Research Strategy. The CRADA Parties will build upon the hypothesis that the EC/CB1R system and iNOS are both pro-fibrogenic, and combined inhibition of these targets by a single compound would improve therapeutic outcome in scleroderma. Parties plan to test the novel dual-target compound MRI-1867 in bleomycin-induced subcutaneous fibrosis model in multi drug resistance 1a and 1b [ ]/ breast cancer resistance protein [ .] Bleomycin-induced scleroderma model Subcutaneous injections of bleomycin induce skin and pulmonary fibrosis (40), quantifiable histologically and biochemically. A recent modification in this protocol generated reproducible and more homogenous skin and lung fibrosis lesions mimicking human SSc, with interstitial lung disease-like manifestations (41). However, IC investigators observed that daily subcutaneous bleomycin administration significantly increased efflux transporters such as [ ,] [ ] and [ ] in skin that resulted in drastically reduced skin exposure to test compount (MRI-1867), which is a substrate for these transporters. Therefore, this experimental artifact would preclude preclinical efficacy testing using wild-type mice in bleomycin-induced skin fibrosis model. The IC investigators found that bleomycin also induced skin fibrosis in [ ] [ ] which was comparable to that in wt mice. Importantly, MRI-1867 skin exposure was not reduced in the [ ] and was similar to that in bleo-treated wildtype mice. Therefore [ ] [ ] will be used in these proposed studies. Specific Aim 1: Previously conducted study will be repeated testing S-MRI-1867 at [ ] dose in [ ] fibrosis model. NIAAA-Vital Spark, Inc. Standard CRADA National Institute on Alcohol Abuse and Alcoholism Approaches for Aim 1:
Research Strategy. The CRADA Parties will build upon the hypothesis that the EC/CB1R system and iNOS are both pro-fibrogenic, and combined inhibition of these targets by a single compound would improve therapeutic outcome in scleroderma. Parties plan to test the novel dual-target compound MRI-1867 in different [ ] of scleroderma such as the [ ] Subcutaneous injections of [ ] induce skin and pulmonary fibrosis (40), quantifiable histologically and biochemically. A recent modification in this protocol generated reproducible and more homogenous skin and lung fibrosis lesions mimicking human SSc, with interstitial lung disease-like manifestations (41). This latter approach will be used in these proposed studies. [ ] a well-established and widely used genetic model of SSc, featuring many skin abnormalities similar to those observed in human disease (40, 42). Using these two experimental models will establish the therapeutic potential of these dual-target compounds. Specific Aim 1: Test the target-specificity of hybrid peripheral CB1R/iNOS inhibitors by [ ]using the subcutaneous [ ] This approach would help to evaluate the relative contribution of the two targets to the therapeutic efficacy of the hybrid inhibitor. Approaches for Aim 1:
Research Strategy. There are seven types of research strategies (Shruti, 2016):
Research Strategy. 9.2.1 Within a reasonable time, Parks Canada shall prepare a research strategy with the advice of the QPMC, the Inuit Heritage Trust, the Nunavut Wildlife Management Board, and others.
Research Strategy. In this thesis project, an exploratory research with a quantitative approach will be used. A valid hypothesis needs to be set, in order to have a solid ground in this approach. As it is described by Xxxxxxxx Xxxxx J and Xxxxx L, ”An hypothesis is a statement or explanation that is suggested by knowledge or observation but has not yet, been proved or disproved”. The type of the hypothesis which we are going to follow is the null hypothesis where according to [4], ”The null hypothesis represents a theory that has been put forward, either because it is believed to be true or because it is to be used as a basis for an argument, but has not been proved.” Concerning the quantitative approach, it is a good fit in this project as far, the origins of the hypothesis are laying on the theory. As a final step an expirement will be able to verify the hypothesis. As it is described in [4] there are 4 steps in the hypothesis testing, with the first one been to state the hypothesis (this will take place in the next chapter).
Research Strategy. The University, under the direction of the Principal Investigator, intends to carry out a systematic research program to exploit and improve upon the theoretical guidance for preparing optimized nanostructured EO materials and to systematically explore the use of nanoscale dendrimers to achieve improvement in the fabrication and utilization of EO materials. Particular attention will be focused on control of aggregation and molecular relaxation events using nano-engineering methods and techniques. Specific attention will be given to phase phenomena and nanoscale phase separation defined by molecular shape-dependent intermolecular electrostatic interactions.
Research Strategy. Defining the research strategy for this study demands establishing a conceptual understanding of the PC’s ontology. Promises, expectations, and obligations are the building blocks of the PC as mentioned in Chapter 3, which in turn can be boiled down to a network of beliefs or, as Xxxxxxxx (1995) presents it, a schema. This is a sophisticated and intertwined network of beliefs acquired over time that are dynamic and gradually changing. Using a basic Venn diagram as a metaphor, the PC could be represented by the collection of beliefs that sit in the overlapping region between what we believe about ourselves and what we believe about the organisation (see Figure 3).
Research Strategy. The University of Canberra is committed to supporting applied research and research training as a part of its core mission. In the last 5 years the University has experienced significant growth in research activity including research outputs, research income and research student load. In the next 5 years, the University will invest and operate under 4 key priorities: Focus, Excellence, Impact, and Partnerships.
Research Strategy. Agents (Combinations of Agents) Proposed for Evaluation (in Vivo) • List three agents (or combinations of agents) for in vivo testing against their proposed tumor panel(s): – Provide a succinct rationale for why these agents warrant prioritization for testing. – Base on the biology of the models in the proposed panel(s) and on the mechanism of action of the agents. • Briefly describe the experimental approach for testing these agents. • Note: PD & PK studies may be proposed as part of the agent evaluations. Research Strategy: Agents (Combinations of Agents) Proposed for Evaluation (in Vitro) • Propose a screening experiment for a set of agents or combinations of agents – Provide a succinct rationale for why these agents warrant prioritization for testing. – Base on the biology of the models in the proposed panel(s) and on the mechanism of action of the agents. • Describe the potential for the experiments to generate hypotheses that the PPTC in vivo Research Programs can further evaluate. • Describe he potential contribution of the screen results to childhood cancer drug development Research Program: Other Attachments
Research Strategy. Given staffing and resourcing limitations, most of CPMEC’s research strategy is designed to support its priority activities and submissions. Because of its extensive internal networks CPMEC is able to access relevant current research and local and international developments. It is supported by a very proactive approach by CPMEC Board and staff to ensure that CPMEC inputs are viewed as a reliable national source of information on prevocational education and training arrangements.
