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Plasmonic lasers advance To push the physical limitations of lasers to the nanoscale regime it is necessary to tackle the fundamental challenge of surpassing the diffraction limit. It has been suggested that surface plasmons — light–matter waves trapped on the surface of a conductor — can be used to tightly confine light on very short length scales, but such approaches have been previously hampered by severe losses. Oulton et al . now demonstrate that it is possible to circumvent this problem by utilizing a hybrid between a dielectric waveguide and a conducting surface supporting a plasmon mode, thereby showing the experimental realization of a nanoscale plasmonic laser with an optical mode a hundred times smaller than the diffraction limit. Such hybrid plasmonic coherent light sources offer the possibility to explore extreme interactions between light and matter, and may open important new avenues in optoelectronics. A key challenge is to realize ultracompact lasers that can directly generate coherent optical fields at the nanometre scale, far beyond the diffraction limit. Surface plasmons could be used to tightly confine light on very short lengthscales, but so far this approach has been hampered by ohmic losses at optical frequencies. The experimental demonstration of nanometre-scale plasmonic lasers is now reported, realized using a hybrid plasmonic waveguide — these lasers can generate optical modes a hundred times smaller than the diffraction limit. Laser science has been successful in producing increasingly high-powered, faster and smaller coherent light sources 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 . Examples of recent advances are microscopic lasers that can reach the diffraction limit, based on photonic crystals 3 , metal-clad cavities 4 and nanowires 5 , 6 , 7 . However, such lasers are restricted, both in optical mode size and physical device dimension, to being larger than half the wavelength of the optical field, and it remains a key fundamental challenge to realize ultracompact lasers that can directly generate coherent optical fields at the nanometre scale, far beyond the diffraction limit 10 , 11 . A way of addressing this issue is to make use of surface plasmons 12 , 13 , which are capable of tightly localizing light, but so far ohmic losses at optical frequencies have inhibited the realization of truly nanometre-scale lasers based on such approaches 14 , 15 . A recent theoretical work predicted that such losses could be significantly reduced while maintaining ultrasmall modes in a hybrid plasmonic waveguide 16 . Here we report the experimental demonstration of nanometre-scale plasmonic lasers, generating optical modes a hundred times smaller than the diffraction limit. We realize such lasers using a hybrid plasmonic waveguide consisting of a high-gain cadmium sulphide semiconductor nanowire, separated from a silver surface by a 5-nm-thick insulating gap. Direct measurements of the emission lifetime reveal a broad-band enhancement of the nanowire’s exciton spontaneous emission rate by up to six times owing to the strong mode confinement 17 and the signature of apparently threshold-less lasing. Because plasmonic modes have no cutoff, we are able to demonstrate downscaling of the lateral dimensions of both the device and the optical mode. Plasmonic lasers thus offer the possibility of exploring extreme interactions between light and matter, opening up new avenues in the fields of active photonic circuits 18 , bio-sensing 19 and quantum information technology 20 .

Two-dimensional magnetic semiconductors provide a platform for studying physical phenomena at atomically thin limit, and promise magneto-optoelectronic devices application. Here, we report light helicity detectors based on graphene-CrI 3 -graphene vdW heterostructures. We investigate the circularly polarized light excited current and reflective magnetic circular dichroism (RMCD) under various magnetic fields in both monolayer and multilayer CrI 3 devices. The devices exhibit clear helicity-selective photoresponse behavior determined by the magnetic state of CrI 3 . We also find abnormal negative photocurrents at higher bias in both monolayer and multilayer CrI 3 . A possible explanation is proposed for this phenomenon. Our work reveals the interplay between magnetic and optoelectronic properties in CrI 3 and paves the way to developing spin-optoelectronic devices. Two-dimensional magnetic semiconductors hold promise for spin- and valleytronic applications. Here, the authors report the realization of light helicity detectors based on graphene/CrI 3 van der Waals heterostructures, exhibiting a photocurrent behaviour determined by the magnetic state of CrI 3 .

Spectrometers with ever-smaller footprints are sought after for a wide range of applications in which minimized size and weight are paramount, including emerging in situ characterization techniques. We report on an ultracompact microspectrometer design based on a single compositionally engineered nanowire. This platform is independent of the complex optical components or cavities that tend to constrain further miniaturization of current systems. We show that incident spectra can be computationally reconstructed from the different spectral response functions and measured photocurrents along the length of the nanowire. Our devices are capable of accurate, visible-range monochromatic and broadband light reconstruction, as well as spectral imaging from centimeter-scale focal planes down to lensless, single-cell–scale in situ mapping.

