in vivo pharmacodynamic modeling for drug discovery
Báo cáo khoa học: Measuring enzyme activities under standardized in vivo-like conditions for systems biology pdf
... enzyme of interest should be investigated in the context of the in vivo- like medium Finally, in vivo, the enzymes are present at much higher concentrations than in typical enzyme assays, in which ... at least three independent cell-free extracts from steady-state samples from a single chemostat culture Enzyme In vivo- like Vmax (mmolÆmin)1Æg protein)1) Flux (mmolÆmin)1Æg protein)1) HXK PGI ... converted per minute per milligram of extracted protein Protein determination was carried out with the bicinchoninic acid kit (BCA Protein Assay Kit; Pierce, Thermo Fisher Scientific, Rockford, IL,...
Ngày tải lên: 06/03/2014, 09:22
scientific american - 2001 08 - cyber cells - simulating life for drug discovery
... adapted for agency use, In- Q-Tel, with offices in the Washington, D.C., area and Silicon Valley, spends a lot of time doing “terrain mapping”— reviewing open-source information on the Internet or in ... used to examine protein interactions one at a time One such method is the yeast two-hybrid system It uses a single bait protein to fish for binding partners in a sea of prey proteins produced ... ics For its part, Myriad is narrowing its definition: it will zero in on “systematically uncovering all protein-protein interactions,” Sahasrabudhe says With a detailed inventory of which proteins...
Ngày tải lên: 12/05/2014, 16:09
computational medicinal chemistry for drug discovery - p. bultinck, et al., (marcel dekker, 2004)
... biotin to streptavidin (Ka = 2.5 1013, DG = 18.3 kcal/mol, DH = 32 kcal/mol) When using the predominating conformation in aqueous Figure 11 Calculated lowest energy conformations for biotin in ... ion-pair in aqueous solution as shown by conformer B, in comparison with the separated ions as in conformer A 6.5 Calculations of Conformational Energy Penalties for LigandProtein Binding Calculated ... Binding Calculated conformation energy penalties for ligand binding are useful in, e.g., pharmacophore modeling and structure-based ligand design In pharmacophore modeling, such energies may...
Ngày tải lên: 12/05/2014, 17:28
synthesis of novel heterocycles for drug discovery using radical cascade reactions
Ngày tải lên: 14/11/2014, 06:18
Chemical and pharmacological studies of ardisia elliptica antiplatelet, anticoagulant activities and multivariate data analysis for drug discovery
... 2009 14 Sanguinarine Sanguinaria canadensis Taxinine, taxinine A, taxinine B, Taxus cuspidata 2-deacetoxytaxinine B, taxacin, taxchinin B, taxol Inhibit collagen, U46619 and thrombin-induced Jeng ... kininogen.) Warfarin had been the most common oral anticoagulant drug used for over 60 years since its introduction in the 1940s (Ahrens et al., 2010) Warfarin prevents coagulation by inhibiting ... prothrombin to thrombin The final stage, fibrin formation occurs when fibrinogen is converted to fibrin by thrombin (Rang et al., 2003; Weitz and Bates, 2005) When screening for haemostasis, tests including...
Ngày tải lên: 10/09/2015, 08:25
Development and interpretation of machine learning models for drug discovery
... the interpretation of machine learning for LBVS will be covered Hence, the following chapter will introduce some basic concepts of in silico modeling for drug discovery Concepts Machine learning ... developed for binary classification of linearly separable data [60] In the following years, extensions for inseparable training data, nonlinear data, and imbalanced problems have been introduced ... Matrices 47 II Insights into Machine Learning in Chemoinformatics 53 Compound Structure-Independent Activity Prediction in High-Dimensional Target Space 55 Systematic Artifacts in Support Vector...
Ngày tải lên: 26/11/2015, 09:59
In silico drug discovery on computational Grids for finding novel drugs against neglected diseases
... Gametocytes 4- Amino Quinolines Chloroquine, Amidoquine Intra-erythrocytic stages, Gametocytes Quinoline-alcohols Quinine, Mefloquine Erythrocytic stages Aryl-alcohols Halofrantine, Pyronaridine Erythrocytic ... MM-PBSA scoring against plasmepsin docking conformations 109 Figure 31: MM-GBSA scoring against plasmepsin docking conformations 110 Figure 32: Analysis procedure employed for final selection ... tested within a short period for finding novel hits, therefore, highly effective screening methods are necessary for today's researchers In view of the above problems in finding new drugs by HTS;...
