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31.
In this study we describe the sociodemographic characteristics of people participating in a clinical trial on the safety and immunogenicity of a H5N1 influenza vaccine and we identify the main motivations for joining it. 相似文献
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Kentaro Futatsugi Vincent Mascitti Cristiano R.W. Guimarães Nao Morishita Cuiman Cai Michael P. DeNinno Hua Gao Michael D. Hamilton Richard Hank Anthony R. Harris Daniel W. Kung Sophie Y. Lavergne Bruce A. Lefker Michael G. Lopaze Kim F. McClure Michael J. Munchhof Cathy Preville Ralph P. Robinson Amit S. Kalgutkar 《Bioorganic & medicinal chemistry letters》2013,23(1):194-197
A novel GPR119 agonist based on the 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole scaffold was designed through lead optimization starting from pyrazole-based GPR119 agonist 1. The design is centered on the conformational restriction of the core scaffold, while minimizing the change in spatial relationships of two key pharmacophoric elements (piperidine-carbamate and aryl sulfone). 相似文献
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Cameron KO Lefker BA Chu-Moyer MY Crawford DT Jardine PD DeNinno SL Gilbert S Grasser WA Ke H Lu B Owen TA Paralkar VM Qi H Scott DO Thompson DD Tjoa CM Zawistoski MP 《Bioorganic & medicinal chemistry letters》2006,16(7):1799-1802
Heptanoic acid lactams, exemplified by 2, were identified as highly selective EP4 agonists via high throughput screening. Lead optimization led to the identification of lactams with a 30-fold increase in EP4 potency in vitro. Compounds demonstrated robust bone anabolic effects when administered in vivo in rat models of osteoporosis. 相似文献
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John A. Lowe Shari L. DeNinno Susan E. Drozda Christopher J. Schmidt Karen M. Ward F. David Tingley Mark Sanner Don Tunucci James Valentine 《Bioorganic & medicinal chemistry letters》2010,20(3):907-911
We describe a novel series of inhibitors of the type 1 glycine transporter (GlyT1) as an approach to relieving the glutamatergic deficit that is thought to underlie schizophrenia. Synthesis and SAR follow-up of a series of octahydro-cyclopenta[c]pyrrole derivatives afforded potent in vitro inhibition of GlyT1 as well as in vivo activity in elevating CSF glycine. We also found that a 3-O(c-pentyl), 4-F substituent may serve as a surrogate for the widely used 3-trifluoromethoxy group, suggesting its application as an isostere for future medicinal chemistry studies. 相似文献
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We describe here a computational morphology-based approach to the investigation of possible causes of chromatin alterations in sperm. A comprehensive set of state-of-the-art and geometric measures are computationally extracted from toluidine blue stained images and analyzed to infer the possible processes leading to normal and abnormal chromatin formation while seeking a possible taxonomy of chromatin alterations and their influence on sperm head morphology. Using this methodology, we have identified higher chromatin fragility at some specific points of the sperm head. Despite the lack of correlation between morphologies of sperm head and chromatin structure, four main morphological types of chromatin alterations in bull spermatozoa have been identified and their possible causes discussed. 相似文献
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Carpino PA Lefker BA Toler SM Pan LC Hadcock JR Cook ER DiBrino JN Campeta AM DeNinno SL Chidsey-Frink KL Hada WA Inthavongsay J Mangano FM Mullins MA Nickerson DF Ng O Pirie CM Ragan JA Rose CR Tess DA Wright AS Yu L Zawistoski MP DaSilva-Jardine PA Wilson TC Thompson DD 《Bioorganic & medicinal chemistry》2003,11(4):581-590
Novel pyrazolinone-piperidine dipeptide derivatives were synthesized and evaluated as growth hormone secretagogues (GHSs). Two analogues, capromorelin (5, CP-424391-18, hGHS-R1a K(i)=7 nM, rat pituicyte EC(50)=3 nM) and the des-methyl analogue 5c (hGHS-R1a K(i)=17 nM, rat pituicyte EC(50)=3 nM), increased plasma GH levels in an anesthesized rat model, with ED(50) values less than 0.05 mg/kg iv. Capromorelin showed enhanced intestinal absorption in rodent models and exhibited superior pharmacokinetic properties, including high bioavailabilities in two animal species [F(rat)=65%, F(dog)=44%]. This short-duration GHS was orally active in canine models and was selected as a development candidate for the treatment of musculoskeletal frailty in elderly adults. 相似文献
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Recent progress in bioinformatics research has led to the accumulation of huge quantities of biological data at various data sources.
The DNA microarray technology makes it possible to simultaneously analyze large number of genes across different samples.
Clustering of microarray data can reveal the hidden gene expression patterns from large quantities of expression data that in turn
offers tremendous possibilities in functional genomics, comparative genomics, disease diagnosis and drug development. The k-
¬means clustering algorithm is widely used for many practical applications. But the original k-¬means algorithm has several
drawbacks. It is computationally expensive and generates locally optimal solutions based on the random choice of the initial
centroids. Several methods have been proposed in the literature for improving the performance of the k-¬means algorithm. A
meta-heuristic optimization algorithm named harmony search helps find out near-global optimal solutions by searching the entire
solution space. Low clustering accuracy of the existing algorithms limits their use in many crucial applications of life sciences. In
this paper we propose a novel Harmony Search-K means Hybrid (HSKH) algorithm for clustering the gene expression data.
Experimental results show that the proposed algorithm produces clusters with better accuracy in comparison with the existing
algorithms. 相似文献