Synthesis of Novel 3-Aryl-N-Methyl-1,2,5,6-Tetrahydropyridine Derivatives by Suzuki coupling: As Acetyl Cholinesterase Inhibitors

Alzheimer’s disease (AD) is a neurodegenerative disorder affecting the central nervous system, which is also associated with progressive loss of memory and cognition. The development of numerous structural classes of compounds with different pharmacological profile could be an evolving, promising therapeutic approach for the treatment of AD. Thus, providing a symptomatic treatment for this disease are cholinomimetics with the pharmacological profile of Acetylcholinesterase (AChE) inhibitors. In view of this, we have synthesized novel 3-aryl-N-methyl-1,2,5,6-tetrahydropyridine derivatives 5a-k by Suzuki coupling and screened the efficacy of these derivatives for their AChE inhibitor activity

Observation of the Smectic C -- Smectic I Critical Point

We report the first observation of the smectic C--smectic I (C--I) critical point by Xray diffraction studies on a binary system. This is in confirmity with the theoretical idea of Nelson and Halperin that coupling to the molecular tilt should induce hexatic order even in the C phase and as such both C and I (a tilted hexatic phase) should have the same symmetry. The results provide evidence in support of the recent theory of Defontaines and Prost proposing a new universality class for critical points in layered systems.Comment: 9 pages Latex and 5 postscript figures available from [email protected] on request, Phys.Rev.Lett. (in press

Experimental protocol for MRI mapping of the blood oxygenation-sensitive parameters T(2)* and T(2) in the kidney

Renal hypoxia is generally accepted as a key pathophysiologic event in acute kidney injury of various origins, and has also been suggested to play a role in the development of chronic kidney disease. Here we describe a step-by-step experimental protocol for indirect monitoring of renal blood oxygenation in rodents via the deoxyhemoglobin sensitive MR parameters T(2)* and T(2)-a contrast mechanism known as the blood oxygenation level dependent (BOLD) effect. Since an absolute quantification of renal oxygenation from T(2)*/T(2) remains challenging, the effects of controlled and standardized variations in the fraction of inspired oxygen are used for bench marking. This MRI method may be useful for investigating renal blood oxygenation of small rodents in vivo under various experimental (patho)physiological conditions.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This experimental protocol chapter is complemented by two separate chapters describing the basic concept and data analysis

Hyperhomocysteinemia is detrimental to pregnancy in mice and is associated with preterm birth

AbstractElevated levels of homocysteine produce detrimental effects in humans but its role in preterm birth is not known. Here we used a mouse model of hyperhomocysteinemia to examine the relevance of homocysteine to preterm birth. The mouse carries a heterozygous deletion of cystathionine β-synthase (Cbs+/−). Gestational period was monitored in wild type and Cbs+/− female mice. Mouse uterine and placental tissues, human primary trophoblast cells, and human myometrial and placental cell lines were used to determine the influence of homocysteine on expression of specific genes in vitro. The activity of BKCa channel in the myometrial cell line was monitored using the patch-clamp technique. We found that hyperhomocysteinemia had detrimental effects on pregnancy and induced preterm birth in mice. Homocysteine increased the expression of oxytocin receptor and Cox-2 as well as PGE2 production in uterus and placenta, and initiated premature uterine contraction. A Cox-2 inhibitor reversed these effects. Gpr109a, a receptor for niacin, induced Cox-2 in uterus. Homocysteine upregulated GPR109A and suppressed BKCa channel activity in human myometrial cells. Deletion of Gpr109a in Cbs+/− mice reversed premature birth. We conclude that hyperhomocysteinemia causes preterm birth in mice through upregulation of the Gpr109a/Cox-2/PGE2 axis and that pharmacological blockade of Gpr109a may have potential in prevention of preterm birth

Diffusion of particles moving with constant speed

The propagation of light in a scattering medium is described as the motion of a special kind of a Brownian particle on which the fluctuating forces act only perpendicular to its velocity. This enforces strictly and dynamically the constraint of constant speed of the photon in the medium. A Fokker-Planck equation is derived for the probability distribution in the phase space assuming the transverse fluctuating force to be a white noise. Analytic expressions for the moments of the displacement $$ along with an approximate expression for the marginal probability distribution function $P(x,t)$ are obtained. Exact numerical solutions for the phase space probability distribution for various geometries are presented. The results show that the velocity distribution randomizes in a time of about eight times the mean free time ($8t^*$) only after which the diffusion approximation becomes valid. This factor of eight is a well known experimental fact. A persistence exponent of $0.435 \pm 0.005$ is calculated for this process in two dimensions by studying the survival probability of the particle in a semi-infinite medium. The case of a stochastic amplifying medium is also discussed.Comment: 9 pages, 9 figures(Submitted to Phys. Rev. E

