A hybrid optical-wireless network for decimetre-level terrestrial positioning.

Global navigation satellite systems (GNSS) are widely used for navigation and time distribution1-3, features that are indispensable for critical infrastructure such as mobile communication networks, as well as emerging technologies such as automated driving and sustainable energy grids3,4. Although GNSS can provide centimetre-level precision, GNSS receivers are prone to many-metre errors owing to multipath propagation and an obstructed view of the sky, which occur particularly in urban areas where accurate positioning is most needed1,5,6. Moreover, the vulnerabilities of GNSS, combined with the lack of a back-up system, pose a severe risk to GNSS-dependent technologies7. Here we demonstrate a terrestrial positioning system that is independent of GNSS and offers superior performance through a constellation of radio transmitters, connected and time-synchronized at the subnanosecond level through a fibre-optic Ethernet network8. Using optical and wireless transmission schemes similar to those encountered in mobile communication networks, and exploiting spectrally efficient virtual wideband signals, the detrimental effects of multipath propagation are mitigated9, thus enabling robust decimetre-level positioning and subnanosecond timing in a multipath-prone outdoor environment. This work provides a glimpse of a future in which telecommunication networks provide not only connectivity but also GNSS-independent timing and positioning services with unprecedented accuracy and reliability.

Diving into the Depths: Uncovering Microplastics in Norwegian Coastal Sediment Cores.

High concentrations of microplastics (MPs) have been documented in the deep-sea surface sediments of the Arctic Ocean. However, studies investigating their high-resolution vertical distribution in sediments from the European waters to the Arctic remain limited. This study examines MPs in five sediment cores from the Norwegian Coastal Current (NCC), encompassing the water-sediment interface and sediment layers up to 19 cm depth. Advanced analytical methods for MP identification down to 11 µm in size were combined with radiometric dating and lithology observations. MPs were present across all sediment cores, including layers predating the introduction of plastics, with concentrations exhibiting significant variation (54-12,491 MP kg-1). The smallest size class (11 µm) predominated in most sediment layers (34-100%). A total of 18 different polymer types were identified across all sediment layers, with polymer diversity and depth correlations varying widely between stations. Our findings suggest that differences in seafloor topography and the impact of anthropogenic activities (e.g., fishing) lead to varying environmental conditions at the sampling sites, influencing the vertical distribution of MPs. This challenges the reliability of using environmental parameters to predict MP accumulation zones and questions the use of MPs in sediment cores as indicators of the Anthropocene.

Optically Active Spin Defects in Few-Layer Thick Hexagonal Boron Nitride.

Optically active spin defects in hexagonal boron nitride (hBN) are promising quantum systems for the design of two-dimensional quantum sensing units offering optimal proximity to the sample being probed. In this Letter, we first demonstrate that the electron spin resonance frequencies of boron vacancy centers (V_{B}^{-}) can be detected optically in the limit of few-atomic-layer thick hBN flakes despite the nanoscale proximity of the crystal surface that often leads to a degradation of the stability of solid-state spin defects. We then analyze the variations of the electronic spin properties of V_{B}^{-} centers with the hBN thickness with a focus on (i) the zero-field splitting parameters, (ii) the optically induced spin polarization rate and (iii) the longitudinal spin relaxation time. This Letter provides important insights into the properties of V_{B}^{-} centers embedded in ultrathin hBN flakes, which are valuable for future developments of foil-based quantum sensing technologies.

Connecting Neurobiological Features with Interregional Dysconnectivity in Social-Cognitive Impairments of Schizophrenia.

