeted for repression by liver-specific miR-122, allows editing in the liver while repressing editing in an unintended tissue (heart muscle) in adult mice. This strategy provides safeguards against off-tissue genome editing by confining Cas9 activity to selected cell types

Delayed and fast rising radio flares from an optical and X-ray detected tidal disruption event in the center of a dwarf galaxy

AT2018cqh is a unique tidal disruption event (TDE) candidate discovered in a dwarf galaxy. Both the light curve fitting and galaxy scaling relationships suggest a central black hole mass in the range of 5.9<logM_BH/M_sun<6.4. A delayed X-ray brightening was found around 590 days after the optical discovery, but shows unusual long-time rising to peak over at least 558 days, which could be coming from delayed accretion of a newly forming debris disk. We report the discovery of delayed radio flares around 1105 days since its discovery, characterized by an initial steep rise of ~>175 days, a flattening lasting about 544 days, and a phase with another steep rise. The rapid rise in radio flux coupled with the slow decay in the X-ray emission points to a delayed launching of outflow, perhaps due to a transition in the accretion state. However, known accretion models can hardly explain the origins of the secondary radio flare that is rising even more rapidly in comparison with the initial one. If confirmed, AT2018cqh would be a rare TDE in a dwarf galaxy exhibiting optical, X-ray and radio flares. We call for continued multi-frequency radio observations to monitor its spectral and temporal evolution, which may help to reveal new physical processes that are not included in standard TDE models.Comment: 11 pages, 5 figures, to appear in ApJ Letter

Phenotypic Pattern-Based Assay for Dynamically Monitoring Host Cellular Responses to Salmonella Infections

The interaction between mammalian host cells and bacteria is a dynamic process, and the underlying pathologic mechanisms are poorly characterized. Limited information describing the host-bacterial interaction is based mainly on studies using label-based endpoint assays that detect changes in cell behavior at a given time point, yielding incomplete information. In this paper, a novel, label-free, real-time cell-detection system based on electronic impedance sensor technology was adapted to dynamically monitor the entire process of intestinal epithelial cells response to Salmonella infection. Changes in cell morphology and attachment were quantitatively and continuously recorded following infection. The resulting impedance-based time-dependent cell response profiles (TCRPs) were compared to standard assays and showed good correlation and sensitivity. Biochemical assays further suggested that TCRPs were correlated with cytoskeleton-associated morphological dynamics, which can be largely attenuated by inhibitions of actin and microtubule polymerization. Collectively, our data indicate that cell-electrode impedance measurements not only provide a novel, real-time, label-free method for investigating bacterial infection but also help advance our understanding of host responses in a more physiological and continuous manner that is beyond the scope of current endpoint assays

Adenovirus-Mediated Somatic Genome Editing of Pten by CRISPR/Cas9 in Mouse Liver in Spite of Cas9-Specific Immune Responses

CRISPR/Cas9 derived from the bacterial adaptive immunity pathway is a powerful tool for genome editing, but the safety profiles of in vivo delivered Cas9 (including host immune responses to the bacterial Cas9 protein) have not been comprehensively investigated in model organisms. Nonalcoholic steatohepatitis (NASH) is a prevalent human liver disease characterized by excessive fat accumulation in the liver. In this study, we used adenovirus (Ad) vector to deliver a Streptococcus pyogenes–derived Cas9 system (SpCas9) targeting Pten, a gene involved in NASH and a negative regulator of the PI3K-AKT pathway, in mouse liver. We found that the Ad vector mediated efficient Pten gene editing even in the presence of typical Ad vector-associated immunotoxicity in the liver. Four months after vector infusion, mice receiving the Pten gene-editing Ad vector showed massive hepatomegaly and features of NASH, consistent with the phenotypes following Cre-loxP-induced Pten deficiency in mouse liver. We also detected induction of humoral immunity against SpCas9 and the potential presence of an SpCas9-specific cellular immune response. Our findings provide a strategy to model human liver diseases in mice and highlight the importance considering Cas9-specific immune responses in future translational studies involving in vivo delivery of CRISPR/Cas9