Biomedical subjects
Publications and source records attributed to V A Efimov.
Thymidine oligonucleotide analogues with phosphodiester bonds fully substituted by carboxamidomethyl phosphonamide, or glycinamide linkages were synthesized on a solid support, and their hybridization properties toward DNA and RNA targets were determined by Tm analysis.
In an attempt to improve physico-chemical and biological properties of peptide nucleic acids (PNAs), particularly water solubility and cellular uptake, the synthesis of chimeric oligomers consisted of PNA and phosphono-PNA analogues (pPNAs) bearing the four natural nucleobases has been accomplished. To produce these chimeras, pPNA monomers of two types containing N-(2-hydroxyethyl)phosphonoglycine, or N-(2-aminoethyl)phosphonoglycine backbone, were used in conjunction with PNA monomers representing derivatives of N-(2-aminoethyl)glycine, or N-(2-hydroxyethyl)glycine. The oligomers obtained were composed of either PNA and pPNA stretches or alternating PNA and pPNA monomers. The examination of hybridization properties of PNA-pPNA chimeras to DNA and RNA complementary strands in comparison with pure PNAs, and pPNAs as well as DNA-pPNA hybrids and DNA fragments confirmed that these chimeras form stable complexes with complementary DNA and RNA fragments. They were found to be resistant to degradation by nucleases. All these properties together with good solubility in water make PNA-pPNA hybrids promising for further evaluation as potential therapeutic agents.
BACKGROUND: The interactions of individuals participating in space simulation studies can give us valuable information about ways that space crew members relate with one another. A promising method of investigating such interactions is based on the Kelly repertory grid technique. HYPOTHESES: We predicted that in a space simulation crew: 1) one's personal self-concept would become closer to concepts about other crew members in a cohesive crew, and vice-versa, and 2) the similarity of one's ego images in the past, present and future influences that person's position in the group. METHOD: Crews from two isolation studies lasting 135 and 90 days at the Institute for Biomedical Problems in Moscow were evaluated using a modification of the Kelly repertory grid technique. Members assessed each other on a monthly basis and during off-nominal simulated docking periods. RESULTS: During both isolations, crew members were unsuccessful in making their personal self-concepts move closer to their concepts about fellow crew members. Crew disintegration resulted, with one member becoming an outsider whose personality was characterized by a disintegrated ego-image and an infantile type of the present ego. CONCLUSIONS: In small isolated groups, failure to make personal self-concepts become more like concepts about other crew members can lead to group disintegration and tension and can result in the appearance of an outsider who has a disintegrated ego-image and an infantile present ego.
The synthesis of a series of DNA mimics--peptide nucleic acids, phosphonate analogues of peptide nucleic acids, and their hybrids--is described. The preparative synthesis of the corresponding monomers and the solid phase automated synthesis of oligomers-mimics are developed. Modified phosphonate analogues of peptide nucleic acids, in particular chiral derivatives and those with additional hydroxyl groups in the side chains of the backbone as well as pyrene derivatives of peptide nucleic acids and their phosphonate analogues, are prepared. The ability of the resulting oligomers specifically to hybridize to DNA and RNA complementary chains is studied. It is shown that phosphonate analogues of peptide nucleic acids and their hybrids with peptide nucleic acids can form complexes with the DNA and RNA complementary strands, the stability of the complexes increasing in parallel with the increase in the number of peptide nucleic acid residues in the chain of the mimic. This property, along with good water solubility, provides the precondition for further evaluation of these compounds as antisense and antigene agents.
The Tth DNA polymerase genes from the thermophilic bacterium Thermus thermophilus (strans HB-8 and Tt-111) were cloned and expressed in Escherichia coli cells. The target protein contained a polyhistidine tag at the N-terminus that allowed its single-stage isolation by affinity chromatography on Ni-NTA-agarose. The isolated enzyme displayed both high DNA polymerase and reverse transcriptase activities.
