A gamma- and X-ray detector for cryogenic, high magnetic field applications

As part of an experiment to measure the spectrum of photons emitted in beta-decay of the free neutron, we developed and operated a detector consisting of 12 bismuth germanate (BGO) crystals coupled to avalanche photodiodes (APDs). The detector was operated near liquid nitrogen temperature in the bore of a superconducting magnet and registered photons with energies from 5 keV to 1000 keV. To enlarge the detection range, we also directly detected soft X-rays with energies between 0.2 keV and 20 keV with three large area APDs. The construction and operation of the detector is presented, as well as information on operation of APDs at cryogenic temperatures

Epidrug-induced upregulation of functional somatostatin type 2 receptors in human pancreatic neuroendocrine tumor cells

Somatostatin receptors are a pivotal target for treatment of pancreatic neuroendocrine tumors (pNET), either with somatostatin analogues (SSA) or radiolabeled SSA. The highest affinity target for the most commonly used SSA is the somatostatin receptor type 2 (sst2). An important factor that may complicate treatment efficacy, is the variable number of receptors expressed on pNETs. Gene expression is subject to complex regulation, in which epigenetics has a central role. In this study we explored the possible role of epigenetic modifications in the variations in sst2 expression levels in two human pNET cell lines, BON-1 and QGP-1. We found upregulation of sst2 mRNA after treatment with the epidrugs 5-aza-2'-deoxycytidine (5-aza-dC) and valproic acid (VPA), an increased uptake of radiolabeled octreotide, as well as increased sensitivity to the SSA octreotide in functional cAMP inhibition. At epigenetic level we observed low methylation levels of the sst2 gene promoter region irrespective of expression. Activating histone mark H3K9Ac can be regulated with epidrug treatment, with an angle of effect corresponding to the effect on mRNA expression. Repressive histone mark H3K27me3 is not regulated by either 5-aza-dC or VPA. We conclude that epidrug treatment, in particular with combined 5-aza-dC and VPA treatment, might hold promise for improving and adding to current SSA treatment strategies of patients with pNETs

Dopaminergic and prefrontal basis of learning from sensory confidence and reward value

Deciding between stimuli requires combining their learned value with one’s sensory confidence. We trained mice in a visual task that probes this combination. Mouse choices reflected not only present confidence and past rewards but also past confidence. Their behavior conformed to a model that combines signal detection with reinforcement learning. In the model, the predicted value of the chosen option is the product of sensory confidence and learned value. We found precise correlates of this variable in the pre-outcome activity of midbrain dopamine neurons and of medial prefrontal cortical neurons. However, only the latter played a causal role: inactivating medial prefrontal cortex before outcome strengthened learning from the outcome. Dopamine neurons played a causal role only after outcome, when they encoded reward prediction errors graded by confidence, influencing subsequent choices. These results reveal neural signals that combine reward value with sensory confidence and guide subsequent learning

The Atmospheric Chemistry Suite (ACS) of Three Spectrometers for the ExoMars 2016 Trace Gas Orbiter

The Atmospheric Chemistry Suite (ACS) package is an element of the Russian contribution to the ESA-Roscosmos ExoMars 2016 Trace Gas Orbiter (TGO) mission. ACS consists of three separate infrared spectrometers, sharing common mechanical, electrical, and thermal interfaces. This ensemble of spectrometers has been designed and developed in response to the Trace Gas Orbiter mission objectives that specifically address the requirement of high sensitivity instruments to enable the unambiguous detection of trace gases of potential geophysical or biological interest. For this reason, ACS embarks a set of instruments achieving simultaneously very high accuracy (ppt level), very high resolving power (>10,000) and large spectral coverage (0.7 to 17 μm—the visible to thermal infrared range). The near-infrared (NIR) channel is a versatile spectrometer covering the 0.7–1.6 μm spectral range with a resolving power of ∼20,000. NIR employs the combination of an echelle grating with an AOTF (Acousto-Optical Tunable Filter) as diffraction order selector. This channel will be mainly operated in solar occultation and nadir, and can also perform limb observations. The scientific goals of NIR are the measurements of water vapor, aerosols, and dayside or night side airglows. The mid-infrared (MIR) channel is a cross-dispersion echelle instrument dedicated to solar occultation measurements in the 2.2–4.4 μm range. MIR achieves a resolving power of >50,000. It has been designed to accomplish the most sensitive measurements ever of the trace gases present in the Martian atmosphere. The thermal-infrared channel (TIRVIM) is a 2-inch double pendulum Fourier-transform spectrometer encompassing the spectral range of 1.7–17 μm with apodized resolution varying from 0.2 to 1.3 cm−1. TIRVIM is primarily dedicated to profiling temperature from the surface up to ∼60 km and to monitor aerosol abundance in nadir. TIRVIM also has a limb and solar occultation capability. The technical concept of the instrument, its accommodation on the spacecraft, the optical designs as well as some of the calibrations, and the expected performances for its three channels are described

