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

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

Spatial Heterogeneity of Seasonal Grazing Pressure Created by Herd Movement Patterns on Hilly Rangelands Using GPS and GIS

The spatial heterogeneity of grazing pressure on extensive rangelands has management implications (Adler et al., 2001) but it has traditionally been difficult to quantify. Combination of technologies based on GPS (Global Positioning System) and GIS (Geographic Information Systems) is a quantum leap in our ability to address this issue. These tools were used to estimate the spatial heterogeneity of grazing pressure at a farm scale, and examine the relation between local landscape features and local grazing pressure

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

Optimum Small Optical Beam Displacement Measurement

We derive the quantum noise limit for the optical beam displacement of a TEM00 mode. Using a multimodal analysis, we show that the conventional split detection scheme for measuring beam displacement is non-optimal with 80% efficiency. We propose a new displacement measurement scheme that is optimal for small beam displacement. This scheme utilises a homodyne detection setup that has a TEM10 mode local oscillator. We show that although the quantum noise limit to displacement measurement can be surpassed using squeezed light in appropriate spatial modes for both schemes, the TEM10 homodyning scheme out-performs split detection for all values of squeezing.Comment: 13 pages, 7 figure

Gerir a diversidade: contributos da aprendizagem cooperativa para a construção de salas de aula inclusivas

The action-research we have held at the primary education, in a school placed near the town of Tomar, in 2009-2010, under the master's degree in Special Education, was the starting point for writing this article. The research had as main objective to promote the successful learning of a heterogeneous group of students, where a child considered with longstanding special educational needs is included – diagnosis of galactosaemia and cognitive impairment. Starting from the educational context of a particular classroom of 2nd and 3rd grades, where we were working as special education teacher, we had created an inclusive learning environment for each student in the class. Through effective collaboration between fellow teachers, we generated changes in methodologies, breaking with some traditional practices in the classroom, when regular teachers and special education are in the same learning space. By a systematic implementation of cooperative learning strategies among students, and applying qualitative data gathering techniques of research, before and after the intervention – interview, naturalistic observation, sociometry and documental research –, we have increased the quality and quantity of learning and promoted another way of ‘looking to’ the difference

Long gamma-ray bursts without visible supernovae: a case study of redshift estimators and alleged novel objects

It has been argued that the observational limits on a supernova (SN) associated with GRB060614 convincingly exclude a SN akin to SN1998bw as its originator, and provide evidence for a new class of long-duration GRBs. We discuss this issue in the contexts of indirect 'redshift estimators' and of the fireball and cannonball models of GRBs. The latter explains the unusual properties of GRB060614: at its debated but favoured low redshift (0.125) they are predicted, as opposed to exceptional, if the associated core-collapse SN is of a recently discovered, very faint type. We take the occasion to discuss the 'association' between GRBs and SNe.Comment: 19 pages, 2 figures. To be published in Ap