Simulation of the conditions of wave excitation for the optimization of the lower hybrid current drive in the Globus-M spherical tokamak

At present, the method of current drive by means of lower hybrid waves is not applied to low-aspect-ratio tokamaks, because, in the traditional approach, it would be necessary to use waves with a very high slowing-down factor. However, studies of new transparency regions for waves in a nonuniform magnetized plasma, performed earlier at the Ioffe Physical Technical Institute, Russian Academy of Sciences, made it possible to develop an approach in which slow waves are excited in the poloidal (rather than toroidal) direction. In this approach, moderately slowed-down waves first propagate in the poloidal direction, but then turn in the toroidalal direction and get into the dense plasma. In this work, this approach is further developed using numerical methods. In particular, the influence of the density profile in the edge plasma on the efficiency of wave excitation for given antenna parameters is studied in detail.     

New inhibitors of 5-lipoxygenase catalytic activity based on 2-(3-methylphenyl)propanoic acid and 4-substituted morpholine derivatives

New potential inhibitors of 5-lipoxygenase (5-LOX) based on the structure of 2-(3-benzoylphenyl)propanoic acid (an active component of the nonsteroidal antiinflammatory drug Ketoprofen) were designed using the SARD-21 program. The docking of these compounds in the active site of 5-LOX suggested that seven compounds can interact with this enzyme. Two of them can also be dual inhibitors of 5-LOX and two isoforms of cyclooxygenase.     

Detection of Alpha-Rod Protein Repeats Using a Neural Network and Application to Huntingtin

A growing number of solved protein structures display an elongated structural domain, denoted here as alpha-rod, composed of stacked pairs of anti-parallel alpha-helices. Alpha-rods are flexible and expose a large surface, which makes them suitable for protein interaction. Although most likely originating by tandem duplication of a two-helix unit, their detection using sequence similarity between repeats is poor. Here, we show that alpha-rod repeats can be detected using a neural network. The network detects more repeats than are identified by domain databases using multiple profiles, with a low level of false positives (<10%). We identify alpha-rod repeats in approximately 0.4% of proteins in eukaryotic genomes. We then investigate the results for all human proteins, identifying alpha-rod repeats for the first time in six protein families, including proteins STAG1-3, SERAC1, and PSMD1-2 & 5. We also characterize a short version of these repeats in eight protein families of Archaeal, Bacterial, and Fungal species. Finally, we demonstrate the utility of these predictions in directing experimental work to demarcate three alpha-rods in huntingtin, a protein mutated in Huntington''s disease. Using yeast two hybrid analysis and an immunoprecipitation technique, we show that the huntingtin fragments containing alpha-rods associate with each other. This is the first definition of domains in huntingtin and the first validation of predicted interactions between fragments of huntingtin, which sets up directions toward functional characterization of this protein. An implementation of the repeat detection algorithm is available as a Web server with a simple graphical output: http://www.ogic.ca/projects/ard. This can be further visualized using BiasViz, a graphic tool for representation of multiple sequence alignments.     

An APD-based iterative reconstruction method for simultaneous technetium-99m/iodine-123 SPECT imaging

Dual-isotope SPECT (DI-SPECT) studies offer significant advantages over sequential scans, foremost among them faster acquisition and perfect image registration. However, reconstructed images may be affected by substantial cross-talk contamination rendering them inadequate for diagnosis. This effect is especially strong for isotopes with close photopeak energies, such as ^99mTc (140 keV) and ¹²³I (159 keV). In this paper we present an iterative DI-SPECT reconstruction method which includes accurate, analytically computed scatter corrections provided by the APD (analytical photon distribution) algorithm. This algorithm calculates first and second order Compton scatter (based on the Klein–Nishina formula) and first order Rayleigh scatter. Both self-scatter and cross-talk between the two isotopes are evaluated using patient specific attenuation maps and an initial activity distribution estimate. To validate our method we performed experiments using the Data Spectrum, Inc. thorax phantom and a SPECT/CT camera system. Reconstructed images demonstrate significant improvement in data quantitation. Their quantitative accuracy increases up to a factor of two, even for activity ratios which strongly enhance cross-talk effects and seriously degrade projections.     

Noninductive plasma generation and current drive in the Globus-M spherical tokamak

Experimental results on the generation and maintenance of the toroidal current in the Globus-M spherical tokamak by using waves in the lower hybrid frequency range without applying an inductive vortex electric field are presented. For this purpose, the original ridge guide antennas forming a field distribution similar to that produced by multiwaveguide grills were used. The high-frequency field (900 MHz) was used for both plasma generation and current drive. The magnitude of the generated current reached 21 kA, and its direction depended on the direction of the vertical magnetic field. Analysis of the experimental results indicates that the major fraction of the current is carried by the suprathermal electron beam.     