Plasmonic nanolasers are a new class of amplifiers that generate coherent light well below the diffraction barrier bringing fundamentally new capabilities to biochemical sensing, super-resolution imaging, and on-chip optical communication. However, a debate about whether metals can enhance the performance of lasers has persisted due to the unavoidable fact that metallic absorption intrinsically scales with field confinement. Here, we report plasmonic nanolasers with extremely low thresholds on the order of 10 kW cm −2 at room temperature, which are comparable to those found in modern laser diodes. More importantly, we find unusual scaling laws allowing plasmonic lasers to be more compact and faster with lower threshold and power consumption than photonic lasers when the cavity size approaches or surpasses the diffraction limit. This clarifies the long-standing debate over the viability of metal confinement and feedback strategies in laser technology and identifies situations where plasmonic lasers can have clear practical advantage. Since the first proposal for plasmonic nanolasers there has been a debate about the limitations on performance posed by the inherent losses in metallic systems. Here, the authors compare over 100 plasmonic and photonic laser devices and find sub-wavelength plasmonic lasers to be advantageous.

Antigen-specific tissue-resident memory T cells (Trms) and neutralizing IgA antibodies provide the most effective protection of the lungs from viral infections. To induce those essential components of lung immunity against SARS-CoV-2, we tested various immunization protocols involving intranasal delivery of a novel Modified Vaccinia virus Ankara (MVA)-SARS-2-spike vaccine candidate. We show that a single intranasal MVA-SARS-CoV-2-S application in mice strongly induced pulmonary spike-specific CD8 + T cells, albeit restricted production of neutralizing antibodies. In prime-boost protocols, intranasal booster vaccine delivery proved to be crucial for a massive expansion of systemic and lung tissue-resident spike-specific CD8 + T cells and the development of Th1 - but not Th2 - CD4 + T cells. Likewise, very high titers of IgG and IgA anti-spike antibodies were present in serum and broncho-alveolar lavages that possessed high virus neutralization capacities to all current SARS-CoV-2 variants of concern. Importantly, the MVA-SARS-2-spike vaccine applied in intramuscular priming and intranasal boosting treatment regimen completely protected hamsters from developing SARS-CoV-2 lung infection and pathology. Together, these results identify intramuscular priming followed by respiratory tract boosting with MVA-SARS-2-S as a promising approach for the induction of local, respiratory as well as systemic immune responses suited to protect from SARS-CoV-2 infections.

Psychotherapy is a learning process. Updating the prediction models of the brain may be the mechanism underlying psychotherapeutic changes. Although developed in different eras and cultures, dialectical behavior therapy (DBT) and Morita therapy are influenced by Zen principles, and both emphasize the acceptance of reality and suffering. This article reviews these two treatments, their common and distinct therapeutic factors, and their neuroscientific implications. Additionally, it proposes a framework that includes the predictive function of the mind, constructed emotions, mindfulness, therapeutic relationship, and changes enabled via reward predictions. Brain networks, including the Default Mode Network (DMN), amygdala, fear circuitry, and reward pathways, contribute to the constructive process of brain predictions. Both treatments target the assimilation of prediction errors, gradual reorganization of predictive models, and creation of a life with step-by-step constructive rewards. By elucidating the possible neurobiological mechanisms of these psychotherapeutic techniques, this article is expected to serve as the first step towards filling the cultural gap and creating more teaching methods based on these concepts.

Canine distemper virus (CDV) is not only an important pathogen of carnivores, but it also serves as a model virus for analyzing measles virus pathogenesis. To get a better picture of the different stages of infection, we used air-liquid interface cultures to analyze the infection of well-differentiated airway epithelial cells by CDV. Canine distemper virus (CDV) is a highly contagious pathogen and is known to enter the host via the respiratory tract and disseminate to various organs. Current hypotheses speculate that CDV uses the homologous cellular receptors of measles virus (MeV), SLAM and nectin-4, to initiate the infection process. For validation, here, we established the well-differentiated air-liquid interface (ALI) culture model from primary canine tracheal airway epithelial cells. By applying the green fluorescent protein (GFP)-expressing CDV vaccine strain and recombinant wild-type viruses, we show that cell-free virus infects the airway epithelium mainly via the paracellular route and only after prior disruption of tight junctions by pretreatment with EGTA; this infection was related to nectin-4 but not to SLAM. Remarkably, when CDV-preinfected DH82 cells were cocultured on the basolateral side of canine ALI cultures grown on filter supports with a 1.0-μm pore size, cell-associated CDV could be transmitted via cell-to-cell contact from immunocytes to airway epithelial cultures. Finally, we observed that canine ALI cultures formed syncytia and started to release cell-free infectious viral particles from the apical surface following treatment with an inhibitor of the JAK/STAT signaling pathway (ruxolitinib). Our findings show that CDV can overcome the epithelial barrier through different strategies, including infection via immunocyte-mediated transmission and direct infection via the paracellular route when tight junctions are disrupted. Our established model can be adapted to other animals for studying the transmission routes and the pathogenicity of other morbilliviruses. IMPORTANCE Canine distemper virus (CDV) is not only an important pathogen of carnivores, but it also serves as a model virus for analyzing measles virus pathogenesis. To get a better picture of the different stages of infection, we used air-liquid interface cultures to analyze the infection of well-differentiated airway epithelial cells by CDV. Applying a coculture approach with DH82 cells, we demonstrated that cell-mediated infection from the basolateral side of well-differentiated epithelial cells is more efficient than infection via cell-free virus. In fact, free virus was unable to infect intact polarized cells. When tight junctions were interrupted by treatment with EGTA, cells became susceptible to infection, with nectin-4 serving as a receptor. Another interesting feature of CDV infection is that infection of well-differentiated airway epithelial cells does not result in virus egress. Cell-free virions are released from the cells only in the presence of an inhibitor of the JAK/STAT signaling pathway. Our results provide new insights into how CDV can overcome the barrier of the airway epithelium and reveal similarities and some dissimilarities compared to measles virus.

