orders of magnitude in drug discovery

In silico methodologies for selection and prioritization of compounds in drug discovery

Ngày tải lên : 08/09/2015, 22:12

... supervised learning and unsupervised learning Supervised learning involves the deduction of a function from training data The training data typically consist of vectors of input variables describing properties ... state of the art of the existing scoring functions is still unable to reliably predict the native binding mode and CHAPTER associate free energy of binding 88 This is because the existing scoring ... the one of their initial cluster The choice of the value of k remains subjective.165 Supervised machine learning methods use a training set of items that have previously been classified into two...

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Báo cáo y học: "Distribution patterns of small-molecule ligands in the protein universe and implications for origin of life and drug discovery" doc

Ngày tải lên : 14/08/2014, 08:20

... Number of domains binding ligand (L) Figure Power-law behaviors of ligand-protein binding Power-law behaviors of ligand-protein binding The number of ligands (N) decays with an increase in 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 ... implicates that the origin of primitive proteins benefited from ligand binding, which is reasonable in terms of the thermodynamics of ligand binding and protein folding revealed in the present study...

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Biointormatics of targeted therapeutics and applications in drug discovery

Ngày tải lên : 12/09/2015, 09:10

... source of courage and happiness i Bioinformatics of Targeted Therapeutics and Applications in Drug Discovery ii Bioinformatics of Targeted Therapeutics and Applications in Drug Discovery Table of ... industry has received roaring attention and showed promising future A tremendous amount of money, time and human resources have been injected into drug discovery, in the hope of finding new drugs ... Bioinformatics of Targeted Therapeutics and Applications in Drug Discovery x Bioinformatics of Targeted Therapeutics and Applications in Drug Discovery List of Tables Chapter Table Statistics of...

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Advanced Computer-Assisted Techniques in Drug Discoveryedited by Han van de Waterbeemd.Methods pot

Ngày tải lên : 29/06/2014, 09:20

... to be involved in the biological interaction, define our pharmacophore In principle, the definition of the relative spatial disposition of the six atoms of the pharmacophore requires 15 interatomic ... series of handbooks and monographs introduces the reader to basic principles and state -of- the-art methods in medicinal chemibtry Topics treated in- depth include W W W W chemical propertiesofdrugs ... step of the PCDD-Ah receptor interaction, seeking patterns in the MEP of PCDDs which could be related to their binding affinities A series of 14 PCDD isomers, which showed a significant range of...

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Báo cáo y học: "he impact of sample storage time on estimates of association in biomarker discovery studies" doc

Ngày tải lên : 10/08/2014, 09:22

... AM, Kristiansen J: Evaluation, including effects of storage and repeated freezing and thawing, of a method for measurement of urinary creatinine Scand J Clin Lab Invest 2003, 63(7-8):521-524 Comstock ... study In summary, our results provide investigators planning exploratory biomarker studies with data on biases due to changes in marker levels that may aid in interpreting findings and planning ... al Journal of Clinical Bioinformatics 2011, 1:9 http://www.jclinbioinformatics.com/content/1/1/9 Page of could lead to missed associations, i.e increased numbers of false negative findings, as...

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solid phase microextraction in drug discovery

Ngày tải lên : 14/11/2014, 09:52

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Implementation of a drug discovery tool for the evaluation of anti fibrotic compounds application in fibrovascular disorders

Ngày tải lên : 09/10/2015, 11:07

... a valuable tool in tissue engineering The presence of collagen fibrils in tissue constructs is essential in maintaining the mechanical strength and defining the shape and form of the tissues Unfortunately, ... tissue constructs In addition, collagen has been used as a scaffold or coating in tissue engineering This collagen mainly comes from various animal origins In the light of increasing concerns over ... occurs in both intracellular and in the extracellular matrix In Escherichia coli, the concentration of total protein inside the cells is in the range of 200-300 mg/ml, whereas that of RNA is in the...

