Differences in SpeB Protease Activity Among Group A Streptococci Associated With Superficial, Invasive, and Autoimmune Disease

The secreted cysteine proteinase SpeB is an important virulence factor of group A streptococci (GAS), whereby SpeB activity varies widely among strains. To establish the degree to which SpeB activity correlates with disease, GAS organisms were recovered from patients with pharyngitis, impetigo, invasive disease or acute rheumatic fever (ARF), and selected for analysis using rigorous sampling criteria; \u3e300 GAS isolates were tested for SpeB activity by casein digestion assays, and each GAS isolate was scored as a SpeB-producer or non-producer. Highly significant statistical differences (p \u3c 0.01) in SpeB production are observed between GAS recovered from patients with ARF (41.5% SpeB-non-producers) compared to pharyngitis (20.5%), invasive disease (16.7%), and impetigo (5.5%). SpeB activity differences between pharyngitis and impetigo isolates are also significant, whereas pharyngitis versus invasive isolates show no significant difference. The disproportionately greater number of SpeB-non-producers among ARF-associated isolates may indicate an altered transcriptional program for many rheumatogenic strains and/or a protective role for SpeB in GAS-triggered autoimmunity

Higher Structures in M-Theory

The key open problem of string theory remains its non-perturbative completion to M-theory. A decisive hint to its inner workings comes from numerous appearances of higher structures in the limits of M-theory that are already understood, such as higher degree flux fields and their dualities, or the higher algebraic structures governing closed string field theory. These are all controlled by the higher homotopy theory of derived categories, generalised cohomology theories, and $L_\infty$-algebras. This is the introductory chapter to the proceedings of the LMS/EPSRC Durham Symposium on Higher Structures in M-Theory. We first review higher structures as well as their motivation in string theory and beyond. Then we list the contributions in this volume, putting them into context.Comment: 22 pages, Introductory Article to Proceedings of LMS/EPSRC Durham Symposium Higher Structures in M-Theory, August 2018, references update

Detection and assignment of the glucose signal in 1H NMR difference spectra of the human brain

The difference between 1H NMR spectra obtained during eu- and hyperglycemia exhibited well-resolved glucose peaks between 3 and 4 ppm as demonstrated by comparison with solution spectra. Estimated increases were consistent with recent 13C NMR quantitations of intracerebral glucose. Difference spectra were measured in 36-ml volumes from the human brain every 3 min

Hyperpolarized Long-T1 Silicon Nanoparticles for Magnetic Resonance Imaging

Silicon nanoparticles are experimentally investigated as a potential hyperpolarized, targetable MRI imaging agent. Nuclear T_1 times at room temperature for a variety of Si nanoparticles are found to be remarkably long (10^2 to 10^4 s) - roughly consistent with predictions of a core-shell diffusion model - allowing them to be transported, administered and imaged on practical time scales without significant loss of polarization. We also report surface functionalization of Si nanoparticles, comparable to approaches used in other biologically targeted nanoparticle systems.Comment: supporting material here: http://marcuslab.harvard.edu/Aptekar_hyper1_sup.pd

Experience Gained From Launch and Early Orbit Support of the Rossi X-Ray Timing Explorer (RXTE)

this paper reports the results to date of early mission support provided by the personnel of the Goddard Space Flight Center Flight Dynamics Division (FDD) for the Rossi X-Ray Timing Explorer (RXTE) spacecraft. For this mission, the FDD supports onboard attitude determination and ephemeris propagation by supplying ground-based orbit and attitude solutions and calibration results. The first phase of that support was to provide launch window analyses. As the launch window was determined, acquisition attitudes were calculated and calibration slews were planned. postlaunch, these slews provided the basis for ground determined calibration. Ground determined calibration results are used to improve the accuracy of onboard solutions. The FDD is applying new calibration tools designed to facilitate use of the simultaneous, high-accuracy star observations from the two RXTE star trackers for ground attitude determination and calibration. An evaluation of the performance of these tools is presented. The FDD provides updates to the onboard star catalog based on preflight analysis and analysis of flight data. The in-flight results of the mission support in each area are summarized and compared with pre-mission expectations

Evidence-Based Professional Development of Science Teachers in Two Countries

The focus of this collaborative research project of King?s College London, and the Weizmann Institute, Israel. project is on investigating the ways in which teachers can demonstrate accomplished teaching in a specific domain of science and on the teacher learning that is generated through continuing professional development programs (CPD) that lead towards such practice. The interest lies in what processes and inputs are required to help secondary school science teachers develop expertise in a specific aspect of science teaching. `It focuses on the design of the CPD programmes and examines the importance of an evidence-based approach through portfolioconstruction in which professional dialogue pathes the way for teacher learning. The set of papers highlight the need to set professional challenge while tailoring CPD to teachers? needs to create the environment in which teachers can advance and transform their practice. The cross-culture perspective added to the richness of the development and enabled the researchers to examine which aspects were fundamental to the design by considering similarities and differences between the domains

Localized 13C NMR spectroscopy in the human brain of amino acid labeling from D-[1-13C]glucose

Cerebral metabolism of D[1-13C]glucose was studied with localized 13C NMR spectroscopy during intravenous infusion of enriched [1-13C]glucose in four healthy subjects. The use of three-dimensional localization resulted in the complete elimination of triacylglycerol resonance that originated in scalp and subcutaneous fat. The sensitivity and resolution were sufficient to allow 4 min of time-resolved observation of label incorporation into the C3 and C4 resonances of glutamate and C4 of glutamine, as well as C3 of aspartate with lower time resolution. [4-13C]Glutamate labeled rapidly reaching close to maximum labeling at 60 min. The label flow into [3- 13C]glutamate clearly lagged behind that of [4-13C]glutamate and peaked at t = 110-140 min. Multiplets due to homonuclear 13C-13C coupling between the C3 and C4 peaks of the glutamate molecule were observed in vivo. Isotopomer analysis of spectra acquired between 120 and 180 min yielded a 13C isotopic fraction at C4 glutamate of 27 ± 2% (n = 4), which was slightly less than one-half the enrichment of the C1 position of plasma glucose (63 ± 1%), p < 0.05. By comparison with an external standard the total amount of [4-13C]glutamate was directly quantified to be 2.4 ± 0.1 μmol/ml-brain. Together with the isotopomer data this gave a calculated brain glutamate concentration of 9.1 ± 0.7 μmol/ml, which agrees with previous estimates of total brain glutamate concentrations. The agreement suggests that essentially all of the brain glutamate is derived from glucose in healthy human brain