Since eighties, 400 and 500 mm thick precast-prestressed concrete hollow core slabs, characterized by increasingly optimized cross-sections with non-circular voids, became very common. However, ...deeper slabs with long spans, which have to resist high line loads acting close to the supports, are subjected to initial web shear cracking and may fail at loads less than those predicted by traditional codes prescriptions. The shear strength capacity of these members without transverse reinforcement is evaluated through a campaign of detailed nonlinear finite element analyses, matching experimental test data collected from past programs. Constitutive models, based on nonlinear fracture mechanisms, are considered to numerically reproduce the experimental response of single span, simply supported, isolated hollow core units, highlighting web-shear failure mechanism, due to short development length and lack of transverse reinforcement. The adopted diffuse smeared fixed cracking constitutive model allows a reliable prediction of shear stress distributions and crack patterns for these members in their inelastic branch. The presence of a variable inclined strut is clearly evident. Peak shear stress is localized at the bottom side of the cross-section, rather than at the level of the centroid. The experienced brittle web-shear failure mechanism is governed by hollow core shapes with circular or non-circular voids, as evidenced by the evolution of the principal tensile strain distributions. Typically, less inclined, more rounded, diagonal crack, controlled by the smooth web width variation along depth, is opposed to a fairly constant variation of the fracture angle inclination, governed by the abrupt and irregular web width drop.
BACKGROUND AND PURPOSE To evaluate the hypothesis that activation of somatodendritic 5‐HT1A autoreceptors in the dorsal raphe nucleus (DRN) produces the anti‐emetic/anti‐nausea effects of cannabidiol ...(CBD), a primary non‐psychoactive cannabinoid found in cannabis.
EXPERIMENTAL APPROACH The potential of systemic and intra‐DRN administration of 5‐HT1A receptor antagonists, WAY100135 or WAY100635, to prevent the anti‐emetic effect of CBD in shrews (Suncus murinus) and the anti‐nausea‐like effects of CBD (conditioned gaping) in rats were evaluated. Also, the ability of intra‐DRN administration of CBD to produce anti‐nausea‐like effects (and reversal by systemic WAY100635) was assessed. In vitro studies evaluated the potential of CBD to directly target 5‐HT1A receptors and to modify the ability of the 5‐HT1A agonist, 8‐OH‐DPAT, to stimulate 35SGTPγS binding in rat brainstem membranes.
KEY RESULTS CBD suppressed nicotine‐, lithium chloride (LiCl)‐ and cisplatin (20 mg·kg−1, but not 40 mg·kg−1)‐induced vomiting in the S. murinus and LiCl‐induced conditioned gaping in rats. Anti‐emetic and anti‐nausea‐like effects of CBD were suppressed by WAY100135 and the latter by WAY100635. When administered to the DRN: (i) WAY100635 reversed anti‐nausea‐like effects of systemic CBD, and (ii) CBD suppressed nausea‐like effects, an effect that was reversed by systemic WAY100635. CBD also displayed significant potency (in a bell‐shaped dose–response curve) at enhancing the ability of 8‐OH‐DPAT to stimulate 35SGTPγS binding to rat brainstem membranes in vitro. Systemically administered CBD and 8‐OH‐DPAT synergistically suppressed LiCl‐induced conditioned gaping.
CONCLUSIONS AND IMPLICATIONS These results suggest that CBD produced its anti‐emetic/anti‐nausea effects by indirect activation of the somatodendritic 5‐HT1A autoreceptors in the DRN.
LINKED ARTICLES This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue‐8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue‐7
The medical use of cannabis has an intricate therapeutic history that finds its roots in ancient China (∼2700 BC). The main psychoactive component of cannabis, Δ9‐tetrahydrocannabinol (Δ9‐THC), was ...discovered in 1964. This was a significant breakthrough, as it allowed the generation of synthetic analogs of Δ9‐THC, the discovery of cannabinoid receptors, and the generation of synthetic small molecules. Despite this, today there is still a paucity of drugs that target the cannabinoid system.
Background and Purpose
To evaluate the ability of cannabidiolic acid (CBDA) to reduce nausea and vomiting and enhance 5‐HT1A receptor activation in animal models.
Experimental Approach
We ...investigated the effect of CBDA on (i) lithium chloride (LiCl)‐induced conditioned gaping to a flavour (nausea‐induced behaviour) or a context (model of anticipatory nausea) in rats; (ii) saccharin palatability in rats; (iii) motion‐, LiCl‐ or cisplatin‐induced vomiting in house musk shrews (Suncus murinus); and (iv) rat brainstem 5‐HT1A receptor activation by 8‐hydroxy‐2‐(di‐n‐propylamino)tetralin (8‐OH‐DPAT) and mouse whole brain CB1 receptor activation by CP55940, using 35SGTPγS‐binding assays.