BAs and boride III-V alloys

Boron arsenide, the typically-ignored member of the III-V arsenide series BAs-AlAs-GaAs-InAs is found to resemble silicon electronically: its Gamma conduction band minimum is p-like (Gamma_15), not s-like (Gamma_1c), it has an X_1c-like indirect band gap, and its bond charge is distributed almost equally on the two atoms in the unit cell, exhibiting nearly perfect covalency. The reasons for these are tracked down to the anomalously low atomic p orbital energy in the boron and to the unusually strong s-s repulsion in BAs relative to most other III-V compounds. We find unexpected valence band offsets of BAs with respect to GaAs and AlAs. The valence band maximum (VBM) of BAs is significantly higher than that of AlAs, despite the much smaller bond length of BAs, and the VBM of GaAs is only slightly higher than in BAs. These effects result from the unusually strong mixing of the cation and anion states at the VBM. For the BAs-GaAs alloys, we find (i) a relatively small (~3.5 eV) and composition-independent band gap bowing. This means that while addition of small amounts of nitrogen to GaAs lowers the gap, addition of small amounts of boron to GaAs raises the gap (ii) boron ``semi-localized'' states in the conduction band (similar to those in GaN-GaAs alloys), and (iii) bulk mixing enthalpies which are smaller than in GaN-GaAs alloys. The unique features of boride III-V alloys offer new opportunities in band gap engineering.Comment: 18 pages, 14 figures, 6 tables, 61 references. Accepted for publication in Phys. Rev. B. Scheduled to appear Oct. 15 200

Non-Abelian Vortices in Supersymmetric Gauge Field Theory via Direct Methods

Vortices in supersymmetric gauge field theory are important constructs in a basic conceptual phenomenon commonly referred to as the dual Meissner effect which is responsible for color confinement. Based on a direct minimization approach, we present a series of sharp existence and uniqueness theorems for the solutions of some non-Abelian vortex equations governing color-charged multiply distributed flux tubes, which provide an essential mechanism for linear confinement. Over a doubly periodic domain, existence results are obtained under explicitly stated necessary and sufficient conditions that relate the size of the domain, the vortex numbers, and the underlying physical coupling parameters of the models. Over the full plane, existence results are valid for arbitrary vortex numbers and coupling parameters. In all cases, solutions are unique.Comment: 38 pages, late

Discovery of an inflated hot Jupiter around a slightly evolved star TOI-1789

Stars and planetary system

Grain Surface Models and Data for Astrochemistry

AbstractThe cross-disciplinary field of astrochemistry exists to understand the formation, destruction, and survival of molecules in astrophysical environments. Molecules in space are synthesized via a large variety of gas-phase reactions, and reactions on dust-grain surfaces, where the surface acts as a catalyst. A broad consensus has been reached in the astrochemistry community on how to suitably treat gas-phase processes in models, and also on how to present the necessary reaction data in databases; however, no such consensus has yet been reached for grain-surface processes. A team of ∼25 experts covering observational, laboratory and theoretical (astro)chemistry met in summer of 2014 at the Lorentz Center in Leiden with the aim to provide solutions for this problem and to review the current state-of-the-art of grain surface models, both in terms of technical implementation into models as well as the most up-to-date information available from experiments and chemical computations. This review builds on the results of this workshop and gives an outlook for future directions

Technical recommendations for clinical translation of renal MRI: a consensus project of the Cooperation in Science and Technology Action PARENCHIMA

Purpose The potential of renal MRI biomarkers has been increasingly recognised, but clinical translation requires more standardisation. The PARENCHIMA consensus project aims to develop and apply a process for generating technical recommendations on renal MRI. Methods A task force was formed in July 2018 focused on fve methods. A draft process for attaining consensus was distributed publicly for consultation and fnalised at an open meeting (Prague, October 2018). Four expert panels completed surveys between October 2018 and March 2019, discussed results and refned the surveys at a face-to-face meeting (Aarhus, March 2019) and completed a second round (May 2019). Results A seven-stage process was defned: (1) formation of expert panels; (2) defnition of the context of use; (3) literature review; (4) collection and comparison of MRI protocols; (5) consensus generation by an approximate Delphi method; (6) reporting of results in vendor-neutral and vendor-specifc terms; (7) ongoing review and updating. Application of the process resulted in 166 consensus statements. Conclusion The process generated meaningful technical recommendations across very diferent MRI methods, while allowing for improvement and refnement as open issues are resolved. The results are likely to be widely supported by the renal MRI community and thereby promote more harmonisation