SUNY Old Westbury

We analyze how investors and information intermediaries perceive auditor tenure. Using earnings response coefficients from returns-earnings regressions as a proxy for investor perceptions of earnings quality, we document a positive association between investor perceptions of earnings quality and tenure. Further, we find that the influence of reported earnings on stock rankings becomes larger with extended tenure, although the association between debt ratings and reported earnings does not vary with tenure. Finally, we find that the influence of past earnings on one-year-ahead earnings forecasts becomes greater as tenure increases. In general, our results are consistent with the hypothesis that investors and information intermediaries perceive auditor tenure as improving audit quality. One implication of our study is that imposing mandatory limits on the duration of the auditor-client relationship might impose unintended costs on capital market participants.

The coronavirus (COVID-19) pandemic has required faculty and students to adapt to an unprecedented challenge and rapidly transition from traditional face-to-face instruction to distance learning formats through virtual classrooms. While most campuses trained faculty to ensure quality and maintenance of the curriculum through virtual classrooms, less consideration has been given to training students, who face equal challenges in adapting to this abrupt change in the delivery of the curriculum. Few approaches have been developed for students to facilitate their involuntary transition to virtual classrooms and maintenance of appropriate online learning behaviours and etiquette. Presented here are a series of propositions to help to maintain and enhance the quality of college student engagement and activity in the virtual classroom. These guidelines are from one example of the State University of New York public educational system perspective, at the pandemic’s epicentre, while serving a diverse student population. Initiating a meaningful dialogue between faculty, who are engaged in efforts to cope and adapt to the pandemic, may prove useful in re-envisioning and re-designing future curriculum. This may facilitate future discussions on creating best practices guidelines for asynchronous/synchronous virtual classrooms post the pandemic. The present rapid communication suggests a framework for faculty to develop such guidelines to address the current gap in the literature.

American Journal of Physical Medicine & Rehabilitation: December 1989 - Volume 68 - Issue 6 - p 302

The endogenous cannabinoid receptor agonist anandamide is present in central and peripheral tissues. As the kidney contains both the amidase that degrades anandamide and transcripts for anandamide receptors, we characterized the molecular components of the anandamide signaling system and the vascular effects of exogenous anandamide in the kidney. We show that anandamide is present in kidney homogenates, cultured renal endothelial cells (EC), and mesangial cells; these cells also contain anandamide amidase. Reverse-transcriptase PCR shows that EC contain transcripts for cannabinoid type 1 (CB1) receptors, while mesangial cells have mRNA for both CB1 and CB2 receptors. EC exhibit specific, high-affinity binding of anandamide (Kd = 27.4 nM). Anandamide (1 microM) vasodilates juxtamedullary afferent arterioles perfused in vitro; the vasodilation can be blocked by nitric oxide (NO) synthase inhibition with L-NAME (0.1 mM) or CB1 receptor antagonism with SR 141716A (1 microM), but not by indomethacin (10 microM). Anandamide (10 nM) stimulates CB1-receptor-mediated NO release from perfused renal arterial segments; a similar effect was seen in EC. Finally, anandamide (1 microM) produces a NO-mediated inhibition of KCl-stimulated [3H]norepinephrine release from sympathetic nerves on isolated renal arterial segments. Hence, an anandamide signaling system is present in the kidney, where it exerts significant vasorelaxant and neuromodulatory effects.

A partial skeleton of a primitive bird, Rahona ostromi, gen. et sp. nov., has been discovered from the Late Cretaceous of Madagascar. This specimen, although exhibiting avian features such as a reversed hallux and ulnar papillae, retains characteristics that indicate a theropod ancestry, including a pubic foot and hyposphene-hypantra vertebral articulations. Rahona has a robust, hyperextendible second digit on the hind foot that terminates in a sicklelike claw, a unique characteristic of the theropod groups Troodontidae and Dromaeosauridae. A phylogenetic analysis places Rahona with Archaeopteryx, making Rahona one of the most primitive birds yet discovered.

Abstract. The time evolution of aerosol concentration and chemical composition in a megacity urban plume was determined based on 8 flights of the DOE G-1 aircraft in and downwind of Mexico City during the March 2006 MILAGRO field campaign. A series of selection criteria are imposed to eliminate data points with non-urban emission influences. Biomass burning has urban and non-urban sources that are distinguished on the basis of CH3CN and CO. In order to account for dilution in the urban plume, aerosol concentrations are normalized to CO which is taken as an inert tracer of urban emission, proportional to the emissions of aerosol precursors. Time evolution is determined with respect to photochemical age defined as −Log10 (NOx/NOy). The geographic distribution of photochemical age and CO is examined, confirming the picture that Mexico City is a source region and that pollutants become more dilute and aged as they are advected towards T1 and T2, surface sites that are located at the fringe of the City and 35 km to the NE, respectively. Organic aerosol (OA) per ppm CO is found to increase 7 fold over the range of photochemical ages studied, corresponding to a change in NOx/NOy from nearly 100% to 10%. In the older samples the nitrate/CO ratio has leveled off suggesting that evaporation and formation of aerosol nitrate are in balance. In contrast, OA/CO increases with age in older samples, indicating that OA is still being formed. The amount of carbon equivalent to the deduced change in OA/CO with age is 56 ppbC per ppm CO. At an aerosol yield of 5% and 8% for low and high yield aromatic compounds, it is estimated from surface hydrocarbon observations that only ~9% of the OA formation can be accounted for. A comparison of OA/CO in Mexico City and the eastern U.S. gives no evidence that aerosol yields are higher in a more polluted environment.

