Proof of Principle

The approach consists of a liquid-phase oxidation using OH Fenton radicals from H2O2 for detemplation [148-150]. The radicals oxidize the organic template into CO2 and H2O while the porosity of the material is developed. The proof-of-principle of this concept is discussed for two case studies. 

Several ways to suppress the 2-oxonium-[3,3]-rearrangements might be envisioned. Apart from the introduction of a bulky substituent R at the aldehyde (Scheme 23) a similar steric repulsion between R and R might also be observed upon introduction of a bulky auxiliary at R. A proof-of-principle for this concept was observed upon by using of a trimethylsilyl group as substituent R in the alkyne moiety (Scheme 25, R = TMS). This improvement provided an efficient access to polysubstituted dihydropyrans via a silyl alkyne-Prins cyclization. Ab initio theoretical calculations support the proposed mechanism. Moreover, the use of enantiomerically enriched secondary homopropargylic alcohols yielded the corresponding oxa-cycles with similar enantiomeric purity [38]. 

Similarly, the number and types of tests completed will influence the cost in ways that can be very complex. Recently, the author was involved in designing a proof-of-principle study intended to assess the ability of a dietary supplement to enhance weight loss among subjects instructed to follow a reduced energy diet. Sample size calculations were run for two scenarios, the first using change in body weight as the primary outcome variable, the... 

In a different way, metallic-core nanoparticles [346-349] (prepared cf. Section 3.10) equipped with biocompatible coats such as L-cysteine or dextrane may be exploited for highly efficient and cell-specific cancer cell targeting, i.e., for improving diagnosis and therapy of human cancer. In a recent proof-of-principle experiment an unexpectedly low toxicity of the L-cysteine-covered cobalt nanoparticles was demonstrated [433] For diagnostic purposes, it is expected to use the advantageous magnetic properties of the metallic-core nanoparticles to obtain a contrast medium for MRI with considerably increased sensitivity, capable to detect micro-metastases in the environment of healthy tissues [434 37]. 

Development is the proof of principle of material design and product applications. 

Liu, J. Li, Q. Yang, X. van Breemen, R. B. Bolton, J. L. Thatcher, G. R. Analysis of protein covalent modification by xenobiotics using a covert oxidatively activated tag raloxifene proof-of-principle study. Chem. Res. Toxicol. 2005, 18, 1485-1496. 

But do the clinical-trial data submitted to the FDA even establish proof of principle Recall that the rather small differences found between drug and placebo in the trials submitted to the FDA could have been due to the breaking of blind on the basis of perceived side effects. It may simply be evidence of an enhanced placebo effect, rather than a true drug effect. As I noted in Chapter i, once side effects are taken into account, the difference between SSRI and placebo is not even statistically significant.30... 

This performance was demonstrated in a proof-of-principle BWA contractor performance test conducted at ORNL early in 2002, and witnessed and reported31 by staff from the Dugway Proving Ground. This test was conducted... 

Since the proof-of-principle test, considerable improvements to the BWA monitoring method hardware and software were made by Hamilton Sund-strand Sensor Systems, and they are now being incorporated into LRIP units for the final phase of BWA method work. The BWA monitoring method and... 

The studies described above are important proof-of-principle investigations pointing to a debate about the carcinogenic hazard of MWNTs in the abdominal cavity. There are a number of open questions that need to be resolved before a final assessment can be made. In this respect, Oberdoster recently summarized such a challenge with three key questions do they (MWNTs) translocate from the deposition site in the lung to the pleura If so, what is the efficiency of such translocation in terms of the dose retained in pleural tissues What are the dimensions (in particular length) of the translocated MWNTs [92]. 

Since the first description was only two decades ago, combinatorial biosynthesis has advanced from a limited set of proof-of-principle experiments into a more mature scientific discipline. To reach the maximal potential of natural product structural diversity, the combination of this approach with other established and emerging technologies will ultimately provide access to a rich variety of unnatural natural products with improved properties or new biological activities for future drug discovery and development. 

Purpose T1D-RAID is a cooperative program of the NIDDK and NCI that is designed to facilitate translation to the clinic of novel, scientifically meritorious, therapeutic interventions for the treatment of Type-1 diabetes. The goal of T1D-RAID is to support the pre-clinical tasks needed for the clinical "proof of principle" to determine if a new molecule merits... 

Although only a dozen known metal complexes were tested in this manner, proof of principle was demonstrated. The test revealed Wilkinson s catalyst to be the most active hydrosilylating agent, its use in this type of reaction being known. However, the study also led to the discovery that a palladacycle, [Pd (o-tolyl)2PC6H4 (OAc)]2, which is usually considered to be potent in Heck reactions, is also an excellent hydrosilylation catalyst.37,38 Control experiments showed that the relative order of catalyst activity is the same when conventional substrates are used in place of the dyes (8). 

A wide variety of proof-of-principle systems have been proposed, synthesized and studied in the field of molecular spin qubits. In fact, due to the fast development of the field, several chemical quantum computation reviews using magnetic molecules as spin qubits have been published over the past decade, covering both experimental and theoretical results [67-69]. Only in a minority of experiments implementing non-trivial one- or two-qubit gates has been carried out, so in this aspect this family is clearly not yet competitive with other hardware candidates.1 Of course, the main interest of the molecular approach that makes it qualitatively different is that molecules can be chemically engineered to tailor their properties and acquire new functionalities. 

Bettuzzi S, Brausi M, Rizzi F, Castagnetti G, Peracchia G and Corti A. 2006. Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia a preliminary report from a one-year proof-of-principle study. Cancer Res 66(2) 1234—1240. 

The iodido-Pt(IV) complexes thus provided a proof-of-principle being photoactive, but the complexes still suffered from slow photoreactions and, importantly, limited stability in the dark especially against biological reducing agents such as glutathione, which results in undesired toxicity of the anticancer agents in the dark. 

The model is also capable of addressing the effects of various medical countermeasure protocols upon casualty flows, e.g. when chemoprophylaxis and/or specific therapeuticals for intoxications are available. At present, this aspect is not parameterized properly and therefore is available only as a prototype to demonstrate proof of principle. 

The example given above shows that CIS can simulate the effect of the complete passive defence chain in a consistent way. The strength of CIS is that it can simulate this effect for a huge number of different situations and thus is able to establish passive defence requirements in a systematic way. The proof of principle for simulating the complete protection chain has been given. Extensive work has to be done to refine this approach, so that CIS can be an effective tool to set requirements for real life situations. 

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