principle proof of concept trials in drug development

... degradation were inhibited by blocking IL-1β but not IL-1α In RA patients, IL-1β is overexpressed in inflamed synovial tissue, in particular in the lining layer and in sublining cells [9], and ... is a crucial cytokine that drives inflammation and joint destruction in RA We report here results of preclinical studies and a proof- ofconcept study in patients with RA, using a fully monoclonal ... Scoring was performed on decoded slides by two separate observers, using the following parameters In the haematoxylin/eosin stained slides the amount of cells infiltrating the synovial lining...

Ngày tải lên: 09/08/2014, 10:23

... consideration in future studies of dynamic risk factors for CAD in a chronic relapsing-remitting disease such as SLE Our findings also underpin the importance of adequate control of SLE disease ... assay (Boehringer Mannheim kit 236691 Indianapolis, IN) and recorded in mmol/L As there are only small, clinically insignificant differences in TC when measured in the fasting or non-fasting state, ... risk of CAD In the case of TC, a hazard ratio of 2.07 (p=0.003) means that for every mmol/L increase in mean (or AM) plasma TC level, the hazard of a CAD outcome increases 2.07 fold In the case of...

Ngày tải lên: 12/08/2014, 18:20

... suspension Feed turned off by clinician Use only insulin intervention Stop all extra insulin infusions Added insulin infusion of U/h over U/h maximum Must meet: • Insulin at ≥5 U/h, for the past ... safety Intervention Increments used Maximum change Insulin 0.0-6.0 U/h in increments of 0.5 U excluding 0.5 U/h +3U (dosing is per hour) reduce to U/h Nutrition 30-100% of ACCP/SCCM goal feed of ... Annals of Intensive Care 2011, 1:38 http://www.annalsofintensivecare.com/content/1/1/38 Page of 12 Table Insulin and nutrition dose increments and limits on rate of change in dose per measurement interval...

Ngày tải lên: 20/06/2014, 23:20

... magnitude of the viral increase in plasma and the size of the latent HIV1 pool, together with findings from SGS of the gag region, indicate that HIV-1 in plasma originated from the pool of latently-infected ... reservoirs in our study increased their serum levels of IL-7 during IVIG treatment, suggesting a role for IL-7 in mediating the effect of IVIG on the latent reservoir The source of IL-7 detected in response ... proviral strainspecific inducer of latent HIV-1 cellular reservoirs of infected individuals on virally suppressive HAART J Clin Invest 2005, 115:128-137 Fry TJ, Mackall CL: Interleukin-7: from...

Ngày tải lên: 10/08/2014, 05:21

... requirement of the patient as the disease process evolves in response to treatment or as a result of healing The goal of this proof- of- concept study is to explore the feasibility of supplementing traditional ... management of an individual patient This project introduces the concept of using empiric data to obtain patient-specific and clinical scenariospecific recommendations in the ICU Prediction of maintenance ... controlled trials 10 11 • The project introduces the concept of mining empiric data using artificial intelligence to obtain patient-specific and clinical scenario-specific recommendations in the...

Ngày tải lên: 13/08/2014, 11:23

... inhibition of aerobiosis in exercising muscle [31] Inhibitory effects of H2S in the presence of increased metabolism in larger mammals warrants further study Page of 10 Our results show that administration ... 294:R1930-1937 40 Henderson PW, Weinstein AL, Sung J, Singh SP, Nagineni V, Spector JA: Hydrogen sulfide attenuates ischemia-reperfusion injury in in vitro and in vivo models of intestine free tissue transfer ... effects of hypothermia on metabolism Whether systemic administration of Na2S reduces metabolic rates in large mammals when normothermia is maintained remains to be determined While our findings...

