113 research outputs found

    Evaluation of lubricants for high-speed high-temperature applications Summary report

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    Rolling disks for evaluation of high speed, high temperature lubricant application

    Characterization of Antiallodynic Actions of ALE-0540, a Novel Nerve Growth Factor Receptor Antagonist, in the Rat1

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    There is growing evidence that nerve growth factor (NGF) may function as a mediator of persistent pain states. We have identified a novel nonpeptidic molecule, ALE-0540, that inhibits the binding of NGF to tyrosine kinase (Trk) A or both p75 and TrkA (IC50 5.88 6 1.87 mM, 3.72 6 1.3 mM, respectively), as well as signal transduction and biological responses mediated by TrkA receptors. ALE-0540 was tested in models of neuropathic pain and thermally-induced inflammatory pain, using two routes of administration, a systemic i.p. and a spinal intrathecal (i.th.) route. Morphine was also tested for comparison in the antiallodynia model using mechanical stimuli. We show that either i.p. or i.th. administration of ALE-0540 in rats produced antiallodynia in the L5/L6 ligation model of neuropathic pain. The calculated A50 values (and 95% confidence intervals) for ALE- 0540 administered i.p. and i.th. were 38 (17.5– 83) mg/kg and 34.6 (17.3– 69.4) mg, respectively. ALE-0540 given i.th., at doses of 30 and 60 mg, also blocked tactile allodynia in the thermal sensitization model. Although morphine displayed greater potency [A50 value of 7.1 (5.6–8.8) mg/kg] than ALE- 0540 in anti-allodynic effect when given i.p. to L5/L6-ligated rats, it was not active when administered i.th. These data suggest that a blockade of NGF bioactivity using a NGF receptor antagonist is capable of blocking neuropathic and inflammatory pain and further support the hypothesis that NGF is involved in signaling pathways associated with these pain states. ALE-0540 represents a nonpeptidic small molecule which can be used to examine mechanisms leading to the development of agents for the treatment of pain

    Bumblebees exhibit the memory spacing effect

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    Associative learning is key to how bees recognize and return to rewarding floral resources. It thus plays a major role in pollinator floral constancy and plant gene flow. Honeybees are the primary model for pollinator associative learning, but bumblebees play an important ecological role in a wider range of habitats, and their associative learning abilities are less well understood. We assayed learning with the proboscis extension reflex (PER), using a novel method for restraining bees (capsules) designed to improve bumblebee learning. We present the first results demonstrating that bumblebees exhibit the memory spacing effect. They improve their associative learning of odor and nectar reward by exhibiting increased memory acquisition, a component of long-term memory formation, when the time interval between rewarding trials is increased. Bombus impatiens forager memory acquisition (average discrimination index values) improved by 129% and 65% at inter-trial intervals (ITI) of 5 and 3 min, respectively, as compared to an ITI of 1 min. Memory acquisition rate also increased with increasing ITI. Encapsulation significantly increases olfactory memory acquisition. Ten times more foragers exhibited at least one PER response during training in capsules as compared to traditional PER harnesses. Thus, a novel conditioning assay, encapsulation, enabled us to improve bumblebee-learning acquisition and demonstrate that spaced learning results in better memory consolidation. Such spaced learning likely plays a role in forming long-term memories of rewarding floral resources

    Modulators of axonal growth and guidance at the brain midline with special reference to glial heparan sulfate proteoglycans

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    Dental Development in Protein-Deprived Infant Rhesus Monkeys

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    This research investigated the effects of protein-deprivation on tooth development in rhesus monkeys (Macaca mulatta). Seventy-three newborn monkeys were fed protein-adequate (n = 44) or protein-restricted (n = 29) diets for the first 120 days of life. Cranial x-rays were taken periodically. Crown-root lengths of deciduous canines, first and second deciduous molars, and first permanent molars were measured on the radiographs. Sample differences were compared using linear regression statistics to determine whether protein restriction delayed the rate of tooth development. Consideration was also given to possible differences in crown size. Buccolingual and mesiodistal dimensions of maxillary and mandibular permanent first molars were measured on dental casts of 29 animals. Expermentally induced protein restriction had only limited effect on tooth size and rate of development. At 120 days, crown-root lengths of deciduous second molars were less than those of controls. This pattern was not observed in the deciduous canine, first molar, or permanent first molar. Crown size of first permanent molars was not measurably affected by temporary restriction of protein

    Theoretical Studies on the Origin of β-sheet Twisting

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