Mono Quaternary Ammonium Salts and Methods for Modulating Neuronal Nicotinic Acetylcholine Receptors

Provided are monoquaternary ammonium compounds which are modulators of nicotinic acetylcholine receptors. Also provided are methods of using the compounds for modulating the function of a nicotinic acetylcholine receptor, and for the prevention and/or treatment of central nervous system disorders, substance use and/or abuse, and or gastrointestinal tract disorders

Mono Quaternary Ammonium Salts and Methods for Modulating Neuronal Nicotinic Acetylcholine Receptors

Provided are monoquaternary ammonium compounds which are modulators of nicotinic acetylcholine receptors. Also provided are methods of using the compounds for modulating the function of a nicotinic acetylcholine receptor, and for the prevention and/or treatment of central nervous system disorders, substance use and/or abuse, and gastrointestinal tract disorders

Bis-Quaternary Ammonium Salts and Methods for Modulating Neuronal Nicotinic Acetylcholine Receptors

Provided are bis-quaternary ammonium compounds which are modulators of nicotinic acetylcholine receptors. Also provided are methods of using the compounds for modulating the function of a nicotinic acetylcholine receptor, and for the prevention and/or treatment of central nervous system disorders, substance use and/or abuse, and or gastrointestinal tract disorders

An estimation-based approach for range image segmentation:on the reliability of primitive extraction

This paper presents a new algorithm for estimation-based range image segmentation. Aiming at surface-primitive extraction from range data, we focus on the reliability of the primitive representation in the process of region estimation. We introduce an optimal description of surface primitives, by which the uncertainty of a region estimate is explicitly represented with a covariance matrix. Then the reliability of an estimate is interpreted in terms of “measure of uncertainty”. The segmentation approach follows the region-growing scheme, in which the regions are estimated in an iterative way. With the probabilistic model proposed in this paper, surface homogeneity is defined and tested by an optimal criterion. A notable feature of the algorithm is that the order of merging is organized to lead the growth towards the most reliable representation of the merged region. Concerned with man-made objects in the scene, we restrict the class of surface primitives to be quadric or planar. The proposed algorithm has been applied to real data and synthetic data and demonstrated with experimental results

Recognition Technology for Four Arithmetic Operations

Numeral recognition is an important research direction in field of pattern recognition, and it has broad application prospects. Aiming at four arithmetic operations of general printed formats, this article adopts a multiple hybrid recognition method and is applied to automatically calculating. This method mainly uses BP neural network and template matching method to distinguish the numerals and operators, in order to increase the operation speed and recognition accuracy. Sample images of four arithmetic operations are extracted from printed books, and they are used for testing the performance of proposed recognition method. The experiments show that the method provides correct recognition rate of 96% and correct calculation rate of 89%

\u3cem\u3eBis\u3c/em\u3e-Quaternary Ammonium Salts and Methods for Modulating Neuronal Nicotinic Acetylcholine Receptors

Provided are bis-quaternary ammonium compounds which are modulators of nicotinic acetylcholine receptors. Also provided are methods of using the compounds for modulating the function of a nicotinic acetylcholine receptor, and for the prevention and/or treatment of central nervous system disorders, substance use and/or abuse, and or gastrointestinal tract disorders

Tris-Quarternary Ammonium Salts and Methods for Modulating Neuronal Nicotinic Acetylcholine Receptors

Provided are tris-quaternary ammonium compounds which are modulators of nicotinic acetylocholine receptors. Also provided are methods of using the compounds for modulating the function of a nicotinic acetylcholine receptor, and for the prevention and/or treatment of central nervous system disorders, substance use and/or abuse and or gastrointestinal tract disorders

1-Methyl-2,6-cis-distyrylpiperidine

The complete molecule of the title compound, C22H25N, is generated by crystallographic mirror symmetry, with two C atoms and the N atom lying on the mirror plane. The central ring adopts a chair conformation and the dihedral angle between the aromatic rings is 56.69 (4)°

(2S,6S)-1-Methyl-2,6-trans-distyryl­piperidinium chloride

In the crystal structure of the title compound, C22H26N+·Cl−, the piperidine ring is in a chair conformation and the two styryl groups are in axial and equatorial positions. The mol­ecule has a hydrogen bond between the NH group and the chloride anion

Inhibition of USP7 activity selectively eliminates senescent cells in part via restoration of p53 activity.

The accumulation of senescent cells (SnCs) is a causal factor of various age-related diseases as well as some of the side effects of chemotherapy. Pharmacological elimination of SnCs (senolysis) has the potential to be developed into novel therapeutic strategies to treat these diseases and pathological conditions. Here we show that ubiquitin-specific peptidase 7 (USP7) is a novel target for senolysis because inhibition of USP7 with an inhibitor or genetic depletion of USP7 by RNA interference induces apoptosis selectively in SnCs. The senolytic activity of USP7 inhibitors is likely attributable in part to the promotion of the human homolog of mouse double minute 2 (MDM2) ubiquitination and degradation by the ubiquitin-proteasome system. This degradation increases the levels of p53, which in turn induces the pro-apoptotic proteins PUMA, NOXA, and FAS and inhibits the interaction of BCL-XL and BAK to selectively induce apoptosis in SnCs. Further, we show that treatment with a USP7 inhibitor can effectively eliminate SnCs and suppress the senescence-associated secretory phenotype (SASP) induced by doxorubicin in mice. These findings suggest that small molecule USP7 inhibitors are novel senolytics that can be exploited to reduce chemotherapy-induced toxicities and treat age-related diseases