Ngày tải lên: 14/08/2014, 07:21

... Mg2+-independent Neutral Sphingomyelinases 84 Alkaline Sphingomyelinase from the Intestinal Tract 85 Bacterial Sphingomyelinase-phospholipase C 85 Sphingomyelinase Mechanism 85 Binding of Magnesium ... Mechanism 264 Involvement of Perilipins 266 Involvement of Lipotransin 268 Intrinsic Activity of HSL 270 Feedback Inhibition 270 Adipocyte Lipid-binding Protein 272 Expression of HSL 274 Release of Lipolytic ... Ions 85 Binding of Substrate 85 Mechanism of Catalysis 86 Sphingomyelinase Assay 88 Sphingomyelinase Inhibitors 89 Sphingomyelinase–Membrane Interactions 89 Lipid Effects on Sphingomyelinase Activity...

Ngày tải lên: 17/02/2014, 05:20

... Depending on the type of ore deposit being mined, tailings can also contain heavy metals like copper, lead, zinc, mercury and arsenic The contaminants in mine waste may be Cooling waters used in industrial ... Figure 19 in the timing and intensity of rainfall, or the period of time without rain, as well as affecting the quality of water in rivers and lakes through changes in the timing and volume of peak ... filtration, and increases the groundwater contamination 38  Figure 13: Mining effects on rainfall drainage Acid Mine Drainage (AMD) is the number one environmental problem facing the mining industry...

Ngày tải lên: 17/02/2014, 10:20

... and/or re-financing of sustainable forestry in the developing world The Programme is divided into three stages This first stage, a Proof of Concept Study, examines the technical feasibility of the ... use of structured commodity finance Page of 140 FINAL 06 August 2007 Forest-Backed Bonds Proof of Concept Study Forum for the Future & EnviroMarket Forest-Backed Bonds Applying the principles of ... any shortfall in information flow against the requirements of structured finance teams, rating agencies and financial regulators involved in the development of a forest-backed bond § Information...

Ngày tải lên: 06/03/2014, 08:20

... workforce by offering instructional programs, matching instruction to the needs of business and industry, and helping individuals learn throughout their lives Instructional Programs Teaching excellence ... Alliance institutions In the past two years, the annual enrollment in Rockford courses increased 11 percent The Role of Higher Education in Economic Development Page of 12 Identifying Needs of Business ... teachers, interns, and consultants for institutions in the region The Role of Higher Education in Economic Development Page of 12 Support to Current Business and Industry Current business and industry...

Ngày tải lên: 17/03/2014, 07:20

... Diet-induced obesity b) Insulin resistance c) Glucose intolerance Fat cells Fig Model for the role of ApoE in the development of diet-induced obesity in mice Dietary lipids are packaged into ... and insulin sensitivity of the ApoE) ⁄ ) · Ay ⁄ + mice, and triggered obesity, indicating that circulating ApoE is involved in increased adiposity and obesity-related metabolic disorders Of note, ... phenotype and insulin and glucose levels became stronger with increasing body mass index [60,61] These findings again raise the interesting possibility that, although hyperplastic types of obesity...

Ngày tải lên: 29/03/2014, 22:21

... Combinatorial Mixture Screening / 103 In Vivo Drug Screening / 106 Pharmacokinetics / 109 In Vitro Drug Screening / 115 Metabolic Stability Screening / 118 Membrane Permeability / 119 Drug- Drug Interaction ... eliminate candidates from the drug development pipeline In this example, the number of compounds in various stages of drug development is represented, using the previously described drug development ... with an earlier introduction of a new drug due to saving days of work from rate-determining activities during the drug development process Two days saved for each of 10 ratedetermining activities...

Ngày tải lên: 11/04/2014, 07:01

... of community in this process, the Training courses were organized in all of pilot communes The method of training is mainly learning by doing the practical exercise The trainees of each training ... Objective of commune development planning : 36 Process of commune development planning 36 Chapter V - Several necessary skills in application of PRA tools in making village development ... Tuyen Hoa district Quang Binh province Temperature Rainfall Spring rice 10 Harve sting Tending Planting Disease Stem disease, yellow leaf Winter tending harvesting Plantin g Disease Stem disease,...