Schizophrenia (SZ) is a devastating psychiatric disorder affecting about 1% of the world's population. Social-cognitive impairments in SZ prevent positive social interactions and lead to progressive social withdrawal. The neurobiological underpinnings of social-cognitive symptoms remain poorly understood, which hinders the development of novel treatments. At the whole-brain level, an abnormal activation of social brain regions and interregional dysconnectivity within social-cognitive brain networks have been identified as major contributors to these symptoms. At the cellular and subcellular levels, an interplay between oxidative stress, neuroinflammation and N-methyl-D-aspartate receptor hypofunction is thought to underly SZ pathology. However, it is not clear how these molecular processes are linked with interregional dysconnectivity in the genesis of social-cognitive symptoms. Here, we aim to bridge the gap between macroscale (connectivity analyses) and microscale (molecular and cellular mechanistic) knowledge by proposing impaired myelination and the disinhibition of local microcircuits as possible causative biological pathways leading to dysconnectivity and abnormal activity of the social brain. Furthermore, we recommend electroencephalography as a promising translational technique that can foster pre-clinical drug development and discuss attractive drug targets for the treatment of social-cognitive symptoms in SZ.

Broad Diversity of Near-Infrared Single-Photon Emitters in Silicon.

We report the detection of individual emitters in silicon belonging to seven different families of optically active point defects. These fluorescent centers are created by carbon implantation of a commercial silicon-on-insulator wafer usually employed for integrated photonics. Single photon emission is demonstrated over the 1.1-1.55 µm range, spanning the O and C telecom bands. We analyze their photoluminescence spectra, dipolar emissions, and optical relaxation dynamics at 10 K. For a specific family, we show a constant emission intensity at saturation from 10 K to temperatures well above the 77 K liquid nitrogen temperature. Given the advanced control over nanofabrication and integration in silicon, these individual artificial atoms are promising systems to investigate for Si-based quantum technologies.

Histamine-4 receptor antagonist ameliorates Parkinson-like pathology in the striatum.

Growing evidence indicates that microglia activation and a neuroinflammatory trigger contribute to dopaminergic cell loss in Parkinson's disease (PD). Furthermore, increased density of histaminergic fibers and enhanced histamine levels have been observed in the substantia nigra of PD-postmortem brains. Histamine-induced microglial activation is mediated by the histamine-4 receptor (H4R). In the current study, gene set enrichment and pathway analyses of a PD basal ganglia RNA-sequencing dataset revealed that upregulation of H4R was in the top functional category for PD treatment targets. Interestingly, the H4R antagonist JNJ7777120 normalized the number of nigrostriatal dopaminergic fibers and striatal dopamine levels in a rotenone-induced PD rat model. These improvements were accompanied by a reduction of α-synuclein-positive inclusions in the striatum. In addition, intracerebroventricular infusion of JNJ7777120 alleviated the morphological changes in Iba-1-positive microglia and resulted in a lower tumor necrosis factor-α release from this brain region, as well as in ameliorated apomorphine-induced rotation behaviour. Finally, JNJ7777120 also restored basal ganglia function by decreasing the levels of γ-aminobutyric acid (GABA) and the 5-hydroxyindoleactic acid to serotonin (5-HIAA/5-HT) concentration ratios in the striatum of the PD model. Our results highlight H4R inhibition in microglia as a promising and specific therapeutic target to reduce or prevent neuroinflammation, and as such the development of PD pathology.

Molecular Effects of FDA-Approved Multiple Sclerosis Drugs on Glial Cells and Neurons of the Central Nervous System.

Multiple sclerosis (MS) is characterized by peripheral and central inflammatory features, as well as demyelination and neurodegeneration. The available Food and Drug Administration (FDA)-approved drugs for MS have been designed to suppress the peripheral immune system. In addition, however, the effects of these drugs may be partially attributed to their influence on glial cells and neurons of the central nervous system (CNS). We here describe the molecular effects of the traditional and more recent FDA-approved MS drugs Fingolimod, Dimethyl Fumarate, Glatiramer Acetate, Interferon-ß, Teriflunomide, Laquinimod, Natalizumab, Alemtuzumab and Ocrelizumab on microglia, astrocytes, neurons and oligodendrocytes. Furthermore, we point to a possible common molecular effect of these drugs, namely a key role for NFκB signaling, causing a switch from pro-inflammatory microglia and astrocytes to anti-inflammatory phenotypes of these CNS cell types that recently emerged as central players in MS pathogenesis. This notion argues for the need to further explore the molecular mechanisms underlying MS drug action.