Investigation of interaction of thrombin-binding aptamer with thrombin and prethrombin-2 by simulation of molecular dynamics

Thrombin is a major component of blood clotting and involved in the formation of a fibrin clot. One of the precursors during thrombin maturation is prethrombin-2, with the presence of Arg363-Ile364 bond between the light and heavy chain of protein, the only distinction from thrombin. Prethrombin-2 is able to interact with less efficiency with a 15-mer thrombin-binding aptamer (TBA). We investigate the interaction of both known conformers of TBA with thrombin and prethrombin-2 by simulation of molecular dynamics. It was shown that TBA could interact with thrombin in both conformations with similar efficiency, although a stable complex of prethrombin-2 with TBA was found only in conformation identical with the aptamer structure, pdb 1HAO. Analysis of molecular dynamics of complexes offered an assumption that the motion of the exosite-1 forming loop Lys428-Ile438 determined the difference in affinity of the complexes of TBA with thrombin and prethrombin-2.     

Dispersion properties of a magnetoactive plasma-filled waveguide in the vicinity of the upper hybrid frequency. Part II

The dispersion properties of a magnetoactive plasma-filled waveguide in the vicinity of the upper hybrid frequency ω₁ = (ω _p ² + ω _B ² )^1/2 (ω₁ ? δ < ω < ω₁) are studied. It is shown that, in this frequency range, the eigenmodes of the plasma-filled waveguide are represented by the families of EH and cyclotron HE modes, the interaction between which is weak everywhere except for the vicinities of certain points in the (ω, k _z ) plane. The equations describing the behavior of the dispersion curves in these vicinities are derived. It is shown that, as a result of the interaction, the high-frequency branches of EH modes acquire the cutoff frequencies corresponding to the high-order propagating HE modes. It is established that the anisotropic HE_+l mode can also interact with cyclotron HE modes. In this case, its dispersion curve enters the lower half-vicinity of the upper hybrid frequency, where it is modified due to the interaction, and then leaves it.     

Toll-like receptors and their adapter molecules

Toll-like receptors (TLR) are among key receptors of the innate mammalian immune system. Receptors of this family are able to recognize specific highly conserved molecular regions (patterns) in pathogen structures, thus initiating reactions of both innate and acquired immune response finally resulting in the elimination of the pathogen. In this case every individual TLR type is able to bind a broad spectrum of molecules of microbial origin characterized by different chemical properties and structures. Recent data demonstrate the existence of a multistep mechanism of the TLR recognition of the pathogen in which, in addition to receptors proper, the involvement of different adapter molecules is necessary. However, functions of separate adapter molecules as well as the principles of formation of a multicomponent system of ligand-specific recognition are still not quite understandable. We describe all identified as well as possible (candidate) adapter TLR molecules by giving their brief characteristics, and we also propose generalized possible variants of the TLR ligand-specific recognition with involvement of adapter molecules.     

Genetic Passive Immunization with Adenoviral Vector Expressing Chimeric Nanobody-Fc Molecules as Therapy for Genital Infection Caused by Mycoplasma hominis

Developing pathogen-specific recombinant antibody fragments (especially nanobodies) is a very promising strategy for the treatment of infectious disease. Nanobodies have great potential for gene therapy application due to their single-gene nature. Historically, Mycoplasma hominis has not been considered pathogenic bacteria due to the lack of acute infection and partially due to multiple studies demonstrating high frequency of isolation of M. hominis samples from asymptomatic patients. However, recent studies on the role of latent M. hominis infection in oncologic transformation, especially prostate cancer, and reports that M. hominis infects Trichomonas and confers antibiotic resistance to Trichomonas, have generated new interest in this field. In the present study we have generated specific nanobody against M. hominis (aMh), for which the identified target is the ABC-transporter substrate-binding protein. aMh exhibits specific antibacterial action against M. hominis. In an attempt to improve the therapeutic properties, we have developed the adenoviral vector-based gene therapy approach for passive immunization with nanobodies against M. hominis. For better penetration into the mucous layer of the genital tract, we fused aMh with the Fc-fragment of IgG. Application of this comprehensive approach with a single systemic administration of recombinant adenovirus expressing aMh-Fc demonstrated both prophylactic and therapeutic effects in a mouse model of genital M. hominis infection.     

Dispersion properties of a magnetoactive plasma-filled waveguide in the vicinity of the upper hybrid frequency. Part I

The dispersion properties of a magnetoactive plasma-filled waveguide in the vicinity of the upper hybrid frequency ω₁ = (ω _p ² + ω _B ² )^1/2 (ω₁ ≤ ω < ω₁ + δ) are studied. In this frequency range, the eigenfrequency spectrum and the structure of the waveguide eigenfields are difficult to analyze, because one of the transverse wavenumbers tends to infinity as the upper hybrid frequency is approached. It is shown that this problem can be solved by transforming the dispersion relation into a form independent of this transverse wavenumber. It is also found that the upper hybrid frequency itself can also be a solution to the dispersion relation. The influence of the properties of the magnetoactive plasma-filled waveguide on such solutions is studied. The structure of the fields for modes with frequencies equal to the upper hybrid frequency and an infinitely large absolute value of one of the transverse wavenumbers is analyzed.