Energy transfer and charge separation in the purple non-sulfur bacterium Roseospirillum parvum

AbstractThe antenna reaction centre system of the recently described purple non-sulfur bacterium Roseospirillum parvum strain 930I was studied with various spectroscopic techniques. The bacterium contains bacteriochlorophyll (BChl) a, 20% of which was esterified with tetrahydrogeranylgeraniol. In the near-infrared, the antenna showed absorption bands at 805 and 909 nm (929 nm at 6 K). Fluorescence bands were located at 925 and 954 nm, at 300 and 6 K, respectively. Fluorescence excitation spectra and time resolved picosecond absorbance difference spectroscopy showed a nearly 100% efficient energy transfer from BChl 805 to BChl 909, with a time constant of only 2.6 ps. This and other evidence indicate that both types of BChl belong to a single LH1 complex. Flash induced difference spectra show that the primary electron donor absorbs at 886 nm, i.e. at 285 cm−1 higher energy than the long wavelength antenna band. Nevertheless, the time constant for trapping in the reaction centre was the same as for almost all other purple bacteria: 55±5 ps. The shape as well as the amplitude of the absorbance difference spectrum of the excited antenna indicated exciton interaction and delocalisation of the excited state over the BChl 909 ring, whereas BChl 805 appeared to have a monomeric nature

DNA computing using single-molecule hybridization detection

DNA computing aims at using nucleic acids for computing. Since micromolar DNA solutions can act as billions of parallel nanoprocessors, DNA computers can in theory solve optimization problems that require vast search spaces. However, the actual parallelism currently being achieved is at least a hundred million-fold lower than the number of DNA molecules used. This is due to the quantity of DNA molecules of one species that is required to produce a detectable output to the computations. In order to miniaturize the computation and considerably reduce the amount of DNA needed, we have combined DNA computing with single-molecule detection. Reliable hybridization detection was achieved at the level of single DNA molecules with fluorescence cross-correlation spectroscopy. To illustrate the use of this approach, we implemented a DNA-based computation and solved a 4-variable 4-clause instance of the computationally hard Satisfiability (SAT) problem

Quantifying the Composition of Human Skin for Glucose Sensor Development

\u3cp\u3eBackground: Glucose is heterogeneously distributed within human skin. In order to develop a glucose measurement method for human skin, both a good quantification of the different compartments of human skin and an understanding of glucose transport processes are essential. This study focused on the composition of human skin. In addition, the extent to which intersubject variability in skin composition alters glucose dynamics in human skin was investigated. Methods: To quantify the composition of the three layers of human skin - epidermis, dermis, and adipose tissue - cell and blood vessel volumes were calculated from skin biopsies. These results were combined with data from the literature. The composition was applied as input for a previously developed computational model that calculates spatiotemporal glucose dynamics in human skin. The model was used to predict the physiological effects of intersubject variability in skin composition on glucose profiles in human skin. Results: According to the model, the lag time of glucose dynamics in the epidermis was sensitive to variation in the volumes of interstitial fluid, cells, and blood of all layers. Data showed most variation/uncertainty in the volume composition of the adipose tissue. This variability mainly influences the dynamics in the adipose tissue. Conclusions: This study identified the intersubject variability in human skin composition. The study shows that this variability has significant influence on the glucose dynamics in human skin. In addition, it was determined which volumes are most critical for the quantification and interpretation of measurements in the different layers.\u3c/p\u3

Quantifying the composition of human skin for glucose sensor development

Background: Glucose is heterogeneously distributed within human skin. In order to develop a glucose measurement method for human skin, both a good quantification of the different compartments of human skin and an understanding of glucose transport processes are essential. This study focused on the composition of human skin. In addition, the extent to which intersubject variability in skin composition alters glucose dynamics in human skin was investigated. Methods: To quantify the composition of the three layers of human skin - epidermis, dermis, and adipose tissue - cell and blood vessel volumes were calculated from skin biopsies. These results were combined with data from the literature. The composition was applied as input for a previously developed computational model that calculates spatiotemporal glucose dynamics in human skin. The model was used to predict the physiological effects of intersubject variability in skin composition on glucose profiles in human skin. Results: According to the model, the lag time of glucose dynamics in the epidermis was sensitive to variation in the volumes of interstitial fluid, cells, and blood of all layers. Data showed most variation/uncertainty in the volume composition of the adipose tissue. This variability mainly influences the dynamics in the adipose tissue. Conclusions: This study identified the intersubject variability in human skin composition. The study shows that this variability has significant influence on the glucose dynamics in human skin. In addition, it was determined which volumes are most critical for the quantification and interpretation of measurements in the different layers

Phase I Testing of a Malaria Vaccine Composed of Hepatitis B Virus Core Particles Expressing Plasmodium falciparum Circumsporozoite Epitopes

We report the first phase I trial to assess the safety and immunogenicity of a malaria vaccine candidate, ICC-1132 (Malarivax), composed of a modified hepatitis B virus core protein (HBc) containing minimal epitopes of the Plasmodium falciparum circumsporozoite (CS) protein. When expressed in Escherichia coli, the recombinant ICC-1132 protein forms virus-like particles that were found to be highly immunogenic in preclinical studies of mice and monkeys. Twenty healthy adult volunteers received a 20- or a 50-μg dose of alum-adsorbed ICC-1132 administered intramuscularly at 0, 2, and 6 months. The majority of volunteers in the group receiving the 50-μg dose developed antibodies to CS repeats as well as to HBc. Malaria-specific T cells that secreted gamma interferon were also detected after a single immunization with ICC-1132-alum. These studies support ICC-1132 as a promising malaria vaccine candidate for further clinical testing using more-potent adjuvant formulations and confirm the potential of modified HBc virus-like particles as a delivery platform for vaccines against other human pathogens

Safety and Enhanced Immunogenicity of a Hepatitis B Core Particle Plasmodium falciparum Malaria Vaccine Formulated in Adjuvant Montanide ISA 720 in a Phase I Trial

Highly purified subunit vaccines require potent adjuvants in order to elicit optimal immune responses. In a previous phase I trial, an alum formulation of ICC-1132, a malaria vaccine candidate comprising hepatitis B core (HBc) virus-like particle containing Plasmodium falciparum circumsporozoite (CS) protein epitopes, was shown to elicit Plasmodium falciparum-specific antibody and cellular responses. The present study was designed as a single-blind, escalating-dose phase I trial to evaluate the safety and immunogenicity of single intramuscular doses of ICC-1132 formulated in the more potent water-in-oil adjuvant Montanide ISA 720 (ICC-1132/ISA 720). The vaccine was safe and well tolerated, with transient injection site pain as the most frequent complaint. All vaccinees that received either 20 μg or 50 μg of ICC-1132/ISA 720 developed antiimmunogen and anti-HBc antibodies. The majority of volunteers in these two groups developed sporozoite-specific antibodies, predominantly of opsonizing immunoglobulin G subtypes. Peak titers and persistence of parasite-specific antibody following a single injection of the ISA 720 formulated vaccine were comparable to those obtained following two to three immunizations with alum-adsorbed ICC-1132. Peripheral blood mononuclear cells of ICC-1132/ISA 720 vaccinees proliferated and released cytokines (interleukin 2 and gamma interferon) when stimulated with recombinant P. falciparum CS protein, and CS-specific CD4(+) T-cell lines were established from volunteers with high levels of antibodies to the repeat region. The promising results obtained with a single dose of ICC-1132 formulated in Montanide ISA 720 encourage further clinical development of this malaria vaccine candidate