The interplay between goal intentions and implementation intentions.

Two studies tested whether action control by implementation intentions is sensitive to the activation and strength of participants' underlying goal intentions. In Study 1, participants formed implementation intentions (or did not) and their goal intentions were measured. Findings revealed a significant interaction between implementation intentions and the strength of respective goal intentions.

Bonding along a linear B...N...B triad.

The synthesis of tris(2,6-dihydroxyphenyl)amine diborate, 4, is reported. This compound contains a linear B..

Design of 2,5-dimethyl-3-(6-dimethyl-4-methylpyridin-3-yl)-7-dipropylaminopyrazolo[1,5-a]pyrimidine (NBI 30775/R121919) and structure--activity relationships of a series of potent and orally active corticotropin-releasing factor receptor antagonists.

We have previously shown that 3-phenylpyrazolo[1,5-a]pyrimidines exemplified by 8 were potent antagonists of the human corticotropin-releasing factor-1 receptor. A series of 3-pyridylpyrazolo[1,5-a]pyrimidines 15, 25-30, 34, and 35 containing a weakly basic pyridine ring at the 3-position of the bicyclic nucleus was designed to reduce lipophilicity from the initial leads such as 7. Here, we showed that these 3-pyridyl compounds exhibited potent antagonists at the human CRF(1) receptor.

Novel asymmetric approach to proline-derived spiro-beta-lactams.

We describe a novel asymmetric approach using Staudinger chemistry to proline-derived spiro-beta-lactams. A chiral group at C-4 of the acid chloride of proline directs the stereoselectivity of Staudinger chemistry and later is sacrificed to obtain optically active 5.4-spiro-beta-lactams.

Synthesis of benzoylpyrimidines as antagonists of the corticotropin-releasing factor-1 receptor.

A series of benzoylpyrimidines derived from the anilinepyrimidine CRF(1) antagonists were synthesized. Several synthetic routes were developed to explore the SAR of this series of compounds. Compounds such as 8d (K(i) = 15 nM) exhibited high binding affinities at the human CRF(1) receptor.

Design, synthesis, and SAR of 2-dialkylamino-4-arylpyrimidines as potent and selective corticotropin-releasing factor(1) (CRF(1)) receptor antagonists.

A series of 2-dialkylamino-4-phenylpyrimidines (7) was designed and synthesized as CRF(1) antagonists. SAR studies of this series resulted in the discovery of potent and selective antagonists 7b and 7n bearing a 4-(2,4,6-trisubstituted-phenyl) ring and a bulky 2-(N-bis(cyclopropane)methyl-N-propyl)amino group.

Solid-phase synthesis of tetrahydro-1,4-benzodiazepine-2-one derivatives as a beta-turn peptidomimetic library.

The beta-turn has been implicated as an important conformation for biological recognition of peptides or proteins. We adapted the concept of general Calpha atom positioning from the cluster analysis and recombination of each ideal beta-turn conformation pattern by Garland and Dean (J. Comput.

Preoperative selective intercostal angiography in patients undergoing thoracoabdominal aneurysm repair.

Objective: This study was designed to test the hypothesis that detection of the location of the major artery supplying the spinal cord, that is, the artery of Adamkiewicz or the great radicular artery (GRA), with angiography would help prevent paraplegia. Knowing which intercostal artery provides this important branch would enable prompt, focused revascularization.

Method: The surgical outcome in 131 patients with Crawford extent 1 and 2 degenerative aneurysms and 69 patients with descending thoracic aortic dissection was correlated with findings on selective intercostal arteriograms.

Application of a novel design paradigm to generate general nonpeptide combinatorial scaffolds mimicking beta turns: synthesis of ligands for somatostatin receptors.

Nonpeptide compounds that mimic bioactive peptides are desirable for a number of clinical indications. We report a new practical method for the design of scaffolds exhibiting drug-like properties that are suitable for the display of peptide pharmacophores. The synthesis of various synthons of 7'-hydroxy-2',3'-dihydro-1'H,2H,5H-spiro[imidazolidine-4,4'-quinoline]-2,5-dione (1) and methods for the introduction of several mimics of amino acid side-chains are described.

Four-week inhalation toxicity study in rats with nylon respirable fibers: rapid lung clearance.

