Neural responses when learning spatial and object sequencing tasks via imitation

Humans often learn new things via imitation. Here we draw on studies of imitation in children to characterise the brain system(s) involved in the imitation of different sequence types using functional magnetic resonance imaging. On each trial, healthy adult participants learned one of two rule types governing the sequencing of three pictures: a motor-spatial rule (in the spatial task) or an object-based rule (in the cognitive task). Sequences were learned via one of three demonstration types: a video of a hand selecting items in the sequence using a joystick (Hand condition), a computer display highlighting each item in order (Ghost condition), or a text-based demonstration of the sequence (Text condition). Participants then used a joystick to execute the learned sequence. Patterns of activation during demonstration observation suggest specialisation for object-based imitation in inferior frontal gyrus, specialisation for spatial sequences in anterior intraparietal sulcus (IPS), and a general preference for imitation in middle IPS. Adult behavioural performance contrasted with that of children in previous studies—indicating that they experienced more difficulty with the cognitive task—while neuroimaging results support the engagement of different neural regions when solving these tasks. Further study is needed on whether children’s differential performance is related to delayed IPS maturation

An evaluation of the performance of the Dynamiker® Fungus (1-3)-β-D-Glucan Assay to 2 assist in the diagnosis of Pneumocystis pneumonia

Invasive fungal disease (IFD) can be caused by a range of pathogens. Conventional diagnosis has the capacity to detect most causes of IFD, but poor performance limits impact. The introduction of non-culture diagnostics, including the detection of (1-3)-β-D-Glucan (BDG), has shown promising performance for the detection of IFD in variety of clinical settings. Recently, the Dynamiker® Fungus (1-3)-β-D-Glucan assay (D-BDG) was released as an IFD diagnostic test. This article describes an evaluation of the D-BDG assay for the diagnosis of invasive aspergillosis (IA), invasive candidiasis (IC) and Pneumocystis pneumonia (PCP) across several high-risk patient cohorts and provides comparative data with the Associates of Cape Cod Fungitell® and BioRad Platelia™ Aspergillus Ag (GM) assays. There were 163 serum samples from 121 patients tested, from 21 probable IA cases, 28 proven IC cases, six probable PCP cases, one probable IFD case, 14 possible IFD cases and 64 control patients. For proven/probable IFD the mean BDG concentration was 209pg/ml, significantly greater than the control population (73pg/ml; P: <.0001). The sensitivity, specificity, and diagnostic odds ratio for proven/probable IFD was 81.4%, 78.1%, and 15.5, respectively. Significant BDG false positivity (9/13) was associated post abdominal surgery. D-BDG showed fair and good agreement with the Fungitell®, and GM assays, respectively. In conclusion, the D-BDG provides a useful adjunct test to aid the diagnosis of IFD, with technical flexibility that will assist laboratories processing low sample numbers. Further, large scale, prospective evaluation is required to confirm the clinical validity and determine clinical utility

Regional astrocyte IFN signaling restricts pathogenesis during neurotropic viral infection

Type I IFNs promote cellular responses to viruses, and IFN receptor (IFNAR) signaling regulates the responses of endothelial cells of the blood-brain barrier (BBB) during neurotropic viral infection. However, the role of astrocytes in innate immune responses of the BBB during viral infection of the CNS remains to be fully elucidated. Here, we have demonstrated that type I IFNAR signaling in astrocytes regulates BBB permeability and protects the cerebellum from infection and immunopathology. Mice with astrocyte-specific loss of IFNAR signaling showed decreased survival after West Nile virus infection. Accelerated mortality was not due to expanded viral tropism or increased replication. Rather, viral entry increased specifically in the hindbrain of IFNAR-deficient mice, suggesting that IFNAR signaling critically regulates BBB permeability in this brain region. Pattern recognition receptors and IFN-stimulated genes had higher basal and IFN-induced expression in human and mouse cerebellar astrocytes than did cerebral cortical astrocytes, suggesting that IFNAR signaling has brain region–specific roles in CNS immune responses. Taken together, our data identify cerebellar astrocytes as key responders to viral infection and highlight the existence of distinct innate immune programs in astrocytes from evolutionarily disparate regions of the CNS