Initial confinement of opiate receptors to the nervous system has recently been broadened to several other cell types. Based on the well established hypotensive effect of morphine, we hypothesized that endothelial cells may represent a target for this opiate substance. Endothelial cells (human arterial and rat microvascular) contain a high affinity, saturable opiate binding site presumed to mediate the morphine effects that is stereoselectively and characteristically antagonized by naloxone. This opiate alkaloid-specific binding site is insensitive to opioid peptides. It is, therefore, considered to be the same subtype of opiate receptor (designated μ3) used in the mediation of morphine in other cell types exhibiting the same binding profile. Experiments with endothelial cultures and the aortic ring of rats cultured in vitro demonstrate that morphine exerts direct modulatory control over the activities of endothelial cells, which leads to vasodilation. It induces the production of nitric oxide, a process that is sensitive to naloxone antagonism and nitric oxide synthase inhibition. In contrast with that of opiates, the administration of opioid peptides does not induce nitric oxide production by endothelial cells. In conclusion, the data presented above reveal a novel site of morphine action, endothelial cells, where a μ3 receptor is coupled to nitric oxide release and vasodilation. Initial confinement of opiate receptors to the nervous system has recently been broadened to several other cell types. Based on the well established hypotensive effect of morphine, we hypothesized that endothelial cells may represent a target for this opiate substance. Endothelial cells (human arterial and rat microvascular) contain a high affinity, saturable opiate binding site presumed to mediate the morphine effects that is stereoselectively and characteristically antagonized by naloxone. This opiate alkaloid-specific binding site is insensitive to opioid peptides. It is, therefore, considered to be the same subtype of opiate receptor (designated μ3) used in the mediation of morphine in other cell types exhibiting the same binding profile. Experiments with endothelial cultures and the aortic ring of rats cultured in vitro demonstrate that morphine exerts direct modulatory control over the activities of endothelial cells, which leads to vasodilation. It induces the production of nitric oxide, a process that is sensitive to naloxone antagonism and nitric oxide synthase inhibition. In contrast with that of opiates, the administration of opioid peptides does not induce nitric oxide production by endothelial cells. In conclusion, the data presented above reveal a novel site of morphine action, endothelial cells, where a μ3 receptor is coupled to nitric oxide release and vasodilation. INTRODUCTIONThe vast majority of pharmacological studies of the properties of opiate substances have long been almost exclusively concerned with their effects on analgesic and antinociceptive phenomena. More recently, a number of experiments have demonstrated that morphine modulates the activity of varieties of cell types, among them the immunocytes of several mammalian and invertebrate species(1.Stefano G.B. Digenis A. Spector S. Leung M.K. Bilfinger T.V. Makman M.H. Scharrer B. Abumrad N.N. Proc. Natl. Acad. Sci. U. S. A. 1993; 90: 11099-11103Crossref PubMed Scopus (251) Google Scholar, 2.Makman M.H. Bilfinger T.V. Stefano G.B. J. Immunol. 1995; 154: 1323-1330PubMed Google Scholar). In addition, this largely down-regulating effect was found to be mediated by a highly specific, opiate alkaloid-sensitive receptor used selectively by opiates(1.Stefano G.B. Digenis A. Spector S. Leung M.K. Bilfinger T.V. Makman M.H. Scharrer B. Abumrad N.N. Proc. Natl. Acad. Sci. U. S. A. 1993; 90: 11099-11103Crossref PubMed Scopus (251) Google Scholar, 2.Makman M.H. Bilfinger T.V. Stefano G.B. J. Immunol. 1995; 154: 1323-1330PubMed Google Scholar). In the present case, the receptor (μ3) accomplishes this by counteracting the cellular responsiveness to a number of immunoexcitatory molecules, e.g. lipopolysaccharides and some cytokines (see (3.Stefano G.B. Scharrer B. Adv. Neuroimmunol. 1994; 4: 57-68Abstract Full Text PDF PubMed Scopus (183) Google Scholar)).In this context, morphine was found to be quite potent in lowering or terminating the activation of human granulocytes and monocytes exposed to the stimulatory activity of plasma obtained from cardiopulmonary bypass patients(4.Bilfinger T.V. Stefano G.B. J. Cardiovasc. Surg. 1993; 34: 129-133PubMed Google Scholar, 5.Stefano G.B. Kushnerik V. Rodriquez M. Bilfinger T.V. Int. J. Immunopharmacol. 1994; 16: 329-334Crossref PubMed Scopus (35) Google Scholar, 6.Stefano G.B. Rodriquez M. Glass R. Casares F. Hughes T.K. Bilfinger T.V. J. Cardiovasc. Surg. 1995; 36: 25-30PubMed Google Scholar, 7.Stefano G.B. Bilfinger T.V. J. Neuroimmunol. 1993; 47: 189-198Abstract Full Text PDF PubMed Scopus (56) Google Scholar). From these observations, we surmised that a proportion of these cells may have been derived from intravascular immune cells whose adhesiveness to the vascular lining may have been altered by the presence of morphine in this tissue.The present study was aimed at the exploration of the possibility that endothelial cells may be under the direct control of the opiates. It provided evidence for the specific binding of morphine to endothelial cells, resulting in stimulation of nitric oxide (NO) 1The abbreviations used are: NOnitric oxide3DHM[3H]dihydromorphineDAGO[D-Ala2,MePhe4,Gly(ol)5]enkephalinMVEmicrovascular endothelial cellsPSSphysiological salt solution. production in a naloxone-reversible manner and relaxation of blood vessels. It also demonstrated that these activities are mediated by the special opiate receptor μ3 present in the endothelial cells.MATERIALS AND METHODSCell CulturesHuman arterial endothelial cells were obtained from a commercial laboratory (Cell Systems, Kirkland, WA) for binding analysis as a prefrozen pellet (107 cells). In addition, microvascular endothelial cells (MVE) were established in our laboratory (8.Tsukahara H. Gordienko D.V. Tonshoff B. Gelato M.C. Goligorsky M.S. Kidney Int. 1994; 45: 598-604Abstract Full Text PDF PubMed Scopus (294) Google Scholar, 9.Tsukahara H. Ende H. Magazine H.I. Bahou W.F. Goligorsky M.S. J. Biol. Chem. 1994; 269: 21778-21785Abstract Full Text PDF PubMed Google Scholar) by SV40 transfection of endothelial cells from microdissected rat renal resistance arteries and cloned by limiting dilution. The cells were characterized as endothelial in origin based on the following criteria: distinct cobblestone-like morphology, tendency for capillary tube formation, positive identification of the factor VIII immunoreactivity, uptake of acetylated low density lipoprotein, and absent immunoreactivity of smooth muscle-specific actin. MVEs were grown in M199 medium (Mediatech, Washington, D.C.) supplemented by 5% fetal bovine serum (HyClone Laboratories, Logan, UT).Opiate Binding AnalysisThe endothelial cells (human arterial and rat microvascular were processed separately) were homogenized in 50 volumes of 0.32 M sucrose, pH 7.4, at 4°C by the use of a Brinkmann Instruments Polytron (30 s, setting no. 5). The crude homogenate was centrifuged at 900 × g for 10 min at 4°C, and the supernatant was preserved on ice. The whitish crude pellet was resuspended by homogenization (15 s, setting no. 5) in 30 volumes of 0.32 M sucrose/Tris-HCl buffer, pH 7.4, and centrifuged at 900 × g for 10 min. The extraction procedure was repeated