Computational design and experimental discovery of an antiestrogenic peptide derived from alpha-fetoprotein.

Breast cancer is the most common cancer among women, and tamoxifen is the preferred drug for estrogen receptor-positive breast cancer treatment. Many of these cancers are intrinsically resistant to tamoxifen or acquire resistance during treatment. Consequently, there is an ongoing need for breast cancer drugs that have different molecular targets.

Do hydroxyl radical-water clusters, OH(H2O)n, n = 1-5, exist in the atmosphere?

It has been speculated that the presence of OH(H2O)n clusters in the troposphere could have significant effects on the solar absorption balance and the reactivity of the hydroxyl radical. We have used the G3 and G3B3 model chemistries to model the structures and predict the frequencies of hydroxyl radical/water clusters containing one to five water molecules. The reaction between hydroxyl radical clusters and methane was examined as a function of water cluster size to gain an understanding of how cluster size affects the hydroxyl radical reactivity.

Global search for minimum energy (H2O)n clusters, n = 3-5.

The Gaussian-3 (G3) model chemistry method has been used to calculate the relative deltaG(o) values for all possible conformers of neutral clusters of water, (H2O)n, where n = 3-5. A complete 12-fold conformational search around each hydrogen bond produced 144, 1728, and 20,736 initial starting structures of the water trimer, tetramer, and pentamer. These structures were optimized with PM3, followed by HF/6-31G* optimization, and then with the G3 model chemistry.

Comparison of model chemistry and density functional theory thermochemical predictions with experiment for formation of ionic clusters of the ammonium cation complexed with water and ammonia; atmospheric implications.

The G2, G3, CBS-QB3, and CBS-APNO model chemistry methods and the B3LYP, B3P86, mPW1PW, and PBE1PBE density functional theory (DFT) methods have been used to calculate deltaH(o) and deltaG(o) values for ionic clusters of the ammonium ion complexed with water and ammonia. Results for the clusters NH4(+) (NH3)n and NH4(+) (H2O)n, where n = 1-4, are reported in this paper and compared against experimental values. Agreement with the experimental values for deltaH(o) and deltaG(o) for formation of NH4(+) (NH3)n clusters is excellent.

Exploration of the potential energy surfaces, prediction of atmospheric concentrations, and prediction of vibrational spectra for the HO2...(H2O)n (n = 1-2) hydrogen bonded complexes.

The hydroperoxy radical (HO2) plays a critical role in Earth's atmospheric chemistry as a component of many important reactions. The self-reaction of hydroperoxy radicals in the gas phase is strongly affected by the presence of water vapor. In this work, we explore the potential energy surfaces of hydroperoxy radicals hydrogen bonded to one or two water molecules, and predict atmospheric concentrations and vibrational spectra of these complexes.

Ortho effect in the Bergman cyclization: electronic and steric effects in hydrogen abstraction by 1-substituted naphthalene 5,8-diradicals.

We present a detailed theoretical study of geometries, electronic structure, and energies of transition states and intermediates completing the full Bergman cycloaromatization pathway of ortho-substituted enediynes with a focus on polar and steric contributions to the kinetics and thermodynamics of hydrogen abstraction. This study provides a rare unambiguous example of remote substitution that affects reactivity of a neutral reactive intermediate through an sigma framework.

Prediction of accurate anharmonic experimental vibrational frequencies for water clusters, (H2O)n, n=2-5.

Accurate anharmonic experimental vibrational frequencies for water clusters consisting of 2-5 water molecules have been predicted on the basis of comparing different methods with MP2/aug-cc-pVTZ calculated and experimental anharmonic frequencies. The combination of using HF/6-31G* scaled frequencies for intramolecular modes and anharmonic frequencies for intermolecular modes gives excellent agreement with experiment for the water dimer and trimer and are as good as the expensive anharmonic MP2 calculations. The water trimer, the cyclic Ci and S4 tetramers, and the cyclic pentamer all have unique peaks in the infrared spectrum between 500 and 800 cm-1 and between 3400 and 3700 cm-1.

