Initial proof of principle

Initial proof of principle studies of ocular carotenoid RRS employed a laboratory-grade high-resolution Raman spectrometer and flat-mounted human cadaver retinas and eyecups. In Fig. 12.10, typical Raman spectra are shown for an excised eyecup, in which the excitation laser was aimed at the center of the macula, the fovea, and at two locations with increased eccentricities. In all cases, RRS spectra are obtained that display the... 

Priestnall et al. (2002) proposed a new concept of MR fuel cells called compact mixed-reactant (CMR) fuel cells, based on the use of a structure containing porous flow-though electrodes. Such a structure can be a single cell or stacks of cells connected in series or parallel. In their initial proof-of-principle experiments, the authors used an alkaline fuel cell system with an electrolyte 0.008 M NBH4 in 10 M KOH saturated with air. 

The principles and instrumentation of this exciting new technology are described in Chapter 23. This approach clearly has major potential in cancer research indeed, several initial proofs of principle applications in tumor characterization, biomarker diagnosis for diagnosis, and even dmg development have been described [50-52]. 

Thus, these initial proof-of-principle experiments demonstrate the ability to use the epitope specificity of antibodies to specifically detect a molecule of interest within the complex intracellular milieu of the cytoplasm, albeit with limitations. However, the small size of these probes did allow for membrane penetration within specific and distinct sub-cellular regions, which perhaps will permit differential localization of target molecules within a cell in the future. 

The second stage is the proof of principle In this phase, we take the initial theoretical library idea and begin to apply chemistry experiments to validate experimental designs and potential library schemes at this stage, one also evaluates the method of library production (solid/solution/hybrid phases). In this phase, which is usually the longest phase in any library production process, we will perform the initial experiments, optimize the chemical yields and purities, modify the experiments to generate easily removable by-products, which can be removed by traditional parallel purification methods (i.e. SPE, Resin capture), and determine the most feasible route to the final product. 

The company has changed its strategy and its underlying assumptions fundamentally in the course of the project. For example, it has learned that it needs to price the product based on long-term positioning rather than current cost, that it needs to build a plant in a low-cost environment, that value chain intermediaries will need an incentive to adopt its product, and that it is sometimes necessary to work with smaller attackers as initial commercialization partners to demonstrate proof of principle, create market pull, and get the big fish to adopt a new product. The increased focus, clear product positioning, and partnering has already resulted in a number of major market introductions over the past year. 

Initial thermodynamic and experimental studies have found a new thermochemical cycle based on uranium. The operating conditions are mild and most of the steps are commercially used in the uranium processing industry. For several of the process steps, there are multiple process options. Additional analysis and experimental work is required before engineering viability (versus scientific proof of principle) can be determined with reasonably credible estimates of efficiencies and economics. 

The components of preclinical drug development can be divided into four general areas that include (1) in vitro studies to define a new agent s pharmacologic properties (2) drug supply and manufacturing, (3) drug formulation, and, finally, (4) in vivo studies in animal models to provide an initial proof of therapeutic principle and demonstrate the potential for clinical efficacy. 

Preclinical studies of BCNU-polymer preparations proceeded in four systematic stages. The first series of experiments examined in vivo release kinetics of BCNU loaded polymers. The initial study involved EVAc copolymer implantation in the rat brain (31). Subsequent to polymer placement, a Brat-ton-Marshall assay measured BCNU concentrations in both cerebral hemispheres, and serum samples were collected at prescribed time points. The hemisphere ipsilateral to polymer placement corresponded with peak BCNU levels at 4 h clinically significant concentrations persisted at day 7. In contrast, both contralateral hemisphere and serum BCNU levels were at least an order of magnitude lower throughout the experiment. Thus, the study served as proof of principle of the ability of polymer technology to simultaneously achieve sustained release and local delivery of chemotherapy within the CNS. 

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