Negative Refraction in Time-Varying Strongly Coupled Plasmonic-Antenna-Epsilon-Near-Zero Systems.

Time-varying metasurfaces are emerging as a powerful instrument for the dynamical control of the electromagnetic properties of a propagating wave. Here we demonstrate an efficient time-varying metasurface based on plasmonic nano-antennas strongly coupled to an epsilon-near-zero (ENZ) deeply subwavelength film. The plasmonic resonance of the metal resonators strongly interacts with the optical ENZ modes, providing a Rabi level spitting of ∼30%. Optical pumping at frequency ω induces a nonlinear polarization oscillating at 2ω responsible for an efficient generation of a phase conjugate and a negative refracted beam with a conversion efficiency that is more than 4 orders of magnitude greater compared to the bare ENZ film. The introduction of a strongly coupled plasmonic system therefore provides a simple and effective route towards the implementation of ENZ physics at the nanoscale.

Quantitative super-resolution imaging with qPAINT.

Counting molecules in complexes is challenging, even with super-resolution microscopy. Here, we use the programmable and specific binding of dye-labeled DNA probes to count integer numbers of targets. This method, called quantitative points accumulation in nanoscale topography (qPAINT), works independently of dye photophysics for robust counting with high precision and accuracy over a wide dynamic range. qPAINT was benchmarked on DNA nanostructures and demonstrated for cellular applications by quantifying proteins in situ and the number of single-molecule FISH probes bound to an mRNA target.

Intimate stimuli result in fronto-parietal activation changes in anorexia nervosa.

BACKGROUND: Intimacy is a key psychological problem in anorexia nervosa (AN). Empirical evidence, including neurobiological underpinnings, is however, scarce. OBJECTIVE: In this study, we evaluated various emotional stimuli including intimate stimuli experienced in patients with AN and non-patients, as well as their cerebral response. METHODS: Functional magnetic resonance imaging was conducted using stimuli with positive, neutral, negative and intimate content. Participants (14 AN patients and 14 non-patients) alternated between passive viewing and explicit emotion regulation. RESULTS: Intimate stimuli were experienced less positively in AN patients compared to non-patients. AN patients showed decreased cerebral responses in superior parietal cortices in response to positive and intimate stimuli. Intimate stimuli led to stronger activation of the orbitofrontal cortex, and lower activation of the bilateral precuneus in AN patients. Orbitofrontal responses decreased in AN patients during explicit emotion regulation. CONCLUSIONS: These results show that intimate stimuli are of particular importance in AN patients, who show experiential differences compared to non-patients and altered activation of orbitofrontal and parietal brain structures. This supports that AN patients have difficulties with intimacy, attachment, self-referential processing and body perception. LEVEL OF EVIDENCE: Level III, case-control study.

Diffusion tensor imaging in multiple sclerosis at different final outcomes.

OBJECTIVES: Methods to evaluate the relative contributions of demyelination vs axonal degeneration over the long-term course of MS are urgently needed. We used magnetic resonance diffusion tensor imaging (DTI) to estimate degrees of demyelination and axonal degeneration in the corpus callosum (CC) in cases of MS with different final outcomes. MATERIALS AND METHODS: We determined DTI measures mean diffusivity (MD), fractional anisotropy (FA), and axial (AD) and radial (RD) diffusivities in the CC of 31 MS patients, of whom 13 presented a secondary progressive course, 11 a non-progressive course, and seven a monophasic course. The study participants were survivors from an incidence cohort of 254 attack-onset MS patients with 50 years of longitudinal follow-up. As reference, we included five healthy individuals without significant morbidity. RESULTS: In patients with secondary progression, compared to all other groups, the corpus callosum showed increased RD and reduced FA, but no change in AD. None of the parameters exhibited differences among non-progressive and monophasic course groups and controls. CONCLUSION: Increased RD was observed in secondary progressive MS, indicating significant myelin loss. Normal RD values observed in the clinically isolated syndrome and non-progressive groups confirm their benign nature. AD was not a characterizing parameter for long-term outcome. Demyelination revealed by increased RD is a distinguishing trait for secondary progression.

Experimental Verification of Entanglement Generated in a Plasmonic System.

