Performance of a superconducting cavity stabilized ruby maser oscillator

We first described an all-cryogenic oscillator system at the 1982 Applied Superconductivity Conference in Knoxville. This oscillator consists of a ruby cavity maser stabilized by a high-Q superconductor-on-sapphire resonator. The maser provides gain with very low noise and small power dissipation, while the sapphire substrate's thermal coefficient of expansion is 100 times smaller than that of superconducting metals. Having tested the major components and proved them satisfactory to the design, we have now assembled the first such oscillator and tested its performance in several preliminary configurations. The results of stability tests in a more advanced configuration will be reported. We shall describe this oscillator and shall report on its performance as a high-stability frequency source

Status of the Stony Brook Superconducting Heavy-Ion Linac

The present status of the Stony Brook Superconducting Heavy-Ion Linear Accelerator is described, with emphasis on recent operational results with a prototype unit of the accelerator. The basic LINAC elements are independently-phased lead-plated copper split-loop resonators operating at 151.7 MHz and optimized for velocities of either ß=v/c= 0.055 or ß=0.10. Resonators are grouped in units of either 4 low-ß or 3 high-ß resonators in compact cryostat modules separated by room-temperature quadrupole-doublet lenses. The LINAC consisting of 4 low-ß and 7 high-ß modules injected with heavy ions of mass A≃16-100 from the Stony Brook EN tandem will produce an additional energy gain of ~18 MeV per unit charge with a total heat dissipation at 4.5K of <300 Watts. In recent tests with low-ß prototype units, individual resonators were operated continuously at accelerating gradients in excess of 3.5 MV/m, and were phase and amplitude stabilized at 3.0 MV/ m using 175 Watts of RF power. Helium-temperature dissipation at 3.0 MV/m is ~8 Watts after helium-gas conditioning. The prototype low-ß module was used to accelerate a 30 Mev ^(16)O^(5+) beam to ~35 MeV

Status of the Stony Brook Superconducting Heavy-Ion Linac

We describe the present status of the State University of New York at Stony Brook Superconducting Heavy-Ion LINAC (SUNYLAC). The LINAC will extend at very modest cost the capabilities of the existing FN tandem Van de Graaff into the energy range 5-10 MeV/A for light heavy-ions from oxygen to bromine. The active elements are 43 lead-plated copper superconducting resonators of the split-loop type optimized for either velocity ß=v/c=0.055 or ß=0.10. Phase and amplitude of each resonator is independently set through RF-feedback controllers interfaced to an overall computer control system. Full scale construction work began in July, 1979 following the in-beam demonstration of a prototype LINAC module containing 4 low-ß resonators, and the majority of the installation work on the beam transport and refrigeration systems was completed in the summer of 1980. The project is now well into its final assembly and testing phase, with the completion of assembly scheduled in early 1982. We describe details of the design of key elements of the LINAC and the initial operating experience with the injection beam path, helium refrigerator and first production accelerator module. The progress of a continuing program aimed at optimizing crucial aspects of the LINAC is also reviewed

Genotyping of Plasmodium falciparum infections by PCR: a comparative multicentre study

Genetic diversity of malaria parasites represents a major issue in understanding several aspects of malaria infection and disease. Genotyping of Plasmodium falciparum infections with polymerase chain reaction (PCR)-based methods has therefore been introduced in epidemiological studies. Polymorphic regions of the msp1, msp2 and glurp genes are the most frequently used markers for genotyping, but methods may differ. A multicentre study was therefore conducted to evaluate the comparability of results from different laboratories when the same samples were analysed. Analyses of laboratory-cloned lines revealed high specificity but varying sensitivity. Detection of low-density clones was hampered in multiclonal infections. Analyses of isolates from Tanzania and Papua New Guinea revealed similar positivity rates with the same allelic types identified. The number of alleles detected per isolate, however, varied systematically between the laboratories especially at high parasite densities. When the analyses were repeated within the laboratories, high agreement was found in getting positive or negative results but with a random variation in the number of alleles detected. The msp2 locus appeared to be the most informative single marker for analyses of multiplicity of infection. Genotyping by PCR is a powerful tool for studies on genetic diversity of P. falciparum but this study has revealed limitations in comparing results on multiplicity of infection derived from different laboratories and emphasizes the need for highly standardized laboratory protocol

A Novel DBL-Domain of the P. falciparum 332 Molecule Possibly Involved in Erythrocyte Adhesion

Plasmodium falciparum malaria is brought about by the asexual stages of the parasite residing in human red blood cells (RBC). Contact between the erythrocyte surface and the merozoite is the first step for successful invasion and proliferation of the parasite. A number of different pathways utilised by the parasite to adhere and invade the host RBC have been characterized, but the complete biology of this process remains elusive. We here report the identification of an open reading frame (ORF) representing a hitherto unknown second exon of the Pf332 gene that encodes a cysteine-rich polypeptide with a high degree of similarity to the Duffy-binding-like (DBL) domain of the erythrocyte-binding-ligand (EBL) family. The sequence of this DBL-domain is conserved and expressed in all parasite clones/strains investigated. In addition, the expression level of Pf332 correlates with proliferation efficiency of the parasites in vitro. Antibodies raised against the DBL-domain are able to reduce the invasion efficiency of different parasite clones/strains. Analysis of the DBL-domain revealed its ability to bind to uninfected human RBC, and moreover demonstrated association with the iRBC surface. Thus, Pf332 is a molecule with a potential role to support merozoite invasion. Due to the high level of conservation in sequence, the novel DBL-domain of Pf332 is of possible importance for development of novel anti-malaria drugs and vaccines

Plasmodium falciparum proteinases: cloning of the putative gene coding for the merozoite proteinase for erythrocyte invasion (MPEI) and determination of hydrolysis sites of spectrin by Pf37 proteinase

Numerous proteinase activities have been shown to be essential for the survival of Plasmodium falciparum. One approach to antimalarial chemotherapy, would be to block specifically one or several of these activities, by using compounds structurally analogous to the substrates of these proteinases. Such a strategy requires a detailed knowledge of the active site of the proteinase, in order to identify the best substrate for the proteinase. Aiming at developing such a strategy, two proteinases previously identified in our laboratory, were chosen for further characterization of their molecular structure and properties: the merozoite proteinase for erythrocytic invasion (MPEI), involved in the erythrocyte invasion by the merozoites, and the Pf37 proteinase, which hydrolyses human spectrin in vitro

cAMP-Signalling Regulates Gametocyte-Infected Erythrocyte Deformability Required for Malaria Parasite Transmission.

Blocking Plasmodium falciparum transmission to mosquitoes has been designated a strategic objective in the global agenda of malaria elimination. Transmission is ensured by gametocyte-infected erythrocytes (GIE) that sequester in the bone marrow and at maturation are released into peripheral blood from where they are taken up during a mosquito blood meal. Release into the blood circulation is accompanied by an increase in GIE deformability that allows them to pass through the spleen. Here, we used a microsphere matrix to mimic splenic filtration and investigated the role of cAMP-signalling in regulating GIE deformability. We demonstrated that mature GIE deformability is dependent on reduced cAMP-signalling and on increased phosphodiesterase expression in stage V gametocytes, and that parasite cAMP-dependent kinase activity contributes to the stiffness of immature gametocytes. Importantly, pharmacological agents that raise cAMP levels in transmissible stage V gametocytes render them less deformable and hence less likely to circulate through the spleen. Therefore, phosphodiesterase inhibitors that raise cAMP levels in P. falciparum infected erythrocytes, such as sildenafil, represent new candidate drugs to block transmission of malaria parasites