Characterization, cloning and immunogenicity of antigens released by lung-stage larvae of Schistosoma mansoni

Lung-stage schistosomula are the target of protective immunity in mice vaccinated with attenuated cercariae of Schistosoma mansoni. Therefore, proteins present at this developmental stage, and in particular those which are secreted, are a potential source of novel vaccine candidates. However, little information is available about such molecules. Here we describe the cDNA clones identified by screening expression libraries with serum raised against proteins released by lung-stage schistosomula. In total, 11 different cDNA species were identified, 6 of which have been described previously in S. mansoni; these included fructose 1,6-bisphosphate aldolase and Sm21.7 which together accounted for two-thirds of all positive clones. Of the 5 newly described schistosome genes, 1 cDNA had a high degree of homology to the s5a subunit of 26S proteasomes, most significant being with the human protein. The remaining 4 clones showed no significant homologies to any genes sequenced previously. Fructose 1,6-bisphosphate aldolase, Sm21.7, the proteasome homologue and 1 unknown clone (A26) have been expressed in a bacterial expression system and serum produced against each recombinant protein. Immunolocalization showed fructose 1,6-bisphosphate aldolase, Sm21.7 and the proteasome homologue to be most abundant in muscle cells whilst clone A26 was distributed throughout many tissues, but was most abundant in the tegument. Analysis of the cellular immune responses of vaccinated mice showed 3 of the 4 expressed clones to be highly immunogenic, inducing the secretion of large quantities of the Th1-type cytokine interferon gamma

Potentiation of tumour growth by endotoxin in serum from syngeneic tumour-bearing mice.

The subcutaneous growth of 2 antigenically distinct syngeneic methylcholanthrene-induced murine fibrosarcomas, designated H1 and H7, were significantly augmented by the concomitant administration of E. coli endotoxin (LPS). Amounts as little as 0.2 micrograms i.p. potentiated tumour growth. The weakly antigenic tumour, H1, was more susceptible to provocation by LPS than the more strongly antigenic H7. Maximum provocation of H1 tumour growth occurred when LPS was injected 1 day before the administration of 5000 tumour cells. In contrast, significant anti-tumour resistance resulted if LPS was administered 6 days before the inoculation of tumour cells. Preliminary evidence indicates that low doses of LPS can facilitate the "sneaking through" phenomenon. Enhancement of tumour growth could not be demonstrated with sera or plasma from tumour-bearing mice, unless the samples were contaminated with endotoxin. The results illustrate the importance of excluding endotoxin from solutions used in studies of experimental tumours

Infrared spectroscopy of cataclysmic variables: III. Dwarf novae below the period gap and novalike variables

We present K-band spectra of the short-period dwarf novae YZ Cnc, LY Hya, BK Lyn, T Leo, SW UMa and WZ Sge, the novalike variables DW UMa, V1315 Aql, RW Tri, VY Scl, UU Aqr and GP Com, and a series of field dwarf stars with spectral types ranging from K2-M6. The spectra of the dwarf novae are dominated by emission lines of HI and HeI. The large velocity and equivalent widths of these lines, in conjunction with the fact that the lines are double-peaked in the highest inclination systems, indicate an accretion disc origin. In the case of YZ Cnc and T Leo, for which we obtained time-resolved data covering a complete orbital cycle, the emission lines show modulations in their equivalent widths which are most probably associated with the bright spot (the region where the gas stream collides with the accretion disc). There are no clear detections of the secondary star in any of the dwarf novae below the period gap, yielding upper limits of 10-30% for the contribution of the secondary star to the observed K-band flux. In conjunction with the K-band magnitudes of the dwarf novae, we use the derived secondary star contributions to calculate lower limits to the distances to these systems. The spectra of the novalike variables are dominated by broad, single-peaked emission lines of HI and HeI - even the eclipsing systems we observed do not show the double-peaked profiles predicted by standard accretion disc theory. With the exception of RW Tri, which exhibits NaI, CaI and 12CO absorption features consistent with a M0V secondary contributing 65% of the observed K-band flux, we find no evidence for the secondary star in any of the novalike variables. The implications of this result are discussed.Comment: 13 pages, 5 figures, to appear in MNRA

Characterization of the Deleted in Autism 1 Protein Family: Implications for Studying Cognitive Disorders