Ngày tải lên: 02/07/2014, 13:13
Báo cáo y học: "Distribution patterns of small-molecule ligands in the protein universe and implications for origin of life and drug discovery" doc
... determining the protein-binding ages of ligands, a rough temporal order (early or late) for ligand-protein binding can be inferred (as shown in Additional data file 3) However, considering the ... proteins of each ligand FAD/NAD(P)-binding domain (c.3) 18 NAD(P)-binding Rossmann-fold domains (c.2) 16 NAD(P)-binding Rossmann-fold domains (c.2) Flavin mononucleotide (FMN) 16 Flavodoxin-like ... during protein folding [74,75] Thus, the free energy release during ligand binding may meet the free energy demand during protein folding It is tempting to examine the conjecture of ligand-induced...
Ngày tải lên: 14/08/2014, 08:20
In silico methodologies for selection and prioritization of compounds in drug discovery
... to extensive in vitro and in vivo testing to determine if it is safe enough for human testing In the next step, the candidate drug enters the development process (clinical trials) in which it ... used in the manufacturing industry for quality engineering purposes In DoE, a design matrix is constructed in a combinatorial fashion that specifies the levels for several different factors for ... 1.1 INTRODUCTION TO COMPUTATIONAL METHODS IN DRUG DISCOVERY INTRODUCTION Figure 1.1 Stages of drug discovery and development Before work is started to discover any potential new medicine for...
Ngày tải lên: 08/09/2015, 22:12
Pharmacokinetics pharmacodynamics driven approach for lead optimization in anti mycobacterial and anti malarial drug discovery
... Arylaminoalcohol 4-aminoquinolines 8-aminoquinolines Artemisinin drugs (Sesquiterpene lactone) Biguanides Diaminopyrimidines Antimalarial drug Quinine (Cinchona alkaloids) Quinidine Mefloquine ... arylaminoalcohol, 4-aminoquinolines, 8amionquinolines, sesquiterpene lactone (artemisinin), biguanides, diaminopyrimidines, sulfonamides, hydroxynaphthoquinone, and antibiotics Quinine and quinidine ... capreomycin, aminosalicylic acid, and fluoroquinolones (including ofloxacin, levofloxacin, gatifloxacin and moxifloxacin)], and is commonly administered for years or longer including daily injections...
Ngày tải lên: 22/09/2015, 15:17
Implementation of a drug discovery tool for the evaluation of anti fibrotic compounds application in fibrovascular disorders
... performed by incubating the cells in a minimal amount (1ml for T-75 flask) of Trypsin-EDTA (1x) for at 37ºC The trypsin was then inactivated by adding excess amount of complete medium TrypsinEDTA ... matrix in fibroblast culture may be a valuable tool in tissue engineering The presence of collagen fibrils in tissue constructs is essential in maintaining the mechanical strength and defining the ... of Singapore Tissue Engineering Program (NUSTEP), Tissue Engineering Laboratory and Tissue Repair Laboratory (TRL) for their assistance in this project and Rainbow Instrument (Singapore) for...
Ngày tải lên: 09/10/2015, 11:07
Human embryonic stem cells as a cellular model for osteogenesis in implant testing and drug discovery
... H&E staining (Figure 2.4) A: Phase contrast B: DAPI staining C: Immunoflurescent staining Oct4 D: Merging E: Phase contrast F: DAPI staining 24 G: Immunoflurescent staining SSEA H: Merging Figure ... These included substituted purines, pyrimidines, indoles, quinazolines, pyrazines, pyrrolopyrimidines, pyrazolopyrimidines, phthalazines, pyridazines and quinoxalines[55] High-throughput screens ... scientific discovery in the creation of adult neurons in adult brain, suggesting ongoing stem cell activity in adults Later in 1963, McCulloch and Till illustrated the presence of self-renewing cells in...
Ngày tải lên: 16/10/2015, 15:38
Stability and in vivo evaluation of pullulan acetate as a drug nanocarrier
... were fixed in 10% phosphate buffered formalin, embedded in paraffin, sectioned, and stained with hematoxylin and eosin (H&E) In vivo pharmacokinetics and bioavailability In vivo pharmacokinetic study ... novel hydrophobized polysaccharide/oncoprotein complex vaccine induces in vitro and in vivo cellular and humoral immune responses against HER2-expressing murine sarcomas Cancer Res 58:3385–90 Gustafson, ... is the driving force for increased tumor targeting (Seymour et al., 1995), Tsuchihashi et al (1999) prepared long circulating liposomes to improve therapeutic efficacy of doxorubicin In this study,...
Ngày tải lên: 23/04/2013, 21:38
Tài liệu Báo cáo khoa học: "Discriminative Lexicon Adaptation for Improved Character Accuracy – A New Direction in Chinese Language Modeling" pptx
... in its own cluster Adding new words into the lexicon, on the other hand, offers explicit reinforcement in PP of the reference characters Such reinforcement offers the main positive boosting for ... discriminative training does not necessarily outperform maximumlikelihood training until we have enough training data (Ng and Jordan, 2001) So it is possible that discriminatively trained model performs ... be used in the construction That is, beginning with only characters in the lexicon and using the training data to alter the current lexicon in each iteration This is also an interesting direction...
