Plasma host protein biomarkers correlating with increasing Mycobacterium tuberculosis infection activity prior to tuberculosis diagnosis in people living with HIV

BACKGROUND: Biomarkers correlating with Mycobacterium tuberculosis infection activity/burden in asymptomatic individuals are urgently needed to identify and treat those at highest risk for developing active tuberculosis (TB). Our main objective was to identify plasma host protein biomarkers that change over time prior to developing TB in people living with HIV (PLHIV). METHODS: Using multiplex MRM-MS, we investigated host protein expressions from 2 years before until time of TB diagnosis in longitudinally collected (every 3-6 months) and stored plasma from PLHIV with incident TB, identified within a South African (SA) and US cohort. We performed temporal trend and discriminant analyses for proteins, and, to assure clinical relevance, we further compared protein levels at TB diagnosis to interferon-gamma release assay (IGRA; SA) or tuberculin-skin test (TST; US) positive and negative cohort subjects without TB. SA and US exploratory data were analyzed separately. FINDINGS: We identified 15 proteins in the SA (n=30) and 10 in the US (n=24) incident TB subjects which both changed from 2 years prior until time of TB diagnosis after controlling for 10% false discovery rate, and were significantly different at time of TB diagnosis compared to non-TB subjects (p<0.01). Five proteins, CD14, A2GL, NID1, SCTM1, and A1AG1, overlapped between both cohorts. Furthermore, after cross-validation, panels of 5 – 12 proteins were able to predict TB up to two years before diagnosis. INTERPRETATION: Host proteins can be biomarkers for increasing Mycobacterium tuberculosis infection activity/burden, incipient TB, and predict TB development in PLHIV. FUNDING: NIH/NIAID AI117927, AI146329, and AI127173 to JMA

Studies of viomycin, an anti-tuberculosis antibiotic: Copper(II) coordination, DNA degradation and the impact on delta ribozyme cleavage activity

Viomycin is a basic peptide antibiotic, which is among the most effective agents against multidrug-resistant tuberculosis. In this paper we provide the characteristics of its acid base properties, coordination preferences towards the Cu(II) ions, as well as the reactivity of the resulting complexes against plasmid DNA and HDV ribozyme. Careful coordination studies throughout the wide pH range allow for the characterisation of all the Cu(II)-viomycin complex species. The assignment of proton chemical shifts was achieved by NMR experiments, while the DTF level of theory was applied to support molecular structures of the studied complexes. The experiments with the plasmid DNA reveal that at the physiological levels of hydrogen peroxide the Cu(II)-viomycin complex is more aggressive against DNA than uncomplexed metal ions. Moreover, the degradation of DNA by viomycin can be carried out without the presence of transition metal ions. In the studies of antigenomic delta ribozyme catalytic activity, viomycin and its complex are shown to modulate the ribozyme functioning. The molecular modelling approach allows the indication of two different locations of viomycin binding sites to the ribozyme

Classification of Light-Induced Desorption of Alkali Atoms in Glass Cells Used in Atomic Physics Experiments

We attempt to provide physical interpretations of light-induced desorption phenomena that have recently been observed for alkali atoms on glass surfaces of alkali vapor cells used in atomic physics experiments. We find that the observed desorption phenomena are closely related to recent studies in surface science, and can probably be understood in the context of these results. If classified in terms of the photon-energy dependence, the coverage and the bonding state of the alkali adsorbates, the phenomena fall into two categories: It appears very likely that the neutralization of isolated ionic adsorbates by photo-excited electron transfer from the substrate is the origin of the desorption induced by ultraviolet light in ultrahigh vacuum cells. The desorption observed in low temperature cells, on the other hand, which is resonantly dependent on photon energy in the visible light range, is quite similar to light-induced desorption stimulated by localized electronic excitation on metallic aggregates. More detailed studies of light-induced desorption events from surfaces well characterized with respect to alkali coverage-dependent ionicity and aggregate morphology appear highly desirable for the development of more efficient alkali atom sources suitable to improve a variety of atomic physics experiments.Comment: 6 pages, 1 figure; minor corrections made, published in e-Journal of Surface Science and Nanotechnology at http://www.jstage.jst.go.jp/article/ejssnt/4/0/4_63/_articl

GRB 080319B: A Naked-Eye Stellar Blast from the Distant Universe

Long duration gamma-ray bursts (GRBs) release copious amounts of energy across the entire electromagnetic spectrum, and so provide a window into the process of black hole formation from the collapse of a massive star. Over the last forty years, our understanding of the GRB phenomenon has progressed dramatically; nevertheless, fortuitous circumstances occasionally arise that provide access to a regime not yet probed. GRB 080319B presented such an opportunity, with extraordinarily bright prompt optical emission that peaked at a visual magnitude of 5.3, making it briefly visible with the naked eye. It was captured in exquisite detail by wide-field telescopes, imaging the burst location from before the time of the explosion. The combination of these unique optical data with simultaneous gamma-ray observations provides powerful diagnostics of the detailed physics of this explosion within seconds of its formation. Here we show that the prompt optical and gamma-ray emissions from this event likely arise from different spectral components within the same physical region located at a large distance from the source, implying an extremely relativistic outflow. The chromatic behaviour of the broadband afterglow is consistent with viewing the GRB down the very narrow inner core of a two-component jet that is expanding into a wind-like environment consistent with the massive star origin of long GRBs. These circumstances can explain the extreme properties of this GRB.Comment: 43 pages, 18 figures, 3 tables, submitted to Nature May 11, 200

