Interferon-γ release assays (IGRA) with Resuscitation promoting factor (Rpf) proteins enhanced tuberculosis (TB) screening and diagnosis in adults but have not been evaluated in children. Children ...often develop paucibacillary TB and their immune response differs from that of adults, which together affect TB disease diagnostics and immunodiagnostics. We assessed the ability of Rpf to identify infection among household TB-exposed children in The Gambia and investigated their ability to discriminate Mycobacterium tuberculosis complex (MTBC) infection from active TB disease in children.
Detailed clinical investigations were done on 93 household TB-exposed Gambian children and a tuberculin skin test (TST) was administered to asymptomatic children. Venous blood was collected for overnight stimulation with ESAT-6/CFP-10-fusion protein (EC), purified protein derivative and RpfA, B, C, D and E. Interferon gamma (IFN-γ) production was measured by ELISA in supernatants and corrected for the background level. Infection status was defined by IGRA with EC and TB disease by mycobacterial confirmation and/or clinical diagnosis. We compared IFN-γ levels between infected and uninfected children and between infected and TB diseased children using a binomial logistic regression model while correcting for age and sex. A Receiver Operating Characteristics analysis was done to find the best cut-off for IFN-γ level and calculate sensitivity and specificity.
Interferon gamma production was significantly higher in infected (IGRA+, n = 45) than in uninfected (IGRA-, n = 20) children after stimulation with RpfA, B, C, and D (P = 0.03; 0.007; 0.03 and 0.003, respectively). Using RpfB and D-specific IFN-γ cut-offs (33.9 pg/mL and 67.0 pg/mL), infection was classified with a sensitivity-specificity combination of 73-92% and 77-72% respectively, which was similar to and better than 65-75% for TST. Moreover, IFN-γ production was higher in infected than in TB diseased children (n = 28, 5 bacteriologically confirmed, 23 clinically diagnosed), following RpfB and D stimulation (P = 0.02 and 0.03, respectively).
RpfB and RpfD show promising results for childhood MTBC infection screening, and both performed similar to and better than the TST in our study population. Additionally, both antigens appear to discriminate between infection and disease in children and thus warrant further investigation as screening and diagnostic antigens for childhood TB.
Huntington's disease (HD) is a fatal and progressive condition with severe debilitating motor defects and muscle weakness. Although classically recognized as a neurodegenerative disorder, there is ...increasing evidence of cell autonomous toxicity in skeletal muscle. We recently demonstrated that skeletal muscle fibers from the R6/2 model mouse of HD have a decrease in specific membrane capacitance, suggesting a loss of transverse tubule (t-tubule) membrane in R6/2 muscle. A previous report also indicated that Cav1.1 current was reduced in R6/2 skeletal muscle, suggesting defects in excitation-contraction (EC) coupling. Thus, we hypothesized that a loss and/or disruption of the skeletal muscle t-tubule system contributes to changes in EC coupling in R6/2 skeletal muscle. We used live-cell imaging with multiphoton confocal microscopy and transmission electron microscopy to assess the t-tubule architecture in late-stage R6/2 muscle and found no significant differences in the t-tubule system density, regularity, or integrity. However, electron microscopy images revealed that the cross-sectional area of t-tubules at the triad were 25% smaller in R6/2 compared with age-matched control skeletal muscle. Computer simulation revealed that the resulting decrease in the R6/2 t-tubule luminal conductance contributed to, but did not fully explain, the reduced R6/2 membrane capacitance. Analyses of bridging integrator-1 (Bin1), which plays a primary role in t-tubule formation, revealed decreased Bin1 protein levels and aberrant splicing of Bin1 mRNA in R6/2 muscle. Additionally, the distance between the t-tubule and sarcoplasmic reticulum was wider in R6/2 compared with control muscle, which was associated with a decrease in junctophilin 1 and 2 mRNA levels. Altogether, these findings can help explain dysregulated EC coupling and motor impairment in Huntington's disease.
Utilizing an application specific integrated circuit (ASIC) with 140 different shift chains, and a wide variety of test modes, a design of experiments (DOE) approach was used to characterize a ...commercial 90 nm CMOS technology for its sensitivity to single event effects (SEE). The variables characterized included: well structure on the wafer, density of well contacts, logic data pattern, angle of indicence, flip-flop redundancy, variation in sensitive node spacing, and the effect of transients as a function of combinatorial logic type. Analysis of the cross section contribution from the clock, flip-flop and SET target circuitry showed that any hardening technique used in a production integrated circuit may be limited in its effectiveness due to other circuits and logic in the integrated circuit.