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Tài liệu Báo cáo khoa học: Role of Kupffer cells in pathogenesis of sepsis-induced drug metabolizing dysfunction pptx

Ngày tải lên : 14/02/2014, 18:20

... signaling is independent of Toll-interleukin receptor domain-containing adaptor protein Drug Metab Dispos 36, 95–101 10 Ghose R, Guo T & Haque N (2009) Regulation of gene expression of hepatic drug ... shown that interactions between KCs and endotoxin comprise the initiating event leading to hepatotoxicity in liver injury, including endotoxemia and ischemia ⁄ reperfusion injury [14] In our studies, ... abnormalities in microsomal drug- metabolizing function during the late phase of sepsis [6] However, the underlying mechanisms involved in hepatic dysfunction during sepsis remain elusive Among...

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Tài liệu Báo cáo khoa học: Treatment of neutral glycosphingolipid lysosomal storage diseases via inhibition of the ABC drug transporter, MDR1 Cyclosporin A can lower serum and liver globotriaosyl ceramide levels in the Fabry mouse model doc

Ngày tải lên : 19/02/2014, 07:20

... staining in Fabry mouse; (C, D) lung – epithelial cell staining increased in Fabry mouse; (E, F) brain microvascular endothelial staining in Fabry mouse Magniﬁcation ·16 no VT1 staining of normal ... staining is brown The section is counter stained with hematoxylin (B) In situ staining of renal VT1 bound in vivo VT1 (50 lg per mouse) injected i.p and bound within the kidney was immunostained ... could be important in determining susceptibility to HUS following VTEC infection Our results indicate the feasibility of using inhibition of MDR1 as an approach to the treatment of Fabry disease...

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Báo cáo khoa học: Inhibition of PI3K/Akt partially leads to the inhibition of PrPC-induced drug resistance in gastric cancer cells pdf

Ngày tải lên : 07/03/2014, 03:20

... maintained in RPMI-1640 containing 10% heat-inactivated newborn bovine serum (SiJiQing, Hangzhou China) at 37° C in a humidified atmosphere of 5% CO2 and 95% air Double immunofluorescence staining ... emission wavelength of 575 nm (A) Fluorescence intensity analysis of intracellular adriamycin in gastric cancer cells (B) Adriamycin releasing index of gastric cancer cells The releasing index = (accumulation ... above in vivo findings PI3K/Akt is involved in PrPC-mediated MDR in gastric cancer In order to study whether activation of the PI3K/Akt signaling pathway played a role in PrPC-induced MDR in gastric...

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Báo cáo khoa học: Nuclear localization of human spermine oxidase isoforms – possible implications in drug response and disease etiology pptx

Ngày tải lên : 07/03/2014, 05:20

... microscopy of immunoﬂuorescent staining of SMO in cells overexpressing each of the isoforms provided direct visualization and conﬁrmation of protein localization 2800 without the possibility of contamination ... C * Put Intracellular polyamines (nmol·mg protein–1) Polyamine oxidase activity of SMO5 and SMO ⁄ PAOh1 was measured using increasing concentrations of either spermine or N1-acetylspermine as ... and catabolism In cancer cells, the regulatory components of polyamine homeostasis are often disrupted, leading to increased levels of intracellular polyamines, thus promoting increased growth...

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POTENTIAL CONFLICT OF INTEREST IN THE PRODUCTION OF DRUG COMPENDIA doc

Ngày tải lên : 09/03/2014, 00:20

... Conflict of interest in the process of making study data available; 3) Conflict of interest leading to biased selection of indications to review, and of evidence sources; and, 4) Bias in the interpretation ... description of compendia processes, delineating points at which conflict of interest may arise; (2) an ethical framework for evaluating the potential presence and influence of conflict of interest in ... authoritative sources of information to support coverage determinations of offlabel uses of anti-cancer drugs and biologics By definition, drug compendia include information that has major financial implications...

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THE PART BORNE BY THE DUTCH IN THE DISCOVERY OF AUSTRALIA 1606-1765 pdf

Ngày tải lên : 15/03/2014, 03:20

... and containing the passage following: "[We] see that Your Worships have again taken up the further exploration of the coast of Nova Guinea in hopes of discovering silver- and gold-mines there ... the Flemmings Pinasse which went upon discovery for Nova Ginny, was returned to Banda, having found the Iland: but in sending their men on shoare to intreate of Trade, there were nine of them ... celebrated voyage of discovery of 1642-1643, I was time and again struck by the fact that the part borne by the Netherlanders in the discovery of the continent of Australia is very insufficiently...

