Immunological Characterization and Neutralizing Ability of Monoclonal Antibodies Directed Against Botulinum Neurotoxin Type H.

BackgroundOnly Clostridium botulinum strain IBCA10-7060 produces the recently described novel botulinum neurotoxin type H (BoNT/H). BoNT/H (N-terminal two-thirds most homologous to BoNT/F and C-terminal one-third most homologous to BoNT/A) requires antitoxin to toxin ratios ≥1190:1 for neutralization by existing antitoxins. Hence, more potent and safer antitoxins against BoNT/H are needed.MethodsWe therefore evaluated our existing monoclonal antibodies (mAbs) to BoNT/A and BoNT/F for BoNT/H binding, created yeast-displayed mutants to select for higher-affinity-binding mAbs by using flow cytometry, and evaluated the mAbs' ability to neutralize BoNT/H in the standard mouse bioassay.ResultsAnti-BoNT/A HCC-binding mAbs RAZ1 and CR2 bound BoNT/H with high affinity. However, only 1 of 6 BoNT/F mAbs (4E17.2A) bound BoNT/H but with an affinity >800-fold lower (equilibrium dissociation binding constant [KD] = 7.56 × 10(-8)M) than its BoNT/F affinity (KD= 9.1 × 10(-11)M), indicating that the N-terminal two-thirds of BoNT/H is immunologically unique. The affinity of 4E17.2A for BoNT/H was increased >500-fold to KD= 1.48 × 10(-10)M (mAb 4E17.2D). A combination of mAbs RAZ1, CR2, and 4E17.2D completely protected mice challenged with 280 mouse median lethal doses of BoNT/H at a mAb dose as low as 5 µg of total antibody.ConclusionsThis 3-mAb combination potently neutralized BoNT/H and represents a potential human antitoxin that could be developed for the prevention and treatment of type H botulism

Efficient table-top dual-wavelength beamline for ultrafast transient absorption spectroscopy in the soft X-ray region.

We present a table-top beamline providing a soft X-ray supercontinuum extending up to 370 eV from high-order harmonic generation with sub-13 fs 1300 nm driving pulses and simultaneous production of sub-5 fs pulses centered at 800 nm. Optimization of high harmonic generation in a long and dense gas medium yields a photon flux of  ~ 1.4 × 106 photons/s/1% bandwidth at 300 eV. The temporal resolution of X-ray transient absorption experiments with this beamline is measured to be 11 fs for 800 nm excitation. This dual-wavelength approach, combined with high flux and high spectral and temporal resolution soft X-ray absorption spectroscopy, is a new route to the study of ultrafast electronic dynamics in carbon-containing molecules and materials at the carbon K-edge

New variable separation approach: application to nonlinear diffusion equations

The concept of the derivative-dependent functional separable solution, as a generalization to the functional separable solution, is proposed. As an application, it is used to discuss the generalized nonlinear diffusion equations based on the generalized conditional symmetry approach. As a consequence, a complete list of canonical forms for such equations which admit the derivative-dependent functional separable solutions is obtained and some exact solutions to the resulting equations are described.Comment: 19 pages, 2 fig

Insights into Hydration Dynamics and Cooperative Interactions in Glycerol-Water Mixtures by Terahertz Dielectric Spectroscopy.

We report relaxation dynamics of glycerol-water mixtures as probed by megahertz-to-terahertz dielectric spectroscopy in a frequency range from 50 MHz to 0.5 THz at room temperature. The dielectric relaxation spectra reveal several polarization processes at the molecular level with different time constants and dielectric strengths, providing an understanding of the hydrogen-bonding network in glycerol-water mixtures. We have determined the structure of hydration shells around glycerol molecules and the dynamics of bound water as a function of glycerol concentration in solutions using the Debye relaxation model. The experimental results show the existence of a critical glycerol concentration of ∼7.5 mol %, which is related to the number of water molecules in the hydration layer around a glycerol molecule. At higher glycerol concentrations, water molecules dispersed in a glycerol network become abundant and eventually dominate, and four distinct relaxation processes emerge in the mixtures. The relaxation dynamics and hydration structure in glycerol-water mixtures are further probed with molecular dynamics simulations, which confirm the physical picture revealed by the dielectric spectroscopy

