Quality of Life After Bilateral Adrenalectomy in MEN 2

Pheochromocytoma is a major cause of morbidity and mortality in the multiple endocrine neoplasia type 2 (MEN 2) syndrome. For the physician, surgical treatment seems well justified even though bilateral adrenalectomy will induce iatrogenically complete loss of adrenocortical function. For the patient this treatment may be a cause of medical problems as well as worry. We have evaluated quality of life after bilateral adrenalectomy in 27 MEN 2 patients through a combined oral and written approach. Mortality was low (one of 27), as was serious morbidity. Most patients had adapted well to the postadrenalectomy state. However, fatigue, worry, and noncompliance with daily medication often caused problems

AFM pulling and the folding of donor-acceptor oligorotaxanes: phenomenology and interpretation

The thermodynamic driving force in the self-assembly of the secondary structure of a class of donor-acceptor oligorotaxanes is elucidated by means of molecular dynamics simulations of equilibrium isometric single-molecule force spectroscopy AFM experiments. The oligorotaxanes consist of cyclobis(paraquat-\emph{p}-phenylene) rings threaded onto an oligomer of 1,5-dioxynaphthalenes linked by polyethers. The simulations are performed in a high dielectric medium using MM3 as the force field. The resulting force vs. extension isotherms show a mechanically unstable region in which the molecule unfolds and, for selected extensions, blinks in the force measurements between a high-force and a low-force regime. From the force vs. extension data the molecular potential of mean force is reconstructed using the weighted histogram analysis method and decomposed into energetic and entropic contributions. The simulations indicate that the folding of the oligorotaxanes is energetically favored but entropically penalized, with the energetic contributions overcoming the entropy penalty and effectively driving the self-assembly. In addition, an analogy between the single-molecule folding/unfolding events driven by the AFM tip and the thermodynamic theory of first-order phase transitions is discussed and general conditions, on the molecule and the cantilever, for the emergence of mechanical instabilities and blinks in the force measurements in equilibrium isometric pulling experiments are presented. In particular, it is shown that the mechanical stability properties observed during the extension are intimately related to the fluctuations in the force measurements.Comment: 42 pages, 17 figures, accepted to the Journal of Chemical Physic

The Distance to the M31 Globular Cluster System

The distance to the centroid of the M31 globular cluster system is determined by fitting theoretical isochrones to the observed red-giant branches of fourteen globular clusters in M31. The mean true distance modulus of the M31 globular clusters is found to be 24.47 +/- 0.07 mag. This is consistent with distance modulii for M31 that have been obtained using other distance indicators.Comment: 11 pages, 2 postscript figures, uses aaspp4.sty, to be published in the May 1998 Astronomical Journa

Blind prediction of distribution in the SAMPL5 challenge with QM based protomer and pK_a corrections

The computation of distribution coefficients between polar and apolar phases requires both an accurate characterization of transfer free energies between phases and proper accounting of ionization and protomerization. We present a protocol for accurately predicting partition coefficients between two immiscible phases, and then apply it to 53 drug-like molecules in the SAMPL5 blind prediction challenge. Our results combine implicit solvent QM calculations with classical MD simulations using the non-Boltzmann Bennett free energy estimator. The OLYP/DZP/SMD method yields predictions that have a small deviation from experiment (RMSD = 2.3 log D units), relative to other participants in the challenge. Our free energy corrections based on QM protomer and pKa calculations increase the correlation between predicted and experimental distribution coefficients, for all methods used. Unfortunately, these corrections are overly hydrophilic, and fail to account for additional effects such as aggregation, water dragging and the presence of polar impurities in the apolar phase. We show that, although expensive, QM-NBB free energy calculations offer an accurate and robust method that is superior to standard MM and QM techniques alone

Surface Enhanced Second Harmonic Generation from Macrocycle, Catenane, and Rotaxane Thin Films: Experiments and Theory

Surface enhanced second harmonic generation (SE SHG) experiments on molecular structures, macrocycles, catenanes, and rotaxanes, deposited as monolayers and multilayers by vacuum sublimation on silver, are reported. The measurements show that the molecules form ordered thin films, where the highest degree of order is observed in the case of macrocycle monolayers and the lowest in the case of rotaxane multilayers. The second harmonic generation activity is interpreted in terms of electric field induced second harmonic (EFISH) generation where the electric field is created by the substrate silver atoms. The measured second order nonlinear optical susceptibility for a rotaxane thin film is compared with that obtained by considering only EFISH contribution to SHG intensity. The electric field on the surface of a silver layer is calculated by using the Delphi4 program for structures obtained with TINKER molecular mechanics/dynamics simulations. An excellent agreement is observed between the calculated and the measured SHG susceptibilities.