We have developed conceptual designs of two petawatt-class pulsed-power accelerators: Z 300 and Z 800. The designs are based on an accelerator architecture that is founded on two concepts: ...single-stage electrical-pulse compression and impedance matching Phys. Rev. ST Accel. Beams 10, 030401 (2007). The prime power source of each machine consists of 90 linear-transformer-driver (LTD) modules. Each module comprises LTD cavities connected electrically in series, each of which is powered by 5-GW LTD bricks connected electrically in parallel. (A brick comprises a single switch and two capacitors in series.) Six water-insulated radial-transmission-line impedance transformers transport the power generated by the modules to a six-level vacuum-insulator stack. The stack serves as the accelerator’s water-vacuum interface. The stack is connected to six conical outer magnetically insulated vacuum transmission lines (MITLs), which are joined in parallel at a 10-cm radius by a triple-post-hole vacuum convolute. The convolute sums the electrical currents at the outputs of the six outer MITLs, and delivers the combined current to a single short inner MITL. The inner MITL transmits the combined current to the accelerator’s physics-package load. Z 300 is 35 m in diameter and stores 48 MJ of electrical energy in its LTD capacitors. The accelerator generates 320 TW of electrical power at the output of the LTD system, and delivers 48 MA in 154 ns to a magnetized-liner inertial-fusion (MagLIF) target Phys. Plasmas 17, 056303 (2010). The peak electrical power at the MagLIF target is 870 TW, which is the highest power throughout the accelerator. Power amplification is accomplished by the centrally located vacuum section, which serves as an intermediate inductive-energy-storage device. The principal goal of Z 300 is to achieve thermonuclear ignition; i.e., a fusion yield that exceeds the energy transmitted by the accelerator to the liner. 2D magnetohydrodynamic (MHD) simulations suggest Z 300 will deliver 4.3 MJ to the liner, and achieve a yield on the order of 18 MJ. Z 800 is 52 m in diameter and stores 130 MJ. This accelerator generates 890 TW at the output of its LTD system, and delivers 65 MA in 113 ns to a MagLIF target. The peak electrical power at the MagLIF liner is 2500 TW. The principal goal of Z 800 is to achieve high-yield thermonuclear fusion; i.e., a yield that exceeds the energy initially stored by the accelerator’s capacitors. 2D MHD simulations suggest Z 800 will deliver 8.0 MJ to the liner, and achieve a yield on the order of 440 MJ. Z 300 and Z 800, or variations of these accelerators, will allow the international high-energy-density-physics community to conduct advanced inertial-confinement-fusion, radiation-physics, material-physics, and laboratory-astrophysics experiments over heretofore-inaccessible parameter regimes.
Neon photoionization experiments driven by Z-pinch radiation Bailey, J.E.; Cohen, D.; Chandler, G.A. ...
Journal of Quantitative Spectroscopy & Radiative Transfer/Journal of quantitative spectroscopy & radiative transfer,
10/2001, Letnik:
71, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Present-day Z-pinch experiments generate
∼2×10
21
erg/
s
peak power,
∼6
ns
full-width at half-maximum X-ray bursts that provide new possibilities to study radiation-heated matter. This source is ...being used to investigate the production of plasmas in which photoionization dominates collisional ionization. Spectroscopic measurements of such plasmas can serve to benchmark atomic physics models of the photoionized plasmas. Beyond intrinsic interest in the atomic physics, these models will be applied to the interpretation of data from the new generation of satellite X-ray spectrographs that will promote the understanding of accretion-powered objects such as X-ray binaries and active galactic nuclei. Moreover, this information is needed for X-ray laser research. Our experiments use a 1-cm-scale neon gas cell to expose
10
18
atoms/
cm
3
to an X-ray flux of
∼5×10
18
erg/
cm
2/
s
. Thin mylar (
1.5
μm
) windows confine the gas and allow the radiation to flow into the cell. The ionization is monitored with absorption spectra recorded with crystal spectrometers, using the pinch as a backlight source. In initial experiments we acquired an absorption spectrum from Li- and He-like Ne, confirming the ability to produce a highly ionized neon plasma.
X-pinches are a source for studying radiative properties of plasmas of very small sizes, high densities and temperatures applicable to high-energy density plasmas such as dense Z-pinches. Recently, ...spatially resolved and spatially integrated X-ray spectral data have been accumulated during Mo and Cu X-pinch experiments on the Zebra generator. During these experiments configurations, other then the 2-wire X-pinches, such as 4-wire X-pinches and asymmetric X-pinches have been spectroscopically studied and computationally analyzed. We present here modeling of the K-shell and L-shell radiation from Cu X-pinches with two and four wires and the comparison with experimental spectra. L-shell radiation from symmetric and asymmetric Mo X-pinches with two wires and X-pinches with four wires have also been analyzed and compared. Dependence of the plasma spatial structure, temperature, and density on wire materials and load configurations are discussed.
Early Lyme borreliosis sera with significant titers of anti-outer surface protein C (OspC) borreliacidal antibodies were identified. Human anti-OspC borreliacidal antibodies could be either IgM or ...IgG. Significant concentrations of borreliacidal activity were detected after vaccination of mice with OspC. Detection of anti-OspC borreliacidal activity was dependent on surface expression of OspC by Borrelia burgdorferi isolate 50772. The ability of OspC to induce borreliacidal antibodies in vivo and after vaccination offers another possible explanation for the ability of vaccination with OspC to protect against infection with B. burgdorferi. Furthermore, detection of anti-OspC borreliacidal antibodies, especially IgM antibodies, in early Lyme borreliosis sera provides additional evidence that borreliacidal antibody detection may be useful for the serodiagnosis of early Lyme borreliosis.
Experimental results of studies of the 1
MA X-pinch X-ray source in a wide spectral region are overviewed. Implosion dynamics and radiative properties of various X-pinches were studied by spatially ...and time-resolved X-ray and optical diagnostics. In particular, dynamics of spatial and temporal developments of the structure of X-ray emitting regions (1–5
keV), temporal characteristics of X-ray pulses, X-ray radiation outputs and electron beam characteristics from symmetric and asymmetric Mo, Cu, and combined asymmetric Mo/W X-pinches with two or four wires were studied. The mechanisms of X-ray multiburst generation are discussed. The future applications of the high-current X-pinch as a 5–10
kJ sub-keV–10
keV radiation driver are considered.
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