BACKGROUND: The communication between space crews and outside monitoring personnel in Mission Control gives us valuable information about crewmember psychological health. Studying the formal parameters of similar communication during ground-based space simulation missions helps us understand the psychological climate of confined groups over time, and this information can be applied to long-term space missions. HYPOTHESES: We hypothesized that psychological closing and information filtration will be observed in a confined crew as the mission progresses and will differ by the type of communication (e.g., audio vs. computer-generated) with the outside monitors in the simulated Mission Control (MC). In addition, communication patterns will vary with the specific group of people on-duty outside. METHOD: Audio and computer communications between space simulation crews and MC teams were analyzed during two isolation studies lasting 135 and 90 d at the Institute for Biomedical Problems in Moscow. A number of temporal, content and quantitative parameters of verbal activity were examined. RESULTS: The total intensity of communication dropped after month 1 of the missions. The Commander had the highest intensity of communication. There was evidence for the presence of psychological closing and information filtration in the crews over time, with some variation based on type of communication. Communication patterns differed with different outside teams. CONCLUSIONS: The communication between confined groups and outside monitoring personnel is affected by psychological closing and information filtration and by the make-up of the teams that comprise the monitoring groups.
Analyzed were indices of communicative activity of crew members during audio- and computer sessions in order to assess status and effectiveness of communicative interaction of crew with external parties. The investigation gave another evidence that an isolated small group develops "closing" and "internal censorship" in contacts with outer personnel. The conclusion was based on limited in intensity, number, topical spectrum and outer companion preference communication. These appeared to be parallel to egocentrism manifested by claims on supreme concern, sensitivity to speech tones and matter of massages of outer supporters, and attempted manipulation with the outer personnel. In the course of the experiment, the subjects were getting more into the habit to use the information channels for expansion of their emotional contacts and "dumping" emotions. Differential attitude to different duty teams and selective manner of communication underlie differences in the intensity of crew-ground personnel communication.
In experiments HUBES and ECOPSY-95 small groups of test-subjects under the conditions of long-term isolation and confinement were noted to split into two fairly stable parts each consisting of two crew members and an "outsider". Strain in the interaction between the "outsider" and the crew tended to grow in acuity as was evidenced by rise in the criteria describing behavior of a small group, and relationship. In both experiments the background for the conflict-threatening strain appeared to be a disintegrated ego-image in both of the "outsiders". Generally, infantilism of ego-image was in hand with hand with low self-assessment. Development by the subjects of ineffective patterns of the attitude system which we consider to be "escape back to the past" and "disintegration" of ego-image overlapped with the most psychologically challenging periods in the experiments, i.e. the start and the end of isolation and confinement, and off-nominal situations.
Dynamics of mental performance, critical periods of adaptation, and cognitive processes were studies in conjunction with extended experimental isolation. Training to simple motor skills was found to be less impeded by prolonged isolation as opposed to operations requiring active involvement of higher psychic functions (memory, concentration, thinking). Experiments HUBES and ECOPSY strengthened the hypothesis concerning possible advent of critical periods in prolonged isolation impacting mental performance. They are the initial period (week 1 in isolation), emergency, arrival of visiting crews, and finishing two weeks. Effect of isolation was not so much evident from changes in absolute meanings of work parameters as from the reduction of their stability in time.
The aim of this study was to investigate the effects of prolonged isolation on the higher psychic functions, like working memory, attention concentration, and intellect (problem solving and decision making), and on sensory-motor skills and stress resistance. Previous Soviet simulation studies and the ISEMSI isolation experiment have indicated that prolonged isolation can affect higher psychic functions. A set of psychological tests in the form of a computer game was presented each workday to the chamber crew and to the ground crew serving as a control group. In analyzing the data it was taken into account that performance can be affected not only by the influence of isolation, but also by a learning process and by subject motivation. In addition, a distinction was made between absolute score and stability (range) of the score. Analysis of the chamber crew's work capability as a function of time showed the occurrence of three distinct periods of adaptation: (1) a period of acute adaptation in week 1, (2) a period of stable adaptation during weeks 3-6, and (3) a period of "final effort" in weeks 8-9. While in general the effect of isolation on the absolute scores was minor, larger ranges for the scores in "working memory," "attention concentration," and "calculation under time deficit" tests are an indication of increased instability, probably due to stress resistance. The 4 female subjects of the combined groups scored significantly higher than the 5 males in "attention concentration/distribution," "spatial orientation," "intuition in visual search," and "logical decision making under time deficit." Males presented higher scores in "calculation under time deficit" and working memory, and higher stability in "attention concentration" and "calculation under time deficit."
