A measurement of the 4He(g,n) reaction from 23 < Eg < 70 MeV

A comprehensive set of 4He(g,n) absolute cross-section measurements has been performed at MAX-lab in Lund, Sweden. Tagged photons from 23 < Eg < 70 MeV were directed toward a liquid 4He target, and neutrons were identified using pulse-shape discrimination and the Time-of-flight Technique in two liquid-scintillator detector arrays. Seven-point angular distributions have been measured for fourteen photon energies. The results have been subjected to complementary Transition-coefficient and Legendre-coefficient analyses. The results are also compared to experimental data measured at comparable photon energies as well as Recoil-Corrected Continuum Shell Model, Resonating Group Method, and Effective Interaction Hyperspherical-Harmonic Expansion calculations. For photon energies below 29 MeV, the angle-integrated data are significantly larger than the values recommended by Calarco, Berman, and Donnelly in 1983.Comment: 16 pages, 14 figures, some more revisions, submitted to Physical Review

Single Molecule Analysis Research Tool (SMART): An Integrated Approach for Analyzing Single Molecule Data

Single molecule studies have expanded rapidly over the past decade and have the ability to provide an unprecedented level of understanding of biological systems. A common challenge upon introduction of novel, data-rich approaches is the management, processing, and analysis of the complex data sets that are generated. We provide a standardized approach for analyzing these data in the freely available software package SMART: Single Molecule Analysis Research Tool. SMART provides a format for organizing and easily accessing single molecule data, a general hidden Markov modeling algorithm for fitting an array of possible models specified by the user, a standardized data structure and graphical user interfaces to streamline the analysis and visualization of data. This approach guides experimental design, facilitating acquisition of the maximal information from single molecule experiments. SMART also provides a standardized format to allow dissemination of single molecule data and transparency in the analysis of reported data

Monoamines as Drug Targets in Chronic Pain: Focusing on Neuropathic Pain

Monoamines are involved in regulating the endogenous pain system and indeed, peripheral and central monoaminergic dysfunction has been demonstrated in certain types of pain, particularly in neuropathic pain. Accordingly, drugs that modulate the monaminergic system and that were originally designed to treat depression are now considered to be first line treatments for certain types of neuropathic pain (e.g., serotonin and noradrenaline (and also dopamine) reuptake inhibitors). The analgesia induced by these drugs seems to be mediated by inhibiting the reuptake of these monoamines, thereby reinforcing the descending inhibitory pain pathways. Hence, it is of particular interest to study the monoaminergic mechanisms involved in the development and maintenance of chronic pain. Other analgesic drugs may also be used in combination with monoamines to facilitate descending pain inhibition (e.g., gabapentinoids and opioids) and such combinations are often also used to alleviate certain types of chronic pain. By contrast, while NSAIDs are thought to influence the monoaminergic system, they just produce consistent analgesia in inflammatory pain. Thus, in this review we will provide preclinical and clinical evidence of the role of monoamines in the modulation of chronic pain, reviewing how this system is implicated in the analgesic mechanism of action of antidepressants, gabapentinoids, atypical opioids, NSAIDs and histaminergic drug

Multiband variability studies and novel broadband SED modeling of Mrk 501 in 2009

