Quantum chemical benchmark databases of gold-standard dimer interaction energies.

Advances in computational chemistry create an ongoing need for larger and higher-quality datasets that characterize noncovalent molecular interactions. We present three benchmark collections of quantum mechanical data, covering approximately 3,700 distinct types of interacting molecule pairs. The first collection, which we refer to as DES370K, contains interaction energies for more than 370,000 dimer geometries.

Mechanism of Na+/H+ antiporting.

Na+/H+ antiporters are central to cellular salt and pH homeostasis. The structure of Escherichia coli NhaA was recently determined, but its mechanisms of transport and pH regulation remain elusive. We performed molecular dynamics simulations of NhaA that, with existing experimental data, enabled us to propose an atomically detailed model of antiporter function.

Transesterification thio effects of phosphate diesters: free energy barriers and kinetic and equilibrium isotope effects from density-functional theory.

Primary and secondary kinetic and equilibrium isotope effects are calculated with density-functional methods for the in-line dianionic methanolysis of the native (unsubstituted) and thio-substituted cyclic phosphates. These reactions represent reverse reaction models for RNA transesterification under alkaline conditions. The effect of solvent is treated with explicit (single and double) water molecules and self-consistently with an implicit (continuum) solvation model.

Density functional study of the in-line mechanism of methanolysis of cyclic phosphate and thiophosphate esters in solution: insight into thio effects in RNA transesterification.

Density functional calculations of thio effects on the in-line mechanism of methanolysis of ethylene phosphate (a reverse reaction model for RNA phosphate transesterification) are presented. A total of 12 reaction mechanisms are examined using the B3LYP functional with large basis sets, and the effects of solvation were treated using the PCM, CPCM, and SM5 solvation models. Single thio substitutions at all of the distinct phosphoryl oxygen positions (2', 3', 5', pro-R) and a double thio substitution at the nonbridging (pro-R/pro-S) positions were considered.

Smooth solvation method for d-orbital semiempirical calculations of biological reactions. 2. Application to transphosphorylation thio effects in solution.

Density-functional and semiempirical quantum methods and continuum dielectric and explicit solvation models are applied to study the role of solvation on the stabilization of native and thio-substituted transphosphorylation reactions. Extensive comparison is made between results obtained from the different methods. For the semiempirical methods, explicit solvation was treated using a hybrid quantum mechanical/molecular mechanical (QM/MM) approach and the implicit solvation was treated using a recently developed smooth solvation model implemented into a d-orbital semiempirical framework (MNDO/d-SCOSMO) within CHARMM.

Smooth solvation method for d-orbital semiempirical calculations of biological reactions. 1. Implementation.

The present paper describes the extension of a recently developed smooth conductor-like screening model for solvation to a d-orbital semiempirical framework (MNDO/d-SCOSMO) with analytic gradients that can be used for geometry optimizations, transition state searches, and molecular dynamics simulations. The methodology is tested on the potential energy surfaces for separating ions and the dissociative phosphoryl transfer mechanism of methyl phosphate. The convergence behavior of the smooth COSMO method with respect to discretization level is examined and the numerical stability of the energy and gradient are compared to that from conventional COSMO calculations.

Variational electrostatic projection (VEP) methods for efficient modeling of the macromolecular electrostatic and solvation environment in activated dynamics simulations.

New methods for the calculation of electrostatic interactions between the active dynamical region and surrounding external solvated macromolecular environment in hybrid quantum mechanical/molecular mechanical (QM/MM) simulations are presented. The variational electrostatic projection (VEP) method, and related variational reverse-mapping procedure (VEP-RVM) utilize an expansion in Gaussian surface elements for representation of electrostatic interactions. The use of a discretized surface that surrounds the active dynamical region greatly reduces the number of interactions with the particles of the external environment.

Holeboard discrimination learning in mice.

We have adapted to mice a holeboard-learning task, which allows simultaneous assessment of spatial working and reference-memory performance. The holeboard apparatus consists of an open-field chamber with a 16-hole floor insert. Across trials, animals have to learn that the same four holes of 16 are always baited.

QCRNA 1.0: a database of quantum calculations for RNA catalysis.

This work outlines a new on-line database of quantum calculations for RNA catalysis (QCRNA) available via the worldwide web at http://theory.chem.umn.

A charge-scaling implementation of the variational electrostatic projection method.

