14,965 research outputs found

    The androgen receptor and signal-transduction pathways in hormone-refractory prostate cancer. Part 1: modifications to the androgen receptor

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    Prostate cancer is the second most common male malignancy in the western world an increasing incidence in an ageing population. Treatment of advanced prostate cancer relies on androgen deprivation. Although the majority of patients initially respond favourably to androgen deprivation therapy, the mean time to relapse is 12-18 months. Currently there are few treatments available for men who have developed resistance to hormone therapy, due to the lack of understanding of the molecular mechanisms underlying development of this disease. Recently, however, major advances have been made in understanding both androgen receptor (AR) dependent and independent pathways which promote development of hormone resistant prostate cancer. This review will focus on modifications to the AR and associated pathways. Molecular modifications to the androgen receptor itself, e.g. mutations and/or amplification, although involved in the development of hormone resistance cannot explain all cases. Phosphorylation of AR, via either Ras/MAP kinase or PI3K/Akt signal transduction pathways, have been shown to activate AR in both a ligand (androgen) dependent and independent fashion. During this review we will discuss the clinical evidence to support AR dependent pathways as mediators of hormone resistance

    Depression, School Performance, and the Veridicality of Perceived Grades and Causal Attributions

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    An external criterion was assessed to test whether depressives have distorted perceptions of covariation information and whether their attributions are consistent with this information. Students’ actual and self-perceived grades, depression status, and attributions for failures were assessed. Furthermore, partici pants estimated average grades. Generally, self-perceived own past grades were inflated. Depressed students and those with low grades distorted their own grades (but not the average grade) more to their favor than individuals low in depression and those with high grades. Depression went along with lower actual grades and with internal, stable, and global failure attributions. Mood differences in attributions were not due to differences in previous grades. Depressed individuals drew (unrealistically) more depressogenic causal inferences when they perceived average grades to be low than when average grades were perceived to be high. However, they (realistically) attributed failure more in a depressogenic fashion than did nondepressives when their own grade history was low

    Mathematical Analysis and Simulations of the Neural Circuit for Locomotion in Lamprey

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    We analyze the dynamics of the neural circuit of the lamprey central pattern generator (CPG). This analysis provides insights into how neural interactions form oscillators and enable spontaneous oscillations in a network of damped oscillators, which were not apparent in previous simulations or abstract phase oscillator models. We also show how the different behaviour regimes (characterized by phase and amplitude relationships between oscillators) of forward/backward swimming, and turning, can be controlled using the neural connection strengths and external inputs.Comment: 4 pages, accepted for publication in Physical Review Letter

    Co-reading: investigating collaborative group reading.

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    Collaborative reading, or co-reading as we call it, is ubiquitous—it occurs, for instance, in classrooms, book-clubs, and in less coordinated ways through mass media. While individual digital reading has been the subject of much investigation, research into co-reading is scarce. We report a two-phase field study of group reading to identify an initial set of user requirements. A co-reading interface is then designed that facilitates the coordination of group reading by providing temporary ‘Point-out’ markers to indicate specific locations within documents. A user study compared this new system with collaborative reading on paper, with a positive outcome; the differences in user behavior between paper and the new interface reveal intriguing insights into user needs and the potential benefits of digital media for co-reading

    Analysis of a new genetic cross between two East African Trypanosoma brucei clones

