The first order convergence law fails for random perfect graphs

We consider first order expressible properties of random perfect graphs. That is, we pick a graph $G_n$ uniformly at random from all (labelled) perfect graphs on $n$ vertices and consider the probability that it satisfies some graph property that can be expressed in the first order language of graphs. We show that there exists such a first order expressible property for which the probability that $G_n$ satisfies it does not converge as $n\to\infty$.Comment: 11 pages. Minor corrections since last versio

Atomic structure and vibrational properties of icosahedral B4_4C boron carbide

The atomic structure of icosahedral B$_4$C boron carbide is determined by comparing existing infra-red absorption and Raman diffusion measurements with the predictions of accurate {\it ab initio} lattice-dynamical calculations performed for different structural models. This allows us to unambiguously determine the location of the carbon atom within the boron icosahedron, a task presently beyond X-ray and neutron diffraction ability. By examining the inter- and intra-icosahedral contributions to the stiffness we show that, contrary to recent conjectures, intra-icosahedral bonds are harder.Comment: 9 pages including 3 figures, accepted in Physical Review Letter

Plasmodium berghei Circumvents Immune Responses Induced by Merozoite Surface Protein 1- and Apical Membrane Antigen 1-Based Vaccines

BACKGROUND: Two current leading malaria blood-stage vaccine candidate antigens for Plasmodium falciparum, the C-terminal region of merozoite surface protein 1 (MSP1(19)) and apical membrane antigen 1 (AMA1), have been prioritized because of outstanding protective efficacies achieved in a rodent malaria Plasmodium yoelii model. However, P. falciparum vaccines based on these antigens have had disappointing outcomes in clinical trials. Discrepancies in the vaccine efficacies observed between the P. yoelii model and human clinical trials still remain problematic. METHODOLOGY AND RESULTS: In this study, we assessed the protective efficacies of a series of MSP1(19)- and AMA1-based vaccines using the P. berghei rodent malarial parasite and its transgenic models. Immunization of mice with a baculoviral-based vaccine (BBV) expressing P. falciparum MSP1(19) induced high titers of PfMSP1(19)-specific antibodies that strongly reacted with P. falciparum blood-stage parasites. However, no protection was achieved following lethal challenge with transgenic P. berghei expressing PfMSP1(19) in place of native PbMSP1(19). Similarly, neither P. berghei MSP1(19)- nor AMA1-BBV was effective against P. berghei. In contrast, immunization with P. yoelii MSP1(19)- and AMA1-BBVs provided 100% and 40% protection, respectively, against P. yoelii lethal challenge. Mice that naturally acquired sterile immunity against P. berghei became cross-resistant to P. yoelii, but not vice versa. CONCLUSION: This is the first study to address blood-stage vaccine efficacies using both P. berghei and P. yoelii models at the same time. P. berghei completely circumvents immune responses induced by MSP1(19)- and AMA1-based vaccines, suggesting that P. berghei possesses additional molecules and/or mechanisms that circumvent the host's immune responses to MSP1(19) and AMA1, which are lacking in P. yoelii. Although it is not known whether P. falciparum shares these escape mechanisms with P. berghei, P. berghei and its transgenic models may have potential as useful tools for identifying and evaluating new blood-stage vaccine candidate antigens for P. falciparum

Leukemia Inhibitory Factor in Rat Fetal Lung Development: Expression and Functional Studies

Background: Leukemia inhibitory factor (LIF) and interleukin-6 (IL-6) are members of the family of the glycoprotein 130 (gp130)-type cytokines. These cytokines share gp130 as a common signal transducer, which explains why they show some functional redundancy. Recently, it was demonstrated that IL-6 promotes fetal lung branching. Additionally, LIF has been implicated in developmental processes of some branching organs. Thus, in this study LIF expression pattern and its effects on fetal rat lung morphogenesis were assessed. Methodology/Principal Findings: LIF and its subunit receptor LIFRa expression levels were evaluated by immunohistochemistry and western blot in fetal rat lungs of different gestational ages, ranging from 13.5 to 21.5 days post-conception. Throughout all gestational ages studied, LIF was constitutively expressed in pulmonary epithelium, whereas LIFRa was first mainly expressed in the mesenchyme, but after pseudoglandular stage it was also observed in epithelial cells. These results point to a LIF epithelium-mesenchyme cross-talk, which is known to be important for lung branching process. Regarding functional studies, fetal lung explants were cultured with increasing doses of LIF or LIF neutralizing antibodies during 4 days. MAPK, AKT, and STAT3 phosphorylation in the treated lung explants was analyzed. LIF supplementation significantly inhibited lung growth in spite of an increase in p44/42 phosphorylation. On the other hand, LIF inhibition significantly stimulated lung growth via p38 and Akt pathways