Probing Unexpected Reactivity in Radiometal Chemistry: Indium-111-Mediated Hydrolysis of Hybrid Cyclen-Hydroxypyridinone Ligands

Chelators based on hydroxypyridinones have utility in incorporating radioactive metal ions into diagnostic and therapeutic agents used in nuclear medicine. Over the course of our hydroxypyridinone studies, we have prepared two novel chelators, consisting of a cyclen (1,4,7,10-tetraazacyclododecane) ring bearing two pendant hydroxypyridinone groups, appended via methylene acetamide motifs at either the 1,4-positions (L1) or 1,7-positions (L2) of the cyclen ring. In radiolabeling reactions of L1 or L2 with the γ-emitting radioisotope, [111In]In3+, we have observed radiometal-mediated hydrolysis of a single amide group of either L1 or L2. The reaction of either [111In]In3+ or [natIn]In3+ with either L1 or L2, in aqueous alkaline solutions at 80 °C, initially results in formation of [In(L1)]+ or [In(L2)]+, respectively. Over time, each of these species undergoes In3+-mediated hydrolysis of a single amide group to yield species in which In3+ remains coordinated to the resultant chelator, which consists of a cyclen ring bearing a single hydroxypyridinone group and a single carboxylate group. The reactivity toward hydrolysis is higher for the L1 complex compared to that for the L2 complex. Density functional theory calculations corroborate these experimental findings and importantly indicate that the activation energy required for the hydrolysis of L1 is significantly lower than that required for L2. This is the first reported example of a chelator undergoing radiometal-mediated hydrolysis to form a radiometalated complex. It is possible that metal-mediated amide bond cleavage is a source of instability in other radiotracers, particularly those in which radiometal complexation occurs in aqueous, basic solutions at high temperatures. This study highlights the importance of appropriate characterization of radiolabeled products

Demonstrating high-precision photometry with a CubeSat: ASTERIA observations of 55 Cancri e

ASTERIA (Arcsecond Space Telescope Enabling Research In Astrophysics) is a 6U CubeSat space telescope (10 cm x 20 cm x 30 cm, 10 kg). ASTERIA's primary mission objective was demonstrating two key technologies for reducing systematic noise in photometric observations: high-precision pointing control and high-stabilty thermal control. ASTERIA demonstrated 0.5 arcsecond RMS pointing stability and $\pm$10 milliKelvin thermal control of its camera payload during its primary mission, a significant improvement in pointing and thermal performance compared to other spacecraft in ASTERIA's size and mass class. ASTERIA launched in August 2017 and deployed from the International Space Station (ISS) November 2017. During the prime mission (November 2017 -- February 2018) and the first extended mission that followed (March 2018 - May 2018), ASTERIA conducted opportunistic science observations which included collection of photometric data on 55 Cancri, a nearby exoplanetary system with a super-Earth transiting planet. The 55 Cancri data were reduced using a custom pipeline to correct CMOS detector column-dependent gain variations. A Markov Chain Monte Carlo (MCMC) approach was used to simultaneously detrend the photometry using a simple baseline model and fit a transit model. ASTERIA made a marginal detection of the known transiting exoplanet 55 Cancri e ($\sim2$~\Rearth), measuring a transit depth of $374\pm170$ ppm. This is the first detection of an exoplanet transit by a CubeSat. The successful detection of super-Earth 55 Cancri e demonstrates that small, inexpensive spacecraft can deliver high-precision photometric measurements.Comment: 23 pages, 9 figures. Accepted in A

Towards the prediction of antimicrobial efficacy for hydrogen bonded, self-associating amphiphiles