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    Two clones of East African Trypanosoma brucei, with distinct homozygous isoenzyme patterns for one of three enzymes examined, were cotransmitted through the tsetse fly vector Glossina morsitans centralis. Flies with mature infections were individually fed on mice and the subsequent bloodstream form populations analysed for the presence of hybrid trypanosomes by isoenzyme analysis. Several combinations have previously been detected using this approach (Schweizer, Tait & Jenni, 1988; Sternberg et al. 1989). Four clones were isolated from one of the hybrid-containing populations. They showed a hybrid phenotype, as would be expected for the F1 progeny in a diploid Mendelian system. The analysis of the progeny clones, using two gene probes which detect restriction fragment length polymorphisms between the two parental stocks, showed that alleles had segregated at each locus and given rise to three different non-parental combinations of alleles in the hybrid progeny. Characterization of the hybrid progeny clones by PFGE (pulsed field gradient gel electrophoresis) revealed that all progeny clones were recombinant for the intermediate size chromosomes. From the analysis of the segregation of the larger chromosomes, marked by P0K (phosphoglycerate kinase) and CP (cysteine protease) gene probes, it was inferred that the progeny clones did not result from a direct fusion of diploid cells. Results with the PGK probe fit into a classical system with meiosis and subsequent fusion of the nuclei to form diploid progeny. On the other hand, blots with the CP probe as well as some of the ethidium bromide stained PFGE gels revealed the existence of non-parental size chromosomes in some of the hybrid progeny. This phenomenon was observed previously (Gibson, 1989) and further investigation is required to elucidate the mechanis

    Relation of Starch to the Strength of Wheat Flour

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    The condition of the starch of wheat flour is undoubtedly a factor that will indicate the strength of flour. A microscopical examination subsequently checked by baking tests shows that flour containing the larger proportion of small starch grains will be a stronger flour. A study of the action of various reagents shows the small grains to be more resistant. This may be indicated by the following studies: 1) by microscopically measuring the swelling of the grains: 2) by measuring the viscosity of flours, and starch from flour: 3) by measuring imbibition of flour, and starch from flour. The following relationships were noted on two typical flours: 1. Large loaf, large absorption, low ash, small starch grains, large imbibition, low imbibition by starch. 2. Small loaf, high ash, large starch grain, small imbibition, low absorption, large imbibition by starch

    Penicillin-binding proteins of protoplast and sporoplast membranes of Streptomyces griseus strains

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    Membrane-bound penicillin-binding proteins (PBPs) of two Streptomyces griseus strains that sporulate well in liquid and solid medium have been investigated during the course of their life-cycle. The PBP patterns were analyzed by sodium dodecylsulphate polyacrylamide-gel electrophoresis and fluorography. One strain (No. 45 H) has only a single band (mol wt: 27,000) in early log phase, and two additional PBPs of higher mol wt (69,000 and 80,000) in the late log phase. The other strain (No. 2682) possessed two bands with mol wts 27,000 and 38,000 which did not change during its vegetative phase. In strain No. 2682, a new PBP with a mol wt of 58,000 appeared in spore membranes while one of those (mol wt 38,000) present in mycelial membranes disappeared. Our results suggest that appearance of the new PBP in the spore may be associated with the sporulation process. The major PBP band (mol wt: 27,000) present in all stages of the life cycle of these strains, may be characteristic of S. griseus while the other PBPs reflect certain stages of the life cycle. A new method was developed for the production of spore protoplasts by consecutive enzymatic treatments.

    Thermal and Surface Core-Electron Binding-Energy Shifts in Metals

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    High-resolution photoemission spectra from the shallow core levels of alkali metals and of In have been obtained between 78 K and room temperature. The data yield values for the alkali-metal surface-atom core-level shift and show thermal shifts of comparable size for bulk and surface. The positive surface shifts are due to the spill-out of conduction-electron charge, which is responsible for the surface dipole layer. The surface shifts are in good agreement with values obtained from a Born-Haber cycle expressed in terms of surface energies. The thermal shifts are proportional to the lattice expansion, and arise from both initial-state and final-state effects. As the lattice expands, the Fermi level decreases, decreasing the core-electron binding energy. At the same time, the expansion of the conduction-electron charge increases rs, thereby decreasing the potential at the core level and increasing the binding energy. The expansion also decreases the relaxation energy, further increasing the core-electron binding energy. In the alkali metals, the combined potential- and relaxation-energy terms dominate the Fermi-level term, making the shifts positive. In divalent metals the three terms tend to cancel, while in trivalent metals it is the Fermi-level term that dominates, making the shifts negative
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