A core process in many quantum tasks is the generation of entanglement. It is being actively studied in a variety of physical settings-from simple bipartite systems to complex multipartite systems. In this work we experimentally study the generation of bipartite entanglement in a nanophotonic system. Entanglement is generated via the quantum interference of two surface plasmon polaritons in a beamsplitter structure, i.e., utilizing the Hong-Ou-Mandel (HOM) effect, and its presence is verified using quantum state tomography. The amount of entanglement is quantified by the concurrence and we find values of up to 0.77 ± 0.04. Verifying entanglement in the output state from HOM interference is a nontrivial task and cannot be inferred from the visibility alone. The techniques we use to verify entanglement could be applied to other types of photonic system and therefore may be useful for the characterization of a range of different nanophotonic quantum devices.

Rapid Sequential in Situ Multiplexing with DNA Exchange Imaging in Neuronal Cells and Tissues.

To decipher the molecular mechanisms of biological function, it is critical to map the molecular composition of individual cells or even more importantly tissue samples in the context of their biological environment in situ. Immunofluorescence (IF) provides specific labeling for molecular profiling. However, conventional IF methods have finite multiplexing capabilities due to spectral overlap of the fluorophores. Various sequential imaging methods have been developed to circumvent this spectral limit but are not widely adopted due to the common limitation of requiring multirounds of slow (typically over 2 h at room temperature to overnight at 4 °C in practice) immunostaining. We present here a practical and robust method, which we call DNA Exchange Imaging (DEI), for rapid in situ spectrally unlimited multiplexing. This technique overcomes speed restrictions by allowing for single-round immunostaining with DNA-barcoded antibodies, followed by rapid (less than 10 min) buffer exchange of fluorophore-bearing DNA imager strands. The programmability of DEI allows us to apply it to diverse microscopy platforms (with Exchange Confocal, Exchange-SIM, Exchange-STED, and Exchange-PAINT demonstrated here) at multiple desired resolution scales (from ∼300 nm down to sub-20 nm). We optimized and validated the use of DEI in complex biological samples, including primary neuron cultures and tissue sections. These results collectively suggest DNA exchange as a versatile, practical platform for rapid, highly multiplexed in situ imaging, potentially enabling new applications ranging from basic science, to drug discovery, and to clinical pathology.

Attosecond physics at the nanoscale.

Recently two emerging areas of research, attosecond and nanoscale physics, have started to come together. Attosecond physics deals with phenomena occurring when ultrashort laser pulses, with duration on the femto- and sub-femtosecond time scales, interact with atoms, molecules or solids. The laser-induced electron dynamics occurs natively on a timescale down to a few hundred or even tens of attoseconds (1 attosecond = 1 as = 10-18 s), which is comparable with the optical field. For comparison, the revolution of an electron on a 1s orbital of a hydrogen atom is ∼152 as. On the other hand, the second branch involves the manipulation and engineering of mesoscopic systems, such as solids, metals and dielectrics, with nanometric precision. Although nano-engineering is a vast and well-established research field on its own, the merger with intense laser physics is relatively recent. In this report on progress we present a comprehensive experimental and theoretical overview of physics that takes place when short and intense laser pulses interact with nanosystems, such as metallic and dielectric nanostructures. In particular we elucidate how the spatially inhomogeneous laser induced fields at a nanometer scale modify the laser-driven electron dynamics. Consequently, this has important impact on pivotal processes such as above-threshold ionization and high-order harmonic generation. The deep understanding of the coupled dynamics between these spatially inhomogeneous fields and matter configures a promising way to new avenues of research and applications. Thanks to the maturity that attosecond physics has reached, together with the tremendous advance in material engineering and manipulation techniques, the age of atto-nanophysics has begun, but it is in the initial stage. We present thus some of the open questions, challenges and prospects for experimental confirmation of theoretical predictions, as well as experiments aimed at characterizing the induced fields and the unique electron dynamics initiated by them with high temporal and spatial resolution.

Multiplexed 3D cellular super-resolution imaging with DNA-PAINT and Exchange-PAINT.

Super-resolution fluorescence microscopy is a powerful tool for biological research, but obtaining multiplexed images for a large number of distinct target species remains challenging. Here we use the transient binding of short fluorescently labeled oligonucleotides (DNA-PAINT, a variation of point accumulation for imaging in nanoscale topography) for simple and easy-to-implement multiplexed super-resolution imaging that achieves sub-10-nm spatial resolution in vitro on synthetic DNA structures. We also report a multiplexing approach (Exchange-PAINT) that allows sequential imaging of multiple targets using only a single dye and a single laser source. We experimentally demonstrate ten-color super-resolution imaging in vitro on synthetic DNA structures as well as four-color two-dimensional (2D) imaging and three-color 3D imaging of proteins in fixed cells.