Strain-Gradient Position Mapping of Semiconductor Quantum Dots.

We introduce a nondestructive method to determine the position of randomly distributed semiconductor quantum dots (QDs) integrated in a solid photonic structure. By setting the structure in an oscillating motion, we generate a large stress gradient across the QDs plane. We then exploit the fact that the QDs emission frequency is highly sensitive to the local material stress to map the position of QDs deeply embedded in a photonic wire antenna with an accuracy ranging from ±35 nm down to ±1 nm. In the context of fast developing quantum technologies, this technique can be generalized to different photonic nanostructures embedding any stress-sensitive quantum emitters.

Stratification of archaeal membrane lipids in the ocean and implications for adaptation and chemotaxonomy of planktonic archaea.

Membrane lipids of marine planktonic archaea have provided unique insights into archaeal ecology and paleoceanography. However, past studies of archaeal lipids in suspended particulate matter (SPM) and sediments mainly focused on a small class of fully saturated glycerol dibiphytanyl glycerol tetraether (GDGT) homologues identified decades ago. The apparent low structural diversity of GDGTs is in strong contrast to the high diversity of metabolism and taxonomy among planktonic archaea. Furthermore, adaptation of archaeal lipids in the deep ocean remains poorly constrained. We report the archaeal lipidome in SPM from diverse oceanic regimes. We extend the known inventory of planktonic archaeal lipids to include numerous unsaturated archaeal ether lipids (uns-AELs). We further reveal (i) different thermal regulations and polar headgroup compositions of membrane lipids between the epipelagic (≤ 100 m) and deep (>100 m) populations of archaea, (ii) stratification of unsaturated GDGTs with varying redox conditions, and (iii) enrichment of tetra-unsaturated archaeol and fully saturated GDGTs in epipelagic and deep oxygenated waters, respectively. Such stratified lipid patterns are consistent with the typical distribution of archaeal phylotypes in marine environments. We, thus, provide an ecological context for GDGT-based paleoclimatology and bring about the potential use of uns-AELs as biomarkers for planktonic Euryarchaeota.

Harvesting, Coupling, and Control of Single-Exciton Coherences in Photonic Waveguide Antennas.

We perform coherent nonlinear spectroscopy of individual excitons strongly confined in single InAs quantum dots (QDs). The retrieval of their intrinsically weak four-wave mixing (FWM) response is enabled by a one-dimensional dielectric waveguide antenna. Compared to a similar QD embedded in bulk media, the FWM detection sensitivity is enhanced by up to 4 orders of magnitude, over a broad operation bandwidth. Three-beam FWM is employed to investigate coherence and population dynamics within individual QD transitions. We retrieve their homogenous dephasing in a presence of low-frequency spectral wandering. Two-dimensional FWM reveals off-resonant Förster coupling between a pair of distinct QDs embedded in the antenna. We also detect a higher order QD nonlinearity (six-wave mixing) and use it to coherently control the FWM transient. Waveguide antennas enable us to conceive multicolor coherent manipulation schemes of individual emitters.

MicroRNA-326 acts as a molecular switch in the regulation of midbrain urocortin 1 expression.