one more time, and the combined supernatants were centrifuged at 900 × g for 10 min. The resulting supernatants (S1′) were used immediately.Immediately prior to the binding experiment, the S1′ supernatant was centrifuged at 30,000 × g for 15 min, and the resulting pellet (P2) was washed once by centrifugation in 50 volumes of the sucrose/Tris-HCl. The P2 pellet was then resuspended with a Dounce hand-held homogenizer (10 strokes) in 100 volumes of buffer. Binding analysis was then performed on the cell membrane suspensions.Aliquots of membrane suspensions from these cells were incubated with nonradioactive compounds at six concentrations for 10 min at 22°C and then with [3H]dihydromorphine (3DHM) for 60 min at 4°C. One hundred percent binding is defined as bound 3DHM in the presence of 10 μM dextrorphan minus bound 3DHM in the presence of 10 μM levorphanol. Ki is defined as the concentration of drug that elicits half-maximal inhibition of specific binding. The mean ± S.E. for three experiments is given. The displacement analysis data indicate the potency of various opioid (Met-enkephalin and D-Ala2-Met5-enkephalin, Sigma) and opiate substances in displacing 3DHM (58 Ci/mM, DuPont NEN) and may give specific information on different receptor populations. The incubation medium for Met-enkephalin contained phosphoramidon (100 μM) and bestatin (100 μM) to inhibit enzyme degradation.Monitoring of NO ReleaseThe cells were incubated in 2 ml of Krebs-Henseleit buffer containing (in mM) 120 NaCl, 4.6 KCl, 1.5 CaCl2, 0.5 MgCl2, 1.5 NaH2PO4, 0.7 Na2HPO4, 10 HEPES, and 10 glucose, pH 7.4.NO release was monitored with an NO-selective microprobe manufactured by Inter Medical Co. (Nagoya, Japan). The working electrode made of platinum/iridium alloy was coated with a film containing KCl, NO-selective nitrocellulose resin (pyroxyline lacquer), and a gas-permeable silicon membrane(10.Ichimori K. Ishida H. Fukabori M. Nakazawa H. Murakami E. Rev. Sci. Instrum. 1994; 65: 1-5Crossref Scopus (177) Google Scholar). A counter electrode was made of carbon fiber. The redox current was detected by a current-voltage converter circuit and continuously recorded. Tip diameter of the probe (25 μm) permitted the use of a micromanipulator (Zeiss-Eppendorff) attached to the stage of an inverted microscope (Nikon Diaphot) to position the sensor, which was enclosed in a Faraday's chamber, 3-5 μm above the cell surface. Calibration of the electrochemical sensor was performed by use of different concentrations of a nitrosothiol donor S-nitroso-N-acetyl-DL-penicillamine, as previously detailed(10.Ichimori K. Ishida H. Fukabori M. Nakazawa H. Murakami E. Rev. Sci. Instrum. 1994; 65: 1-5Crossref Scopus (177) Google Scholar).Vascular Relaxation ExperimentsMale Sprague-Dawley rats, 6-8 weeks of age, were anesthetized with 1 cc of sodium pentobarbital, followed by removal of the thoracic aorta for evaluation of developed isometric tension. The procedure was performed as described elsewhere in detail(11.Magazine H.I. Bruner C.A. Anderson T.T. Malik A.B. Am. J. Physiol. 1994; 226: H1620-H1625Google Scholar). The vessel was placed in physiological salt solution (PSS), and excess connective tissue was removed. The preparation was cut into 3-mm rings, mounted on metal tissue holders, and placed in a 5-ml tissue bath (Kent Scientific Corp.) containing aerated (95% O2, 5% CO2) PSS buffer maintained at 37°C. Relaxation of rings precontracted with 1 nM phenylephrine was detected by computer-interfaced force transducers (Kent Scientific Corp.) set at a sampling rate of 6/min. Data are expressed as percent maximal relaxation in response to 1 μM morphine. Opiate receptor specificity was evaluated by measurement of vascular relaxation in response to treatment with 1 μM morphine rings pretreated for 10 min with 5 μM naloxone or, for μ3 identity, with 10 μM [D-Ala2,MePhe4,Gly(ol)5]enkephalin (DAGO).Rings of thoracic aorta (3 mm) were placed in PSS, and NO release in response to 1 μM morphine was evaluated by use of a computer-interfaced NO-specific amperometric probe as described above.RESULTSMembrane homogenates of human arterial and rat microvascular endothelial cells revealed opiate binding sites and their ligand specification (Fig. 1 and Table 1). Saturation and Scatchard analysis showed a single, relatively high affinity binding site with Kd values of 38 and 19 nM, with Bmax values of 1,167 and 1,098 fmol/mg membrane protein for human and rat-derived endothelial cells, respectively (Fig. 1 and Table 1). Nonspecific binding increased linearly with respect to the concentration of the binding ligand (Fig. 1, inset). Furthermore, a variety of opioid peptides was found to be ineffective in displacing specifically bound 3DHM (Table 1). By contrast, the opiate alkaloid ligands were the most potent, and κ ligands dynorphin 1-17 and ethylketocyclazocine were weak. Interestingly, fentanyl was quite poor in this regard. Naloxone was found to be less potent than naltrexone in counteracting 3DHM binding. Of interest was the finding that the μ opioid peptide DAGO was ineffective in displacing 3DHM (Table 1). Of equal interest was that the displacement profile for all ligands in both types of endothelial cells was identical. This profile demonstrating opiate alkaloid sensitivity and opioid peptide insensitivity is characteristic of the presence of the μ3 opiate receptor (1.Stefano G.B. Digenis A. Spector S. Leung M.K. Bilfinger T.V. Makman M.H. Scharrer B. Abumrad N.N. Proc. Natl. Acad. Sci. U. S. A. 1993; 90: 11099-11103Crossref PubMed Scopus (251) Google Scholar).Tabled 1 Open table in a new tab Experiments with endothelial cells and aortic rings examined in vitro have revealed a direct modulating influence of morphine on the activities of these cells. Morphine resulted in a dose-dependent release of NO from endothelial cells (Fig. 2, Fig. 3). The effect was blocked by naloxone. By contrast, opioid peptides or the μ opioid receptive DAGO (10 μM) did not effect any changes in NO release (data not shown). For comparison, the effect of a well established stimulator of NO release, bradykinin, is presented. The effect of morphine is qualitatively and quantitatively similar to that of bradykinin, with no delay in NO release (Fig. 2). Furthermore, pretreatment of the human endothelial cells with L-nitroarginine methyl ester (10-4M for 5 min before morphine exposure), a nitric oxide synthase inhibitor, also abolished morphine-induced (10-6M) NO release (data not shown).Fig. 2In vitro stimulation of NO production by morphine. Representative recordings of NO in the incubation medium prior to and following opiate and opioid exposure are shown (arrow, M, morphine). a, 50 nM morphine; b, 100 nM morphine; c, 200 nM morphine; d, 200 nM naloxone + 200 nM morphine. ME, 100 nM Met-enkephalin; DAME, 100 nM [D-Ala2,Met5]enkephalin. Bradykinin (BK, 10-6M) was added for comparison.View Large Image Figure ViewerDownload Hi-res image Download (PPT)In intact aortic rings, morphine (1 μM) induced relaxation, a phenomenon that was attributable to NO and that was naloxone-reversible (Fig. 3). DAGO (10 μM) did not cause relaxation of the vascular rings (data not shown). In aortic rings denuded of the endothelial layer all opiate actions were lost.Fig. 3Morphine-induced relaxation of rat aorta. Morphine (1 μM) was added to aortic rings in the absence (boldface line) or presence (narrow line) of naloxone (5 μM). The data shown are representative of n = 4 experiments, which did not vary. Inset, stimulation of aortic rings with morphine (1 μM) resulted in a marked increase in NO release (boldface line) that was abrogated by pretreatment with naloxone (5 μM, narrow line). The data shown are representative of n = 4 experiments, which did not vary.View Large Image Figure ViewerDownload Hi-res image Download (PPT)In view of the distinct vasorelaxing action of morphine (12.Randich A. Robertson J.D. Willingham T. Brain Res. 1993; 603: 186-200Crossref PubMed Scopus (29) Google Scholar) and the presence of the μ3 opiate receptors on endothelial cells expressed with comparative density at the level of conduit and resistance arteries, the effects of morphine on vascular endothelium can be considered to be direct and not via interaction with the neural or neuroendocrine systems.DISCUSSIONThe present report demonstrates the following. 