The 2.0-Å resolution crystal structure of a trimeric antibody fragment with noncognate VH–VL domain pairs shows a rearrangement of VH CDR3

The 2.0-Å resolution x-ray crystal structure of a novel trimeric antibody fragment, a “triabody,” has been determined. The trimer is made up of polypeptides constructed in a manner identical to that previously described for some “diabodies”: a V_L domain directly fused to the C terminus of a V_H domain—i.e., without any linker sequence. The trimer has three Fv heads with the polypeptides arranged in a cyclic, head-to-tail fashion. For the particular structure reported here, the polypeptide was constructed with a V_H domain from one antibody fused to the V_L domain from an unrelated antibody giving rise to “combinatorial” Fvs upon formation of the trimer. The structure shows that the exchange of the V_L domain from antibody B1-8, a V_λ domain, with the V_L domain from antibody NQ11, a V_κ domain, leads to a dramatic conformational change in the V_H CDR3 loop of antibody B1-8. The magnitude of this change is similar to the largest of the conformational changes observed in antibody fragments in response to antigen binding. Combinatorial pairing of V_H and V_L domains constitutes a major component of antibody diversity. Conformationally flexible antigen-binding sites capable of adapting to the specific CDR3 loop context created upon V_H–V_L pairing may be employed by the immune system to maximize the structural diversity of the immune response.     

Influence of tumours on normal cells and optimal chemotherapy regimens: the case of several drugs and toxicity constraints.

Cancer chemotherapy with the application of several drugs is studied. The negative and inhibiting effect of the tumour on normal cells is taken into account. Under certain hypotheses, we determine the optimal regimen that minimizes the tumour burden at the end of a fixed period of therapy while maintaining several normal cell populations above prescribed levels. More precisely, it is demonstrated that the optimal drug administration corresponds to the strategy of intensive chemotherapy.     

Metrological aspects of radionuclide absorption measurements in bone tissue

Scientific-Research Institute for Medical Instrument Engineering, Moscow. Translated from Meditsinskaya Tekhnika, No. 6, p. 8, November–December, 1992.     

The prognosis of the professional fitness of sailors for action under extreme conditions]

The researches described in this article made it possible to substantiate a number of important professional qualities of seamen which are indispensable in extreme situations. Three professional categories, namely command duty officers, operators and specialists of the local posts were the matter of these researches. A combination of symptom complexes of individual qualities which predetermines a successful duty performance in extreme situations was disclosed. A complex of valid methods was substantiated for quantitative estimation of individual psychological qualities. On the basis of these symptom complexes the authors worked out the estimation criteria for prognostication of professional ability of seamen to act in extreme situations.     

Measurement of absolute intensities of some prompt gamma-lines from the 91Zr, 143Nd, 177Hf and 116,118-120,122,124Sn(n,gamma) reactions and isomeric cross-sections of 123m,125mSn by in-beam gamma-spectroscopy method.

The previously unknown absolute intensities of 28 prompt gamma-rays from the thermal neutron capture in 91Zr, 143Nd, 177Hf and 116,118-120,122,124Sn were measured by an in-beam gamma-spectroscopy method at the WWR-M reactor (PNPI, Gatchina). Cross sections of the production of isomers 123m,125mSn were also measured.