BACKGROUND: Altered levels of urocortin 1 (Ucn1) in the centrally projecting Edinger-Westphal nucleus (EWcp) of depressed suicide attempters or completers mediate the brain's response to stress, while the mechanism regulating Ucn1 expression is unknown. We tested the hypothesis that microRNAs (miRNAs), which are vital fine-tuners of gene expression during the brain's response to stress, have the capacity to modulate Ucn1 expression. METHODS: Computational analysis revealed that the Ucn1 3' untranslated region contained a conserved binding site for miR-326. We examined miR-326 and Ucn1 levels in the EWcp of depressed suicide completers. In addition, we evaluated miR-326 and Ucn1 levels in the serum and the EWcp of a chronic variable mild stress (CVMS) rat model of behavioural despair and after recovery from CVMS, respectively. Gain and loss of miR-326 function experiments examined the regulation of Ucn1 by this miRNA in cultured midbrain neurons. RESULTS: We found reduced miR-326 levels concomitant with elevated Ucn1 levels in the EWcp of depressed suicide completers as well as in the EWcp of CVMS rats. In CVMS rats fully recovered from stress, both serum and EWcp miR-326 levels rebounded to nonstressed levels. While downregulation of miR-326 levels in primary midbrain neurons enhanced Ucn1 expression levels, miR-326 overexpression selectively reduced the levels of this neuropeptide. LIMITATIONS: This study lacked experiments showing that in vivo alteration of miR-326 levels alleviate depression-like behaviours. We show only correlative data for miR-325 and cocaine- and amphetamine-regulated transcript levels in the EWcp. CONCLUSION: We identified miR-326 dysregulation in depressed suicide completers and characterized this miRNA as an upstream regulator of the Ucn1 neuropeptide expression in midbrain neurons.

QUEST: Eliminating Online Supervised Learning for Efficient Classification Algorithms.

In this work, we introduce QUEST (QUantile Estimation after Supervised Training), an adaptive classification algorithm for Wireless Sensor Networks (WSNs) that eliminates the necessity for online supervised learning. Online processing is important for many sensor network applications. Transmitting raw sensor data puts high demands on the battery, reducing network life time. By merely transmitting partial results or classifications based on the sampled data, the amount of traffic on the network can be significantly reduced. Such classifications can be made by learning based algorithms using sampled data. An important issue, however, is the training phase of these learning based algorithms. Training a deployed sensor network requires a lot of communication and an impractical amount of human involvement. QUEST is a hybrid algorithm that combines supervised learning in a controlled environment with unsupervised learning on the location of deployment. Using the SITEX02 dataset, we demonstrate that the presented solution works with a performance penalty of less than 10% in 90% of the tests. Under some circumstances, it even outperforms a network of classifiers completely trained with supervised learning. As a result, the need for on-site supervised learning and communication for training is completely eliminated by our solution.

Molecular correlates of cortical network modulation by long-term sensory experience in the adult rat barrel cortex.

Modulation of cortical network connectivity is crucial for an adaptive response to experience. In the rat barrel cortex, long-term sensory stimulation induces cortical network modifications and neuronal response changes of which the molecular basis is unknown. Here, we show that long-term somatosensory stimulation by enriched environment up-regulates cortical expression of neuropeptide mRNAs and down-regulates immediate-early gene (IEG) mRNAs specifically in the barrel cortex, and not in other brain regions. The present data suggest a central role of neuropeptides in the fine-tuning of sensory cortical circuits by long-term experience.

MicroRNA-137 regulates a glucocorticoid receptor-dependent signalling network: implications for the etiology of schizophrenia.

BACKGROUND: Schizophrenia is a highly heritable neurodevelopmental disorder. A genetic variant of microRNA-137 (miR-137) has yielded significant genome-wide association with schizophrenia, suggesting that this miRNA plays a key role in its etiology. Therefore, a molecular network of interacting miR-137 targets may provide insights into the biological processes underlying schizophrenia. METHODS: We first used bioinformatics tools to obtain and analyze predicted human and mouse miR-137 targets. We then determined miR-137 levels in rat barrel cortex after environmental enrichment (EE), a neuronal plasticity model that induces upregulation of several predicted miR-137 targets. Subsequently, expression changes of these predicted targets were examined through loss of miR-137 function experiments in rat cortical neurons. Finally, we conducted bioinformatics and literature analyses to examine the targets that were upregulated upon miR-137 downregulation. RESULTS: Predicted human and mouse miR-137 targets were enriched in neuronal processes, such as axon guidance, neuritogenesis and neurotransmission. The miR-137 levels were significantly downregulated after EE, and we identified 5 novel miR-137 targets through loss of miR-137 function experiments. These targets fit into a glucocorticoid receptor-dependent signalling network that also includes 3 known miR-137 targets with genome-wide significant association with schizophrenia. LIMITATIONS: The bioinformatics analyses involved predicted human and mouse miR-137 targets owing to lack of information on predicted rat miR-137 targets, whereas follow-up experiments were performed with rats. Furthermore, indirect effects in the loss of miR-137 function experiments cannot be excluded. CONCLUSION: We have identified a miR-137-regulated protein network that contributes to our understanding of the molecular basis of schizophrenia and provides clues for future research into psychopharmacological treatments for schizophrenia.