Prospective Monitoring Reveals Dynamic Levels of T Cell Immunity to Mycobacterium Tuberculosis in HIV Infected Individuals

Monitoring of latent Mycobacterium tuberculosis infection may prevent disease. We tested an ESAT-6 and CFP-10-specific IFN-γ Elispot assay (RD1-Elispot) on 163 HIV-infected individuals living in a TB-endemic setting. An RD1-Elispot was performed every 3 months for a period of 3–21 months. 62% of RD1-Elispot negative individuals were positive by cultured Elispot. Fluctuations in T cell response were observed with rates of change ranging from −150 to +153 spot-forming cells (SFC)/200,000 PBMC in a 3-month period. To validate these responses we used an RD1-specific real time quantitative PCR assay for monokine-induced by IFN-γ (MIG) and IFN-γ inducible protein-10 (IP10) (MIG: r = 0.6527, p = 0.0114; IP-10: r = 0.6967, p = 0.0056; IP-10+MIG: r = 0.7055, p = 0.0048). During follow-up 30 individuals were placed on ARVs and 4 progressed to active TB. Fluctuations in SFC did not correlate with CD4 count, viral load, treatment initiation, or progression to active TB. The RD1-Elispot appears to have limited value in this setting

Investigating distribution of practice effects for the learning of foreign language verb morphology in the young learner classroom

Within limited-input language classrooms, understanding the effect of distribution of practice (spacing between practice) on learning is critical, yet evidence is conflicting and of limited relevance for young learners. For second language (L2) grammar learning, some studies reveal advantages for spacing of 7 days or more (Bird, 2010; Rogers, 2015), but others for shorter spacing (Suzuki, 2017). Further, little is known about the role of cognitive individual differences (e.g., language analytic ability) in mediating practice distribution effects for L2 grammatical knowledge development and retention (Suzuki & DeKeyser, 2017). To address this gap, this classroom-based study investigated whether distribution of practice and language analytic ability moderated the effectiveness of explicit, input-based grammar instruction for young first language (L1) English learners of French (aged 8 to 11). The study revealed minimal differences between longer (7-day) versus shorter (3.5-day) spacing of practice for learning an L2 French verb inflection subsystem, at either post- or delayed post-test. Minimal group-level gains and substantial within-group variation in performance at post-tests was observed. Accuracy of practice during training and language analytic ability were significantly associated with post-test performance under both practice schedules. These findings indicated that within an ecologically valid classroom context, differences in distribution of practice had limited impact on learner performance on our tests; rather, individual learner differences were more critical in moderating learning. This highlights the importance of considering individual learner differences in the development of resources and the potential of digital tools for dynamically adapting instruction to suit individuals

Challenges in QCD matter physics - The Compressed Baryonic Matter experiment at FAIR

Substantial experimental and theoretical efforts worldwide are devoted to explore the phase diagram of strongly interacting matter. At LHC and top RHIC energies, QCD matter is studied at very high temperatures and nearly vanishing net-baryon densities. There is evidence that a Quark-Gluon-Plasma (QGP) was created at experiments at RHIC and LHC. The transition from the QGP back to the hadron gas is found to be a smooth cross over. For larger net-baryon densities and lower temperatures, it is expected that the QCD phase diagram exhibits a rich structure, such as a first-order phase transition between hadronic and partonic matter which terminates in a critical point, or exotic phases like quarkyonic matter. The discovery of these landmarks would be a breakthrough in our understanding of the strong interaction and is therefore in the focus of various high-energy heavy-ion research programs. The Compressed Baryonic Matter (CBM) experiment at FAIR will play a unique role in the exploration of the QCD phase diagram in the region of high net-baryon densities, because it is designed to run at unprecedented interaction rates. High-rate operation is the key prerequisite for high-precision measurements of multi-differential observables and of rare diagnostic probes which are sensitive to the dense phase of the nuclear fireball. The goal of the CBM experiment at SIS100 (sqrt(s_NN) = 2.7 - 4.9 GeV) is to discover fundamental properties of QCD matter: the phase structure at large baryon-chemical potentials (mu_B > 500 MeV), effects of chiral symmetry, and the equation-of-state at high density as it is expected to occur in the core of neutron stars. In this article, we review the motivation for and the physics programme of CBM, including activities before the start of data taking in 2022, in the context of the worldwide efforts to explore high-density QCD matter.Comment: 15 pages, 11 figures. Published in European Physical Journal

Control system for ion Penning traps at the AEgIS experiment at CERN

The AEgIS experiment located at the Antiproton Decelerator at CERN aims to measure the gravitational fall of a cold antihydrogen pulsed beam. The precise observation of the antiatoms in the Earth gravitational field requires a controlled production and manipulation of antihydrogen. The neutral antimatter is obtained via a charge exchange reaction between a cold plasma of antiprotons from ELENA decelerator and a pulse of Rydberg positronium atoms. The current custom electronics designed to operate the 5 and 1 T Penning traps are going to be replaced by a control system based on the ARTIQ & Sinara open hardware and software ecosystem. This solution is present in many atomic, molecular and optical physics experiments and devices such as quantum computers. We report the status of the implementation as well as the main features of the new control system

High-resolution MCP-TimePix3 imaging/timing detector for antimatter physics

We present a hybrid imaging/timing detector for force sensitive inertial measurements designed for measurements on positronium, the metastable bound state of an electron and a positron, but also suitable for applications involving other low intensity, low energy beams of neutral (antimatter)-atoms, such as antihydrogen. The performance of the prototype detector was evaluated with a tunable low energy positron beam, resulting in a spatial resolution of approximate t