Ngày tải lên: 20/02/2014, 07:20
Báo cáo khoa học: Activator-binding domains of the SWI ⁄ SNF chromatin remodeling complex characterized in vitro are required for its recruitment to promoters in vivo pot
... function of the increasingly large group of proteins that have been shown to contain intrinsically unstructured regions The intrinsic conformation flexibility that is inherent in this binding mechanism ... Protein A Agarose ⁄ Salmon Sperm DNA incubation for no more than h Beads were washed twice for 15 in lysis buffer containing 150 mm NaCl, followed by a 15-min wash in lysis buffer containing 500 ... min), in strain YPP310 (light grey bars, DDABDswi1 + snf5) lacking both activator-binding domains (SWI1D329-655, SNF5D2-327), strain YPP211 (white bars, DABDsnf5) lacking the Snf5 activator-binding...
Ngày tải lên: 07/03/2014, 00:20
Báo cáo khoa học: A simple in vivo assay for measuring the efficiency of gene length-dependent processes in yeast mRNA biogenesis doc
... Kokubo T (2001) Mutations in the TATA-binding protein, affecting transcriptional activation, show synthetic lethality with the TAF145 gene lacking the TAF N-terminal domain in Saccharomyces cerevisiae ... biogenesis complex, involved in mRNP formation, show the lowest GLAM ratios measured in this work This is not the case in other RNA processing mutants that have been analyzed in this work In agreement ... timeconsuming and not easy to carry out in a high number of samples In addition, the information obtained by nuclear run-on shows the location of active polymerases, but it gives no information...
Ngày tải lên: 07/03/2014, 12:20
Báo cáo khoa học: A steady-state modeling approach to validate an in vivo mechanism of the GAL regulatory network in Saccharomyces cerevisiae ppt
... both in the nucleus and in the cytoplasm [11,23] The above two studies indicate the existence of following two contrasting in vivo mechanisms for GAL protein expression: (a) regulatory protein ... genes through its N-terminal DNA binding site Gal80p inhibits the transcriptional activity of Gal4p by binding to its 28 amino acid region at the carboxyl terminal [25–27] In vitro studies have ... [11] In this work, the basis for identifying the in vivo mechanism was based on comparing the input (galactose concentration)–output (fractional protein expression) steady-state responses for...
Ngày tải lên: 07/03/2014, 16:20
Báo cáo khoa học: A mouse model for in vivo tracking of the major dust mite allergen Der p 2 after inhalation docx
... selenocysteine residue in a C-terminal Sel-tag [18] Der p carrying the Sel-tag had an intact core sequence and maintained allergen-specific IgE-binding epitopes and the use of a Sel-tag enabled labelling ... inhalation In this study, we tracked inhaled Der p in vivo using the recently developed Sel-tag method in a mouse model for Der p 2-sensitization Based upon our findings we conclude that the in ammatory ... In vivo tracking of 75 Se-labelled Der p intrinsic biological properties of the allergens may all contribute to their allergenicity [1–4] The intrinsic properties required for evoking an...
Ngày tải lên: 07/03/2014, 21:20
Báo cáo khoa học: "Probabilistic Document Modeling for Syntax Removal in Text Summarization" ppt
... Markov Chain Monte Carlo In Practice Chapman and Hall/CRC Thomas L Griffiths, Mark Steyvers, David M Blei, and Joshua B Tenenbaum 2005 Integrating topics and syntax In In Advances in Neural Information ... statistically significant increases Conclusions and Future Work This paper has described using a domainindependent document modeling approach of avoiding low-content syntax words in an NLP task where ... Association for Computational Linguistics, pages 362–370, Morristown, NJ, USA Association for Computational Linguistics Chin-Yew Lin 2004 Rouge: A package for automatic evaluation of summaries In Stan...
Ngày tải lên: 07/03/2014, 22:20
Báo cáo khoa học: Quantitative modeling of triacylglycerol homeostasis in yeast – metabolic requirement for lipolysis to promote membrane lipid synthesis and cellular growth potx
... is already determined by the input data, we were especially interested in identifying conditions with high lipolytic activity in silico to explain the experimental data Therefore, maximum LD ... phosphatidylcholine; PE, phosphatidylethanolamine; PI, phosphatidylinositol; PS, phosphatidylserine; SE, steryl esters permitting or forbidding a flux from TAG degradation products to virtual MP, in DFBA, ... CDP-ethanolamine and CDP-choline to DAG if choline and ethanolamine are present in the medium In our study, this pathway was disabled to reduce the complexity of analysis, thus forcing the cells...
Ngày tải lên: 16/03/2014, 04:20