Herein, we report 50 structurally related supramolecular self-associating amphiphilic (SSA) salts and related compounds. These SSAs are shown to act as antimicrobial agents, active against model Gram-positive (Methicillin-Resistant Staphylococcus aureus) and/or Gram-negative (Escherichia coli) bacteria of clinical interest. Through a combination of solution state, gas phase, solid state and in silico measurements we determine 14 different physicochemical parameters for each of these 50 structurally related compounds. These parameter sets are then used to identify molecular structure – physicochemical property – antimicrobial activity relationships for our model Gram-negative and Gram-positive bacteria, while simultaneously providing insight towards the elucidation of SSA mode of antimicrobial action

The SDSS-III Baryon Oscillation Spectroscopic Survey: Quasar Target Selection for Data Release Nine

The SDSS-III Baryon Oscillation Spectroscopic Survey (BOSS), a five-year spectroscopic survey of 10,000 deg^2, achieved first light in late 2009. One of the key goals of BOSS is to measure the signature of baryon acoustic oscillations in the distribution of Ly-alpha absorption from the spectra of a sample of ~150,000 z>2.2 quasars. Along with measuring the angular diameter distance at z\approx2.5, BOSS will provide the first direct measurement of the expansion rate of the Universe at z > 2. One of the biggest challenges in achieving this goal is an efficient target selection algorithm for quasars over 2.2 < z < 3.5, where their colors overlap those of stars. During the first year of the BOSS survey, quasar target selection methods were developed and tested to meet the requirement of delivering at least 15 quasars deg^-2 in this redshift range, out of 40 targets deg^-2. To achieve these surface densities, the magnitude limit of the quasar targets was set at g <= 22.0 or r<=21.85. While detection of the BAO signature in the Ly-alpha absorption in quasar spectra does not require a uniform target selection, many other astrophysical studies do. We therefore defined a uniformly-selected subsample of 20 targets deg^-2, for which the selection efficiency is just over 50%. This "CORE" subsample will be fixed for Years Two through Five of the survey. In this paper we describe the evolution and implementation of the BOSS quasar target selection algorithms during the first two years of BOSS operations. We analyze the spectra obtained during the first year. 11,263 new z>2.2 quasars were spectroscopically confirmed by BOSS. Our current algorithms select an average of 15 z > 2.2 quasars deg^-2 from 40 targets deg^-2 using single-epoch SDSS imaging. Multi-epoch optical data and data at other wavelengths can further improve the efficiency and completeness of BOSS quasar target selection. [Abridged]Comment: 33 pages, 26 figures, 12 tables and a whole bunch of quasars. Submitted to Ap

Imperfect Tests, Pervasive Pathogens, and Variable Demographic Performance: Thoughts on Managing Bighorn Sheep Respiratory Disease

Respiratory disease (pneumonia) has been a persistent challenge for bighorn sheep (Ovis canadensis) conservation and its cause has been attributed to numerous bacteria including Mycoplasma ovipneumoniae and several Pasteurellaceae family species. This study sought to investigate efficacy of diagnostic protocols in detecting Pasteurellaceae and Mycoplasma ovipneumoniae, generate sampling recommendations for different protocols, assess the distribution of these disease agents among 17 bighorn sheep populations in Montana and Wyoming, and evaluate what associations existed between detection of these agents and demographic performance of bighorn sheep populations. Analysis of replicate samples from individual bighorn sheep revealed that detection probability for regularlyused diagnostic protocols was generally low (&lt;50%) for Pasteurellaceae and was high (&gt;70%) for Mycoplasma ovipneumoniae, suggesting that routine pathogen sampling likely mischaracterizes respiratory pathogen communities. Power analyses found that most pathogen species could be detected with 80% confidence at the population-level by conducting regularly-used protocols multiple times per animal. Each pathogen species was detected in over half of the study populations, but after accounting for detection probability there was low confidence in negative test results for populations where Pasteurellaceae species were not detected. Seventy-six percent of study populations hosted both Mycoplasma ovipneumoniae and Pasteurellaceae pathogens, yet a number of these populations were estimated to have positive population growth rates and recruitment rates greater than 30%. Overall, the results of this work suggest that bighorn sheep respiratory disease may be mitigated by manipulating population characteristics and respiratory disease epizootics could be caused by pathogens already resident in bighorn sheep population