Photon statistics of a random laser

A general relationship is presented between the statistics of thermal radiation from a random medium and its scattering matrix S. Familiar results for black-body radiation are recovered in the limit S to 0. The mean photocount is proportional to the trace of 1-SS^dagger, in accordance with Kirchhoff's law relating emissivity and absorptivity. Higher moments of the photocount distribution are related to traces of powers of 1-SS^dagger, a generalization of Kirchhoff's law. The theory can be applied to a random amplifying medium (or "random laser") below the laser threshold, by evaluating the Bose-Einstein function at a negative temperature. Anomalously large fluctuations are predicted in the photocount upon approaching the laser threshold, as a consequence of overlapping cavity modes with a broad distribution of spectral widths.Comment: 26 pages, including 9 figure

Ordered mesoporous titania from highly amphiphilic block copolymers: tuned solution conditions enable highly ordered morphologies and ultra-large mesopores

Crystalline transition metal oxides with controlled mesopore architectures are in increasing demand to enhance the performance of energy conversion and storage devices. Solution based block copolymer self-assembly routes to achieve ordered mesoporous and crystalline titania have been studied for more than a decade, but have so far mostly been limited to water and alcohol dispersible polymers. This constraint has limited the accessible morphology space as well as structural dimensions. Moreover, synthetic approaches are mostly performed in a trial-and-error fashion using chemical intuition rather than being based on well-defined design parameters. We present solubility design guidelines that facilitate coassembly with highly amphiphilic block copolymers, enabling the formation of ordered structures with diverse length scales (d10 = 13.8–63.0 nm) and bulk-type morphologies. Thus, highly ordered and crystalline titania with the largest reported pores (d = 32.3 nm) was demonstrated for such a coassembly approach without the use of pore-expanders. Furthermore, the use of an ABC triblock terpolymer system led to a 3D ordered network morphology. In all cases, subsequent calcination treatments, such as the CASH procedure, enabled the formation of highly crystalline mesoporous materials while preserving the mesostructure

T-cell epitope polymorphisms of the Plasmodium falciparum circumsporozoite protein among field isolates from Sierra Leone: age-dependent haplotype distribution?

<p>Abstract</p> <p>Background</p> <p>In the context of the development of a successful malaria vaccine, understanding the polymorphisms exhibited by malaria antigens in natural parasite populations is crucial for proper vaccine design. Recent observations have indicated that sequence polymorphisms in the C-terminal T-cell epitopes of the <it>Plasmodium falciparum </it>circumsporozoite protein (Pf<it>csp</it>) are rather low and apparently stable in low endemic areas. This study sought to assess the pattern in a malaria endemic setting in Africa, using samples from Freetown, Sierra Leone.</p> <p>Methods</p> <p>Filter-paper blood samples were collected from subjects at a teaching hospital in Freetown during September–October 2006 and in April–May 2007. The C-terminal portion of the Pf<it>csp </it>gene spanning the Th2R and Th3R epitopes was amplified and directly sequenced; sequences were analysed with subject parameters and polymorphism patterns in Freetown were compared to that in other malaria endemic areas.</p> <p>Results and Discussion</p> <p>Overall, the genetic diversity in Freetown was high. From a total of 99 sequences, 42 haplotypes were identified with at least three accounting for 44.4% (44/99): the 3D7-type (19.2%), a novel type, P-01 (17.2%), and E12 (8.1%). Interestingly, all were unique to the African sub-region and there appeared to be predilection for certain haplotypes to distribute in certain age-groups: the 3D7 type was detected mainly in hospitalized children under 15 years of age, while the P-01 type was common in adult antenatal females (Pearson Chi-square = 48.750, degrees of freedom = 34, <it>P </it>= 0.049). In contrast, the single-haplotype predominance (proportion > 50%) pattern previously identified in Asia was not detected in Freetown.</p> <p>Conclusion</p> <p>Haplotype distribution of the T-cell epitopes of Pf<it>csp </it>in Freetown appeared to vary with age in the study population, and the polymorphism patterns were similar to that observed in neighbouring Gambia, but differed significantly at the sequence level from that observed in Asia. The findings further emphasize the role of local factors in generating polymorphisms in the T-cell epitopes of the <it>P. falciparum </it>circumsporozoite protein.</p

Extreme CD8 T Cell Requirements for Anti-Malarial Liver-Stage Immunity following Immunization with Radiation Attenuated Sporozoites

