Positive allosteric modulators of the μ‐opioid receptor: a novel approach for future pain medications

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109803/1/bph12599.pd

The effect of host structure on the selectivity and mechanism of supramolecular catalysis of Prins cyclizations.

The effect of host structure on the selectivity and mechanism of intramolecular Prins reactions is evaluated using K12Ga4L6 tetrahedral catalysts. The host structure was varied by modifying the structure of the chelating moieties and the size of the aromatic spacers. While variation in chelator substituents was generally observed to affect changes in rate but not selectivity, changing the host spacer afforded differences in efficiency and product diastereoselectivity. An extremely high number of turnovers (up to 840) was observed. Maximum rate accelerations were measured to be on the order of 105, which numbers among the largest magnitudes of transition state stabilization measured with a synthetic host-catalyst. Host/guest size effects were observed to play an important role in host-mediated enantioselectivity

NRQCD Results on Form Factors

We report results on $f_B$ and semi-leptonic $B$ decay form factors using NRQCD. We investigate $1/M$ scaling behavior of decay amplitudes. For $f_B$ Effect of higher order relativistic correction terms are also studied.Comment: 9 pgs. 10 figures. Latex2e. espcrc2.sty included. Talk presented at the Internatioal Workshop "LATTICE QCD ON PARALLEL COMPUTERS", March 1997, Tsukub

Heavy quark mass dependence of semileptonic form factors for B decays

We present our study of the dependence of the heavy-to-light semileptonic B decay form factors on the heavy-light meson mass $M_{PS}$. Simulations are made over a range of the heavy quark mass covering both the charm and bottom quarks using the $O(a)$-improved clover action at $\beta=5.9$ on a $16^3\times 40$ and $24^3\times 64$ lattice. We find that a weak dependence of form factors on $M_{PS}$ observed in previous studies in the region of charm quark persists up to the region of$b$ quark. The soft pion relation $f^0(q^2_{max})=f_B/f_\pi$ is examined and found to be largely violated.Comment: 3 pages, latex source-file, 4 figures as epsf-file, uses espcrc2.sty. Talk presented by S. Tominaga at Lattice 97, Edinburgh, Scotland, 22-26 Jul 199

Prospects for Sorghum Improvement for Phosphorus Efficiency

Phosphorus (P) deficiency is common in sorghum-grbwing regions of the semi-arid tropics (SAT) (Sallanpaa, 1982). and ranks second in importance only after nitrogen (N) deficiency. In addition to the deficiencies of these two nutrients, other nutrient disorders may be common. For example, zinc (Zn) deficiency is common in India. pqi~sium (K) and sulphur (S) deficiency in West Africa, and 'alhinum (A]) toxicity in Latin America (SBnchez and Salinas, 1981). Amelioration of P deficiency by application of P fertilizers is costly. Thus, improved farming practices have the best chance of adoption by the small subsistence farmers with limited financial resources if they involve only moderate amounts of low-cost inputs. To achieve this, we need to determine efficient fertilizer practices in conjunction with the development of P-efficient cultivars

Task analysis for error identification: Theory, method and validation

This paper presents the underlying theory of Task Analysis for Error Identification. The aim is to illustrate the development of a method that has been proposed for the evaluation of prototypical designs from the perspective of predicting human error. The paper presents the method applied to representative examples. The methodology is considered in terms of the various validation studies that have been conducted, and is discussed in the light of a specific case study

The role of TRPC6 calcium channels and P2 purinergic receptors in podocyte mechanical and metabolic sensing

Podocyte calcium (Ca2+) signaling plays important roles in the (patho)physiology of the glomerular filtration barrier. Overactivation of podocyte transient receptor potential canonical (TRPC) channels including TRPC6 and purinergic signaling via P2 receptors that are known mechanosensors can increase podocyte intracellular Ca2+ levels ([Ca2+]i) and cause cell injury, proteinuria and glomerular disease including in diabetes. However, important mechanistic details of the trigger and activation of these pathways in vivo in the intact glomerular environment are lacking. Here we show direct visual evidence that podocytes can sense mechanical overload (increased glomerular capillary pressure) and metabolic alterations (increased plasma glucose) via TRPC6 and purinergic receptors including P2Y2. Multiphoton microscopy of podocyte [Ca2+]i was performed in vivo using wild-type and TRPC6 or P2Y2 knockout (KO) mice expressing the calcium reporter GCaMP3/5 only in podocytes and in vitro using freshly dissected microperfused glomeruli. Single-nephron intra-glomerular capillary pressure elevations induced by obstructing the efferent arteriole lumen with laser-induced microthrombus in vivo and by a micropipette in vitro triggered >2-fold increases in podocyte [Ca2+]i. These responses were blocked in TRPC6 and P2Y2 KO mice. Acute elevations of plasma glucose caused >4-fold increases in podocyte [Ca2+]i that were abolished by pharmacological inhibition of TRPC6 or P2 receptors using SAR7334 or suramin treatment, respectively. This study established the role of Ca2+ signaling via TRPC6 channels and P2 receptors in mechanical and metabolic sensing of podocytes in vivo, which are promising therapeutic targets in conditions with high intra-glomerular capillary pressure and plasma glucose, such as diabetic and hypertensive nephropathy. © 2021 The Author(s)

Potential Models for Radiative Rare B Decays

We compute the branching ratios for the radiative rare decays of B into K-Meson states and compare them to the experimentally determined branching ratio for inclusive decay b -> s gamma using non relativistic quark model, and form factor definitions consistent with HQET covariant trace formalism. Such calculations necessarily involve a potential model. In order to test the sensitivity of calculations to potential models we have used three different potentials, namely linear potential, screening confining potential and heavy quark potential as it stands in QCD.We find the branching ratios relative to the inclusive b ->s gamma decay to be (16.07\pm 5.2)% for B -> K^* (892)gamma and (7.25\pm 3.2)% for B -> K_2^* (1430)gamma for linear potential. In the case of the screening confining potential these values are (19.75\pm 5.3)% and (4.74\pm 1.2)% while those for the heavy quark potential are (11.18\pm 4.6)% and (5.09\pm 2.7)% respectively. All these values are consistent with the corresponding present CLEO experimental values: (16.25\pm 1.21)% and (5.93\pm 0.46)%.Comment: RevTeX, 6 pages, 1 eps figur