Aims. We present an extensive study of the BL Lac object Mrk 501 based on a data set collected during the multi-instrument campaign spanning from 2009 March 15 to 2009 August 1, which includes, among other instruments, MAGIC, VERITAS, Whipple 10 m, and Fermi-LAT to cover the gamma-ray range from 0.1 GeV to 20 TeV; RXTE and Swift to cover wavelengths from UV to hard X-rays; and GASP-WEBT, which provides coverage of radio and optical wavelengths. Optical polarization measurements were provided for a fraction of the campaign by the Steward and St. Petersburg observatories. We evaluate the variability of the source and interband correlations, the gamma-ray flaring activity occurring in May 2009, and interpret the results within two synchrotron self-Compton (SSC) scenarios.Methods. The multiband variability observed during the full campaign is addressed in terms of the fractional variability, and the possible correlations are studied by calculating the discrete correlation function for each pair of energy bands where the significance was evaluated with dedicated Monte Carlo simulations. The space of SSC model parameters is probed following a dedicated grid-scan strategy, allowing for a wide range of models to be tested and offering a study of the degeneracy of model-to-data agreement in the individual model parameters, hence providing a less biased interpretation than the "single-curve SSC model adjustment" typically reported in the literature.Results. We find an increase in the fractional variability with energy, while no significant interband correlations of flux changes are found on the basis of the acquired data set. The SSC model grid-scan shows that the flaring activity around May 22 cannot be modeled adequately with a one-zone SSC scenario (using an electron energy distribution with two breaks), while it can be suitably described within a two (independent) zone SSC scenario. Here, one zone is responsible for the quiescent emission from the averaged 4.5-month observing period, while the other one, which is spatially separated from the first, dominates the flaring emission occurring at X-rays and very-high-energy (> 100 GeV, VHE) gamma-rays. The flaring activity from May 1, which coincides with a rotation of the electric vector polarization angle (EVPA), cannot be satisfactorily reproduced by either a one-zone or a two-independent-zone SSC model, yet this is partially affected by the lack of strictly simultaneous observations and the presence of large flux changes on sub-hour timescales (detected at VHE gamma rays).Conclusions. The higher variability in the VHE emission and lack of correlation with the X-ray emission indicate that, at least during the 4.5-month observing campaign in 2009, the highest energy (and most variable) electrons that are responsible for the VHE gamma rays do not make a dominant contribution to the similar to 1 keV emission. Alternatively, there could be a very variable component contributing to the VHE gamma-ray emission in addition to that coming from the SSC scenario. The studies with our dedicated SSC grid-scan show that there is some degeneracy in both the one-zone and the two-zone SSC scenarios probed, with several combinations of model parameters yielding a similar model-to-data agreement, and some parameters better constrained than others. The observed gamma-ray flaring activity, with the EVPA rotation coincident with the first gamma-ray flare, resembles those reported previously for low frequency peaked blazars, hence suggesting that there are many similarities in the flaring mechanisms of blazars with different jet properties

Chemogenetic Silencing of Differentiating Cortical Neurons Impairs Dendritic and Axonal Growth

Gasterstadt I, Schroder M, Cronin L, et al. Chemogenetic Silencing of Differentiating Cortical Neurons Impairs Dendritic and Axonal Growth. Frontiers in Cellular Neuroscience . 2022;16: 941620.Electrical activity is considered a key driver for the neurochemical and morphological maturation of neurons and the formation of neuronal networks. Designer receptors exclusively activated by designer drugs (DREADDs) are tools for controlling neuronal activity at the single cell level by triggering specific G protein signaling. Our objective was to investigate if prolonged silencing of differentiating cortical neurons can influence dendritic and axonal maturation. The DREADD hM4Di couples to G(i/o) signaling and evokes hyperpolarization via GIRK channels. HM4Di was biolistically transfected into neurons in organotypic slice cultures of rat visual cortex, and activated by clozapine-N-oxide (CNO) dissolved in H2O; controls expressed hM4Di, but were mock-stimulated with H2O. Neurons were analyzed after treatment for two postnatal time periods, DIV 5-10 and 10-20. We found that CNO treatment delays the maturation of apical dendrites of L2/3 pyramidal cells. Further, the number of collaterals arising from the main axon was significantly lower, as was the number of bouton terminaux along pyramidal cell and basket cell axons. The dendritic maturation of L5/6 pyramidal cells and of multipolar interneurons (basket cells and bitufted cells) was not altered by CNO treatment. Returning CNO-treated cultures to CNO-free medium for 7 days was sufficient to recover dendritic and axonal complexity. Our findings add to the view that activity is a key driver in particular of postnatal L2/3 pyramidal cell maturation. Our results further suggest that inhibitory G protein signaling may represent a factor balancing the strong driving force of neurotrophic factors, electrical activity and calcium signaling