Radiation-attenuated Plasmodium sporozoites (RAS) are the only vaccine shown to induce sterilizing protection against malaria in both humans and rodents. Importantly, these “whole-parasite” vaccines are currently under evaluation in human clinical trials. Studies with inbred mice reveal that RAS-induced CD8 T cells targeting liver-stage parasites are critical for protection. However, the paucity of defined T cell epitopes for these parasites has precluded precise understanding of the specific characteristics of RAS-induced protective CD8 T cell responses. Thus, it is not known whether quantitative or qualitative differences in RAS-induced CD8 T cell responses underlie the relative resistance or susceptibility of immune inbred mice to sporozoite challenge. Moreover, whether extraordinarily large CD8 T cell responses are generated and required for protection following RAS immunization, as has been described for CD8 T cell responses following single-antigen subunit vaccination, remains unknown. Here, we used surrogate T cell activation markers to identify and track whole-parasite, RAS-vaccine-induced effector and memory CD8 T cell responses. Our data show that the differential susceptibility of RAS-immune inbred mouse strains to Plasmodium berghei or P. yoelii sporozoite challenge does not result from host- or parasite-specific decreases in the CD8 T cell response. Moreover, the surrogate activation marker approach allowed us for the first time to evaluate CD8 T cell responses and protective immunity following RAS-immunization in outbred hosts. Importantly, we show that compared to a protective subunit vaccine that elicits a CD8 T cell response to a single epitope, diversifying the targeted antigens through whole-parasite RAS immunization only minimally, if at all, reduced the numerical requirements for memory CD8 T cell-mediated protection. Thus, our studies reveal that extremely high frequencies of RAS-induced memory CD8 T cells are required, but may not suffice, for sterilizing anti-Plasmodial immunity. These data provide new insights into protective CD8 T cell responses elicited by RAS-immunization in genetically diverse hosts, information with relevance to developing attenuated whole-parasite vaccines

AGEs Secreted by Bacteria Are Involved in the Inflammatory Response

Advanced Glycated End Products (AGEs) are formed by non-enzymatic protein glycation and are implicated in several physiological aspects including cell aging and diseases. Recent data indicate that bacteria – although short lived – produce, metabolize and accumulate AGEs. Here we show that Escherichia coli cells secret AGEs by the energy-dependent efflux pump systems. Moreover, we show that in the presence of these AGEs there is an upshift of pro-inflammatory cytokins by mammalian cells. Thus, we propose that secretion of AGEs by bacteria is a novel avenue of bacterial-induced inflammation which is potentially important in the pathophysiology of bacterial infections. Moreover, the sensing of AGEs by the host cells may constitute a warning system for the presence of bacteria

Promiscuous Expression of α-Tubulin II in Maturing Male and Female Plasmodium falciparum Gametocytes

BACKGROUND: Antimalarial interventions designed to impact on the transmissible sexual stages of Plasmodium falciparum are evaluated by measurement of peripheral gametocyte carriage in vivo and infectivity to mosquitoes. Drug or vaccine-elicited effects may differentially affect the relative abundance of mature male and female sexual forms, and this can be measured by estimation of sex ratios before and after intervention in vivo and in vitro. Measuring the impact of anti-gametocyte drugs on sexual commitment of immature gametocyte stages in vitro is not currently possible as male and female parasites cannot be distinguished by morphology alone prior to stage IV. METHODOLOGY/PRINCIPAL FINDINGS: We have modified an existing immunofluorescence-based approach for distinguishing male and female gametocytes during development in vitro, by using highly synchronised magnetically-enriched gametocyte preparations at different stages of maturity. Antibodies recognising α-tubulin II (males) and Pfg377 (females) were used to attempt to discriminate the sexes. Transcription of these two proteins was not coordinated during in vitro development, with pfg377 transcripts accumulating only late in development, immediately prior to immunofluorescent signals from the PfG377 protein appearing in stage IV gametocytes. Contrary to previous descriptions of this protein as male-specific in P. falciparum, α-tubulin II recognised both male and female gametocytes at stages I to IV, but evidence of differential expression levels of this protein in late stage male and female gametocytes was found. Using antibodies recognising PfG377 as the primary marker and α-tubulin II as a secondary marker, robust estimates of sex ratio in in vitro cultures were obtained for gametocytes at stage IV or later, and validated by light microscopic counts. However, sex ratio estimation was not possible for early stage gametocytes due to the promiscuity of α-tubulin II protein expression, and the relatively late accumulation of PfG377 during the development process. CONCLUSIONS/SIGNIFICANCE: This approach is a feasible method for the evaluation of drug impacts on late-stage gametocyte sex ratio in in vitro studies. Additional sex-specific antigens need to be evaluated for sex ratio estimation in early stage gametocyte preparations