Differences in the chemical composition of organic-walled dinoflagellate resting cysts from phototrophic and heterotrophic dinoflagellates.

Dinoflagellates constitute a large proportion of the planktonic biomass from marine to freshwater environments. Some species produce a preservable organic-walled resting cyst (dinocyst) during the sexual phase of their life cycle that is an important link between the organisms, the environment in which their parent motile theca grew, and the sedimentary record. Despite their abundance and widespread usage as proxy indicators for environmental conditions, there is a lack of knowledge regarding the dinocyst wall chemical composition. It is likely that numerous factors, including phylogeny and life strategy, determine the cyst wall chemistry. However, the extent to which this composition varies based on inherent (phylogenetic) or variable (ecological) factors has not been studied. To address this, we used micro-Fourier transform infrared spectroscopy to analyze nine cyst species produced by either phototrophic or heterotrophic dinoflagellates from the extant orders Gonyaulacales, Gymnodiniales, and Peridiniales. Based on the presence of characteristic functional groups, two significantly different cyst wall compositions are observed that correspond to the dinoflagellate's nutritional strategy. The dinocyst wall compositions analyzed appeared carbohydrate-based, but the cyst wall produced by phototrophic dinoflagellates suggested a cellulose-like glucan, while heterotrophic forms produced a nitrogen-rich glycan. This constitutes the first empirical evidence nutritional strategy is related to different dinocyst wall chemistries. Our results indicated phylogeny was less important for predicting composition than the nutritional strategy of the dinoflagellate, suggesting potential for cyst wall chemistry to infer past nutritional strategies of extinct taxa preserved in the sedimentary record.

[Myringoplasties for anterior tympanic perforations: Our surgical technique]. / Myringoplastie pour les perforations tympaniques antérieures: notre technique opératoire.

Anterior tympanic perforations are actually the most difficult to close and a number of different techniques exist. This article represents the author's surgical procedure for type I tympanoplasties (myringoplasties) for this kind of perforation using the tragal cartilage and the perichondrium after preparation (revival, cleaning) of the perforation edge with a laser. This technique does not use a skin incision of external auditory meatus, when this one is large.

[Reconstruction of bone defects in the earcanal with hydroxyapatite]. / Reconstruction des defects osseux du conduit auditif externe par ciment d'hydroxyapatite.

Traditional reconstruction methods of osseous defects within the tympanic frame, most often being the atticotomy, within the framework of chronic otitis media surgery, still do not produce stable or definitive results, usually due to displacement or partial lyse of the transplanted material (cartilage, bone ...). The reconstruction procedure with the aid of hydroxyapatite cement as presented by the authors, allows for a complete, stable and definitive reconstruction.

Climate change, society, and pandemic disease in Roman Italy between 200 BCE and 600 CE.

Records of past societies confronted with natural climate change can illuminate social responses to environmental stress and environment-disease connections, especially when locally constrained high-temporal resolution paleoclimate reconstructions are available. We present a temperature and precipitation reconstruction for ~200 BCE to ~600 CE, from a southern Italian marine sedimentary archive-the first high-resolution (~3 years) climate record from the heartland of the Roman Empire, stretching from the so-called Roman Climate Optimum to the Late Antique Little Ice Age. We document phases of instability and cooling from ~100 CE onward but more notably after ~130 CE. Pronounced cold phases between ~160 to 180 CE, ~245 to 275 CE, and after ~530 CE associate with pandemic disease, suggesting that climate stress interacted with social and biological variables. The importance of environment-disease dynamics in past civilizations underscores the need to incorporate health in risk assessments of climate change.