Indoleamine 2,3-Dioxygenase (IDO) Expression Is an Independent Prognostic Marker in Esophageal Adenocarcinoma

Background. Indoleamine 2,3-dioxygenase (IDO) is an interferon-inducible immune checkpoint expressed on tumor-infiltrating lymphocytes (TILs). IDO is known as a poor prognostic marker in esophageal squamous cell cancer, while a positive effect was shown for breast cancer. A comprehensive analysis of IDO expression in a well-defined cohort of esophageal adenocarcinoma (EAC) is missing.Methods. We analyzed 551 patients with EAC using single-protein and multiplex immunohistochemistry as well as mRNA in situ technology for the expression and distribution of IDO on subtypes of TILs (INF-gamma mRNA and CD4- and CD8-positive T lymphocytes).Results. IDO expression on TILs was seen in up to 59.6% of tumors, and expression on tumor cells was seen in 9.2%. We found a strong positive correlation of IDO-positive TILs, CD3-positive T lymphocytes, and INF-gamma mRNA-producing TILs in the tumor microenvironment of EACs showing significantly better overall survival (47.7 vs. 22.7 months,p<0.001) with emphasis on early tumor stages (pT1/2: 142.1 vs. 37.1 months,p<0.001). In multivariate analysis, IDO is identified as an independent prognostic marker.Conclusions. Our study emphasizes the importance of immunomodulation in EAC marking IDO as a potential biomarker. Beyond this, IDO might indicate a subgroup of EAC with an explicit survival benefit

Manufacture and characterization of graphene membranes with suspended silicon proof masses for MEMS and NEMS applications

Graphene's unparalleled strength, chemical stability, ultimate surface-to-volume ratio and excellent electronic properties make it an ideal candidate as a material for membranes in micro- and nanoelectromechanical systems (MEMS and NEMS). However, the integration of graphene into MEMS or NEMS devices and suspended structures such as proof masses on graphene membranes raises several technological challenges, including collapse and rupture of the graphene. We have developed a robust route for realizing membranes made of double-layer CVD graphene and suspending large silicon proof masses on membranes with high yields. We have demonstrated the manufacture of square graphene membranes with side lengths from 7 mu m to 110 mu m, and suspended proof masses consisting of solid silicon cubes that are from 5 mu mx5 mu mx16.4 mu m to 100 mu mx100 mu mx16.4 mu m in size. Our approach is compatible with wafer-scale MEMS and semiconductor manufacturing technologies, and the manufacturing yields of the graphene membranes with suspended proof masses were >90%, with >70% of the graphene membranes having >90% graphene area without visible defects. The measured resonance frequencies of the realized structures ranged from tens to hundreds of kHz, with quality factors ranging from 63 to 148. The graphene membranes with suspended proof masses were extremely robust, and were able to withstand indentation forces from an atomic force microscope (AFM) tip of up to 7000nN. The proposed approach for the reliable and large-scale manufacture of graphene membranes with suspended proof masses will enable the development and study of innovative NEMS devices with new functionalities and improved performances

Resistive graphene humidity sensors with rapid and direct electrical readout

We demonstrate humidity sensing using a change of the electrical resistance of single-layer chemical vapor deposited (CVD) graphene that is placed on top of a SiO2 layer on a Si wafer. To investigate the selectivity of the sensor towards the most common constituents in air, its signal response was characterized individually for water vapor (H2O), nitrogen (N-2), oxygen (O-2), and argon (Ar). In order to assess the humidity sensing effect for a range from 1% relative humidity (RH) to 96% RH, the devices were characterized both in a vacuum chamber and in a humidity chamber at atmospheric pressure. The measured response and recovery times of the graphene humidity sensors are on the order of several hundred milliseconds. Density functional theory simulations are employed to further investigate the sensitivity of the graphene devices towards water vapor. The interaction between the electrostatic dipole moment of the water and the impurity bands in the SiO(2)d substrate leads to electrostatic doping of the graphene layer. The proposed graphene sensor provides rapid response direct electrical readout and is compatible with back end of the line (BEOL) integration on top of CMOS-based integrated circuits