Relationship Between Opioid-Receptor Occupancy and Stimulation of Low- K m GTPase in Brain Membranes

Treatment of rat brain membranes with the irreversible opioid ligand cis -3-methylfentanylisothiocyanate (Superfit) was used to reduce gradually the number of available binding sites for the Δ-selective agonist [ 3 H][d-Ser 2 , Leu 5 lenkephalin-Thr 6 ([ 3 H]DSLET). Subsequently, the correlation between ligand binding and low- K m GTPase was investigated. Alkylation with 10 ΜM and 25 ΜM Superfit inactivated 66% and 71% of high-affinity ( K D , 1 n M ) binding sites without decreasing the affinity of the remaining sites and the stimulation of low-. K m GTPase by DSLET. Following exposure of the membranes to 50 ΜM and 75 ΜM Superfit, ligand binding was confined to the low-affinity ( K D , 20 n M ) sites. In these membranes, the Δ-agonists DSLET and [d-Pen 2 ,D-Pen 5 ]enkephalin still stimulated low- K m GTPase, and these effects were blocked by ICI 174864 ( N,N- diallyl-Tyr-AIB-AIB-Phe-Leu-OH; AIB, Α-aminoisobutyric acid), a Δ-selective antagonist. A similar relationship between low-affinity ligand binding and GTPase stimulation was observed following alkylation of the Δ-opioid receptor with the nonselective irreversible antagonist Β-chlomaltrexamine in the presence of protective concentrations of DSLET. The results reveal spare receptor sites in the coupling of the Δ-opioid receptor to low- K m GTPase in brain and identify low-affinity ligand binding as a functional component in the process.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65675/1/j.1471-4159.1989.tb01862.x.pd

Unusual Digital Patterns In EPS: Evidence On The Association Between Earnings Management And Company Characteristics

Prior studies (Thomas, 1989; Das and Zhang, 2003) provide evidence of earnings manipulation to achieve cognitive reference points in EPS.  The current study extends this line of research by examining the relation between unusual digital patterns in the right EPS position and specific firm characteristics.  Results suggest that the propensity to manage earnings to effect desired EPS results is particularly associated with company size and to a lesser degree with operating performance and the level of debt leverage employed

Production of Acetaldehyde from Ethanol in Coastal Waters

Interest in understanding the cycling of ethanol in the environment has grown as ethanol use as a gasoline additive has increased. The production of acetaldehyde from ethanol was measured in Southern California coastal seawater. The rate of increase of acetaldehyde was positively correlated with the rate constant for ethanol biodegradation and bacteria count and was consistent with two consecutive first-order reactions where acetaldehyde is first biologically produced from ethanol then consumed. Correlation with bacteria counts suggested that acetaldehyde degradation was also a biological process. The rate constants for acetaldehyde production from ethanol and acetaldehyde loss averaged 3.0 ± 3.4 × 10−3 min−1 and 2.3 ± 4.5 × 10−2 min−1 respectively. The branching ratio for acetaldehyde production from ethanol was 0.46 ± 0.26 and estimated acetaldehyde biological production rates ranged from 0.022 to 0.800 nM min−1. With high bacterial counts, biological production rates from ethanol exceeded photochemical production rates from chromophoric dissolved organic matter. Overall, acetaldehyde production rates were larger than biodegradation rates, suggesting these waters are a source of acetaldehyde to the atmosphere. Extrapolation to higher ethanol concentrations associated with spills suggests that the production rate of acetaldehyde will initially increase and then decrease as ethanol concentrations increase

Unusual Digital Patterns in EPS: Evidence On the Association Between Earnings Management and Company Characteristics

Prior studies (Thomas, 1989; Das and Zhang, 2003) provide evidence of earnings manipulation to achieve cognitive reference points in EPS. The current study extends this line of research by examining the relation between unusual digital patterns in the right EPS position and specific firm characteristics. Results suggest that the propensity to manage earnings to effect desired EPS results is particularly associated with company size and to a lesser degree with operating performance and the level of debt leverage employed

Preliminary Evidence Of SFAS No. 130's Effect On Gains Trading In The Insurance Industry

Gains trading represents a form of earnings management whereby appreciated marketable securities are sold at a gain while those with a loss are retained. By not requiring unrealized gains and losses on available-for-sale securities to flow through income, SFAS No. 115 failed to close the door on this type of earnings management. With SFAS No. 130, however, these unrealized gains and losses must now be reported prominently in a financial statement as a component of comprehensive income. By examining the level of gains trading for a sample of companies in the insurance industry both before and after the implementation of SFAS No. 130, the current study provides evidence suggesting that this form of earnings management subsided subsequent to the adoption of SFAS No. 130

Membrane Microviscosity Modulates Μ-Opioid Receptor Conformational Transitions and Agonist Efficacy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66282/1/j.1471-4159.1999.0730289.x.pd

Tip Reporting In Independent Food And Beverage Establishments

Tip reporting has always been an issue for the IRS. What happens when individuals under-report their tip income? History has shown that a large burden is placed upon the restaurants for the additional taxes that are lost due to unreported tip income. Using focus group interviews and survey research, this study addresses four research questions: 1. Do restaurant employers understand the tip reporting requirements? ; 2. Where does the IRS place the burden of record keeping and payment of lost taxes? ; 3. Are restaurants aware of the tip reporting resources available to them? ; 4. What are the implications of under-reporting tip income

