Wideband Direct Detection Constraints on Hidden Photon Dark Matter with the QUALIPHIDE Experiment.

We report direction detection constraints on the presence of hidden photon dark matter with masses between 20-30 µeV c^{-2}, using a cryogenic emitter-receiver-amplifier spectroscopy setup designed as the first iteration of QUALIPHIDE (quantum limited photons in the dark experiment). A metallic dish sources conversion photons, from hidden photon kinetic mixing, onto a horn antenna which is coupled to a C band kinetic inductance traveling wave parametric amplifier, providing for near quantum-limited noise performance. We demonstrate a first probing of the kinetic mixing parameter χ to the 10^{-12} level for the majority of hidden photon masses in this region. These results not only represent stringent constraints on new dark matter parameter space, but are also the first demonstrated use of wideband quantum-limited amplification for astroparticle applications.

Interrelationships Between Spinal Sympathetic Preganglionic Neurons, Autonomic Systems and Electrical Synapses Formed by Connexin36-containing Gap Junctions.

Spinal sympathetic preganglionic neurons (SPNs) are among the many neuronal populations in the mammalian central nervous system (CNS) where there is evidence for electrical coupling between cell pairs linked by gap junctions composed of connexin36 (Cx36). Understanding the organization of this coupling in relation to autonomic functions of spinal sympathetic systems requires knowledge of how these junctions are deployed among SPNs. Here, we document the distribution of immunofluorescence detection of Cx36 among SPNs identified by immunolabelling of their various markers, including choline acetyltransferase, nitric oxide and peripherin in adult and developing mouse and rat. In adult animals, labelling of Cx36 was exclusively punctate and dense concentrations of Cx36-puncta were distributed along the entire length of the spinal thoracic intermediolateral cell column (IML). These puncta were also seen in association with SPN dendritic processes in the lateral funiculus, the intercalated and central autonomic areas and those within and extending medially from the IML. All labelling for Cx36 was absent in spinal cords of Cx36 knockout mice. High densities of Cx36-puncta were already evident among clusters of SPNs in the IML of mouse and rat at postnatal days 10-12. In Cx36BAC::eGFP mice, eGFP reporter was absent in SPNs, thus representing false negative detection, but was localized to some glutamatergic and GABAergic synaptic terminals. Some eGFP+ terminals were found contacting SPN dendrites. These results indicate widespread Cx36 expression in SPNs, further supporting evidence of electrical coupling between these cells, and suggest that SPNs are innervated by neurons that themselves may be electrically coupled.

Noncanonical Role of Telomerase in Regulation of Microvascular Redox Environment With Implications for Coronary Artery Disease.

Telomerase reverse transcriptase (TERT) (catalytic subunit of telomerase) is linked to the development of coronary artery disease (CAD); however, whether the role of nuclear vs. mitchondrial actions of TERT is involved is not determined. Dominant-negative TERT splice variants contribute to decreased mitochondrial integrity and promote elevated reactive oxygen species production. We hypothesize that a decrease in mitochondrial TERT would increase mtDNA damage, promoting a pro-oxidative redox environment. The goal of this study is to define whether mitochondrial TERT is sufficient to maintain nitric oxide as the underlying mechanism of flow-mediated dilation by preserving mtDNA integrity.Immunoblots and quantitative polymerase chain reaction were used to show elevated levels of splice variants α- and ß-deletion TERT tissue from subjects with and without CAD. Genetic, pharmacological, and molecular tools were used to manipulate TERT localization. Isolated vessel preparations and fluorescence-based quantification of mtH2O2 and NO showed that reduction of TERT in the nucleus increased flow induced NO and decreased mtH2O2 levels, while prevention of mitochondrial import of TERT augmented pathological effects. Further elevated mtDNA damage was observed in tissue from subjects with CAD and initiation of mtDNA repair mechanisms was sufficient to restore NO-mediated dilation in vessels from patients with CAD. The work presented is the first evidence that catalytically active mitochondrial TERT, independent of its nuclear functions, plays a critical physiological role in preserving NO-mediated vasodilation and the balance of mitochondrial to nuclear TERT is fundamentally altered in states of human disease that are driven by increased expression of dominant negative splice variants.

Quantitative composition determination by ADF-STEM at a low-angular regime: a combination of EFSTEM and 4DSTEM.

