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

Fireballs and cannonballs confront the afterglow of GRB 991208

Galama et al. have recently reported their follow-up measurements of the radio afterglow (AG) of the Gamma Ray Burst (GRB) 991208, up to 293 days after burst, and their reanalysis of the broad-band AG, in the framework of standard fireball models. They advocate a serious revision of their prior analysis and conclusions, based on optical data and on their earlier observations during the first two weeks of the AG. We comment on their work and fill a lacuna: these authors have overlooked the possibility of comparing their new data to the available predictions of the cannonball (CB) model, based --like their incorrect predictions-- on the first round of data. The new data are in good agreement with these CB-model predictions. This is in spite of the fact that, in comparison to the fireball models, the CB model is much simpler, much more predictive, has many fewer parameters, practically no free choices... and it describes well --on a universal basis-- all the measured AGs of GRBs of known redshift

Adaptive Subcarrier PSK Intensity Modulation in Free Space Optical Systems

We propose an adaptive transmission technique for free space optical (FSO) systems, operating in atmospheric turbulence and employing subcarrier phase shift keying (S-PSK) intensity modulation. Exploiting the constant envelope characteristics of S-PSK, the proposed technique offers efficient utilization of the FSO channel capacity by adapting the modulation order of S-PSK, according to the instantaneous state of turbulence induced fading and a pre-defined bit error rate (BER) requirement. Novel expressions for the spectral efficiency and average BER of the proposed adaptive FSO system are presented and performance investigations under various turbulence conditions and target BER requirements are carried out. Numerical results indicate that significant spectral efficiency gains are offered without increasing the transmitted average optical power or sacrificing BER requirements, in moderate-to-strong turbulence conditions. Furthermore, the proposed variable rate transmission technique is applied to multiple input multiple output (MIMO) FSO systems, providing additional improvement in the achieved spectral efficiency as the number of the transmit and/or receive apertures increases.Comment: Submitted To IEEE Transactions On Communication

REACTIVITY OF CHLOROPHYLL a/b-PROTEINS AND MICELLAR TRITON X-100 COMPLEXES OF CHLOROPHYLLS a OR b WITH BOROHYDRIDE

The reaction of several plant chlorophyll-protein complexes with NaBH4 has been studied by absorption spectroscopy. In all the complexes studied, chlorophyll b is more reactive than Chi a, due to preferential reaction of its formyl substituent at C-7. The complexes also show large variations in reactivity towards NaBH4 and the order of reactivity is: LHCI > PSII complex > LHCII > PSI > P700 (investigated as a component of PSI). Differential pools of the same type of chlorophyll have been observed in several complexes. Parallel work was undertaken on the reactivity of micellar complexes of chlorophyll a and of chlorophyll b with NaBH4 to study the effect of aggregation state on this reactivity. In these complexes, both chlorophyll a and b show large variations in reactivity in the order monomer > oligomer > polymer with chlorophyll b generally being more reactive than chlorophyll a. It is concluded that aggregation decreases the reactivity of chlorophylls towards NaBH4 in vitro, and may similarly decrease reactivity in naturally-occurring chlorophyll-protein complexes

Portable Diagnostics Technology Assessment for Space Missions

The changes in the scope of NASA s mission in the coming decade are profound and demand nimble, yet insightful, responses. On-board clinical and environmental diagnostics must be available for both mid-term lunar and long-term Mars exploration missions in an environment marked by scarce resources. Miniaturization has become an obvious focus. Despite solid achievements in lab-based devices, broad-based, robust tools for application in the field are not yet on the market. The confluence of rapid, wide-ranging technology evolution and internal planning needs are the impetus behind this work. This report presents an analytical tool for the ongoing evaluation of promising technology platforms based on mission- and application-specific attributes. It is not meant to assess specific devices, but rather to provide objective guidelines for a rational down-select of general categories of technology platforms. In this study, we have employed our expertise in the microgravity operation of fluidic devices, laboratory diagnostics for space applications, and terrestrial research in biochip development. A rating of the current state of technology development is presented using the present tool. Two mission scenarios are also investigated: a 30-day lunar mission using proven, tested technology in 5 years; and a 2- to 3-year mission to Mars in 10 to 15 years

Ambient Isotopic Meshing of Implicit Algebraic Surface with Singularities

A complete method is proposed to compute a certified, or ambient isotopic, meshing for an implicit algebraic surface with singularities. By certified, we mean a meshing with correct topology and any given geometric precision. We propose a symbolic-numeric method to compute a certified meshing for the surface inside a box containing singularities and use a modified Plantinga-Vegter marching cube method to compute a certified meshing for the surface inside a box without singularities. Nontrivial examples are given to show the effectiveness of the algorithm. To our knowledge, this is the first method to compute a certified meshing for surfaces with singularities.Comment: 34 pages, 17 Postscript figure