Fluorescent Nanoparticles for the Measurement of Ion Concentration in Biological Systems

Tightly regulated ion homeostasis throughout the body is necessary for the prevention of such debilitating states as dehydration.1 In contrast, rapid ion fluxes at the cellular level are required for initiating action potentials in excitable cells.2 Sodium regulation plays an important role in both of these cases; however, no method currently exists for continuously monitoring sodium levels in vivo3 and intracellular sodium probes 4 do not provide similar detailed results as calcium probes. In an effort to fill both of these voids, fluorescent nanosensors have been developed that can monitor sodium concentrations in vitro and in vivo.5,6 These sensors are based on ion-selective optode technology and consist of plasticized polymeric particles in which sodium specific recognition elements, pH-sensitive fluorophores, and additives are embedded.7-9 Mechanistically, the sodium recognition element extracts sodium into the sensor. 10 This extraction causes the pH-sensitive fluorophore to release a hydrogen ion to maintain charge neutrality within the sensor which causes a change in fluorescence. The sodium sensors are reversible and selective for sodium over potassium even at high intracellular concentrations.6 They are approximately 120 nm in diameter and are coated with polyethylene glycol to impart biocompatibility. Using microinjection techniques, the sensors can be delivered into the cytoplasm of cells where they have been shown to monitor the temporal and spatial sodium dynamics of beating cardiac myocytes.11 Additionally, they have also tracked real-time changes in sodium concentrations in vivo when injected subcutaneously into mice.3 Herein, we explain in detail and demonstrate the methodology for fabricating fluorescent sodium nanosensors and briefly demonstrate the biological applications our lab uses the nanosensors for: the microinjection of the sensors into cells; and the subcutaneous injection of the sensors into mice

Coupling of multiple opioid receptors to GTPase following selective receptor alkylation in brain membranes

Opioid agonists of the mu, kappa and delta types stimulated low-Km guanosine triphosphatase (GTPase) in membranes, from the brain of the rat by up to 34%, with potencies the rank order of which corresponded to the respective binding affinities to opioid receptor. In general, kappa ligands stimulated GTPase to a lesser degree than mu or delta opiates. The coupling of a given type of opioid receptor to GTPase was resolved by direct or protective alkylation of the other receptors. Treatment of the membranes with [beta]-funaltrexamine abolished the stimulation of GTPase by sufentanil and levorphanol (mu), but not by bremazocine (kappa) or DSLET (delta). On the other hand, prior incubation with Superfit, an alkylating agent with selectivity for the delta opioid receptor, specifically eliminated the effect of DSLET. Partial alkylation by increasing concentrations of Superfit gradually reduced the extent of stimulation of GTPase by DSLET. The successive treatment of membranes with Superfit and [beta]-funaltrex-amine blocked the actions of DSLET, sufentanil and levorphanol, but had no effect on the stimulation of the GTPase by bremazocine. Selective coupling of an opioid receptor to GTPase was also obtained after incubation of membranes with [beta]-chlornaltrexamine in the presence of protective concentrations of mu, kappa or delta opioid ligands. Alkylation resolved the coupling of the non-selective opiate etorphine: the sum of stimulation of GTPase in the receptor-selective membranes equalled maximal stimulation of enzyme in untreated membranes. Naloxone blocked the stimulation of GTPase by mu, kappa or delta agonists, but ICI-174,864 specifically inhibited the effect of DSLET. The results describe the use of receptor-selective membranes from brain to characterize the coupling of multiple opioid receptors to high-affinity GTPase, the inhibitory binding protein for GTP of the adenylate cyclase complex.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26499/1/0000035.pd

Clinical adoption patterns of 0.35 Tesla MR-guided radiation therapy in Europe and Asia

BACKGROUND Magnetic resonance-guided radiotherapy (MRgRT) utilization is rapidly expanding, driven by advanced capabilities including better soft tissue imaging, continuous intrafraction target visualization, automatic triggered beam delivery, and the availability of on-table adaptive replanning. Our objective was to describe patterns of 0.35 Tesla (T)-MRgRT utilization in Europe and Asia among early adopters of this novel technology. METHODS Anonymized administrative data from all 0.35T-MRgRT treatment systems in Europe and Asia were extracted for patients who completed treatment from 2015 to 2020. Detailed treatment information was analyzed for all MR-linear accelerators (linac) and -cobalt systems. RESULTS From 2015 through the end of 2020, there were 5796 completed treatment courses delivered in 46,389 individual fractions. 23.5% of fractions were adapted. Ultra-hypofractionated (UHfx) dose schedules (1-5 fractions) were delivered for 63.5% of courses, with 57.8% of UHfx fractions adapted on-table. The most commonly treated tumor types were prostate (23.5%), liver (14.5%), lung (12.3%), pancreas (11.2%), and breast (8.0%), with increasing compound annual growth rates (CAGRs) in numbers of courses from 2015 through 2020 (pancreas: 157.1%; prostate: 120.9%; lung: 136.0%; liver: 134.2%). CONCLUSIONS This is the first comprehensive study reporting patterns of utilization among early adopters of a 0.35T-MRgRT system in Europe and Asia. Intrafraction MR image-guidance, advanced motion management, and increasing adoption of on-table adaptive RT have accelerated a transition to UHfx regimens. MRgRT has been predominantly used to treat tumors in the upper abdomen, pelvis and lungs, and increasingly with adaptive replanning, which is a radical departure from legacy radiotherapy practices