Autism spectrum disorders (ASDs) are a group of commonly occurring, highly-heritable developmental disabilities. Human genes c3orf58 or Deleted In Autism-1 (DIA1) and cXorf36 or Deleted in Autism-1 Related (DIA1R) are implicated in ASD and mental retardation. Both gene products encode signal peptides for targeting to the secretory pathway. As evolutionary medicine has emerged as a key tool for understanding increasing numbers of human diseases, we have used an evolutionary approach to study DIA1 and DIA1R. We found DIA1 conserved from cnidarians to humans, indicating DIA1 evolution coincided with the development of the first primitive synapses. Nematodes lack a DIA1 homologue, indicating Caenorhabditis elegans is not suitable for studying all aspects of ASD etiology, while zebrafish encode two DIA1 paralogues. By contrast to DIA1, DIA1R was found exclusively in vertebrates, with an origin coinciding with the whole-genome duplication events occurring early in the vertebrate lineage, and the evolution of the more complex vertebrate nervous system. Strikingly, DIA1R was present in schooling fish but absent in fish that have adopted a more solitary lifestyle. An additional DIA1-related gene we named DIA1-Like (DIA1L), lacks a signal peptide and is restricted to the genomes of the echinoderm Strongylocentrotus purpuratus and cephalochordate Branchiostoma floridae. Evidence for remarkable DIA1L gene expansion was found in B. floridae. Amino acid alignments of DIA1 family gene products revealed a potential Golgi-retention motif and a number of conserved motifs with unknown function. Furthermore, a glycine and three cysteine residues were absolutely conserved in all DIA1-family proteins, indicating a critical role in protein structure and/or function. We have therefore identified a new metazoan protein family, the DIA1-family, and understanding the biological roles of DIA1-family members will have implications for our understanding of autism and mental retardation

Improving the Army's joint platform allocation tool (JPAT)

The U.S. Army's joint platform allocation tool (JPAT) is an integer linear program that was developed by the Army's Training and Doctrine Command Analysis Center and the Naval Postgraduate School to help inform acquisition decisions involving aerial reconnaissance and surveillance (R&S) resources. JPAT evaluates inputs such as mission requirements, locations of available equipment, and budgetary constraints to determine an effective assignment of unmanned aerial R&S assets to missions. As of September 2013, JPAT is solved using a rolling horizon approach, which produces a sub-optimal solution, and requires substantial computational resources to solve a problem of realistic size. Because JPAT is an integer linear program, it is a suitable candidate for using decomposition techniques to improve its computational efficiency. This thesis conducts an analysis of multiple approaches for increasing JPAT's computational efficiency. First, we reformulate JPAT using Benders decomposition. Then, we solve both the original and decomposed formulations using the simplex and barrier algorithms with multiple size datasets. In addition, we experiment with an initial heuristic solution and other techniques in our attempts to improve JPAT's runtime. We find that while Benders decomposition does not result in significant improvements in computation time for the instances considered in this thesis, initial solution heuristics and other modifications to the model improve JPAT's performance.http://archive.org/details/improvingarmysjo1094537635Lieutenant, United States NavyApproved for public release; distribution is unlimited

UBVRI photopolarimetry of the long period eclipsing AM Herculis binary V1309

We report simultaneous UBVRI photo-polarimetric observations of the long period (7.98 h) AM Her binary V1309 Ori. The length and shape of the eclipse ingress and egress varies from night to night. We suggest this is due to the variation in the brightness of the accretion stream. By comparing the phases of circular polarization zero-crossovers with previous observations, we confirm that V1309 Ori is well synchronized, and find an upper limit of 0.002 percent for the difference between the spin and orbital periods. We model the polarimetry data using a model consisting of two cyclotron emission regions at almost diametrically opposite locations, and centered at colatitude 35 (deg) and 145 (deg) on the surface of the white dwarf. We also present archive X-ray observations which show that the negatively polarised accretion region is X-ray bright.Comment: 11 pages, 12 figures (2 colour), Fig1 and Fig 4 are in lower resolution than in original paper, accepted for publication in Monthly Notices of the Royal Astronomical Societ

Mapping the contribution of Allied Health Professions to the wider public health workforce : a rapid review of evidence-based interventions

Objectives: The objective was to identify a selection of the best examples of the public health contributions by Allied Health Professionals (AHPs) in order to encourage a wider awareness and participation from that workforce to public health practice. Study design: A mapping exercise was used to identify evidence-based interventions that could lead to health improvements across a population. Methods: A rapid review was undertaken to identify evidence, followed by a survey of Allied Health Profession (AHP) practitioners and an expert panel consensus method to select the examples of AHP public health interventions. Results: Nine evidence-based interventions are identified and selected as examples of current AHP good practice. These examples represent a contribution to public health and include screening interventions, secondary prevention and risk management. Conclusions: This study contributes to a strategy for AHPs in public health by appraising the effectiveness and impact of some exemplar AHP practices that contribute to health improvement. There is a need for AHPs to measure the impact of their interventions and to demonstrate evidence of outcomes at population level. Keywords: allied health professions; Applied Health Professionals; evidence-based practice; health improvement; public health; rapid revie