1) Endothelial cells (human arterial and rat microvascular) contain a high affinity saturable opiate binding site that is stereoselectively and characteristically antagonized by naloxone. 2) This binding site is opiate alkaloid-specific and opioid peptide-insensitive. 3) The binding to this site as well as to other cell types exhibiting this novel binding profile (Table 1) is designated to be of the μ3 opiate receptor subtype. 4) Morphine can induce the production of NO from MVE cells and rat aortic ring endothelial cells in vitro, a phenomenon that is sensitive to naloxone antagonism. 5) Aortic rings respond to morphine by relaxation which was endothelial dependent. 6) Opioid peptides do not induce in vitro NO production or relaxation of the aortic ring. 6) Endothelial NO production, therefore, appears to be mediated by the μ3 opiate alkaloid-specific receptor.With regard to the interaction of NO and opiate substances mentioned earlier, recent studies suggest a definite link. Nitric oxide has been associated with antinociception (13.Duarte J. PubMed Scopus Google Scholar, R. H. B. Sci. 1993; PubMed Scopus Google Scholar, J. 1994; 269: Google Scholar) as well as the of and B. H. R. 1994; PubMed Scopus Google Scholar). morphine J. PubMed Scopus Google Scholar). A NO K. J. Immunol. 1994; Google Scholar). Morphine and NO have been in K. J. 1994; PubMed Scopus Google Scholar) and in A. S. M. Res. PubMed Scopus Google Scholar, A. F. J. 1993; PubMed Scopus Google Scholar). the present report this for the time, in endothelial cells mediated by of the μ3 specificity of the opiate receptor subtype (μ3) in endothelial NO production the of opiate or similar substances in this process and the of opioid peptides. The μ3 receptor has been found on human monocytes and G.B. Digenis A. Spector S. Leung M.K. Bilfinger T.V. Makman M.H. Scharrer B. Abumrad N.N. Proc. Natl. Acad. Sci. U. S. A. 1993; 90: 11099-11103Crossref PubMed Scopus (251) Google Scholar, 2.Makman M.H. Bilfinger T.V. Stefano G.B. J. Immunol. 1995; 154: 1323-1330PubMed Google invertebrate and E. F. M. Stefano Scharrer B. Stefano G.B. Proc. Natl. Acad. Sci. U. S. A. 1994; PubMed Scopus Google Scholar, K. Makman M.H. Stefano G.B. Brain Res. 1995; PubMed Scopus Google cell M.H. Adv. Neuroimmunol. 1994; 4: Full Text PDF Scopus Google in a on specific invertebrate B. in Scholar) (see Table 1). the presence of a highly opiate receptor that substances that use of this In this morphine appears to be a G.B. Scharrer B. Adv. Neuroimmunol. 1994; 4: 57-68Abstract Full Text PDF PubMed Scopus (183) Google present study demonstrates that opiate have the to mediate by of of NO suggest that opiates, in this mediate their effects by of the nervous of morphine in the rat response and A. Robertson J.D. Willingham T. Brain Res. 1993; 603: 186-200Crossref PubMed Scopus (29) Google Scholar). have demonstrated that the specific μ opioid receptor effects of morphine. of were by the the the effects of DAGO not induced by A. Robertson J.D. Willingham T. Brain Res. 1993; 603: 186-200Crossref PubMed Scopus (29) Google Scholar). In morphine at a high (1 induced in mean and arterial did not or vascular C.A. Am. J. Physiol. Google Scholar). data indicate that in the that an response to morphine, changes were largely induced by from well established morphine has been shown to to or K. J. E. T. 1994; PubMed Scopus Google Scholar). Furthermore, the effect of of in rats was by administration of morphine; morphine of blood in these 1993; PubMed Scopus Google Scholar). In a study on morphine-induced A. F. PubMed Scopus Google Scholar) that was mediated by Based on the of the present endothelial cells are of a direct action of morphine or studies be concerned with this phenomenon and in the of INTRODUCTIONThe vast majority of pharmacological studies of the properties of opiate substances have long been almost exclusively concerned with their effects on analgesic and antinociceptive phenomena. More recently, a number of experiments have demonstrated that morphine modulates the activity of varieties of cell types, among them the immunocytes of several mammalian and invertebrate species(1.Stefano G.B. Digenis A. Spector S. Leung M.K. Bilfinger T.V. Makman M.H. Scharrer B. Abumrad N.N. Proc. Natl. Acad. Sci. U. S. A. 1993; 90: 11099-11103Crossref PubMed Scopus (251) Google Scholar, 2.Makman M.H. Bilfinger T.V. Stefano G.B. J. Immunol. 1995; 154: 1323-1330PubMed Google Scholar). In addition, this largely down-regulating effect was found to be mediated by a highly specific, opiate alkaloid-sensitive receptor used selectively by opiates(1.Stefano G.B. Digenis A. Spector S. Leung M.K. Bilfinger T.V. Makman M.H. Scharrer B. Abumrad N.N. Proc. Natl. Acad. Sci. U. S. A. 1993; 90: 11099-11103Crossref PubMed Scopus (251) Google Scholar, 2.Makman M.H. Bilfinger T.V. Stefano G.B. J. Immunol. 1995; 154: 1323-1330PubMed Google Scholar). In the present case, the receptor (μ3) accomplishes this by counteracting the cellular responsiveness to a number of immunoexcitatory molecules, e.g. lipopolysaccharides and some cytokines (see (3.Stefano G.B. Scharrer B. Adv. Neuroimmunol. 1994; 4: 57-68Abstract Full Text PDF PubMed Scopus (183) Google Scholar)).In this context, morphine was found to be quite potent in lowering or terminating the activation of human granulocytes and monocytes exposed to the stimulatory activity of plasma obtained from cardiopulmonary bypass patients(4.Bilfinger T.V. Stefano G.B. J. Cardiovasc. Surg. 1993; 34: 129-133PubMed Google Scholar, 5.Stefano G.B. Kushnerik V. Rodriquez M. Bilfinger T.V. Int. J. Immunopharmacol. 1994; 16: 329-334Crossref PubMed Scopus (35) Google Scholar, 6.Stefano G.B. Rodriquez M. Glass R. Casares F. Hughes T.K. Bilfinger T.V. J. Cardiovasc. Surg. 1995; 36: 25-30PubMed Google Scholar, 7.Stefano G.B. Bilfinger T.V. J. Neuroimmunol. 1993; 47: 189-198Abstract Full Text PDF PubMed Scopus (56) Google Scholar). From these observations, we surmised that a proportion of these cells may have been derived from intravascular immune cells whose adhesiveness to the vascular lining may have been altered by the presence of morphine in this tissue.The present study was aimed at the exploration of the possibility that endothelial cells may be under the direct control of the opiates. It provided evidence for the specific binding of morphine to endothelial cells, resulting in stimulation of nitric oxide (NO) 1The abbreviations used are: NOnitric oxide3DHM[3H]dihydromorphineDAGO[D-Ala2,MePhe4,Gly(ol)5]enkephalinMVEmicrovascular endothelial cellsPSSphysiological salt solution. production in a naloxone-reversible manner and relaxation of blood vessels. It also demonstrated that these activities are mediated by the special opiate receptor μ3 present in the endothelial cells.