Structural and mechanical properties of TiB 2 and TiC prepared by self-propagating high-temperature synthesis/dynamic compaction

Titanium-diboride and titanium-carbide compacts with diameters of 100 mm and thicknesses of 25 mm were fabricated by self-propagating high-temperature synthesis/dynamic compaction (SHS/DC) of the elemental powders. Under the best conditions, the densities were greater than 99% and 96.8% of the theoretical densities for TiB 2 and TiC, respectively. The microhardness, compressive strength, and elastic modulus of the TiB 2 prepared by the SHS/DC method were comparable to reported values for hot-pressed TiB 2 . While the microhardness and elastic modulus of the TiC compacts were comparable to those for hotpressed TiC, the compressive strength was lower due to extensive cracks in the compacts. The TiB 2 prepared using a low-purity boron powder (1–5% carbon impurity) compacted to higher densities and had less cracking than that prepared using a high-purity boron powder (0.2% carbon). This result could have an impact on the cost of producing TiB 2 /TiC structural components by the SHS/DC process.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44732/1/10853_2005_Article_BF01162518.pd

Why Functional Pre-Erythrocytic and Bloodstage Malaria Vaccines Fail: A Meta-Analysis of Fully Protective Immunizations and Novel Immunological Model

Background: Clinically protective malaria vaccines consistently fail to protect adults and children in endemic settings, and at best only partially protect infants. Methodology/Principal Findings: We identify and evaluate 1916 immunization studies between 1965-February 2010, and exclude partially or nonprotective results to find 177 completely protective immunization experiments. Detailed reexamination reveals an unexpectedly mundane basis for selective vaccine failure: live malaria parasites in the skin inhibit vaccine function. We next show published molecular and cellular data support a testable, novel model where parasite-host interactions in the skin induce malaria-specific regulatory T cells, and subvert early antigen-specific immunity to parasite-specific immunotolerance. This ensures infection and tolerance to reinfection. Exposure to Plasmodium-infected mosquito bites therefore systematically triggers immunosuppression of endemic vaccine-elicited responses. The extensive vaccine trial data solidly substantiate this model experimentally. Conclusions/Significance: We conclude skinstage-initiated immunosuppression, unassociated with bloodstage parasites, systematically blocks vaccine function in the field. Our model exposes novel molecular and procedural strategies to significantly and quickly increase protective efficacy in both pipeline and currently ineffective malaria vaccines, and forces fundamental reassessment of central precepts determining vaccine development. This has major implications fo

A study of the biological activity of toxic material derived from nematocysts of the cubomedusan Chironex fleckeri

Nematocysts of the cubomedusan Chironex fleckeri have been isolated in quantity. Five types of nematocyst were distinguished. Protein, carbohydrate, cystine-containing compounds and 3-indolyl derivatives were detected in all types of nematocyst. Saline extracts of the contents of nematocysts were highly toxic to prawns and fish and were capable of eliciting fatal systemic effects within seconds if administered to rats and mice via the i.v. route. Saline extracts of toxic material from ruptured nematocysts elicited a powerful contracture of the striated musculature of barnacles and of skeletal, respiratory and extravascular smooth musculature of rats. In each case, the contracture was sustained for a period and then the musculature involved became paralysed in the relaxed condition. When exposed to toxin extracts the perfused heart of the toad and the exposed heart of the rat showed a progressive failure to relax during successive cardiac cycles and the hearts became paralysed in systole. Prior blockade of neuromuscular junctions with d-tubocurarine did not modify the response of rat diaphragm musculature to toxin extracts. Conduction in the sciatic nerve of the toad was not obviously affected by prolonged exposure to toxin extracts. Preliminary results indicate that C. fleckeri nematocyst toxin is antigenic