High-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) is a valuable method for composition determination of nanomaterials. However, light elements do not scatter efficiently into the scattering angles employed for HAADF-STEM which hinders the composition determination of material systems containing light elements by HAADF-STEM. This makes the usage of lower scattering angles favourable. Moreover, static atomic displacements (SADs) caused by the small covalent radius of the substituting light elements in semiconductor alloys increase the scattering intensity at low angles. Nevertheless, at low angles, a quantitative match between complementary image simulations and experiments is not straight forward, since e.g. inelastic scattering and correlated phonon movement is often neglected in simulations. In this study, we establish a method to quantify material systems containing light elements at low angles by resolving the remaining sources of discrepancy. An outstanding agreement between simulations and experiments is achieved by using a combination of an in-column energy filter and a fast pixelated detector. By applying this method to GaNxAs1-x quantum wells, a good agreement of the TEM results with results from high-resolution x-ray diffraction is obtained. The method developed enables the nanoscale analysis of functional materials containing light elements, especially in the presence of SADs.

On the Organization of Connexin36 Expression in Electrically Coupled Cholinergic V0c Neurons (Partition Cells) in the Spinal Cord and Their C-terminal Innervation of Motoneurons.

Large cholinergic neurons (V0c neurons; aka, partition cells) in the spinal cord project profusely to motoneurons on which they form C-terminal contacts distinguished by their specialized postsynaptic subsurface cisterns (SSCs). The V0c neurons are known to be rhythmically active during locomotion and release of acetylcholine (ACh) from their terminals is known to modulate the excitability of motoneurons in what appears to be a task-dependent manner. Here, we present evidence that a subpopulation of V0c neurons express the gap junction forming protein connexin36 (Cx36), indicating that they are coupled by electrical synapses. Based on immunofluorescence imaging and the use of Cx36BAC-enhanced green fluorescent protein (eGFP) mice in which C-terminals immunolabelled for their marker vesicular acetylcholine transporter (vAChT) are also labelled for eGFP, we found a heterogeneous distribution of eGFP+ C-terminals on motoneurons at cervical, thoracic and lumber spinal levels. The density of C-terminals on motoneurons varied as did the proportion of those that were eGFP+ vs. eGFP-. We present evidence that fast vs. slow motoneurons have a greater abundance of these terminals and fast motoneurons also have the highest density that were eGFP+. Thus, our results indicate that a subpopulation of V0c neurons projects preferentially to fast motoneurons, suggesting that the capacity for synchronous activity conferred by electrical synapses among networks of coupled V0c neurons enhances their dynamic capabilities for synchronous regulation of motoneuron excitability during high muscle force generation. The eGFP+ vs. eGFP- V0c neurons were more richly innervated by serotonergic terminals, suggesting their greater propensity for regulation by descending serotonergic systems.

Optimization of imaging conditions for composition determination by annular dark field STEM.

Quantitative scanning transmission electron microscopy (STEM) allows composition determination for nanomaterials at an atomic scale. To improve the accuracy of the results obtained, optimized imaging parameters should be chosen for annular dark field imaging. In a simulation study, we investigate the influence of imaging parameters on the accuracy of the composition determination with the example of ternary III-V semiconductors. It is shown that inner and outer detector angles and semi-convergence angle can be optimized, also in dependence on specimen thickness. Both, a minimum sampling of the image and a minimum electron dose are required. These findings are applied experimentally by using a fast pixelated detector to allow free choice of detector angles.

Cis-regulatory evolution spotlights species differences in the adaptive potential of gene expression plasticity.

Phenotypic plasticity is the variation in phenotype that a single genotype can produce in different environments and, as such, is an important component of individual fitness. However, whether the effect of new mutations, and hence evolution, depends on the direction of plasticity remains controversial. Here, we identify the cis-acting modifications that have reshaped gene expression in response to dehydration stress in three Arabidopsis species. Our study shows that the direction of effects of most cis-regulatory variants differentiating the response between A. thaliana and the sister species A. lyrata and A. halleri depends on the direction of pre-existing plasticity in gene expression. A comparison of the rate of cis-acting variant accumulation in each lineage indicates that the selective forces driving adaptive evolution in gene expression favors regulatory changes that magnify the stress response in A. lyrata. The evolutionary constraints measured on the amino-acid sequence of these genes support this interpretation. In contrast, regulatory changes that mitigate the plastic response to stress evolved more frequently in A. halleri. Our results demonstrate that pre-existing plasticity may be a stepping stone for adaptation, but its selective remodeling differs between lineages.

Single-photon detection in the mid-infrared up to 10 µm wavelength using tungsten silicide superconducting nanowire detectors.

We developed superconducting nanowire single-photon detectors based on tungsten silicide, which show saturated internal detection efficiency up to a wavelength of 10 µm. These detectors are promising for applications in the mid-infrared requiring sub-nanosecond timing, ultra-high gain stability, low dark counts, and high efficiency, such as chemical sensing, LIDAR, dark matter searches, and exoplanet spectroscopy.