Understanding the control of gene expression is critical for our understanding of the relationship between genotype and phenotype. The need for reliable assessment of transcript abundance in biological samples has driven scientists to develop novel technologies such as DNA microarray and RNA-Seq to meet this demand. This review focuses on comparing the two most useful methods for whole transcriptome gene expression profiling. Microarrays are reliable and more cost effective than RNA-Seq for gene expression profiling in model organisms. RNA-Seq will eventually be used more routinely than microarray, but right now the techniques can be complementary to each other. Microarrays will not become obsolete but might be relegated to only a few uses. RNA-Seq clearly has a bright future in bioinformatic data collection.

The discovery of the ability of the nervous system to communicate through "public" circuits with other systems of the body is attributed to Ernst and Berta Scharrer, who described the neurosecretory process in 1928. Indeed, the immune system has been identified as another important neuroendocrine target tissue. Opioid peptides are involved in this communication (i.e., neuroimmune) and with that of autoimmunoregulation (communication between immunocytes). The significance of opioid neuropeptide involvement with the immune system is ascertained from the presence of novel delta, mu, and kappa receptors on inflammatory cells that result in modulation of cellular activity after activation, as well as the presence of specific enzymatic degradation and regulation processes. In contrast to the relatively uniform antinociceptive action of opiate and opioid signal molecules in neural tissues, the presence of naturally occurring morphine in plasma and a novel mu3, opiate-specific receptor on inflammatory cells adds to the growing knowledge that opioid and opiate signal molecules may have antagonistic actions in select tissues. In examining various disorders (e.g., human immunodeficiency virus, substance abuse, parasitism, and the diffuse inflammatory response associated with surgery) evidence has also been found for the involvement of opiate/opioid signaling in prominent mechanisms. In addition, the presence of similar mechanisms in man and organisms 500 million years divergent in evolution bespeaks the importance of this family of signal molecules. The present review provides an overview of recent advances in the field of opiate and opioid immunoregulatory processes and speculates as to their significance in diverse biological systems.

