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. 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. 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. There are seven types of research strategies (Shruti, 2016):
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.
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. 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. 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. Present an overview of the state of the science, current status and relevance of the trial, discussion of the clinical protocol, and relevance to the research mission of the NIAID. Applicants must propose a hypothesis-driven clinical trial, and show that the clinical trial is ready for implementation at the time of award, and describe the clinical trial stages, criteria for completion of the stages and contingency plans for each stage to accommodate any anticipated impediments that could require a revision in the timeline. Identify and clearly indicate the primary and secondary endpoints. A summary of the statistical methods appropriate for the study design is required. More detailed descriptions of the statistical methods must be presented in separate documents in the PHS Human Subjects and Clinical Trials Information form. The Research Strategy should discuss, address, and/or summarize the following: Prior Studies and Rationale for Development: The major findings of the pre-clinical and clinical studies that led to the proposed clinical trial should be presented. Data from pre-clinical and pilot studies demonstrating the need for and the feasibility of the trial should also be presented. Conceptualization and planning must have progressed to a stage sufficient to allow for an overall assessment of the likelihood of trial success. Indicate the significance of the problem being studied, the need for the trial, and the potential impact of the results of the trial, including adequate definition of the study objective(s) and how well the clinical trial will test the hypothesis(es) proposed; The overall strategy, methodology and analyses to be used to accomplish the goals and specific aims of the trial; Do not duplicate information found in the Human Subjects section of the application; A justification of the intervention and/or study agent(s) to be tested and the protocol to be followed in each arm of the trial; Plans for acquisition and handling of study agent(s); For proposed mechanistic studies: Discuss the feasibility of the approach(es) and how these studies contribute to the understanding or treatment of the disease/condition; For proposed multi-center clinical trials: Discuss the methods for ensuring adherence to the clinical protocol, and standardization and quality control of distribution of study agent(s) and data collection; A description of expertise in areas to include the clinical problem under study, administration of complex projects and study...