Risk of chronic kidney disease in people living with HIV by tenofovir disoproxil fumarate (TDF) use and baseline D:A:D chronic kidney disease risk score.

OBJECTIVES: To assess the risk of chronic kidney disease (CKD) associated with tenofovir disoproxil fumarate (TDF) use by baseline D:A:D CKD risk score. METHODS: Adult antiretroviral therapy (ART)-naïve people living with HIV (PLWH) initiating treatment, with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 , were identified in the OPERA cohort. CKD was defined as two or more consecutive eGFR < 60 mL/min/1.73 m2 , > 90 days apart. Associations between TDF use, baseline D:A:D CKD risk and incident CKD were assessed with incidence rates (IRs; Poisson regression) and adjusted pooled logistic regression. The impact of pharmacoenhancers on the observed association between TDF and CKD was also evaluated. RESULTS: Of 9802 PLWH included, 6222 initiated TDF and 3580 did not (76% and 79% low D:A:D CKD risk, respectively). Overall, 125 CKD events occurred over 24 382 person-years of follow-up. Within strata of D:A:D CKD risk score, IRs were similar across TDF exposure, with high baseline CKD risk associated with highest incidence. Compared with the low-risk group without TDF, there was no statistical difference in odds of incident CKD in the low-risk group with TDF (adjusted odds ratio = 0.55, 95% confidence interval: 0.19-1.54). Odds of incident CKD did not differ statistically significantly by pharmacoenhancer exposure, with or without TDF. CONCLUSIONS: In this large cohort of ART-naïve PLWH, incident CKD following ART initiation was infrequent and strongly associated with baseline CKD risk. TDF-containing regimens did not increase the odds of CKD in those with a low baseline D:A:D CKD risk, the largest group of ART-naïve PLWH, and may remain a viable treatment option in appropriate settings.

Validation of the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) chronic kidney disease risk score in HIV-infected patients in the USA.

OBJECTIVES: The aim of the study was to assess the validity of an easy-to-calculate chronic kidney disease (CKD) risk score developed by the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) group in a longitudinal observational study of people living with HIV (PLWH) in the USA. METHODS: PLWH (2002-2016) without prior exposure to potentially nephrotoxic antiretroviral agents and with at least three estimated glomerular filtration rate (eGFR) test results were identified in the Observational Pharmaco-Epidemiology Research and Analysis (OPERA® ) cohort. Three samples were drawn independently using the same eligibility criteria but each using a different eGFR equation, specifically the Cockcroft-Gault (C-G), Modification of Diet in Renal Disease (MDRD) or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR estimation method. Full and short D:A:D risk scores were applied. CKD was defined as a confirmed decrease in eGFR to < 60 mL/min/1.73 m2 (stages 3-5). Poisson models estimated the association between CKD incidence and a one-point increase in the continuous risk score. The incidence rate ratio (IRR), adjusted IRR (aIRR), and Harrell's discrimination statistic were used to assess validity. RESULTS: There were 19 444, 22 727 and 22 748 PLWH in the OPERA C-G, CKD-EPI and MDRD samples, respectively. The median (minimum-maximum) follow-up duration was 6.1 (0.3-9.1) years in the D:A:D cohort and ranged from 3.2 to 3.5 (0.2-15.5) years in the OPERA validation samples. The observation time for the majority of PLWH in the D:A:D cohort began prior to 2006, in stark contrast to the OPERA validation samples, where the majority of PLWH were observed after 2011. The CKD incidence ranged from 7.3 per 1000 person-years [95% confidence interval (CI) 6.8, 7.9 per 1000 person-years] in OPERA C-G to 11.0 (95% CI 10.4, 11.6 per 1000 person-years) in OPERA MDRD. In OPERA samples, IRRs by risk group and adjusted IRRs (full risk score) were similar to those in the D:A:D derivation cohort (adjusted IRR 1.3; 95% CI 1.3, 1.3). Harrell's c-statistic ranged from 0.87 to 0.92 in the OPERA samples, comparable to that in the derivation cohort (0.92). Results for short scores were similar. CONCLUSIONS: The findings support the validity of the D:A:D risk scoring method for assessing CKD (stages 3-5) probability in an exclusively USA-based sample regardless of eGFR method.

Composition determination for quaternary III-V semiconductors by aberration-corrected STEM.