X-ray triple rings around the M87 jets in the central Virgo cluster

The Chandra X-ray data of the central Virgo cluster are re-examined to reveal a triple-ring structure around the galaxy M87, reminiscent of the spectacular triple-ring pattern of the SN1987A in the Large Magellanic Cloud (LMC). In the sky plane, the two apparent smaller ellipses are roughly aligned along the M87 jets; the larger ring centers at the M87 nucleus and is likely a circle roughly perpendicular to the M87 jet. Certain similarities of these two triple-ring structures might hint at similar processes that operate in these two systems with entirely different sizes and mass scales. We suspect that a major merging event of two galaxies with nuclear supermassive black holes (SMBHs) might create such a triple-ring structure and drove acoustic and internal gravity waves far and near. The M87 jets are perhaps powered by a spinning SMBH resulting from this catastrophic merging event.Comment: accepted by ApJ

Current-Controlled Negative Differential Resistance due to Joule Heating in TiO2

We show that Joule heating causes current-controlled negative differential resistance (CC-NDR) in TiO2 by constructing an analytical model of the voltage-current V(I) characteristic based on polaronic transport for Ohm's Law and Newton's Law of Cooling, and fitting this model to experimental data. This threshold switching is the 'soft breakdown' observed during electroforming of TiO2 and other transition-metal-oxide based memristors, as well as a precursor to 'ON' or 'SET' switching of unipolar memristors from their high to their low resistance states. The shape of the V(I) curve is a sensitive indicator of the nature of the polaronic conduction.Comment: 13 pages, 2 figure

The Phenomenon of Collaboration: A Phenomenologic Study of Collaboration between Family Medicine and Obstetrics and Gynecology Departments at an Academic Medical Center

Collaboration is essential to manage complex real world problems. We used phenomenologic methods to elaborate a description of collaboration between two departments at an academic medical center who considered their relationship to represent a model of effective collaboration. Key collaborative structures included a shared vision and commitment by leaders, rigorous quality improvement, clear delineation of roles with built-in flexibility, ongoing commitment to formal and informal communication channels and conflict resolution, relationship development grounded in respect and responsiveness, and shared training in a supportive learning environment with legitimate participation fostering skill development. This study reveals the complexity and resources required for collaboration which both explains why collaboration is not as easy to achieve and identifies processes that foster collaboration

λϕ4\lambda\phi^4 model and Higgs mass in standard model calculated by Gaussian effective potential approach with a new regularization-renormalization method

Basing on new regularization-renormalization method, the $\lambda\phi^4$ model used in standard model is studied both perturbatively and nonperturbatively (by Gaussian effective potential). The invariant property of two mass scales is stressed and the existence of a (Landau) pole is emphasized. Then after coupling with the SU(2)$\times$U(1) gauge fields, the Higgs mass in standard model (SM) can be calculated as $m_H\approx$138GeV. The critical temperature ($T_c$) for restoration of symmetry of Higgs field, the critical energy scale ($\mu_c$, the maximum energy scale under which the lower excitation sector of the GEP is valid) and the maximum energy scale ($\mu_{max}$, at which the symmetry of the Higgs field is restored) in the standard model are $T_c\approx$476 GeV, $\mu_c\approx 0.547\times 10^{15}$GeV and $\mu_{\max}\approx 0.873 \times 10^{15}$ GeVv respectively.Comment: 12 pages, LaTex, no figur

Effects of substituting rare-earth ion R by non-magnetic impurities in R2BaNiO5R_2BaNiO_5 - theory and numerical DMRG results

In this paper we study the effect of substituting R (rare-earth ion) by non-magnetic ions in the spin-1 chain material $R_2BaNiO_5$. Using a strong-coupling expansion and numerical density matrix renormalization group calculations, we show that spin-wave bound states are formed at the impurity site. Experimental consequences of the bound states are pointed out.Comment: 5 pages, 4 postscript figure