Changes in Parasite Virulence Induced by the Disruption of a Single Member of the 235 kDa Rhoptry Protein Multigene Family of Plasmodium yoelii

Invasion of the erythrocyte by the merozoites of the malaria parasite is a complex process involving a range of receptor-ligand interactions. Two protein families termed Erythrocyte Binding Like (EBL) proteins and Reticulocyte Binding Protein Homologues (RH) play an important role in host cell recognition by the merozoite. In the rodent malaria parasite, Plasmodium yoelii, the 235 kDa rhoptry proteins (Py235) are coded for by a multigene family and are members of the RH. In P. yoelii Py235 as well as a single member of EBL have been shown to be key mediators of virulence enabling the parasite to invade a wider range of host erythrocytes. One member of Py235, PY01365 is most abundantly transcribed in parasite populations and the protein specifically binds to erythrocytes and is recognized by the protective monoclonal antibody 25.77, suggesting a key role of this particular member in virulence. Recent studies have indicated that overall levels of Py235 expression are essential for parasite virulence. Here we show that disruption of PY01365 in the virulent YM line directly impacts parasite virulence. Furthermore the disruption of PY01365 leads to a reduction in the number of schizonts that express members of Py235 that react specifically with the mcAb 25.77. Erythrocyte binding assays show reduced binding of Py235 to red blood cells in the PY01365 knockout parasite as compared to YM. While our results identify PY01365 as a mediator of parasite virulence, they also confirm that other members of Py235 are able to substitute for PY01365

Real-time phase-contrast x-ray imaging: a new technique for the study of animal form and function

BACKGROUND: Despite advances in imaging techniques, real-time visualization of the structure and dynamics of tissues and organs inside small living animals has remained elusive. Recently, we have been using synchrotron x-rays to visualize the internal anatomy of millimeter-sized opaque, living animals. This technique takes advantage of partially-coherent x-rays and diffraction to enable clear visualization of internal soft tissue not viewable via conventional absorption radiography. However, because higher quality images require greater x-ray fluxes, there exists an inherent tradeoff between image quality and tissue damage. RESULTS: We evaluated the tradeoff between image quality and harm to the animal by determining the impact of targeted synchrotron x-rays on insect physiology, behavior and survival. Using 25 keV x-rays at a flux density of 80 μW/mm(-2), high quality video-rate images can be obtained without major detrimental effects on the insects for multiple minutes, a duration sufficient for many physiological studies. At this setting, insects do not heat up. Additionally, we demonstrate the range of uses of synchrotron phase-contrast imaging by showing high-resolution images of internal anatomy and observations of labeled food movement during ingestion and digestion. CONCLUSION: Synchrotron x-ray phase contrast imaging has the potential to revolutionize the study of physiology and internal biomechanics in small animals. This is the only generally applicable technique that has the necessary spatial and temporal resolutions, penetrating power, and sensitivity to soft tissue that is required to visualize the internal physiology of living animals on the scale from millimeters to microns

The Puf-Family RNA-Binding Protein Puf2 Controls Sporozoite Conversion to Liver Stages in the Malaria Parasite

Malaria is a vector-borne infectious disease caused by unicellular, obligate intracellular parasites of the genus Plasmodium. During host switch the malaria parasite employs specialized latent stages that colonize the new host environment. Previous work has established that gametocytes, sexually differentiated stages that are taken up by the mosquito vector, control expression of genes required for mosquito colonization by translational repression. Sexual parasite development is controlled by a DEAD-box RNA helicase of the DDX6 family, termed DOZI. Latency of sporozoites, the transmission stage injected during an infectious blood meal, is controlled by the eIF2alpha kinase IK2, a general inhibitor of protein synthesis. Whether RNA-binding proteins participate in translational regulation in sporozoites remains to be studied. Here, we investigated the roles of two RNA-binding proteins of the Puf-family, Plasmodium Puf1 and Puf2, during sporozoite stage conversion. Our data reveal that, in the rodent malaria parasite P. berghei, Puf2 participates in the regulation of IK2 and inhibits premature sporozoite transformation. Inside mosquito salivary glands puf2(-) sporozoites transform over time to round forms resembling early intra-hepatic stages. As a result, mutant parasites display strong defects in initiating a malaria infection. In contrast, Puf1 is dispensable in vivo throughout the entire Plasmodium life cycle. Our findings support the notion of a central role for Puf2 in parasite latency during switch between the insect and mammalian hosts