Altered white matter integrity in adults with autism spectrum disorder and an IQ >100: a diffusion tensor imaging study.

OBJECTIVE: White matter (WM) alterations have been reported in children and adults with autism spectrum disorder (ASD). In particular, impaired connectivity of limbic structures may be related to social deficits. Heterogeneous findings could be explained in terms of differences in sample characteristics and methodology. In this context, non-syndromic forms might differ substantially in WM structure from secondary ASD forms. METHOD: In an attempt to recruit a homogeneous study sample, we included adults with high-functioning ASD and an IQ > 100 to decrease the influence of syndromic forms being often associated with cognitive deficits. Diffusion tensor imaging (DTI) was performed in 30 participants with ASD and 30 pairwise-matched controls. Fractional anisotropy (FA) and mean diffusivity (MD) as surrogate imaging markers for WM integrity were calculated. RESULTS: We found a significant FA decrease in the ASD group in the genu and body of the corpus callosum (CC). Increased MD was detected in the subgenual anterior cingulate cortex (sACC). CONCLUSION: The finding of decreased WM integrity in the genu of the CC is in line with earlier studies reporting a decreased number of interhemispheric fibers in the frontal lobe of ASD. Alterations in the sACC might be associated with 'Theory of mind' deficits.

Graphene gas sensing using a non-contact microwave method.

We report a non-contact CVD graphene gas sensing method that utilises a high Q microwave dielectric resonator perturbation technique. A graphene sample is coupled to the evanescent field of a dielectric resonator whereupon nitrogen dioxide (NO2), a p-doping gas, is detected by monitoring the change in the linewidth and frequency of the resonant mode. The resonant peak shape is dependent on the number of carriers in the graphene sheet. Therefore, the linewidth perturbation can be converted to a measurement of the graphene sheet resistance. To demonstrate the strength of this technique, sensor response curves for NO2 at different concentrations and temperatures are measured showing sub ppm sensitivity. This technique eliminates interactions between the trace gas and metal contacts that otherwise effect the sensor response of the graphene device.

ABH-Glycan Microarray Characterizes ABO Subtype Antibodies: Fine Specificity of Immune Tolerance After ABO-Incompatible Transplantation.

Organ transplantation from ABO blood group-incompatible (ABOi) donors requires accurate detection, effective removal and subsequent surveillance of antidonor antibodies. Because ABH antigen subtypes are expressed differently in various cells and organs, measurement of antibodies specific for the antigen subtypes in the graft is essential. Erythrocyte agglutination, the century-old assay used clinically, does not discriminate subtype-specific ABO antibodies and provides limited information on antibody isotypes. We designed and created an ABO-glycan microarray and demonstrated the precise assessment of both the presence and, importantly, the absence of donor-specific antibodies in an international study of pediatric heart transplant patients. Specific IgM, IgG, and IgA isotype antibodies to nonself ABH subtypes were detected in control participants and recipients of ABO-compatible transplants. Conversely, in children who received ABOi transplants, antibodies specific for A subtype II and/or B subtype II antigens-the only ABH antigen subtypes expressed in heart tissue-were absent, demonstrating the fine specificity of B cell tolerance to donor/graft blood group antigens. In contrast to the hemagglutination assay, the ABO-glycan microarray allows detailed characterization of donor-specific antibodies necessary for effective transplant management, representing a major step forward in precise ABO antibody detection.

On-Demand Single Photons with High Extraction Efficiency and Near-Unity Indistinguishability from a Resonantly Driven Quantum Dot in a Micropillar.

Scalable photonic quantum technologies require on-demand single-photon sources with simultaneously high levels of purity, indistinguishability, and efficiency. These key features, however, have only been demonstrated separately in previous experiments. Here, by s-shell pulsed resonant excitation of a Purcell-enhanced quantum dot-micropillar system, we deterministically generate resonance fluorescence single photons which, at π pulse excitation, have an extraction efficiency of 66%, single-photon purity of 99.1%, and photon indistinguishability of 98.5%. Such a single-photon source for the first time combines the features of high efficiency and near-perfect levels of purity and indistinguishabilty, and thus opens the way to multiphoton experiments with semiconductor quantum dots.

DAT isn't all that: cocaine reward and reinforcement require Toll-like receptor 4 signaling.