Quantitative scanning transmission electron microscopy (STEM) is a powerful tool for the characterization of nano-materials. Absolute composition determination for ternary III-V semiconductors by direct comparison of experiment and simulation is well established. Here, we show a method to determine the composition of quaternary III-V semiconductors with two elements on each sub lattice from the intensities of one STEM image. As an example, this is applied to (GaIn)(AsBi). The feasibility of the method is shown in a simulation study that also explores the influence of detector angles and specimen thickness. Additionally, the method is applied to an experimental STEM image of a (GaIn)(AsBi) quantum well grown by metal organic vapour phase epitaxy. The obtained concentrations are in good agreement with X-ray diffraction and photoluminescence results.

Simultaneous determination of local thickness and composition for ternary III-V semiconductors by aberration-corrected STEM.

Scanning transmission electron microscopy (STEM) is a suitable method for the quantitative characterization of nanomaterials. For an absolute composition determination on an atomic scale, the thickness of the specimen has to be known locally with high accuracy. Here, we propose a method to determine both thickness and composition of ternary III-V semiconductors locally from one STEM image as shown for the example material systems Ga(AsBi) and (GaIn)As. In a simulation study, the feasibility of the method is proven and the influence of specimen thickness and detector angles used is investigated. An application to an experimental STEM image of a Ga(AsBi) quantum well grown by metal organic vapour phase epitaxy yields an excellent agreement with composition results from high resolution X-ray diffraction.

Composition determination of semiconductor alloys towards atomic accuracy by HAADF-STEM.

This paper presents a comprehensive investigation of an extended method to determine composition of materials by scanning transmission electron microscopy (STEM) high angle annular darkfield (HAADF) images and using complementary multislice simulations. The main point is to understand the theoretical capabilities of the algorithm and address the intrinsic limitations of using STEM HAADF intensities for composition determination. A special focus is the potential of the method regarding single-atom accuracy. All-important experimental parameters are included into the multislice simulations to ensure the best possible fit between simulation and experiment. To demonstrate the capabilities of the extended method, results for three different technical important semiconductor samples are presented. Overall the method shows a high lateral resolution combined with a high accuracy towards single-atom accuracy.

Three-dimensional structure of antiphase domains in GaP on Si(0 0 1).

Antiphase domains are three-dimensional crystal defects commonly arising at the interface of III-V semiconductors and Si. While control over their formation has been achieved, the geometry of the antiphase domain itself that is separated from the mainphase of the crystal by the so-called antiphase boundary, has not yet been fully understood. In this work, we first investigate the interface between GaP and Si itself by cross-sectional scanning tunneling microscopy (XSTM) to reveal possible intermixing within an 8 monolayers wide region. Furthermore, we present an extensive analysis combining transmission electron microscopy and XSTM to elucidate the shape of antiphase domains in GaP. To create a true-to-scale, three-dimensional model of an antiphase domain, firstly, plan-view transmission electron microscopy images are drawn on. Subsequently, the progression of many antiphase boundaries through the GaP crystal as viewed from the (1 1 0) and (1 [Formula: see text] 0) cleavage planes is analyzed all the way down to the atomic level by means of XSTM. This enables a detailed analysis of the shape and physical dimensions of the antiphase domains. A typical measured extension in growth directions is found to be a maximum of 60 nm and the maximum measured extension of the base plane in [[Formula: see text] 1 0] and [1 1 0] directions is about 160 nm and 50 nm, respectively. They appear as pyramids with anisotropic base planes whose side facets kink many times.

Second-harmonic generation as a probe for structural and electronic properties of buried GaP/Si(0 0 1) interfaces.

Optical second-harmonic generation is demonstrated to be a sensitive probe of the buried interface between the lattice-matched semiconductors gallium phosphide and silicon with (0 0 1) orientation. Ex situ rotational anisotropy measurements on GaP/Si heterostructures show a strong isotropic component of the second-harmonic response not present for pure Si(0 0 1) or GaP(0 0 1). The strength of the overlaying anisotropic response directly correlates with the quality of the interface as determined by atomically resolved scanning transmission electron microscopy. Systematic comparison of samples fabricated under different growth conditions in metal-organic vapor phase epitaxy reveals that the anisotropy for different polarization combinations can be used as a selective fingerprint for the occurrence of anti-phase domains and twins. This all-optical technique can be applied as an in situ and non-invasive monitor even during growth.

Thermally Introduced Bismuth Clustering in Ga(P,Bi) Layers under Group V Stabilised Conditions Investigated by Atomic Resolution In Situ (S)TEM.