Key Results
In shrews, CBDA (0.1 and/or 0.5 mg·kg−1 i.p.) reduced toxin‐ and motion‐induced vomiting, and increased the onset latency of the first motion‐induced emetic episode. In rats, CBDA (0.01 and 0.1 mg·kg−1 i.p.) suppressed LiCl‐ and context‐induced conditioned gaping, effects that were blocked by the 5‐HT1A receptor antagonist, WAY100635 (0.1 mg·kg−1 i.p.), and, at 0.01 mg·kg−1 i.p., enhanced saccharin palatability. CBDA‐induced suppression of LiCl‐induced conditioned gaping was unaffected by the CB1 receptor antagonist, SR141716A (1 mg·kg−1 i.p.). In vitro, CBDA (0.1–100 nM) increased the Emax of 8‐OH‐DPAT.
Conclusions and Implications
Compared with cannabidiol, CBDA displays significantly greater potency at inhibiting vomiting in shrews and nausea in rats, and at enhancing 5‐HT1A receptor activation, an action that accounts for its ability to attenuate conditioned gaping in rats. Consequently, CBDA shows promise as a treatment for nausea and vomiting, including anticipatory nausea for which no specific therapy is currently available.
The seismic performance of concentrically braced frame systems, with braces designed in order to buckle inelastically under a severe earthquake loading, mainly depends on the hysteretic response of ...the steel braces. As observed in past earthquakes and in experimental programs available in the literature, rectangular hollow section shape braces are more susceptible to early fatigue failures compared to other section shapes.
This research, in particular, is focused on the evaluation of the hysteretic response of rectangular hollow section shape braces through appropriate low-cycle fatigue model implemented in a fiber-based element computer program. Firstly, the main influence regarding the number of integration points, number of subdivisions for single brace members, and initial camber on the local response of fiber-based inelastic beam-column element models based on force formulation is investigated. Secondly, the peak strain distribution is used to calibrate the input parameters of the low-cycle fatigue material model. Several data obtained from past experimental programs developed at the Universities of Montreal, Washington, and Calgary are also considered. Finally, an eight-story steel building is designed in order to evaluate the performance levels through incremental time history analyses.
A bent lithium niobate strip was exposed to a 400-GeV/c proton beam at the external lines of CERN Super Proton Synchrotron to probe its capabilities versus coherent interactions of the particles with ...the crystal such as channeling and volume reflection. Lithium niobate (LiNbO3) exhibits an interplanar electric field comparable to that of Silicon (Si) and remarkable piezoelectric properties, which could be exploited for the realization of piezo-actuated devices for the control of high-energy particle beams. In contrast to Si and germanium (Ge), LiNbO3 shows an intriguing effect; in spite of a low channeling efficiency (3%), the volume reflection maintains a high deflection efficiency (83%). Such discrepancy was ascribed to the high concentration (10(4) per cm2) of dislocations in our sample, which was obtained from a commercial wafer. Indeed, it has been theoretically shown that a channeling efficiency comparable with that of Si or Ge would be attained with a crystal at low defect concentration (less than ten per cm2). To better understand the role of dislocations on volume reflection, we have worked out computer simulation via dynecharm++ Monte Carlo code to study the effect of dislocations on volume reflection. The results of the simulations agree with experimental records, demonstrating that volume reflection is more robust than channeling in the presence of dislocations.
We studied the dechanneling length of 150 GeV/cπ− interacting with a short bent silicon crystal. Dechanneling length measures the rate and the strength of incoherent interactions of channeled ...particles in a crystal. The mechanism of dechanneling of negatively charged particles has been elucidated through simulation and experiment. It was found that the dechanneling length for negative particles is comparable to the nuclear dechanneling length for positive charges. Indeed, dechanneling of negative particles occurs as a result of incoherent interactions with the nuclei because the trajectories of such particles always intersect atomic planes, explaining the lower channeling efficiency for such particles. Obtained results can be useful for the design of crystals for manipulating high-energy negative particle beams through channeling.
The trend of volume reflection parameters (deflection angle and efficiency) in a bent (110) silicon crystal has been investigated as a function of the crystal curvature with 400 GeV/c protons on the ...H8 beam line at the CERN Super Proton Synchrotron. This Letter describes the analysis performed at six different curvatures showing that the optimal radius for volume reflection is approximately 10 times greater than the critical radius for channeling. A strong scattering of the beam by the planar potential is also observed for a bend radius close to the critical one.
Past experimental data are collected to review the essential parameters of the design of ductile concentrically braced frames subjected to earthquake loading. The initial buckling load, the effective ...length of a brace, the degradation of compression resistance under cyclic loading, and the out-of-plane brace deformation will be examined in this study. The proposed equations for these parameters in the current seismic provisions are compared to the experimental data. In addition, new design equations are proposed for each parameter and verified with the experimental data. The current research is limited to rectangular hollow sections (RHS) because of their ease of connection to existing frames and their high radius of gyration compared to the other sections, such as wide-flange and double-tee sections.
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