Ten year longitudinal study of neuropsychological functioning subsequent to a first episode of schizophrenia.

We previously reported relative stability in neuropsychological functions over a 4- to 5-year period after the onset of a first episode of schizophrenia, with patients demonstrating less improvement than controls on some functions [Hoff, A.L., Sakuma, M.

First-principle studies of intermolecular and intramolecular catalysis of protonated cocaine.

We have performed a series of first-principles electronic structure calculations to examine the reaction pathways and the corresponding free energy barriers for the ester hydrolysis of protonated cocaine in its chair and boat conformations. The calculated free energy barriers for the benzoyl ester hydrolysis of protonated chair cocaine are close to the corresponding barriers calculated for the benzoyl ester hydrolysis of neutral cocaine. However, the free energy barrier calculated for the methyl ester hydrolysis of protonated cocaine in its chair conformation is significantly lower than for the methyl ester hydrolysis of neutral cocaine and for the dominant pathway of the benzoyl ester hydrolysis of protonated cocaine.

MR arthrography of rotator interval, long head of the biceps brachii, and biceps pulley of the shoulder.

The rotator interval and the long head of the biceps brachii tendon are anatomically closely associated structures believed to confer stability to the shoulder joint. Abnormalities of the rotator interval may be acquired or congenital and are associated with instability of the long head of the biceps brachii tendon. Clinical and arthroscopic diagnoses of rotator interval abnormalities and subtle instability patterns of the long head of the biceps brachii tendon are difficult.

Comparison of CBS-QB3, CBS-APNO, G2, and G3 thermochemical predictions with experiment for formation of ionic clusters of hydronium and hydroxide ions complexed with water.

The GAUSSIAN 2, GAUSSIAN 3, complete basis set-QB3, and complete basis set-APNO methods have been used to calculate DeltaH( composite function) and DeltaG( composite function) values for ionic clusters of hydronium and hydroxide ions complexed with water. Results for the clusters H3O+(H2O)n and OH-(H2O)n, where n=1-4 are reported in this paper, and compared against experimental values contained in the National Institutes of Standards and Technology (NIST) database. Agreement with experiment is excellent for the three ab initio methods for formation of these clusters.

Hand preference and hand skill in families with schizophrenia.

Direction and degree of handedness in humans are variable between individuals and thought to be in part inherited. Several studies have shown an increase in non-right handedness among patients with schizophrenia, and some have included unaffected relatives. The present study was designed to determine whether reduced right handedness is more frequent among individuals with schizophrenia as compared with their well relatives and whether it clusters within families having multiple ill members.

Thermodynamics of forming water clusters at various temperatures and pressures by Gaussian-2, Gaussian-3, complete basis set-QB3, and complete basis set-APNO model chemistries; implications for atmospheric chemistry.

The Gaussian-2, Gaussian-3, complete basis set- (CBS-) QB3, and CBS-APNO methods have been used to calculate Delta H degrees and Delta G degrees values for neutral clusters of water, (H(2)O)(n), where n = 2-6. The structures are similar to those determined from experiment and from previous high-level calculations. The thermodynamic calculations by the G2, G3, and CBS-APNO methods compare well against the estimated MP2(CBS) limit.

Correlation between facial pain or headache and computed tomography in rhinosinusitis in Canadian and U.S. subjects.

Objectives: Objectives were 1) to determine whether a correlation exists between facial pain or headache and sinus disease severity by computed tomography (CT) scan in patients with rhinosinusitis and 2) to compare disease severity and pain perception in two geographically diverse North American patient populations.

Study Design: Prospective patient questionnaire before CT scan of the paranasal sinuses.

Methods: Patients with refractory rhinosinusitis were recruited at the University of Texas Medical Branch (Galveston, TX) and the University of Alberta (Edmonton, Alberta, Canada).

Validation of the Canadian clinical probability model for acute venous thrombosis.

Objective: To validate the predictive value of the Canadian clinical probability model for acute venous thrombosis, which, to the best of the authors' knowledge, has not been done in emergency department (ED) settings outside of Canada.

