A Three Monoclonal Antibody Combination Potently Neutralizes Multiple Botulinum Neurotoxin Serotype E Subtypes.

Human botulism is most commonly caused by botulinum neurotoxin (BoNT) serotypes A, B, and E. For this work, we sought to develop a human monoclonal antibody (mAb)-based antitoxin capable of binding and neutralizing multiple subtypes of BoNT/E. Libraries of yeast-displayed single chain Fv (scFv) antibodies were created from the heavy and light chain variable region genes of humans immunized with pentavalent-toxoid- and BoNT/E-binding scFv isolated by Fluorescence-Activated Cell Sorting (FACS). A total of 10 scFv were isolated that bound one or more BoNT/E subtypes with nanomolar-level equilibrium dissociation constants (KD). By diversifying the V-regions of the lead mAbs and selecting for cross-reactivity, we generated three scFv that bound all four BoNT/E subtypes tested at three non-overlapping epitopes. The scFvs were converted to IgG that had KD values for the different BoNT/E subtypes ranging from 9.7 nM to 2.28 pM. An equimolar combination of the three mAbs was able to potently neutralize BoNT/E1, BoNT/E3, and BoNT/E4 in a mouse neutralization assay. The mAbs have potential utility as therapeutics and as diagnostics capable of recognizing multiple BoNT/E subtypes. A derivative of the three-antibody combination (NTM-1633) is in pre-clinical development with an investigational new drug (IND) application filing expected in 2018

Terrestrial Myriametric Radio Burst Observed by IMAGE and Geotail Satellites

We report IMAGE and Geotail simultaneous observations of a terrestrial myriametric radio burst (TMRB) detected on August 19, 2001. The TMRB was confined in time (0830-1006 UT) and frequency (12-50 kHz), suggesting a fan beam-like emission pattern from a single discrete source. Analysis and comparisons with existing TMR radiations strongly suggest that the TMRB is a distinct emission perhaps resulting from dayside magnetic reconnection instigated by northward interplanetary field condition

Terrestrial Myriametric Radio Burst Observed by IMAGE and Geotail Satellites

We report the simultaneous detection of a terrestrial myriametric radio burst (TMRB) by IMAGE and Geotail on 19 August 2001. The TMRB was confined in time (0830-1006 UT) and frequency (12-50kHz). Comparisons with all known nonthermal myriametric radiation components reveal that the TMRB might be a distinct radiation with a source that is unrelated to the previously known radiation. Considerations of beaming from spin-modulation analysis and observing satellite and source locations suggest that the TMRB may have a fan beamlike radiation pattern emitted by a discrete, dayside source located along the poleward edge of magnetospheric cusp field lines. TMRB responsiveness to IMF Bz and By orientations suggests that a possible source of the TMRB could be due to dayside magnetic reconnection instigated by northward interplanetary field condition

Cognitive Information Processing

Contains reports on four research projects.Associated Press (Grant)Providence Gravure, Inc. (Grant)Taylor Publishing Company (Grant

Ethnobotanical knowledge and crop diversity in swidden fields: a study in a native Amazonian society

Crop diversity protects food consumption in poor households within developing nations. Here we estimate the association between crop diversity on swidden fields and ethnobotanical knowledge. We conducted research among 215 male household heads from a native Amazonian society. Using multivariate regressions, we found higher crop diversity among households that depend on agricultural production for household consumption. We also found a statistically significant and positive, but low, association between the ethnobotanical knowledge of the male household head and crop diversity. Doubling the stock of ethnobotanical knowledge of the male household head is associated with a 9% increase in the number of crops sown by a household. The association remained after we controlled for the household level of market exposure, but vanished after we controlled for the social capital of the male household head. Future research should compare the association between ethnobotanical knowledge and crop diversity across different agricultural systems (i.e., home gardens, fallow fields)

Extraction and inhibition of enzymatic activity of botulinum neurotoxins /B1, /B2, /B3, /B4, and /B5 by a panel of monoclonal anti-BoNT/B antibodies