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Chemicoenzymatic synthesis and cloning of a gene encoding the Fc domain of human immunoglobulin G1 were carried out. The artificial gene was expressed in Escherichia coli cells in plasmid vectors under control of a late T7 promoter. The recombinant protein isolated from the bacterial cells is capable of forming dimers and binding protein A from Staphylococcus aureus.
The aim of this study was to investigate changes in the psychological state of the crew members and the needs for psychological support during prolonged isolation. For the purpose methods employed that have been widely used in psychological evaluation during Soviet spaceflights. Communication between Commander and Crew Interface Coordinator (CIC) was analyzed. Crew disposition was observed and analyzed for information about the process of group formation and the role of each crew member in this process. Operation of the CIC's was investigated for evidence of a psychological support function. During isolation certain adaptive changes in communication took place: (1) use of unplanned contacts and intensive contacts with a preferred ground crew member, (2) resistance to penetration in the life of the crew (increase of aggressive statements and self-justifications, reduction of report length and claims), and (3) closing communication to "outsiders" by using a special code and decreasing discussion of problems. A process of group formation was noted in the course of isolation, but the final structure of the group was not stable. The relations of subjects B, D and G were crucial in the creation of an effective crew. The woman in the crew was never involved in conflicts and acted as a peacemaker. The crew regarded the communication channel between Commander and CIC as belonging to the entire crew for expressing feelings about crew relations, administration and services, and the CIC can provide needed psychological support, confirming earlier experience from Soviet simulated and actual spaceflights.
To verify experimentally the molecular recognition theory, plasmids were constructed that provided the efficient synthesis of hybrid proteins composed of human calcitonin or miniproinsulin, the corresponding antisense peptides, and a histidine-rich metal-binding peptide. A method for isolation of the hybrid proteins by metal-chelating chromatography, cleavage, and renaturation was developed.
A set of new sulfurizing agents representing disulfides of arylsulfonic acids has been developed for the automated synthesis of phosphorothioate oligonucleotide analogues via the phosphoramidite method. These reagents, such as bis(benzenesulfonyl)disulfide, bis(p-toluenesulfonyl)disulfide, bis(p-methoxybenzensulfonyl)disulfide, and bis (p-chlorobenzenesulfonyl) disulfide, are easily prepared crystalline solid compounds. They are relatively inexpensive, easy to handle, and efficiently convert internucleotide cyanoethyl phosphite to the phosphorothioate triester within 1-2 min. The efficiency of phosphorothioate oligonucleotide synthesis with the use of these reagents is comparable to that of phosphodiester oligonucleotides.
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Described is a computerized technique for assessment of psychic performance. It includes a battery of tests in the form of computer games to score recent memory, attention, cognitive power, spatial awareness, and oculomotor orientation. The game-type tests and the possibility of feedback enforce motivation for diagnostic testing. The technique can be advantage for artificial or extreme environments as it can be fulfilled by subjects themselves without assistance of expert.
Plasmid vectors providing a high level expression in Escherichia coli cells of genes for heterologous polypeptides and proteins fused to peptides containing homohistidine clusters have been constructed. The obtained vectors have been used to achieve expression of genes for streptavidin, proinsulin and calcitonin. The hybrid proteins were isolated by affinity chromatography on Ni-agarose columns.