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21.
Denhart DJ Purandare AV Catt JD King HD Gao A Deskus JA Poss MA Stark AD Torrente JR Johnson G Mattson RJ 《Bioorganic & medicinal chemistry letters》2004,14(16):4249-4252
The present studies have identified a series of diaminopyrimidines and diaminopyridines as novel 5-HT(7) receptor ligands. Three regiosiomeric classes of pyrimidines and four regioisomeric classes of pyridines were synthesized and analyzed for binding to the 5-HT(7) receptor. The 5-HT(7) binding affinities of different regioisomers show clearly the structure-activity relationship with position of ring nitrogens. 相似文献
22.
23.
Guillaume Chouinard-Pelletier Mathieu Leduc David Guay Sylvain Coulombe Richard L Leask Elizabeth AV Jones 《Biomedical engineering online》2012,11(1):1-12
Background
Abnormal blood glucose (BG) concentrations have been associated with increased morbidity and mortality in both critically ill adults and infants. Furthermore, hypoglycaemia and glycaemic variability have both been independently linked to mortality in these patients. Continuous Glucose Monitoring (CGM) devices have the potential to improve detection and diagnosis of these glycaemic abnormalities. However, sensor noise is a trade-off of the high measurement rate and must be managed effectively if CGMs are going to be used to monitor, diagnose and potentially help treat glycaemic abnormalities.Aim
To develop a tool that will aid clinicians in identifying unusual CGM behaviour and highlight CGM data that potentially need to be interpreted with care.Methods
CGM data and BG measurements from 50 infants at risk of hypoglycaemia were used. Unusual CGM measurements were classified using a stochastic model based on the kernel density method and historical CGM measurements from the cohort. CGM traces were colour coded with very unusual measurements coloured red, highlighting areas to be interpreted with care. A 5-fold validation of the model was Monte Carlo simulated 25 times to ensure an adequate model fit.Results
The stochastic model was generated using ~67,000 CGM measurements, spread across the glycaemic range ~2-10?mmol/L. A 5-fold validation showed a good model fit: the model 80% confidence interval (CI) captured 83% of clinical CGM data, the model 90% CI captured 91% of clinical CGM data, and the model 99% CI captured 99% of clinical CGM data. Three patient examples show the stochastic classification method in use with 1) A stable, low variability patient which shows no unusual CGM measurements, 2) A patient with a very sudden, short hypoglycaemic event (classified as unusual), and, 3) A patient with very high, potentially un-physiological, glycaemic variability after day 3 of monitoring (classified as very unusual).Conclusions
This study has produced a stochastic model and classification method capable of highlighting unusual CGM behaviour. This method has the potential to classify important glycaemic events (e.g. hypoglycaemia) as true clinical events or sensor noise, and to help identify possible sensor degradation. Colour coded CGM traces convey the information quickly and efficiently, while remaining computationally light enough to be used retrospectively or in real-time. 相似文献24.
Smita M. Purandare Heidi Huntsman Breidenbach Ying Li Xiao Lin Zhu Shun'ichi Sawada Shannon M. Neil Arthur Brothman Ray White Richard Cawthon David Viskochil 《Genomics》1995,30(3)
Using fluorescence in situ hybridization (FISH), we have identified seven NF1-related loci, two separate loci on chromosome 2, at bands 2q21 and 2q33-q34, and one locus each on five other chromosomes at bands 14q11.2, 15q11.2, 18p11.2, 21q11.2-q21, and 22q11.2. Application of PCR using NF1 primer pairs and genomic DNA from somatic cell hybrids confirmed the above loci, identified additional loci on chromosomes 12 and 15, and showed that the various loci do not share homology beyond NF1 exon 27b. Sequenced PCR products representing segments corresponding to NF1 exons from these loci demonstrated greater than 95% sequence identity with the NF1 locus. We used sequence differences between bona fide NF1 and NF1 -homologous loci to strategically design primer sets to specifically amplify 30 of 36 exons within the 5′ end of the NF1 gene. These developments have facilitated mutation analysis at the NF1 locus using genomic DNA as template. 相似文献
25.
Binding sites for gonadotropins in the mouse ovary were studied using the immunohistochemical technique. Binding sites for LH were localized in the interstitial cells and theca as well as granulosa cells of large follicles. Binding sites for FSH were demonstrated in the interstitial cells and granulosa cells of small follicles. In immature mice very few binding sites for both the gonadotropins were observed until day 21 of age. An intense staining reaction for peroxidase was observed in the ovary of 24-day old mouse. In adult mice, maximum number of binding sites for FSH were demonstrated in the ovary in estrus and metestrus stage of the cycle, respectively. A good correlation between the circulating levels of gonadotropins and binding sites for them in the ovary could be noted in the cycling but not in the prepubertal mice. 相似文献
26.
V.N. Purandare A.C. Ganguli R.M. Gharse U.R. Krishna 《Prostaglandins & other lipid mediators》1977,13(2):349-354
Midtrimester abortions were induced in 796 women by Hypertonic Saline and Prostaglandins. Intra-amniotic and Extra-amniotic routes were used for saline and Intra-amniotic, Extra-amniotic and Intra-muscular routes were used for Prostaglandins. Seven patients had cervico-vaginal injuries. All were young nulliparous patients. None of them developed any signs and symptoms of shock. Five out of the seven injuries were posteriorly situated. The etio-pathology and preventive measures of such injuries are discussed here. 相似文献
27.