We report the formation of Bi clusters in Ga(P1-x,Bix) layers during an in situ (scanning) transmission electron microscopy ((S)TEM) annealing investigation. The non-destructive temperature regime in dependence on the tertiarybutylphosphine (TBP) pressure in the in situ cell was investigated to ensure that the results are not distorted by any destructive behaviour of the crystal during the thermal treatment. The following annealing series of the Ga(P92.6Bi7.4) and Ga(P96.4Bi3.6) layers reveals that the threshold temperature at which the Bi clustering takes place is 600 °C in the Ga(P92.6Bi7.4) layer. Further thermal treatments up to 750 °C show a relationship between the Bi fraction in the Ga(P1-x,Bix) layer and the initial temperature at which the Bi clustering takes place. Finally, we investigate one Bi cluster at atomic resolution conditions. In these conditions, we found that the Bi cluster crystallized in a rhombohedral phase, aligning with its {101} planes parallel to the Ga(P,Bi) {202} planes.

UV superconducting nanowire single-photon detectors with high efficiency, low noise, and 4 K operating temperature.

For photon-counting applications at ultraviolet wavelengths, there are currently no detectors that combine high efficiency (> 50%), sub-nanosecond timing resolution, and sub-Hz dark count rates. Superconducting nanowire single-photon detectors (SNSPDs) have seen success over the past decade for photon-counting applications in the near-infrared, but little work has been done to optimize SNSPDs for wavelengths below 400 nm. Here, we describe the design, fabrication, and characterization of UV SNSPDs operating at wavelengths between 250 and 370 nm. The detectors have active areas up to 56 µm in diameter, 70 - 80% efficiency at temperatures up to 4.2 K, timing resolution down to 60 ps FWHM, blindness to visible and infrared photons, and dark count rates of ∼ 0.25 counts/hr for a 56 µm diameter pixel. These performance metrics make UV SNSPDs ideal for applications in trapped-ion quantum information processing, lidar studies of the upper atmosphere, UV fluorescent-lifetime imaging microscopy, and photon-starved UV astronomy.

Atomic structure of 'W'-type quantum well heterostructures investigated by aberration-corrected STEM.

The atomic structure of (GaIn)As/Ga(AsSb)/(GaIn)As-'W'-type quantum well heterostructures ('W'-QWHs) is investigated by scanning transmission electron microscopy (STEM). These structures were grown by metal organic vapour phase epitaxy and are built for type-II laser systems in the infrared wavelength regime. For two samples grown at 525°C and 550°C, intensity profiles are extracted from the STEM images for each sublattice separately. These intensity profiles are compared to the one obtained from an image simulation of an ideal 'W'-QWH that is modelled in close agreement with the experiment. From the intensity profiles, the width of the different quantum wells (QWs) can be determined. Additionally, characteristics connected to the growth of the structures, such as segregation coefficients and material homogeneity, are calculated. Finally, composition profiles are derived from the STEM intensity profiles to a first approximation. For these composition profiles, the expected photoluminescence (PL) is computed based using the semiconductor luminescence equations. The PL spectra are then compared to experimental measurements for both samples.

Towards the liquid phase exfoliation of bismuth iodide.

Liquid phase exfoliation (LPE) of layered compounds towards few- or monolayers has been established as one of the prime methods in the growing field of 2D material research. Here, we present first steps towards an effective LPE of bismuth(iii) iodide, a semiconductor with potential as a photovoltaic absorber material. We highlight guidelines in the choice of exfoliating solvent, which differ significantly from those used with transition metal dichalcogenides or graphene. We also present first evidence of successful few-layer formation from spectroscopic, electron microscopy and electron diffraction investigations.

Xenopus as a model organism to study heterotrimeric G-protein pathway during collective cell migration of neural crest.

Collective cell migration is essential in many fundamental aspects of normal development, like morphogenesis, organ formation, wound healing, and immune responses, as well as in the etiology of severe pathologies, like cancer metastasis. In spite of the huge amount of data accumulated on cell migration, such a complex process involves many molecular actors, some of which still remain to be functionally characterized. One of these signals is the heterotrimeric G-protein pathway that has been studied mainly in gastrulation movements. Recently we have reported that Ric-8A, a GEF for Gα proteins, plays an important role in neural crest migration in Xenopus development. Xenopus neural crest cells, a highly migratory embryonic cell population induced at the border of the neural plate that migrates extensively in order to differentiate in other tissues during development, have become a good model to understand the dynamics that regulate cell migration. In this review, we aim to provide sufficient evidence supporting how useful Xenopus model with its different tools, such as explants and transplants, paired with improved in vivo imaging techniques, will allow us to tackle the multiple signaling mechanisms involved in neural crest cell migration.