Pediatric mesenchymal stem cells exhibit immunomodulatory properties toward allogeneic T and B cells under inflammatory conditions

Mesenchymal stem cells from pediatric patients (pMSCs) are an attractive cell source in regenerative medicine, due to their higher proliferation rates and better differentiation abilities compared to adult MSCs (aMSCs). We have previously characterized the immunomodulatory abilities of pMSCs on T cells under co-culture. It has also been reported that aMSCs can inhibit B cell proliferation and maturation under inflammatory conditions. In this study, we therefore aimed to clarify the immunomodulatory effect of pMSCs toward T and B cells in an inflammatory microenvironment. Bone marrow derived pMSCs were primed to simulate inflammatory conditions by exposure with 50 ng/mL of IFN-γ for 3 days. To analyze the interaction between pMSCs and T cells, CD3/CD28 stimulated peripheral blood mononuclear cells (PBMCs) were co-cultured with primed or unprimed pMSCs. To investigate B cell responses, quiescent B cells obtained from spleens by CD43 negative selection were stimulated with anti-IgM, anti-CD40, IL-2, and co-cultured with either IFN-γ primed or unprimed pMSC. pMSC phenotype, B and T cell proliferation, and B cell functionality were analyzed. Gene expression of indoleamine 2,3-dioxygenease (IDO), as well as the expression of HLA-ABC, HLA-DR and the co-stimulatory molecules CD80 and CD86 was upregulated on pMSCs upon IFN-γ priming. IFN-γ did not alter the immunomodulatory abilities of pMSCs upon CD4+ nor CD8+ stimulated T cells compared to unprimed pMSCs. IFN-γ primed pMSCs but not unprimed pMSCs strongly inhibited naïve (CD19+CD27-), memory (CD19+CD27+), and total B cell proliferation. Antibody-producing plasmablast (CD19+CD27highCD38high) formation and IgG production were also significantly inhibited by IFN-γ primed pMSCs compared to unprimed pMSCs. Collectively, these results show that pMSCs have immunomodulatory effects upon the adaptive immune response which can be potentiated by inflammatory stimuli. This knowledge is useful in regenerative medicine and allogeneic transplantation applications toward tailoring pMSCs function to best modulate the immune response for a successful implant engraftment and avoidance of a strong immune reaction

Applications of electrified dust and dust devil electrodynamics to Martian atmospheric electricity

Atmospheric transport and suspension of dust frequently brings electrification, which may be substantial. Electric fields of 10 kVm-1 to 100 kVm-1 have been observed at the surface beneath suspended dust in the terrestrial atmosphere, and some electrification has been observed to persist in dust at levels to 5 km, as well as in volcanic plumes. The interaction between individual particles which causes the electrification is incompletely understood, and multiple processes are thought to be acting. A variation in particle charge with particle size, and the effect of gravitational separation explains to, some extent, the charge structures observed in terrestrial dust storms. More extensive flow-based modelling demonstrates that bulk electric fields in excess of 10 kV m-1 can be obtained rapidly (in less than 10 s) from rotating dust systems (dust devils) and that terrestrial breakdown fields can be obtained. Modelled profiles of electrical conductivity in the Martian atmosphere suggest the possibility of dust electrification, and dust devils have been suggested as a mechanism of charge separation able to maintain current flow between one region of the atmosphere and another, through a global circuit. Fundamental new understanding of Martian atmospheric electricity will result from the ExoMars mission, which carries the DREAMS (Dust characterization, Risk Assessment, and Environment Analyser on the Martian Surface)-MicroARES (Atmospheric Radiation and Electricity Sensor) instrumentation to Mars in 2016 for the first in situ measurements

