Pain and discomfort associated with common hospital procedures and experiences

BACKGROUND: Protein kinases play a central role in controlling diverse signal transduction pathways in all cells. The identification of the direct cellular substrates of individual protein kinases remains the key challenge in the field. RESULTS: We describe the protein engineering of v-Src to produce a kinase which preferentially uses an ATP analog, N6-(benzyl) ATP, as a substrate, rather than the natural v-Src substrate, ATP. The sidechain of a single residue (Ile338) controls specificity for N6-substituted ATP analogs in the binding pocket of v-Src. Elimination of this sidechain by mutation to glycine produces a v-Src kinase which preferentially utilizes N6-(benzyl) ATP as a phosphodonor substrate. Our engineering strategy is generally applicable to the Src family kinases: mutation of the corresponding residue (Thr339 to glycine) in the Fyn kinase confers specificity for N6-(benzyl) ATP on Fyn. CONCLUSIONS: The v-Src tyrosine kinase has been engineered to exhibit specificity for an unnatural ATP analog, N6-(benzyl) ATP, even in a cellular context where high concentrations of natural ATP are present (1-5 mM), where preferential use of the ATP analog by the mutant kinase is essential. The mutant v-Src transfers phosphate more efficiently with the designed unnatural analog than with ATP. As the identical mutation in the Src-family kinase Fyn confers on Fyn the ability to recognize the same unnatural ATP analog, our strategy is likely to be generally applicable to other protein kinases and may help to identify the direct targets of specific kinases.     

Characterization of the rhesus monkey galactocerebrosidase (GALC) cDNA and gene and identification of the mutation causing globoid cell leukodystrophy (Krabbe disease) in this primate

Spreading depression (SD) of electroencephalographic activity is a dynamic wave phenomenon in the central nervous system (CNS). The retina, especially the isolated chicken retina, is an excellent constituent of the CNS in which to observe the dynamic behavior of the SD wave fronts, because it changes its optical properties during a SD attack. The waves become visible as milky fronts on a black background. It is still controversial what the basic mechanistic steps of SD are, but certainly SD belongs to the self-organization phenomena occurring in neuronal tissue. In this work, spiral-shaped wave fronts are analyzed using digital video imaging techniques. We report how the inner end of the wave front, the spiral tip, breaks away repeatedly. This separation process is associated with a Z-shaped trajectory (extension approximately 1.2 mm) that is described by the tip over one spiral revolution (period 2.45+/-0.1 min). The Z-shaped trajectory does not remain fixed, but performs a complex motion across the retina with each period. This is the first time, to our knowledge, that established imaging methods have been applied to the study of the two-dimensional features of SD wave propagation and to obtaining quantitative data of their dynamics. Since these methods do not interfere with the tissue, it is possible to observe the intrinsic properties of the phenomenon without any external influence.     

Discovery of a novel, selective, and orally bioavailable class of thrombin inhibitors incorporating aminopyridyl moieties at the P1 position

A novel class of thrombin inhibitors incorporating aminopyridyl moieties at the P1 position has been discovered. Four of these thrombin inhibitors (13b,c,e and 14d) showed nanomolar potency (Ki 0.8-12 nM), 300-1500-fold selectivity for thrombin compared with trypsin, and good oral bioavailability (F = 40-76%) in rats or dogs. The neutral P1 was expected to increase metabolic stability and oral absorption. Identification of this novel aminopyridyl group at P1 was a key step in our search for a clinical candidate.     

Construct validity for measures of childhood depression: Application of multitrait–multimethod methodology.

In Exp I, 24 emotionally disturbed inpatients (aged 7 yrs 1 mo to 15 yrs 8 mo) were administered a battery of measures of depression including the Children's Depression Inventory (CDI), the Piers-Harris Self-Concept Scale (P-H), a DSM-III rating scale, a measure of learned helplessness, and a peer-nomination inventory. Results show that the CDI was significantly related to the P-H and the measure of learned helplessness. In Exp II, 133 2nd–8th graders were used to investigate the convergent and discriminant validity of several measures of depression and anger in a multimethod–multitrait matrix. Measures of depression and anger were obtained from the CDI, peers, and teachers. Results show a method effect twice as large as the trait effect. Both convergent and discriminant validities were supported for the measures as a group. However, the method of measurement was as important a source of variance as was the trait being measured. (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Electron field emission from the 2D hole gas in hydrogen terminated,polycrystalline diamond

The results of field emission measurements from hydrogen and non-hydrogen terminated polycrystalline, B-doped and undoped diamond surfaces are reported. The field emission from the undoped polycrystalline diamond show different current density vs. electric field characteristics than field emission from hydrogen terminated polycrystalline B-doped diamond and from hydrogen terminated single crystal undoped diamond. These differences are attributed to differences in the conduction mechanisms, being bulk conductivity in B-doped diamond and surface conductivity in undoped hydrogen terminated single crystalline and polycrystalline diamond. In contrast to the hydrogen terminated single crystal undoped diamond case, where discrete jumps in the current density vs. electric field curves are observed [L. Gan, E. Baskin, C. Saguy and R. Kalish, Phys. Rev. Lett. 96, 196808 (2006).] the results for the undoped polycrystalline case follow the Fowler Nordheim formalism, reflecting the presence of an ensemble of 2D surface energy states due to the various angles between the crystallite surfaces and the electric field. The parameters extracted from the Fowler Nordheim representation of the data for hydrogen terminated B-doped and undoped polycrystalline diamond, yield a Fermi energy level near the surface region for of 0.34 eV below the valance band maximum for the undoped sample.     

Oxidation Behavior of Uranium Monophosphide

Oxidation of UP at moderate temperatures was studied using DTA, X-ray diffraction, TGA, and chemical analysis. Heating rates, atmosphere, and particle size were varied. Oxidation behavior of UP was significantly different from that of UC, UN, US, and UAs, all of which possess the NaCl-type crystal structure. The greater oxidation resistance of UP was attributed to surface formation of an amorphous phase containing P₂O₅ and UO₂. Existence of this coating was thought to be responsible for the nontarnishing and generally nonpyrophoric nature of UP at room temperature.     

Sorption of hydrogen fluoride by the chemisorptive fibres VION AN-1 and VION AN-3

Conclusions -- It has been found that to remove hydrogen fluoride from a gas-air mixture at a concentration down to 15 mg/m³, one should use the chemisorptive fibrous sorbents VION AN-1 or VION AN-3; this ensures a high degree of clean-up down to a concentration considerably lower than the limiting allowable one in the workplace.-- In the sorption of hydrogen fluoride from a gas-air mixture, it is recommended to use the KHVF filter instead of scrubber purification; this ensures high technical-economic indices for the process.Translated from Khimicheskie Volokna, No. 5, pp. 22–24, September–October, 1990.     

High-Speed Digital Data Acquisition of Sarcomere Length from Isolated Skeletal and Cardiac Muscle Cells

A digital data acquisition system has been developed which obtains sarcomere length data from a contracting skeletal muscle fiber or cardiac myocyte. The design is such that it can be used on any computer system capable of data channel operation (direct memory access).