The initial reinforcing properties of drugs of abuse, such as cocaine, are largely attributed to their ability to activate the mesolimbic dopamine system. Resulting increases in extracellular dopamine in the nucleus accumbens (NAc) are traditionally thought to result from cocaine's ability to block dopamine transporters (DATs). Here we demonstrate that cocaine also interacts with the immunosurveillance receptor complex, Toll-like receptor 4 (TLR4), on microglial cells to initiate central innate immune signaling. Disruption of cocaine signaling at TLR4 suppresses cocaine-induced extracellular dopamine in the NAc, as well as cocaine conditioned place preference and cocaine self-administration. These results provide a novel understanding of the neurobiological mechanisms underlying cocaine reward/reinforcement that includes a critical role for central immune signaling, and offer a new target for medication development for cocaine abuse treatment.

[Characterisation of Postoperative Immune Suppression by Validated Parameters in Visceral Surgery]. / Validierbare Parameter zur Beschreibung der Immunsuppression nach viszeralchirurgischen Eingriffen.

BACKGROUND: Surgical interventions induce changes in postoperative immune competence due to the surgical trauma. Consequently, the immune system cannot react sufficiently in case of septic complications. The dimension of postoperative immune suppression can be determined by HLA-DR surface expression on circulating monocytes. MATERIAL AND METHODS: In the present study relevant literature was researched and patients with visceral and thoracic surgery were included. 17 patients underwent minor surgery, i.e., cholecystectomy, thyroidectomy or hernia repair. 101 patients underwent major surgery, i.e., visceral or thoracic resections. Expression of HLA-DR on circulating monocytes (HLA-DR) was analysed by FACS, whereas gene expression of T-cells was determined by gene-array methods. RESULTS: Postoperative complications or postoperative acquired sepsis were predominantly seen in patients with significantly reduced HLA-DR. The postoperative immune suppression was influenced by the type of operation itself: following colon surgery there was a longer-lasting immune suppression compared to that after surgery on the thorax or rectum. In addition, postoperative immune suppression depends on preoperative existing risk factors: adipositas and further risk factors cause a decrease of HLA-DR. Gene expression analysis revealed a distinct down-regulation of transcriptional activity of T-cells following surgical intervention. This effect is much more pronounced in patients with septic complications. CONCLUSION: The expression of HLA-DR is a useful parameter to describe postoperative immune suppression. Furthermore, regulation of transcriptional T-cell activity can provide additional information on the postoperative immune status.

Nonlinear interactions in an organic polariton condensate.

Under the right conditions, cavity polaritons form a macroscopic condensate in the ground state. The fascinating nonlinear behaviour of this condensate is largely dictated by the strength of polariton-polariton interactions. In inorganic semiconductors, these result principally from the Coulomb interaction between Wannier-Mott excitons. Such interactions are considerably weaker for the tightly bound Frenkel excitons characteristic of organic semiconductors and were notably absent in the first reported demonstration of organic polariton lasing. In this work, we demonstrate the realization of an organic polariton condensate, at room temperature, in a microcavity containing a thin film of 2,7-bis[9,9-di(4-methylphenyl)-fluoren-2-yl]-9,9-di(4-methylphenyl)fluorene. On reaching threshold, we observe the spontaneous formation of a linearly polarized condensate, which exhibits a superlinear power dependence, long-range order and a power-dependent blueshift: a clear signature of Frenkel polariton interactions.

Spatially resolved electron energy loss spectroscopy of crescent-shaped plasmonic antennas.

We present a study of the optical properties of gold crescent-shaped antennas by means of electron energy loss spectroscopy. These structures exhibit particularly large field enhancement near their sharp features, support two non-degenerate dipolar (i.e., optically active) localised surface plasmon resonances, and are widely tunable by a choice of their shape and dimensions. Depending on the volume and shape, we resolved up to four plasmon resonances in metallic structures under study in the energy range of 0.8 - 2.4 eV: two dipolar and quadrupolar mode and a multimodal assembly. The boundary-element-method calculations reproduced the observed spectra and helped to identify the character of the resonances. The two lowest modes are of particular importance owing to their dipolar nature. Remarkably, they are both concentrated near the tips of the crescent, spectrally well resolved and their energies can be tuned between 0.8 - 1.5 eV and 1.2 - 2.0 eV, respectively. As the lower spectral range covers the telecommunication wavelengths 1.30 and 1.55 µm, we envisage the possible use of such nanostructures in infrared communication technology.

Spatial Coherence and Stability in a Disordered Organic Polariton Condensate.