Replacing natural wetlands with stormwater management facilities: biophysical and perceived social values

Urban expansion replaces wetlands of natural origin with artificial stormwater management facilities. The literature suggests that efforts to mimic natural wetlands in the design of stormwater facilities can expand the provision of ecosystem services. Policy developments seek to capitalize on these improvements, encouraging developers to build stormwater wetlands in place of stormwater ponds; however, few have compared the biophysical values and social perceptions of these created wetlands to those of the natural wetlands they are replacing. We compared four types of wetlands: natural references sites, natural wetlands impacted by agriculture, created stormwater wetlands, and created stormwater ponds. We anticipated that they would exhibit a gradient in biodiversity, ecological integrity, chemical and hydrologic stress. We further anticipated that perceived values would mirror measured biophysical values. We found higher biophysical values associated with wetlands of natural origin (both reference and agriculturally impacted). The biophysical values of stormwater wetlands and stormwater ponds were lower and indistinguishable from one another. The perceived wetland values assessed by the public differed from the observed biophysical values. This has important policy implications, as the public are not likely to perceive the loss of values associated with the replacement of natural wetlands with created stormwater management facilities. We conclude that 1) agriculturally impacted wetlands provide biophysical values equivalent to those of natural wetlands, meaning that land use alone is not a great predictor of wetland value; 2) stormwater wetlands are not a substantive improvement over stormwater ponds, relative to wetlands of natural origin; 3) stormwater wetlands are poor mimics of natural wetlands, likely due to fundamental distinctions in terms of basin morphology, temporal variation in hydrology, ground water connectivity, and landscape position; 4) these drivers are relatively fixed, thus, once constructed, it may not be possible to modify them to improve provision of biophysical values; 5) these fixed drivers are not well perceived by the public and thus public perception may not capture the true value of natural wetlands, including those impacted by agriculture

A consensus statement on detection of hippocampal sharp wave ripples and differentiation from other fast oscillations

Decades of rodent research have established the role of hippocampal sharp wave ripples (SPW-Rs) in consolidating and guiding experience. More recently, intracranial recordings in humans have suggested their role in episodic and semantic memory. Yet, common standards for recording, detection, and reporting do not exist. Here, we outline the methodological challenges involved in detecting ripple events and offer practical recommendations to improve separation from other high-frequency oscillations. We argue that shared experimental, detection, and reporting standards will provide a solid foundation for future translational discovery.This work was funded by K23NS104252 (A.A.L.) R01 MH117777 (E.B., J.W.R.) Whitehall Foundation (KH) 5F31NS120783-02 (Z.L.) 1U19NS104590 (A.L.) R01NS106611-02 (J.S., M.K.) MTEC-20-06-MOM013 (J.S., M.K.) 1U19NS107609-01 (I.S., J.L.) 1U19NS104590 (A.L., J.S.F., I.S.) 1U19NS107609 (E.A.B., J.W.R., J.J.L., I.S.) La Caixa LCF/PR/HR21/52410030 (A.N.O., L.dl.P) European Research Council Consolidator Grant 101001121 (B.P.S.) U.S.-Israel BSF grant 2017015 (RM)U01-NS113198 (J.J.) NSF CAREER IOS-1844935 (M.vdM.) 1R01NS121764-01 (B.L.M.) R01 MH122391 (G.B.) 30MH126483 (J.A.G.) Fondation pour la Recherche Médicale EQU202103012768 (M.Z.) 1R16-NS131108-01 (L.L.)