Narayan P Subramaniyam Outi RM Väisänen Katrina E Wendel Jaakko AV Malmivuo 《Nonlinear biomedical physics》2010,4(Z1):S4
Background
The electroencephalography (EEG) is an attractive and a simple technique to measure the brain activity. It is attractive due its excellent temporal resolution and simple due to its non-invasiveness and sensor design. However, the spatial resolution of EEG is reduced due to the low conducting skull. In this paper, we compute the potential distribution over the closed surface covering the brain (cortex) from the EEG scalp potential. We compare two methods – L-curve and generalised cross validation (GCV) used to obtain the regularisation parameter and also investigate the feasibility in applying such techniques to N170 component of the visually evoked potential (VEP) data.Methods
Using the image data set of the visible human man (VHM), a finite difference method (FDM) model of the head was constructed. The EEG dataset (256-channel) used was the N170 component of the VEP. A forward transfer matrix relating the cortical potential to the scalp potential was obtained. Using Tikhonov regularisation, the potential distribution over the cortex was obtained.Results
The cortical potential distribution for three subjects was solved using both L-curve and GCV method. A total of 18 cortical potential distributions were obtained (3 subjects with three stimuli each – fearful face, neutral face, control objects).Conclusions
The GCV method is a more robust method compared to L-curve to find the optimal regularisation parameter. Cortical potential imaging is a reliable method to obtain the potential distribution over cortex for VEP data.28.
Harikrishnan LS Kamau MG Wan H Inghrim JA Zimmermann K Sang X Mastalerz HA Johnson WL Zhang G Lombardo LJ Poss MA Trainor GL Tokarski JS Lorenzi MV You D Gottardis MM Baldwin KF Lippy J Nirschl DS Qiu R Miller AV Khan J Sack JS Purandare AV 《Bioorganic & medicinal chemistry letters》2011,21(5):1425-1428
SAR studies of pyrrolo[1,2-f]triazines as JAK2 inhibitors is presented. Achieving JAK2 inhibition selectively over JAK3 is discussed. 相似文献
29.
Ian M. McLeod Jemma Purandare Chris Gillies Adam Smith Damien Burrows 《Ecological Management & Restoration》2018,19(1):E1-E5
Summary
Globally, coastal habitat restoration is growing in recognition as a viable management tool to repair and reinstate valuable coastal habitats and species, such as mangrove and macroalgae forests, salt marshes, seagrass meadows, shellfish and coral reefs (Aronson & Alexander ( 2013 ), Restoration Ecology, 293; Anthony et al. ( 2017 ) Nature Ecology and Evolution, 1420; TNC ( 2017 ) Caribbean: A revolution to save coral reefs in the Caribbean and beyond). In Australia, there is increasing interest and investment in coastal restoration and habitat conservation, particularly with respect to growing national concerns around habitat loss, coastal inundation and erosion, loss of fisheries and climate change (Maggini et al. ( 2013 ) Protecting and restoring habitat to help Australia's threatened species adapt to climate change; GBRMPA ( 2017 ) Reef summit sets new course of action for the Great Barrier Reef). This has led to new community of practices being formed for shellfish reef restoration (Shellfish Reef Restoration Network shellfishrestoration.org.au), seagrass restoration (Seagrass Restoration Network seagrassrestoration.net), and saltmarsh and mangrove (Saltmarsh and Mangrove Network, amsn.net.au) conservation. However, despite this interest, there has been no national coordination, network or society with coastal restoration as a primary focus. The inaugural Australian Coastal Restoration Symposium brought together 60 Australian restoration practitioners, researchers and managers at James Cook University, Townsville for three days from the 31st of August 2017. The symposium goals were to enhance collaboration and national coordination amongst coastal restoration projects and practitioners, as well as to connect researchers and practitioners working in the restoration space with one another. Three international keynote speakers shared their experiences and advice. Delegates were enthusiastic about continuing to meet at future symposiu, meetings and workshops, and noted the value of being able to connect, share project experiences and learnings, and collaborate. The Australian Coastal Restoration Network has been formed with the goal of meeting annually to continue to share knowledge and improve collaboration. View a video about the symposium by following this link – https://www.youtube.com/watch?v=lukSpo3mM-4 相似文献30.
Nonglutamate pore residues in ion selection and conduction in voltage-gated Ca(2+) channels 下载免费PDF全文
High-affinity, intrapore binding of Ca(2+) over competing ions is the essential feature in the ion selectivity mechanism of voltage-gated Ca(2+) channels. At the same time, several million Ca(2+) ions can travel each second through the pore of a single open Ca(2+) channel. How such high Ca(2+) flux is achieved in the face of tight Ca(2+) binding is a current area of inquiry, particularly from a structural point of view. The ion selectivity locus comprises four glutamate residues within the channel's pore. These glutamates make unequal contributions to Ca(2+) binding, underscoring a role for neighboring residues in pore function. By comparing two Ca(2+) channels (the L-type alpha(1C), and the non-L-type alpha(1A)) that differ in their pore properties but only differ at a single amino acid position near the selectivity locus, we have identified the amino-terminal neighbor of the glutamate residue in motif III as a determinant of pore function. This position is more important in the function of alpha(1C) channels than in alpha(1A) channels. For a systematic series of mutations at this pore position in alpha(1C), both unitary Ba(2+) conductance and Cd(2+) block of Ba(2+) current varied with residue volume. Pore mutations designed to make alpha(1C) more like alpha(1A) and vice versa revealed that relative selectivity for Ba(2+) over K(+) depended almost solely on pore sequence and not channel type. Analysis of thermodynamic mutant cycles indicates that the motif III neighbor normally interacts in a cooperative fashion with the locus, molding the functional behavior of the pore. 相似文献