Two new charge-scaling methods for efficient modeling of the solvated macromolecular environment in hybrid QM/MM calculations of biological reactions are presented. The methods are extensions of the variational electrostatic projection (VEP) method, and allows a subset of atomic charges in the external environment to be adjusted to mimic, in the active dynamical region, the electrostatic potential and field due to the large surrounding macromolecule and solvent. The method has the advantages that it offers improved accuracy, does not require the use of a three-dimensional grid or auxiliary set of fitting points, and requires only minor molecular simulation code modifications.

High-order discretization schemes for biochemical applications of boundary element solvation and variational electrostatic projection methods.

A series of high-order surface element discretization schemes for variational boundary element methods are introduced. The surface elements are chosen in accord with angular quadrature rules for integration of spherical harmonics. Surface element interactions are modeled by Coulomb integrals between spherical Gaussian functions with exponents chosen to reproduce the exact variational energy and Gauss's law for a point charge in a spherical cavity.

Gene delivery of human apolipoprotein E alters brain Abeta burden in a mouse model of Alzheimer's disease.

Apolipoprotein E (apoE) alleles are important genetic risk factors for Alzheimer's disease (AD), with the epsilon4 allele increasing and the epsilon2 allele decreasing risk for developing AD. ApoE has been shown to influence brain amyloid-beta peptide (Abeta) and amyloid burden, both in humans and in transgenic mice. Here we show that direct intracerebral administration of lentiviral vectors expressing the three common human apoE isoforms differentially alters hippocampal Abeta and amyloid burden in the PDAPP mouse model of AD.

Hybrid QM/MM study of thio effects in transphosphorylation reactions: the role of solvation.

Transphosphorylation thio effects in solution are studied using hybrid QM/MM calculations with a d-orbital semiempirical Hamiltonian. Activated dynamics simulations were performed for a 3' ribose-phosphate model in an explicit 20 A sphere of TIP3P water surrounded by a solvent boundary potential, and free energy analysis was performed using the weighted histogram analysis method. Single thio-substitutions at all of the phosphoryl oxygen positions and a double thio-substitution at the nonbridging positions were considered.

Hybrid QM/MM study of thio effects in transphosphorylation reactions.

Results of a series of hybrid quantum mechanical/molecular mechanical (QM/MM) activated dynamics simulations of thio effects in the transphosphorylation (methanolysis) of a 2'-ribose, 5'-methyl phosphate-diester under basic conditions are presented. Single and double substitutions in the nonbridging oxygen positions exhibit thio effects in accord with experimental data and show the existence of a stable intermediate. Thio substitution at the 2' and 5' positions resulted in reactions having a single transition state with increased and decreased free energy barriers, respectively, relative to the unsubstituted reaction.

[Bladder tumor antigen test versus urinary cytology in patients with bladder tumors].

The value of the BARD bladder tumour antigen (BTA) test for the diagnosis of bladder tumour was compared to urinary cytology. A total of 60 patients with bladder tumours (Category Ta: 39 patients and Category T1-4: 21 patients) were investigated. Urinary cytology was found to be more sensitive than the BTA test.

Influence of a single dose of indomethacin on some biochemical changes and postoperative intestinal paralysis following minor surgery. A prospective randomized double-blind study.

The influence of a single dose of indomethacin on the surgical stress response was investigated in a double-blind study including 43 patients scheduled for elective operation of inguinal hernia. Indomethacin or placebo was administered rectally 1 h before the start of operation. All patients had a standardized general anaesthetic.

The female condom. A pilot study of the acceptability of a new female barrier method.

The best available prevention against sexually transmitted diseases is limited to a consistent and correct use of a condom by the male. A new barrier method has been developed for the female. As it can be inserted into the vagina before sexual intercourse starts, and as it covers the entrance of the vagina, the opening of the urethra and the root of the penis, it is presumed to give a high degree of protection against sexually transmitted diseases and unwanted pregnancy.

Giant incisional hernias closed with polypropylene mesh.

Giant incisional hernias are treated in many different ways involving risks and various degrees of mutilation. We prefer the use of polypropylene mesh (PPM) which is manufactured as Prolene or Marlex mesh. It is easy to handle, has great tensile strength and produces minimum tissue reaction.

Experience with the latissimus dorsi flap.

A review of 65 applications of the latissimus dorsi flap based on the thoraco-dorsal vessels to recipient sites in the head and neck area (10), on the torso (22), in the upper extremity (9) and in the lower extremity (24) in 62 patients with malignancies (28) and congenital deformities (6) is presented. Thirty-five flaps were transplanted with microsurgical vascular technique, while 30 flaps were pedicled. Vascular thrombosis at the anastomotic site was seen in 4/35 free tissue transplants and was successfully managed in 3 cases with an overall survival rate of 97% in this group, while all pedicled flaps survived.