This inhalation toxicity study in rats was conducted to assess the hazard potential for workers inhaling Nylon respirable fibers. Groups of 48 male rats each were exposed, nose-only, 6h per day, 5 days per week, for 4 weeks to aerosols of uncoated, finish-free Nylon respirable-sized, fiber-shaped particulates (RFP) at concentrations of 0, 4, 15 and 57 fibers (f)/cm3. Nylon RFPs were prepared using flock rotary cutters followed by vigorous opening procedures.

Assessing the role of neutrophil apoptosis in the resolution of particle-induced pulmonary inflammation.

Following inflammatory-cell recruitment in the lung, neutrophil apoptosis and subsequent engulfment by macrophages are regarded as important components in the resolution of pulmonary inflammation. The goal of this study was to further investigate the role of apoptosis and its influence, if any, on the pulmonary inflammatory process following exposures to the following particulate types: amorphous (AMO) or crystalline silica (Si), lipopolysaccharide (LPS), or pigment-grade titanium dioxide (TiO2). Rats were intratracheally instilled either with TiO2, AMO, or Si particles at doses of 1 or 5 mg/kg or 6 microg LPS.

Synthesis and SAR of 8-arylquinolines as potent corticotropin-releasing factor1 (CRF1) receptor antagonists.

A series of 4-substituted 8-aryl-2-methylquinolines 4 was designed and synthesized as highly potent antagonists for the human CRF(1) receptor. This series of compounds displayed parallel SAR to other bicyclic systems such as pyrazolo[1,5-a]pyrimidines, with several compounds possessing low nanomolar binding affinity. In addition to the high potency, the basicity of this 4-aminoquinoline core may offer CRF(1) antagonists with lower lipophilicity.

On the heritability of geographic range sizes.

Within taxonomic groups, most species are restricted in their geographic range sizes, with only a few being widespread. The possibility that species-level selection on range sizes contributes to the characteristic form of such species-range size distributions has previously been raised. This would require that closely related species have similar range sizes, an indication of "heritability" of range sizes at the species level.

Long-term survival in a patient with del(18)(q12.2q21.1).

The 18q- syndrome is relatively common among cytogenetic abnormalities occurring in approximately 1 in 40,000 live births. However, interstitial deletions involving 18q12.2 to q21.

Synthesis of purine- and pyrimidine-substituted heptadienes. The stereochemistry of cyclization and cyclopolymerization products.

A series of 1,6-heptadienes, substituted in the 4 position with nucleic acid bases 1-6, have been synthesized via Mitsunobu condensations. Guanine, adenine, thymine, and uracil derivatives can be prepared directly by coupling the protected base with 1,6-heptadien-4-ol (7). However, coupling protected cytosine and 7 gives an O-alkylated product.

Quinazolines as adenosine receptor antagonists: SAR and selectivity for A2B receptors.

We have recently reported the discovery of numerous new compounds that are selective inhibitors of all of the subtypes of the adenosine receptor family via a pharmacophore database searching and screening strategy. During the course of this work we made the unexpected discovery of a potent A(2B) receptor antagonist, 4-methyl-7-methoxyquinazolyl-2-(2'-amino-4'-imidazolinone) (38, CMB 6446), which showed selectivity for this receptor and functioned as an antagonist, with a binding K(i) value of 112 nM. We explored the effects of both substituent- and ring-structural variations on the receptor affinity in this series of derivatives, which were found to be mostly non-selective adenosine receptor ligands with K(i) values in the micromolar range.

Sulfuranes Lacking Benzoannelation. Sulfuranes and Other Hypervalent Molecules Studied by (17)O-NMR.

The rates of hydrolysis of benzoannelated vs nonbenzoannelated sulfuranes, viz. 5 vs 3 or 5 vs 4, were compared. Benzoannelation was found to provide very modest kinetic stabilization.

Crystal Structure, Electronic Structure, and Temperature-Dependent Raman Spectra of Tl[Ag(CN)(2)]: Evidence for Ligand-Unsupported Argentophilic Interactions.

The structure of thallium dicyanoargentate(I) has been determined crystallographically. The crystal structure shows an Ag-Ag distance of 3.11 Å.