Convolutional Networks for Fast, Energy-Efficient Neuromorphic Computing

Deep networks are now able to achieve human-level performance on a broad spectrum of recognition tasks. Independently, neuromorphic computing has now demonstrated unprecedented energy-efficiency through a new chip architecture based on spiking neurons, low precision synapses, and a scalable communication network. Here, we demonstrate that neuromorphic computing, despite its novel architectural primitives, can implement deep convolution networks that i) approach state-of-the-art classification accuracy across 8 standard datasets, encompassing vision and speech, ii) perform inference while preserving the hardware's underlying energy-efficiency and high throughput, running on the aforementioned datasets at between 1200 and 2600 frames per second and using between 25 and 275 mW (effectively > 6000 frames / sec / W) and iii) can be specified and trained using backpropagation with the same ease-of-use as contemporary deep learning. For the first time, the algorithmic power of deep learning can be merged with the efficiency of neuromorphic processors, bringing the promise of embedded, intelligent, brain-inspired computing one step closer.Comment: 7 pages, 6 figure

Developing young people's sense of self and place through sport

Previous research has recognized positive health implications, both physical and mental, as an outcome of participation in leisure pursuits. They provide opportunities for self-expression and stress reduction, as well as an environment in which people can socialize. Leisure activities, specifically sport activities, can play a significant role in young people's identity development. This paper explores the leisure activities in which young people in Adelaide, Australia participate. It examines the role of leisure activities in terms of young people's identity and feelings towards their hometown. This study consisted of semi-structured focus groups conducted with 24 senior high school students, followed by a survey resulting in 226 useable responses. Respondents were aged between 16 and 18 years of age. From the range of activities identified and explored, the results revealed sports activities to have the greatest impact on young people's lives. The results demonstrated that frequency of participation has a significant effect on young people's involvement levels and how they identify with the activity

A guanosine 5′-triphosphate-dependent protein kinase is localized in the outer envelope membrane of pea chloroplasts

A guanosine 5-triphosphate (GTP)-dependent protein kinase was detected in preparations of outer chloroplast envelope membranes of pea (Pisum sativum L.) chloroplasts. The protein-kinase activity was capable of phosphorylating several envelope-membrane proteins. The major phosphorylated products were 23- and 32.5-kilo-dalton proteins of the outer envelope membrane. Several other envelope proteins were labeled to a lesser extent. Following acid hydrolysis of the labeled proteins, most of the label was detected as phosphoserine with only minor amounts detected as phosphothreonine. Several criteria were used to distinguish the GTP-dependent protein kinase from an ATP-dependent kinase also present in the outer envelope membrane. The ATP-dependent kinase phosphorylated a very different set of envelope-membrane proteins. Heparin inhibited the GTP-dependent kinase but had little effect upon the ATP-dependent enzyme. The GTP-dependent enzyme accepted phosvitin as an external protein substrate whereas the ATP-dependent enzyme did not. The outer membrane of the chloroplast envelope also contained a phosphotransferase capable of transferring labeled phosphate from [-32P]GTP to ADP to yield (-32P]ATP. Consequently, addition of ADP to a GTP-dependent protein-kinase assay resulted in a switch in the pattern of labeled products from that seen with GTP to that typically seen with ATP

The source ambiguity problem: Distinguishing the effects of grammar and processing on acceptability judgments

Judgments of linguistic unacceptability may theoretically arise from either grammatical deviance or significant processing difficulty. Acceptability data are thus naturally ambiguous in theories that explicitly distinguish formal and functional constraints. Here, we consider this source ambiguity problem in the context of Superiority effects: the dispreference for ordering a wh-phrase in front of a syntactically “superior” wh-phrase in multiple wh-questions, e.g., What did who buy? More specifically, we consider the acceptability contrast between such examples and so-called D-linked examples, e.g., Which toys did which parents buy? Evidence from acceptability and self-paced reading experiments demonstrates that (i) judgments and processing times for Superiority violations vary in parallel, as determined by the kind of wh-phrases they contain, (ii) judgments increase with exposure, while processing times decrease, (iii) reading times are highly predictive of acceptability judgments for the same items, and (iv) the effects of the complexity of the wh-phrases combine in both acceptability judgments and reading times. This evidence supports the conclusion that D-linking effects are likely reducible to independently motivated cognitive mechanisms whose effects emerge in a wide range of sentence contexts. This in turn suggests that Superiority effects, in general, may owe their character to differential processing difficulty