Ngày tải lên: 26/05/2014, 23:30

... skill after nine days of training Note the absence of flexion in the middle, ring and pinky fingers In this study, fractionation score (FS) is calculated as the angle of the active finger s metacarpophalangeal ... his fingers again diminished but improved after further training with this amount of assistance from 36 to 38 degrees Proof of concept testing results As a group, the four subjects improved in ... individual finger motion in three of his four fingers when using algorithm B (on the right of the vertical line) Subject demonstrated an increase in peak fractionation of 48 degrees for index finger,...

Ngày tải lên: 19/06/2014, 08:20

... localization of inducible nitric oxide synthase and 3-nitrotyrosine in preneoplastic and neoplastic rat livers induced by continuous infusion of N-nitrodiethyl amine with osmotic mini-pumps Carcinogenesis ... activity increased continuously during our study The effect of carcinogenesis on the free radicals concentration needs further examination In the present study, DEN administration initially 57 induced ... diethylnitro samine in the rat Institute of Basic Science of Inhwa University 1992, 13(2), 85-96 Luciana, T., Paolo, P and Mario, U D Mechanisms of the enhanced liver carcinogenesis by choline in female...

Ngày tải lên: 07/08/2014, 14:23

... protein-protein interactions by parsimony principle (nInferPPI), inferring protein-protein interactions based on multi-domain cooperation (nMDCinfer), molecular network aligner (nMNAligner), detecting drug ... type of biomarkers with protein–protein interactions was initiated and investigated with the integration of knowledge on protein annotations, interaction, and signaling pathway A number of methodologies ... emerging science combining clinical informatics, bioinformatics, medical informatics, information technology, mathematics and omics science together [5] Clinical bioinformatics was initially proposed...

Ngày tải lên: 10/08/2014, 09:22

... kb 5' of the TSS The validation framework that we use, combining genomewide ranking with LOOCV, could also be useful in evaluating or comparing hypotheses regarding the working principles of transcription ... of ModuleMiner prompted us to apply the algorithm to gene sets obtained from clustering microarray data In nine out of ten microarray clusters, ModuleMiner succeeded in finding similar CRMs in ... results in ten clusters with sizes ranging from 26 to 214 genes Large clusters were randomly divided in a training set of 50 genes, and a test set containing the remaining genes The performance of...

Ngày tải lên: 14/08/2014, 08:21

... stimulating proliferation, serum exposure induces a wound healing response in fibroblasts, involving the activation of genes that play a role in intercellular signaling and remodeling of the extracellular ... against both ovarian and renal carcinoma, but not against Wilms' tumor or lung adenocarcinoma Interestingly, a recent paper that examined gene expression in mouse models of colon carcinoma in ... expression in cancer and development presented here suggest that the developmental information content of most human cancers indeed is significant The developmental signature of cancers originating...

Ngày tải lên: 14/08/2014, 20:22

... transcription initiation [58], it is unlikely that drug response profiling using microarrays will be helpful to understand the mode of action of drugs in Leishmania Results using MTX as a lead drug and ... occurred at the level of the inverted repeats (as, for example, during a block in DNA replication) Indeed, we obtained a product of the expected size with these pairs of primers in L infantum MTX20.5 ... operating grants to MOu JMU is a Strategic Training Fellow of the Strategic Training Program in Microbial Resistance, a partnership of the CIHR Institute of Infection and Immunity and the Fonds de...

Ngày tải lên: 14/08/2014, 20:22

... calmodulin-binding kinesin-like motor protein (Oppenheimer et al., 1997) ZWI interacts with two other proteins involved with trichome branching: ANGUSTAFOLIA and KCBP-interacting Ca2+ binding protein ... of epidermal cell fate determination by interactions between proteins involved in trichome patterning A combination of a MYB protein (either GL1 or MYB23) with a bHLH dimer (any combination of ... determination in Arabidopsis trichomes (Larkin et al., 1997) A spacing pattern governed by lateral inhibition would consist of an initiation factor and inhibitory factor acting within a field of...

Ngày tải lên: 14/11/2014, 11:55