Ecological partnerships, or mutualisms, are globally widespread, sustaining agriculture and biodiversity. Mutualisms evolve through the matching of functional traits between partners, such as tongue length of pollinators and flower tube depth of plants. Long-tongued pollinators specialize on flowers with deep corolla tubes, whereas shorter-tongued pollinators generalize across tube lengths. Losses of functional guilds because of shifts in global climate may disrupt mutualisms and threaten partner species. We found that in two alpine bumble bee species, decreases in tongue length have evolved over 40 years. Co-occurring flowers have not become shallower, nor are small-flowered plants more prolific. We argue that declining floral resources because of warmer summers have favored generalist foraging, leading to a mismatch between shorter-tongued bees and the longer-tubed plants they once pollinated.

Organizational agility may be considered the integration of organizational processes, characteristics, and members with advanced technology. Agility enhances the organization’s ability to provide high quality products and services and is, therefore, crucial to organizational competitiveness. Integrates the production/operations, general management, and sociotechnical views to develop a model of organizational agility. Briefly reviews the literature in these fields and offers a model of agility based on suppliers, organizational members, and customers united through information technology. It is proposed that these connections rest on a foundation of leadership, organization culture, and employee reward systems that create a relationship between people and technology. These relationships include involving people in decision making, creating process and product quality by offering enriched jobs, training in technology, and providing a reward system which reinforces agility‐promoting efforts.

