132 research outputs found
Measurements of space charge and finite geometry effects on emittance in the University og Maryland high perveance electron gun
The newly developed CRF1-receptor antagonists, NGD 98-2 and NGD 9002, suppress acute stress-induced stimulation of colonic motor function and visceral hypersensitivity in rats.
Corticotropin releasing factor receptor 1 (CRF1) is the key receptor that mediates stress-related body responses. However to date there are no CRF1 antagonists that have shown clinical efficacy in stress-related diseases. We investigated the inhibitory effects of a new generation, topology 2 selective CRF1 antagonists, NGD 98-2 and NGD 9002 on exogenous and endogenous CRF-induced stimulation of colonic function and visceral hypersensitivity to colorectal distension (CRD) in conscious rats. CRF1 antagonists or vehicle were administered orogastrically (og) or subcutaneously (sc) before either intracerebroventricular (icv) or intraperitoneal (ip) injection of CRF (10 µg/kg), exposure to water avoidance stress (WAS, 60 min) or repeated CRD (60 mmHg twice, 10 min on/off at a 30 min interval). Fecal pellet output (FPO), diarrhea and visceromotor responses were monitored. In vehicle (og)-pretreated rats, icv CRF stimulated FPO and induced diarrhea in >50% of rats. NGD 98-2 or NGD 9002 (3, 10 and 30 mg/kg, og) reduced the CRF-induced FPO response with an inhibitory IC50 of 15.7 and 4.3 mg/kg respectively. At the highest dose, og NGD 98-2 or NGD 9002 blocked icv CRF-induced FPO by 67-87% and decreased WAS-induced-FPO by 23-53%. When administered sc, NGD 98-2 or NGD 9002 (30 mg/kg) inhibited icv and ip CRF-induced-FPO. The antagonists also prevented the development of nociceptive hyper-responsivity to repeated CRD. These data demonstrate that topology 2 CRF1 antagonists, NGD 98-2 and NGD 9002, administered orally, prevented icv CRF-induced colonic secretomotor stimulation, reduced acute WAS-induced defecation and blocked the induction of visceral sensitization to repeated CRD
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Measurements of emittance growth through the achromatic bend at the BNL Accelerator Test Facility
Measurements of emittance growth in a high peak current beam as it passes through an achromatic double bend are summarized. Experiments were performed using the ATF at Brookhaven National Laboratory by X.J. Wang and D. Kehne as a collaboration resulting from the proposal attached at the end of the document. The ATF consists off an RF gun (1 MeV), two sections of linac (40-75 MeV), a diagnostic section immediately following the linac, a 20{degree} bend magnet, a variable aperture slit at a high dispersion point, 5 quadrupoles, then another 20{degree} bend followed by another diagnostic section. The TRANSPORT deck describing the region from the end of the linac to the end of the diagnostic line following the achromatic bends is attached to the end of this document. Printouts of the control screens are also attached
The Distortion of Binomial Voting Defies Expectation
In computational social choice, the distortion of a voting rule quantifies
the degree to which the rule overcomes limited preference information to select
a socially desirable outcome. This concept has been investigated extensively,
but only through a worst-case lens. Instead, we study the expected distortion
of voting rules with respect to an underlying distribution over voter
utilities. Our main contribution is the design and analysis of a novel and
intuitive rule, binomial voting, which provides strong expected distortion
guarantees for all distributions
Representation with Incomplete Votes
Platforms for online civic participation rely heavily on methods for
condensing thousands of comments into a relevant handful, based on whether
participants agree or disagree with them. These methods should guarantee fair
representation of the participants, as their outcomes may affect the health of
the conversation and inform impactful downstream decisions. To that end, we
draw on the literature on approval-based committee elections. Our setting is
novel in that the approval votes are incomplete since participants will
typically not vote on all comments. We prove that this complication renders
non-adaptive algorithms impractical in terms of the amount of information they
must gather. Therefore, we develop an adaptive algorithm that uses information
more efficiently by presenting incoming participants with statements that
appear promising based on votes by previous participants. We prove that this
method satisfies commonly used notions of fair representation, even when
participants only vote on a small fraction of comments. Finally, an empirical
evaluation using real data shows that the proposed algorithm provides
representative outcomes in practice
Electrophysiological evidence for rapid 5-HT1A autoreceptor inhibition by vilazodone, a 5-HT1A receptor partial agonist and 5-HT reuptake inhibitor
Abstract This study examined the effect of vilazodone, a combined serotonin (5-HT) reuptake inhibitor and 5-HT 1A receptor partial agonist, paroxetine and fluoxetine on the sensitivity of 5-HT 1A autoreceptors of serotonergic dorsal raphe nucleus neurons in rats. These effects were assessed by determining the intravenous dose of (±)-8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) required to suppress the basal firing rate of these neurons by 50% (ID 50 ) in anesthetized rats using in vivo electrophysiology. 5-HT uptake inhibition was determined by the ability of the compounds to reverse (±)- p -chloroamphetamine (PCA)-induced rat hypothalamic 5-HT depletion ex vivo . Acute vilazodone administration (0.63 and 2.1 µmol/kg, s.c.), compared with vehicle, significantly increased (2–3-fold) the ID 50 of 8-OH-DPAT at 4 h, but not 24 h after administration. Subchronic administration (3 days) significantly increased the ID 50 value at 4 h (3–4-fold) and at 24 h (~2-fold). In contrast, paroxetine and fluoxetine at doses that were supramaximal for 5-HT uptake inhibition did not significantly alter the ID 50 value of 8-OH-DPAT after acute or subchronic administration. Vilazodone antagonized the action of PCA 3.5 h and 5 h after a single dose (ID 50 1.49 and 0.46 µmol/kg, s.c., respectively), but was inactive 18 h post-administration, corroborating the electrophysiological results at 24 h following acute administration. The results are consistent with the concept of rapid and, following repeated treatment, prolonged inhibition of 5-HT 1A autoreceptors by vilazodone. This effect could occur by either direct interaction with, or desensitization of, these receptors, an effect which cannot be ascribed to vilazodone's 5-HT reuptake inhibiting properties
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