The Natural Protoalkaloid Methyl-2-Amino-3-Methoxybenzoate (MAM) Alleviates Positive as well as Cognitive Symptoms in Rat and Mouse Schizophrenia Models.

The development of new antipsychotics with pro-cognitive properties and less side effects represents a priority in schizophrenia drug research. In this study, we present for the first time a preclinical exploration of the effects of the promising natural atypical antipsychotic Methyl-2-Amino-3- Methoxybenzoate (MAM), a brain-penetrable protoalkaloid from the seed of the plant Nigella damascena. Using animal models related to hyperdopaminergic activity, namely the pharmacogenetic apomorphine (D2/D1 receptor agonist)-susceptible (APO-SUS) rat model and pharmacologically induced mouse and rat models of schizophrenia, we found that MAM reduced gnawing stereotypy and climbing behaviours induced by dopaminergic agents. This predicts antipsychotic activity. In line, MAM antagonized apomorphine-induced c-Fos and NPAS4 mRNA levels in post-mortem brain nucleus accumbens and dorsolateral striatum of APO-SUS rats. Furthermore, phencyclidine (PCP, an NMDA receptor antagonist) and 2,5-Dimethoxy-4-iodoamphetamine (DOI, a 5HT2A/2C receptor agonist) induced prepulse inhibition deficits, reflecting the positive symptoms of schizophrenia, which were rescued by treatment with MAM and atypical antipsychotics alike. Post-mortem brain immunostaining revealed that MAM blocked the strong activation of both PCP- and DOI-induced c-Fos immunoreactivity in a number of cortical areas. Finally, during a 28-day subchronic treatment regime, MAM did not induce weight gain, hyperglycemia, hyperlipidemia or hepato- and nephrotoxic effects, side effects known to be induced by atypical antipsychotics. MAM also did not show any cataleptic effects. In conclusion, its brain penetrability, the apparent absence of preclinical side effects, and its ability to antagonize positive and cognitive symptoms associated with schizophrenia make MAM an exciting new antipsychotic drug that deserves clinical testing.

Spatial distribution of small microplastics in the Norwegian Coastal Current.

High concentrations of microplastic (MP) particles have been reported in the Arctic Ocean. However, studies on the high-resolution lateral and vertical transport of MPs from the European waters to the Arctic are still scarce. Here, we provide information about the concentrations and compositions of MPs in surface, subsurface, and deeper waters (< 1 m, ∼ 4 m, and 17-1679 m) collected at 18 stations on six transects along the Norwegian Coastal Current (NCC) using an improved Neuston Catamaran, the COntinuos MicroPlastic Automatic Sampling System (COMPASS), and in situ pumps, respectively. FTIR microscopy and spectroscopy were applied to measure MP concentration, polymer composition, and size distribution. Results indicate that the concentrations of small microplastics (SMPs, <300 µm) varied considerably (0-1240 MP m-3) within the water column, with significantly higher concentrations in the surface (189 MP m-3) and subsurface (38 MP m-3) waters compared to deeper waters (16 MP m-3). Furthermore, the average concentration of SMPs in surface water samples was four orders of magnitude higher than the abundance of large microplastics (LMPs, >300 µm), and overall, SMPs <50 µm account for >80 % of all detected MPs. However, no statistically significant geographical patterns were observed in SMP concentrations in surface/subsurface seawaters between the six sampling transects, suggesting a relatively homogeneous horizontal distribution of SMPs in the upper ocean within the NCC/Norwegian Atlantic Current (NwAC) interface. The Lagrangian particle dispersal simulation model further enabled us to assess the large-scale transport of MPs from the Northern European waters to the Arctic.