Tetracyclines are now recognized to have non-antimicrobial properties with therapeutic potential--for example, these agents can inhibit pathologic collagenolysis by blocking mammalian collagenases and other matrix-degrading metalloproteinases. In the current study, adult human subjects with moderate chronic periodontitis were administered specially formulated capsules of doxycycline, containing lower-than-usual amounts of this semi-synthetic tetracycline, on a daily basis for 2 weeks prior to a full-thickness flap procedure; control subjects were administered placebo capsules. The gingiva excised during this surgical procedure were extracted, the extracts partially purified and analyzed for collagenase activity using [3H-methyl] collagen as substrate and the techniques of SDS-PAGE/fluorography or liquid scintillation spectrometry. In the absence of any drug pre-treatment, or after a 2-wk regimen of placebo capsules, the gingival extracts exhibited pathologically-excessive mammalian collagenase activity. The 2-wk regimen of low-dose doxycycline capsules reduced this activity by approximately 60-80% (p less than 0.05 and less than 0.01, respectively); in vitro exposure of the gingival extract to doxycycline also inhibited its collagenase activity. Collagenase activity in the crevicular fluid of periodontal pockets of an additional group of subjects was also significantly reduced, as was the severity of inflammation at the same gingival sites. The results suggest that a regimen of low-dose doxycycline capsules may provide a safe (other studies indicate that this regimen may not induce tetracycline resistance in the subgingival plaque) and effective adjunct to instrumentation therapy in the management of pathologic collagenolysis in the periodontal patient. However, further studies are necessary to confirm this hypothesis.

Black sexual minority women are triply marginalized due to their race, gender, and sexual orientation. We compared three dimensions of discrimination-frequency (regularity of occurrences), scope (number of types of discriminatory acts experienced), and number of bases (number of social statuses to which discrimination was attributed)-and self-reported mental health (depressive symptoms, psychological well-being, and social well-being) between 64 Black sexual minority women and each of two groups sharing two of three marginalized statuses: (a) 67 White sexual minority women and (b) 67 Black sexual minority men. Black sexual minority women reported greater discrimination frequency, scope, and number of bases and poorer psychological and social well-being than White sexual minority women and more discrimination bases, a higher level of depressive symptoms, and poorer social well-being than Black sexual minority men. We then tested and contrasted dimensions of discrimination as mediators between social status (race or gender) and mental health outcomes. Discrimination frequency and scope mediated the association between race and mental health, with a stronger effect via frequency among sexual minority women. Number of discrimination bases mediated the association between gender and mental health among Black sexual minorities. Future research and clinical practice would benefit from considering Black sexual minority women's mental health in a multidimensional minority stress context.

Purpose The purpose of this paper is to investigate whether gender diversity of audit committees has a significant impact on the firm's earnings management. Design/methodology/approach This paper uses a performance‐adjusted discretionary accrual model to examine the association between gender variables and the firm's earnings management. Regression analysis is applied using 320 firms from the S&P Small Cap 600 . Findings The authors find consistent evidence to show that the presence of a female director on the audit committee constrains earnings management by increasing negative (income‐decreasing) discretionary accruals. Research limitations/implications Future research can explore the behavior of female managers by applying the gender theory. Furthermore, the paper's evidence has implications for regulators and policy makers, since the presence of a female director in the audit committee may affect management decisions and audit quality in a positive way. Therefore, gender diversity on the board should be more strongly emphasized. Moreover, the presence of female members on the board may further enhance public confidence. Originality/value This research contributes to the existing literature on gender in four aspects. First, this research provides new evidence to reinforce the existing gender literature that women are more risk averse, cautious and ethical than men. Second, the findings showcase that gender theory can be applied into the research of management behavior. Third, the findings are significantly important in contemporary corporate governance discussions over the SOX enactment and audit committee characteristics Fourth, this study sheds further light on the importance of having women on corporate boards and the positive outcomes that are associated with it, thereby serving as an encouraging force against the existence of the glass ceiling effect.

