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Neural Computing and Applications - In this paper, we present and investigate the analytical properties of a new set of orthogonal basis functions derived from the block-pulse functions. Also, we...  相似文献   
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This study is meant to characterize the serum proteome in a small geographical cluster of sporadic ALS subjects originating from a restricted geographical area and sharing the same environmental exposure, in a broader context of evaluating the relevance of environmental factors to disease onset, status, and progression. An Artificial Neural Network based software is used to compare the relative abundance of proteins identified as different (by means of bi‐dimensional electrophoresis and mass spectrometry) in the serum proteome of patients and age‐matched healthy controls. The patient's group is characterized by altered levels of acute phase reactants and of proteins involved in lipid homeostasis, along with over‐representation of the APOE*4 allele. Characterization of the serum proteome in a small cluster of sporadic ALS patients, originating from a geographically restricted area with a high prevalence of the disease and evaluation of the results with software based on artificial neural networks, highlights the association of the relative abundance of some proteins (most notably, acute phase reactants and lipid homeostasis proteins) with the disease presence and status.  相似文献   
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In recent years, cannabinoid type 2 receptors (CB2R) have emerged as promising therapeutic targets in a wide variety of diseases. Selective ligands of CB2R are devoid of the psychoactive effects typically observed for CB1R ligands. Based on our recent studies on a class of pyridazinone 4‐carboxamides, further structural modifications of the pyridazinone core were made to better investigate the structure–activity relationships for this promising scaffold with the aim to develop potent CB2R ligands. In binding assays, two of the new synthesized compounds [6‐(3,4‐dichlorophenyl)‐2‐(4‐fluorobenzyl)‐cisN‐(4‐methylcyclohexyl)‐3‐oxo‐2,3‐dihydropyridazine‐4‐carboxamide ( 2 ) and 6‐(4‐chloro‐3‐methylphenyl)‐cisN‐(4‐methylcyclohexyl)‐3‐oxo‐2‐pentyl‐2,3‐dihydropyridazine‐4‐carboxamide ( 22 )] showed high CB2R affinity, with Ki values of 2.1 and 1.6 nm , respectively. In addition, functional assays of these compounds and other new active related derivatives revealed their pharmacological profiles as CB2R inverse agonists. Compound 22 displayed the highest CB2R selectivity and potency, presenting a favorable in silico pharmacokinetic profile. Furthermore, a molecular modeling study revealed how 22 produces inverse agonism through blocking the movement of the toggle‐switch residue, W6.48.  相似文献   
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The distinct effects of the estrogen and progestin components of hormonal therapy on the metabolism of apolipoprotein (apo) B‐containing lipoproteins have not been studied. We enrolled eight healthy postmenopausal women in a placebo‐controlled, randomized, double‐blind crossover study. Each subject received placebo, conjugated equine estrogen (CEE, 0.625 mg/day) and CEE plus medroxyprogesterone acetate (MPA, 2.5 mg/day) for 8 weeks in a randomized order, with a 4‐week washout between phases. Main outcomes were the fractional catabolic rate (FCR) and production rate (PR) of apo B100 in triglyceride‐rich lipoproteins (TRL), intermediate‐density lipoproteins (IDL) and low ‐density lipoprotein (LDL) and of apo B48 in TRL. Compared to placebo, CEE increased TRL apo B100 PR (p = 0.04). CEE also increased LDL apo B100 FCR (p = 0.02), but this effect was offset by a significant increase in LDL apo B100 PR (p = 0.04). Adding MPA to CEE negated the CEE effects resulting in no significant changes in TRL apo B100 PR and LDL apo B100 FCR and PR relative to placebo. Relative to placebo, during CEE there was a trend toward a reduction in plasma apo B48 concentrations and PR (p = 0.07 and p = 0.12, respectively). Compared with CEE, CEE + MPA significantly increased TRL apo B48 FCR (p = 0.02) as well as apo B48 PR (p = 0.01), resulting in no significant changes in apo B48 concentration. Estrogen and progestin have independent and opposing effects on the metabolism of the atherogenic apo B100‐ and apo B48‐containing lipoproteins.  相似文献   
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Biotechnological processes harnessing living organisms' metabolism are low‐cost routes to nanostructured materials for applications in photonics, electronics, and nanomedicine. In the pursuit of photonic biohybrids, diatoms microalgae are attractive given the properties of the porous micro‐to‐nanoscale structures of the biosilica shells (frustules) they produce. The investigations have focused on in vivo incorporation of tailored molecular fluorophores into the frustules of Thalassiosira weissflogii diatoms, using a procedure that paves the way for easy biotechnological production of photonic nanostructures. The procedure ensures uniform staining of shells in the treated culture and permits the resulting biohybrid photonic nanostructures to be isolated with no damage to the dye and periodic biosilica network. Significantly, this approach ensures that light emission from the dye embedded in the isolated biohybrid silica is modulated by the silica's nanostructure, whereas no modulation of photoluminescence is observed upon grafting the fluorophore onto frustules by an in vitro approach based on surface chemistry. These results pave the way to the possibility of easy production of photonic nanostructures with tunable properties by simple feeding the diatoms algae with tailored photoactive molecules.  相似文献   
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