<p>Abstract</p> <p>Background</p> <p>Botulism is caused by botulinum neurotoxins (BoNTs), extremely toxic proteins which can induce respiratory failure leading to long-term intensive care or death. Treatment for botulism includes administration of antitoxins, which must be administered early in the course of the intoxication; therefore, rapid determination of human exposure to BoNT is an important public health goal. In previous work, our laboratory reported on Endopep-MS, a mass spectrometry-based activity method for detecting and differentiating BoNT/A, /B, /E, and /F in clinical samples. We also demonstrated that antibody-capture is effective for purification and concentration of BoNTs from complex matrices such as clinical samples. However, some antibodies inhibit or neutralize the enzymatic activity of BoNT, so the choice of antibody for toxin extraction is critical.</p> <p>Results</p> <p>In this work, we evaluated 24 anti-BoNT/B monoclonal antibodies (mAbs) for their ability to inhibit the <it>in vitro </it>activity of BoNT/B1, /B2, /B3, /B4, and /B5 and to extract those toxins. Among the mAbs, there were significant differences in ability to extract BoNT/B subtypes and inhibitory effect on BoNT catalytic activity. Some of the mAbs tested enhanced the <it>in vitro </it>light chain activity of BoNT/B, suggesting that BoNT/B may undergo conformational change upon binding some mAbs.</p> <p>Conclusions</p> <p>In addition to determining <it>in vitro </it>inhibition abilities of a panel of mAbs against BoNT/B1-/B5, this work has determined B12.2 and 2B18.2 to be the best mAbs for sample preparation before Endopep-MS. These mAb characterizations also have the potential to assist with mechanistic studies of BoNT/B protection and treatment, which is important for studying alternative therapeutics for botulism.</p

Space-Borne Radio-Sounding Investigations Facilitated by the Virtual Wave Observatory (VWO)

The goal of the Virtual Wave Observatory (VWO) is to provide userfriendly access to heliophysics wave data. While the VWO initially emphasized the vast quantity of wave data obtained from passive receivers, the VWO infrastructure can also be used to access active sounder data sets. Here we use examples from some half-million Alouette-2, ISIS-1, and ISIS-2 digital topside-sounder ionograms to demonstrate the desirability of such access to the actual ionograms for investigations of both natural and sounder-stimulated plasma-wave phenomena. By this demonstration, we wish to encourage investigators to make other valuable space-borne sounder data sets accessible via the VWO

Effects of galactic dark halo rotation on WIMP direct detection

The effects of a possible rotation of the galactic dark halo on the calculation of the direct detection rates for particle dark matter are analyzed, with special attention to the extraction of the upper limits on the WIMP--nucleon scalar cross section from the experimental data. We employ a model of dark halo rotation which describes the maximal possible effects. For WIMP masses above 50 GeV, the upper limit exclusion plot is modified by less than a factor of two when rotation is included. For lighter masses the effect can be stronger, suggesting the necessity to develop specific models of halo rotation in order to provide more accurate conclusions.Comment: 14 pages, 7 figures included as PS file

Equilibrium shapes and energies of coherent strained InP islands

The equilibrium shapes and energies of coherent strained InP islands grown on GaP have been investigated with a hybrid approach that has been previously applied to InAs islands on GaAs. This combines calculations of the surface energies by density functional theory and the bulk deformation energies by continuum elasticity theory. The calculated equilibrium shapes for different chemical environments exhibit the {101}, {111}, {\=1\=1\=1} facets and a (001) top surface. They compare quite well with recent atomic-force microscopy data. Thus in the InP/GaInP-system a considerable equilibration of the individual islands with respect to their shapes can be achieved. We discuss the implications of our results for the Ostwald ripening of the coherent InP islands. In addition we compare strain fields in uncapped and capped islands.Comment: 10 pages including 6 figures. Submitted to Phys. Rev. B. Related publications can be found at http://www.fhi-berlin.mpg.de/th/paper.htm

Paediatric obsessive-compulsive disorder and depressive symptoms: clinical correlates and CBT treatment outcomes.

Depression frequently co-occurs with paediatric obsessive-compulsive disorder (OCD), yet the clinical correlates and impact of depression on CBT outcomes remain unclear. The prevalence and clinical correlates of depression were examined in a paediatric specialist OCD-clinic sample (N = 295; Mean = 15 [7 - 18] years, 42 % female), using both dimensional (Beck Depression Inventory-youth; n = 261) and diagnostic (Development and Wellbeing Assessment; n = 127) measures of depression. The impact of depressive symptoms and suspected disorders on post-treatment OCD severity was examined in a sub-sample who received CBT, with or without SSRI medication (N = 100). Fifty-one per-cent of patients reported moderately or extremely elevated depressive symptoms and 26 % (95 % CI: 18 - 34) met criteria for a suspected depressive disorder. Depressive symptoms and depressive disorders were associated with worse OCD symptom severity and global functioning prior to CBT. Individuals with depression were more likely to be female, have had a psychiatric inpatient admission and less likely to be attending school (ps < 0.01). OCD and depressive symptom severity significantly decreased after CBT. Depressive symptoms and depressive disorders predicted worse post-treatment OCD severity (βs = 0.19 and 0.26, ps < 0.05) but became non-significant when controlling for pre-treatment OCD severity (βs = 0.05 and 0.13, ns). Depression is common in paediatric OCD and is associated with more severe OCD and poorer functioning. However, depression severity decreases over the course of CBT for OCD and is not independently associated with worse outcomes, supporting the recommendation for treatment as usual in the presence of depressive symptoms