A simple approach to the correlation of rotovibrational states in four-atomic molecules

The problem of correlation between quantum states of four-atomic molecules in different geometrical configurations is reviewed in detail. A general, still simple rule is obtained which allows one to correlate states of a linear four-atomic molecule with those of any kind of non-linear four-atomic molecule.Comment: 16 pages (+8 figures), Postscript (ready to print!

Structural stability of aluminum stabilized alpha nickel hydroxide as a positive electrode material for alkaline secondary batteries

10.1016/S0378-7753(00)00391-8Journal of Power Sources89140-45JPSO

Safety, efficacy, and pharmacokinetics of gremubamab (MEDI3902), an anti-Pseudomonas aeruginosa bispecific human monoclonal antibody, in P. aeruginosa-colonised, mechanically ventilated intensive care unit patients: a randomised controlled trial.

Ventilator-associated pneumonia caused by Pseudomonas aeruginosa (PA) in hospitalised patients is associated with high mortality. The effectiveness of the bivalent, bispecific mAb MEDI3902 (gremubamab) in preventing PA nosocomial pneumonia was assessed in PA-colonised mechanically ventilated subjects. EVADE (NCT02696902) was a phase 2, randomised, parallel-group, double-blind, placebo-controlled study in Europe, Turkey, Israel, and the USA. Subjects ≥ 18 years old, mechanically ventilated, tracheally colonised with PA, and without new-onset pneumonia, were randomised (1:1:1) to MEDI3902 500, 1500 mg (single intravenous dose), or placebo. The primary efficacy endpoint was the incidence of nosocomial PA pneumonia through 21 days post-dose in MEDI3902 1500 mg versus placebo, determined by an independent adjudication committee. Even if the initial sample size was not reached because of low recruitment, 188 subjects were randomised (MEDI3902 500/1500 mg: n = 16/87; placebo: n = 85) between 13 April 2016 and 17 October 2019. Out of these, 184 were dosed (MEDI3902 500/1500 mg: n = 16/85; placebo: n = 83), comprising the modified intent-to-treat set. Enrolment in the 500 mg arm was discontinued due to pharmacokinetic data demonstrating low MEDI3902 serum concentrations. Subsequently, enrolled subjects were randomised (1:1) to MEDI3902 1500 mg or placebo. PA pneumonia was confirmed in 22.4% (n = 19/85) of MEDI3902 1500 mg recipients and in 18.1% (n = 15/83) of placebo recipients (relative risk reduction [RRR]: - 23.7%; 80% confidence interval [CI] - 83.8%, 16.8%; p = 0.49). At 21 days post-1500 mg dose, the mean (standard deviation) serum MEDI3902 concentration was 9.46 (7.91) μg/mL, with 80.6% (n = 58/72) subjects achieving concentrations > 1.7 μg/mL, a level associated with improved outcome in animal models. Treatment-emergent adverse event incidence was similar between groups. The bivalent, bispecific monoclonal antibody MEDI3902 (gremubamab) did not reduce PA nosocomial pneumonia incidence in PA-colonised mechanically ventilated subjects. Trial registration Registered on Clinicaltrials.gov ( NCT02696902 ) on 11th February 2016 and on EudraCT ( 2015-001706-34 ) on 7th March 2016

Antigen-specific B and T cells in human/mouse radiation chimera following immunization in vivo

Adoptive transfer of human peripheral blood mononuclear cells (PBMC) into mice with severe combined immunodeficiency (SCID) or into lethally irradiated BALB/c mice radioprotected with SCID bone marrow, leads to marked engraftment of human T and B cells. In such chimeras, human serum antibody responses can be stimulated readily by vaccination with recall antigens, but the detection of antigen-specific functional T or B cells has been extremely difficult. In the present study, we were able to detect by Elispot analysis high frequencies of immunoglobulin G (IgG)-secreting B cells and mitogen-responsive interferon-γ (IFN-γ) or interleukin-4 (IL-4)-secreting T cells in peritoneum and spleen of human/BALB/c chimeric mice during the first 3 weeks after PBMC transfer. Moreover, specific memory responses were elicited by vaccination with tetanus toxoid (TT) or hepatitis B virus (HBV) surface (HBs) antigen of chimeric mice transplanted with PBMC derived from TT- or HBV-immune donors. Substantially higher TT-specific B-cell frequencies were found during the first 3 weeks after vaccination in mice challenged with the specific antigen compared to the levels found in control animals. High numbers of TT-specific IFN-γ-secreting T cells persisted in the peritoneum of vaccinated, but not of unvaccinated, animals during the entire observation period, but only low numbers of specific IL-4-secreting T cells were found in vaccinated mice. Similar results were achieved following vaccination with HBs antigen of chimeric mice, transplanted with PBMC of HBV immunized donors. Thus, TT or HBsAg-specific antibody responses in our model correlate closely with the existence of specific IFN-γ-secreting T helper 1/0 cells. Furthermore, these results show that adoptive transfer of human PBMC into lethally irradiated mice provides an efficient approach to generate specific B-cell fusion partners for the production of human monoclonal antibodies and specific T-cell lines for adoptive cell therapy of malignant or infectious diseases