Methods: Demographic and clinical information, rapid D-dimer testing, and venous ultrasound imaging were obtained among patients presenting with clinically suspected venous thrombosis at a university-affiliated ED. A diagnosis of deep venous thrombosis (DVT) was made based on venous ultrasound test results or objectively documented venous thromboembolism during a 12-week follow-up period.

Absolute pK(a) determinations for substituted phenols.

The CBS-QB3 method was used to calculate the gas-phase free energy difference between 20 phenols and their respective anions, and the CPCM continuum solvation method was applied to calculate the free energy differences of solvation for the phenols and their anions. The CPCM solvation calculations were performed on both gas-phase and solvent-phase optimized structures. Absolute pK(a) calculations with solvated phase optimized structures for the CPCM calculations yielded standard deviations and root-mean-square errors of less than 0.

A genome-wide scan for linkage to chromosomal regions in 382 sibling pairs with schizophrenia or schizoaffective disorder.

Objective: Some genome-wide scans and association studies for schizophrenia susceptibility genes have yielded significant positive findings, but there is disagreement between studies on their locations, and no mutation has yet been found in any gene. Since schizophrenia is a complex disorder, a study with sufficient power to detect a locus with a small or moderate gene effect is necessary.

Method: In a genome-wide scan of 382 sibling pairs with a diagnosis of schizophrenia or schizoaffective disorder, 396 highly polymorphic markers spaced approximately 10 centimorgans apart throughout the genome were genotyped in all individuals.

Mitochondrial phylogeography of moose (Alces alces): late pleistocene divergence and population expansion.

We examined phylogeographic relationships of moose (Alces alces) worldwide to test the proposed existence of two geographic races and to infer the timing and extent of demographic processes underpinning the expansion of this species across the Northern Hemisphere in the late Pleistocene. Sequence variation within the left hypervariable domain of the control region occurred at low or moderate levels worldwide and was structured geographically. Partitioning of genetic variance among regions indicated that isolation by distance was the primary agent for differentiation of moose populations but does not support the existence of distinct eastern and western races.

Simultaneous Antiferromagnetic Order and Spin-Glass-like Behavior in MnAsO(4).

A low-temperature time-of-flight neutron powder diffraction study of a simple new solid, MnAsO(4), in a sample also containing 20% Mn(2)As(2)O(7) has been performed. MnAsO(4) orders magnetically at 14.5(5) K, and the unusual antiferromagnetic structure below this temperature has been determined.

Accurate pK(a) calculations for carboxylic acids using complete basis set and Gaussian-n models combined with CPCM continuum solvation methods.

Complete Basis Set and Gaussian-n methods were combined with CPCM continuum solvation methods to calculate pK(a) values for six carboxylic acids. An experimental value of -264.61 kcal/mol for the free energy of solvation of H(+), DeltaG(s)(H(+)), was combined with a value for G(gas)(H(+)) of -6.

Cholesterol levels in mood disorders: high or low?

Objectives: To assess cholesterol levels in patients with mood disorders.

Methods: All consecutively admitted patients meeting inclusion criteria (n = 50) who were hospitalized in an affective disorders unit received assessments of cholesterol levels. Correlations were made with diagnosis using DSM-IV criteria, current mood states, and other clinical and demographic features of illness.

Automatic detection of molecular symmetry in the Cambridge Structural Database.

A method for the detection of approximate molecular symmetry in crystal structures has been developed. The point-group symmetry is assigned to each molecule and the relevant symmetry elements can be visualized, superimposed on the molecule. The method has been validated against reference structures with exact symmetry subjected to small random perturbation.

No evidence for a parent-of-origin effect detected in the pattern of inheritance of schizophrenia.

Background: Schizophrenia is a complex genetic disorder with no clear pattern of inheritance. Epigenetic modification of genes may thus play a role in its transmission.

Methods: In our study, 439 families with at least two ill siblings with schizophrenia (208 with unilineal transmission) were examined for evidence of a parent-of-origin effect (e.