The SARS-CoV-2 spike (S) glycoprotein is synthesized as a large precursor protein and must be activated by proteolytic cleavage into S1 and S2. A recombinant modified vaccinia virus Ankara (MVA) expressing native, full-length S protein (MVA-SARS-2-S) is currently under investigation as a candidate vaccine in phase I clinical studies. Initial results from immunogenicity monitoring revealed induction of S-specific antibodies binding to S2, but low-level antibody responses to the S1 domain. Follow-up investigations of native S antigen synthesis in MVA-SARS-2-S-infected cells revealed limited levels of S1 protein on the cell surface. In contrast, we found superior S1 cell surface presentation upon infection with a recombinant MVA expressing a stabilized version of SARS-CoV-2 S protein with an inactivated S1/S2 cleavage site and K986P and V987P mutations (MVA-SARS-2-ST). When comparing immunogenicity of MVA vector vaccines, mice vaccinated with MVA-SARS-2-ST mounted substantial levels of broadly reactive anti-S antibodies that effectively neutralized different SARS-CoV-2 variants. Importantly, intramuscular MVA-SARS-2-ST immunization of hamsters and mice resulted in potent immune responses upon challenge infection and protected from disease and severe lung pathology. Our results suggest that MVA-SARS-2-ST represents an improved clinical candidate vaccine and that the presence of plasma membrane-bound S1 is highly beneficial to induce protective antibody levels.

Canine distemper virus (CDV), belonging to the genus Morbillivirus, is a highly contagious pathogen. It is infectious in a wide range of host species, including domestic and wildlife carnivores, and causes severe systemic disease with involvement of the respiratory tract. In the present study, canine precision-cut lung slices (PCLSs) were infected with CDV (strain R252) to investigate temporospatial viral loads, cell tropism, ciliary activity, and local immune responses during early infection ex vivo. Progressive viral replication was observed during the infection period in histiocytic and, to a lesser extent, epithelial cells. CDV-infected cells were predominantly located within the bronchial subepithelial tissue. Ciliary activity was reduced in CDV-infected PCLSs, while viability remained unchanged when compared to controls. MHC-II expression was increased in the bronchial epithelium on day three postinfection. Elevated levels of anti-inflammatory cytokines (interleukin-10 and transforming growth factor-β) were observed in CDV-infected PCLSs on day one postinfection. In conclusion, the present study demonstrates that PCLSs are permissive for CDV. The model reveals an impaired ciliary function and an anti-inflammatory cytokine response, potentially fostering viral replication in the lung during the early phase of canine distemper.

East Asia will face a skewed monsoon cycle with soaring flood, drought, and weather whiplash risks in a warming climate. In our objective eight-intraseasonal-monsoon-stage framework, we uncover a ‘dry-get-wetter’ paradigm in East Asia, contesting the fallen ‘rich-get-richer’ common belief. On timing, the Mid-summer and Fall periods are stretching at the expense of three delayed, shortened, and weakened winter stages, especially near the end of the twenty-first century. On threats, entire East Asia will experience up to 14–20 more heavy precipitation days during the rainy Spring to Mid-summer stages. Specifically, the Yangtze basin will suffer from an earlier pluvial period with escalating flood risks. Moreover, societal security and ecosystem resilience in the Huai-Yellow basin, South Japan, and the Korean Peninsula will be challenged by more frequent weather whiplash. Under the monsoon-stage framework, a complete moisture budget decomposition sheds light on the causes of a slower precipitation scaling and the ‘dry-get-wetter’ paradigm.