Free energy reconstruction from nonequilibrium single-molecule pulling experiments

Laser tweezers and atomic force microscopes are increasingly used to probe the interactions and mechanical properties of individual molecules. Unfortunately, using such time-dependent perturbations to force rare molecular events also drives the system away from equilibrium. Nevertheless, we show how equilibrium free energy profiles can be extracted rigorously from repeated nonequilibrium force measurements on the basis of an extension of Jarzynski's remarkable identity between free energies and the irreversible work.     

1,4‐Bisbenzil: Visible‐Light‐ and Heat‐Assisted Crosslinking of Polystyrene Films

Polystyrene (PS) film containing 1,4‐bisbenzil is efficiently crosslinked in two steps. In the first step, visible light (λ > 400 nm) causes molecular oxygen to insert between two carbonyl groups of one of the 1,2‐dicarbonyl groups. The peroxide is subsequently decomposed by absorption of another photon, forming acyloxy radicals, which add to the aromatic ring of the PS chain. The remaining 1,2‐dicarbonyl group is then photoperoxidized to form PS with pendant benzoyl peroxide moieties. In the second step, pendant benzoyl peroxide groups are decomposed thermally to form acyloxy macroradicals responsible for the crosslinking. Crosslinking proceeds simultaneously with degradation. Finally, the gel content in the film may exceed 80 wt%.

     

Theory of the energy transfer efficiency and fluorescence lifetime distribution in single-molecule FRET

In single-molecule FRET experiments with pulsed lasers, not only the colors of the photons but also the fluorescence lifetimes can be monitored. Although these quantities appear to be random, they are modulated by conformational dynamics. In order to extract information about such dynamics, we develop the theory of the joint distribution of FRET efficiencies and fluorescence lifetimes determined from bins (or bursts) of photons. Our starting point is a rigorous formal expression for the distribution of the numbers of donor and acceptor photons and donor lifetimes in a bin that treats the influence of conformational dynamics on all timescales. This formula leads to an analytic result for a two-state system interconverting on a timescale slower than the interphoton time and to an efficient simulation algorithm for multistate dynamics. The shape of the joint distribution contains more information about conformational dynamics than the FRET efficiency histogram alone. In favorable cases, the connectivity of the underlying conformational states can be determined directly by simple inspection of the projection of the joint distribution on the efficiency-lifetime plane.     

Declining rates of deceased donor renal transplantation in the United States over successive years of listing

ObjectiveRenal transplantation is the best treatment for end-stage renal disease. However, limited availability of donor organs is a problem. We analyzed the changing trends of transplantation and mortality in subjects listed for deceased donor renal transplantation over successive years.MethodsBy using US Renal Data System data, we identified Medicare patients receiving dialysis who were listed for their first deceased donor renal transplant between January 1996 and December 2005. Subjects were followed to the first occurrence of transplant, death, or September 30, 2007. The effect of the year of listing was analyzed adjusting for age, sex, race, vintage, panel reactive antibody, and cause of end-stage renal disease.ResultsThere were 70,891 subjects (mean age 50.1 ± 14.3 years, 59.9% were men, 54% were white, average duration of dialysis 2 ± 2.2 years). Multivariate analysis revealed that compared with patients listed in 1996, for patients listed in subsequent years the cumulative incidence of death remained within a narrow boundary and the cumulative incidence of transplant progressively declined. For example, for subjects listed in 1998, 2000, 2002, and 2004, the cumulative incidence of death relative to 1996 was 1.02 (95% confidence interval [CI], 1.01-1.03), 1.02 (CI, 1.01-1.03), 0.99 (CI, 0.98-0.99), and 0.94 (CI, 0.93-0.94), respectively, 12 months after listing. However, correspondingly for these subjects at the 12-month follow-up time point, the cumulative incidence of transplant relative to 1996 was 0.85 (CI, 0.84-0.86), 0.73 (CI, 0.71-0.74), 0.63 (CI, 0.62-0.64), and 0.58 (CI, 0.57-0.59), respectively.ConclusionThere is a progressive unfavorable pattern of declining transplantation rates with each successive year of listing in patients listed for deceased donor renal transplantation.     

Recommendations in the event of a suspected transfusion-related acute lung injury (TRALI)

The following recommendations, which aim at improving the clinical diagnosis ofTRALI and the laboratory investigations that can support it, were drawn up by a working group of the Superior Health Council. TRALI is a complication of blood transfusion that is both serious and underreported. Systematic reporting may help to develop preventive actions. Therefore, the Superior Health Council recommends that there should be a more stringent surveillance of patients who receive a blood component transfusion. The clinician should pay very close attention to any change in the patient's respiratory status (cf. dyspnoea and arterial desaturation), which should be notified systematically to the haemovigilance contact person in the hospital.