Although only a handful of organic materials have shown polariton condensation, their study is rapidly becoming more accessible. The spontaneous appearance of long-range spatial coherence is often recognized as a defining feature of such condensates. In this Letter, we study the emergence of spatial coherence in an organic microcavity and demonstrate a number of unique features stemming from the peculiarities of this material set. Despite its disordered nature, we find that correlations extend over the entire spot size, and we measure g(1)(r,r') values of nearly unity at short distances and of 50% for points separated by nearly 10 µm . We show that for large spots, strong shot-to-shot fluctuations emerge as varying phase gradients and defects, including the spontaneous formation of vortices. These are consistent with the presence of modulation instabilities. Furthermore, we find that measurements with flat-top spots are significantly influenced by disorder and can, in some cases, lead to the formation of mutually incoherent localized condensates.

Dynamic microglial alterations underlie stress-induced depressive-like behavior and suppressed neurogenesis.

The limited success in understanding the pathophysiology of major depression may result from excessive focus on the dysfunctioning of neurons, as compared with other types of brain cells. Therefore, we examined the role of dynamic alterations in microglia activation status in the development of chronic unpredictable stress (CUS)-induced depressive-like condition in rodents. We report that following an initial period (2-3 days) of stress-induced microglial proliferation and activation, some microglia underwent apoptosis, leading to reductions in their numbers within the hippocampus, but not in other brain regions, following 5 weeks of CUS exposure. At that time, microglia displayed reduced expression of activation markers as well as dystrophic morphology. Blockade of the initial stress-induced microglial activation by minocycline or by transgenic interleukin-1 receptor antagonist overexpression rescued the subsequent microglial apoptosis and decline, as well as the CUS-induced depressive-like behavior and suppressed neurogenesis. Similarly, the antidepressant drug imipramine blocked the initial stress-induced microglial activation as well as the CUS-induced microglial decline and depressive-like behavior. Treatment of CUS-exposed mice with either endotoxin, macrophage colony-stimulating factor or granulocyte-macrophage colony-stimulating factor, all of which stimulated hippocampal microglial proliferation, partially or completely reversed the depressive-like behavior and dramatically increased hippocampal neurogenesis, whereas treatment with imipramine or minocycline had minimal or no anti-depressive effects, respectively, in these mice. These findings provide direct causal evidence that disturbances in microglial functioning has an etiological role in chronic stress-induced depression, suggesting that microglia stimulators could serve as fast-acting anti-depressants in some forms of depressive and stress-related conditions.

Disturbed cingulate glutamate metabolism in adults with high-functioning autism spectrum disorder: evidence in support of the excitatory/inhibitory imbalance hypothesis.

Over the last few years, awareness of autism spectrum disorder (ASD) in adults has increased. The precise etiology of ASD is still unresolved. Animal research, genetic and postmortem studies suggest that the glutamate (Glu) system has an important role, possibly related to a cybernetic imbalance between neuronal excitation and inhibition. To clarify the possible disruption of Glu metabolism in adults with high-functioning autism, we performed a magnetic resonance spectroscopy (MRS) study investigating the anterior cingulate cortex (ACC) and the cerebellum in adults with high-functioning ASD. Twenty-nine adult patients with high-functioning ASD and 29 carefully matched healthy volunteers underwent MRS scanning of the pregenual ACC and the left cerebellar hemisphere. Metabolic data were compared between groups and were correlated with psychometric measures of autistic features. We found a significant decrease in the cingulate N-acetyl-aspartate (NAA) and the combined Glu and glutamine (Glx) signals in adults with ASD, whereas we did not find other metabolic abnormalities in the ACC or the cerebellum. The Glx signal correlated significantly with psychometric measures of autism, particularly with communication deficits. Our data support the hypothesis that there is a link between disturbances of the cingulate NAA and Glx metabolism, and autism. The findings are discussed in the context of the hypothesis of excitatory/inhibitory imbalance in autism. Further research should clarify the specificity and dynamics of these findings regarding other neuropsychiatric disorders and other brain areas.

Gateless patterning of epitaxial graphene by local intercalation.

We present a technique to pattern the charge density of a large-area epitaxial graphene sheet locally without using metallic gates. Instead, local intercalation of the graphene-substrate interface can selectively be established in the vicinity of graphene edges or predefined voids. It provides changes of the work function of several hundred meV, corresponding to a conversion from n-type to p-type charge carriers. This assignment is supported by photoelectron spectroscopy, scanning tunneling microscopy, scanning electron microscopy and Hall effect measurements. The technique introduces materials contrast to a graphene sheet in a variety of geometries and thus allows for novel experiments and novel functionalities.