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Báo cáo khoa học: Role of the plasma membrane leaﬂets in drug uptake and multidrug resistance ppt

Ngày tải lên : 29/03/2014, 08:20

... obtained by sequential exposure of cells to increasing concentrations of doxorubicin and was maintained in the presence of 0.5 lm doxorubicin 2008 parental cells and their MRP1 over-expressing ... the initial fast phase of ﬂuorescence in the Pgp-over-expressing cells or ﬂuorescence quenching in wild-type cells (Fig 5) Inhibition of Pgp with cyclosporine A caused a parallel increase in the ... accumulation of drug within this would be accomplished prior to saturation of the total cellular content of the drug By contrast, in the case where there is no kinetic barrier, drug accumulation within...

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Báo cáo khoa học: "A Joint Model for Discovery of Aspects in Utterances" potx

Ngày tải lên : 30/03/2014, 17:20

... Proc of the Annual Meeting of the Association of Computational Linguistics (ACL) J Reisinger and M Pasca 2011 Fine-grained class label markup of search queries In Proc of the Annual Meeting of ... Nud + αA d The Nu is the number of occurrences of domain topic d in utterance u, Na|ud is the number of occurrences of act a given d in u During sampling of a Domain p(Sujd = k Nujd + β k N(.) ... 2004 Interactive machine learning techniques for improving slu models In Proceedings of the HLT-NAACL 2004 Workshop on Spoken Language Understanding for Conversational Systems and Higher Level Linguistic...

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Báo cáo sinh học: " Discovery of herpesviruses in multi-infected primates using locked nucleic acids (LNA) and a bigenic PCR approach" pdf

Ngày tải lên : 18/06/2014, 18:20

... contains mismatches within the LNA binding region Two of the mismatches were LNA-substituted (Figure 2) In the presence or absence of the LNA, a similar amount of amplimer was obtained in real-time ... central part of the consensus sequence is represented by the dotted line The 3'- ends of the binding regions of the inner consensus primers TGV (sense) and IYG (antisense) are indicated Page of 15 (page ... 350 = Inosine $ approximate values carried out as described for the DPOL gene, with an annealing temperature of 45°C For the major DNA binding protein (MDBP) gene amplification of members of the...

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báo cáo hóa học: " Magnitude and meaningfulness of change in SF-36 scores in four types of orthopedic surgery" ppt

Ngày tải lên : 18/06/2014, 19:20

... an individual level are essential for interpretation of intra-individual change as they help to determine clinical meaningfulness of the observed change in individual scores Estimates of individual ... minimal clinically important change in SF-36 scores in orthopedic settings, we caution against using SF-36 to monitor health status of individual patients undergoing orthopedic surgery Competing ... changes in individual scores if MDCind were smaller than the normative values of 95% CI: 12 points for PF, 23 points for RP, 15 points for BP, 18 points for GH, 16 points for VT, 26 points for...

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Báo cáo hóa học: " Discovery of frameshifting in Alphavirus 6K resolves a 20-year enigma" docx

Ngày tải lên : 20/06/2014, 01:20

... proteins Immunofluorescence of SFV-infected cells showing location of 6K and TF proteins Green fluorescence indicates Abs binding to target peptides Cell nuclei are stained blue Cells fixed in ... codons in Aura virus, and reaching 50 codons in Ndumu virus) resulting, after presumed cleavage at the N-terminus of 6K, in the alternative protein TF (Figure 5) The N-terminal end of TF retains ... defective in the processing and transport of envelope proteins (as expected since the C-term of 6K contains the signal peptide for E1) and in plaque phenotype A revertant virus, containing a point...

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DRUG DISCOVERY RESEARCH IN PHARMACOGNOSY ppt

Ngày tải lên : 27/06/2014, 10:20

... importance in preparing good fingerprints of herbal medicines As a single herbal medicine may contain a great many natural constituents, and a combination of several herbs might give rise to interactions ... definition, a chromatographic fingerprint of an herbal drug is, in practice, a chromatographic pattern of the extract of some common chemical components of Analytical Evaluation of Herbal Drugs ... researches into medicinal constituents of plants, involve qualitative and quantitative analyses There is rationale behind each experimental work involving definite steps and processes; having in mind...

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