Transcriptome and genome data from twenty stony coral species and a selection of reference bilaterians were studied to elucidate coral evolutionary history. We identified genes that encode the proteins responsible for the precipitation and aggregation of the aragonite skeleton on which the organisms live, and revealed a network of environmental sensors that coordinate responses of the host animals to temperature, light, and pH. Furthermore, we describe a variety of stress-related pathways, including apoptotic pathways that allow the host animals to detoxify reactive oxygen and nitrogen species that are generated by their intracellular photosynthetic symbionts, and determine the fate of corals under environmental stress. Some of these genes arose through horizontal gene transfer and comprise at least 0.2% of the animal gene inventory. Our analysis elucidates the evolutionary strategies that have allowed symbiotic corals to adapt and thrive for hundreds of millions of years.

The presence of morphine-like and codeine-like substances was demonstrated in the pedal ganglia, hemolymph, and mantle tissues of the mollusc Mytilus edulis. The pharmacological activities of the endogenous morphine-like material resemble those of authentic morphine. Both substances were found to counteract, in a dose-dependent manner, the stimulatory effect of tumor necrosis factor alpha or interleukin 1 alpha on human monocytes and Mytilus immunocytes, when added simultaneously to the incubation medium. The immunosuppressive effect of this opiate material expresses itself in a lowering of chemotactic activity, cellular velocity, and adherence. Codeine mimics the activity of authentic morphine, but only at much higher concentrations. Specific high-affinity receptor sites (mu 3) for morphine have been identified on human monocytes and Mytilus immunocytes. In Mytilus recovering from experimentally induced stress, the return of "altered" immunocytes to a more inactive state appears to be due to a significant rise in the content of morphine-like material in the pedal ganglia and hemolymph at this time. Thus, morphine may have a role in calming or terminating the state of immune alertness.

Obesity is a global epidemic representing a serious public health burden as it is a major risk factor for the development of cardiovascular disease, stroke and all-cause mortality. Chronic low-grade systemic inflammation, also known as meta-inflammation, is thought to underly obesity's negative health consequences, which include insulin resistance and the development of type 2 diabetes. Meta-inflammation is characterized by the accumulation of immune cells in adipose tissue, a deregulation in the synthesis and release of adipokines and a pronounced increase in the production of proinflammatory factors. In this state, the infiltration of macrophages and their metabolic activation contributes to complex paracrine and autocrine signaling, which sustains a proinflammatory microenvironment. A key signaling pathway mediating the response of macrophages and adipocytes to a microenvironment of excessive nutrients is the phosphoinositide 3-kinase (PI3K)/Akt pathway. This multifaceted network not only transduces metabolic information but also regulates macrophages' intracellular changes, which are responsible for their phenotypic switch towards a more proinflammatory state. In the present review, we discuss how the crosstalk between macrophages and adipocytes contributes to meta-inflammation and provide an overview on the involvement of the PI3K/Akt signaling pathway, and how its impairment contributes to the development of insulin resistance.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTwo-Stage Kinetics of Single-Chain Collapse. Polystyrene in CyclohexaneBenjamin Chu, Qicong Ying, and Alexander Yu. GrosbergCite this: Macromolecules 1995, 28, 1, 180–189Publication Date (Print):January 1, 1995Publication History Published online1 May 2002Published inissue 1 January 1995https://pubs.acs.org/doi/10.1021/ma00105a024https://doi.org/10.1021/ma00105a024research-articleACS PublicationsRequest reuse permissionsArticle Views738Altmetric-Citations195LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

Observations of ozone (O 3 ) and O 3 precursors taken from aircraft flights over Houston, TX, Nashville, TN; New York, NY; Phoenix, AZ, and Philadelphia, PA show that high concentrations of reactive volatile organic compounds (VOCs) in the Houston atmosphere lead to calculated O 3 production rates that are 2 to 5 times higher than in the other 4 cities even though NO x concentrations are comparable. Within the Houston metropolitan area, concentrations of VOCs and O 3 production rates are highest in the Ship Channel region; the location of one of the largest petrochemical complexes in the world. As a consequence the concentration of O 3 in the Houston metropolitan area has recently exceeded 250 ppb, the highest value observed in the U.S within the past 5 years.

An expression for the production rate of O 3 , P(O 3 ), is derived based on a radical budget equation applicable to low and high NO x conditions. Differentiation of this equation with respect to NO or hydrocarbons (HC) gives an approximate analytic formula in which the relative sensitivity of P(O 3 ) to changes in NO or HC depends only on the fraction of radicals which are removed by reactions with NO x . This formula is tested by comparison with results from a photochemical calculation driven by trace gas observations from the 1995 Southern Oxidants Study (SOS) campaign in Nashville, Tennessee.