Hurdle approach

The limitations of IAP are the harsh conditions needed for the recovery of antigens and the cost associated with use of antibodies on a large scale. To overcome these hurdles approaches such as more efficient immobilization protocols, increased life of immobilized antibodies (including electro-elution), milder recovery protocols, proper screening to select the appropriate antibodies are under investigation (138-140). 

As previously noted, a common strategy is to apply a combination of treatments rather than rely on a single treatment to prevent all types of degradation. This is called the "hurdle" approach, where each treatment presents a hurdle to the degradation process. 

The initial hurdle to overcome in the biosensor application of a nucleic acid is that involving its stable attachment on a transducing element which commonly includes a metallic electrode. In the first part of this chapter, we wish to introduce our approach for DNA immobilization (Scheme 1). A detailed characterization of the immobilization chemistry is also presented. In the second part, we follow the development of work from our laboratory on chemical sensor applications of the DNA-modified electrode involving a biosensor for DNA-binding molecules and an electrochemical gene sensor. 

Evans and Baranyai [51, 52] have explored what they describe as a nonlinear generalization of Prigogine s principle of minimum entropy production. In their theory the rate of (first) entropy production is equated to the rate of phase space compression. Since phase space is incompressible under Hamilton s equations of motion, which all real systems obey, the compression of phase space that occurs in nonequilibrium molecular dynamics (NEMD) simulations is purely an artifact of the non-Hamiltonian equations of motion that arise in implementing the Evans-Hoover thermostat [53, 54]. (See Section VIIIC for a critical discussion of the NEMD method.) While the NEMD method is a valid simulation approach in the linear regime, the phase space compression induced by the thermostat awaits physical interpretation even if it does turn out to be related to the rate of first entropy production, then the hurdle posed by Question (3) remains to be surmounted. 

RNAi technology has obvious therapeutic potential as an antisense agent, and initial therapeutic targets of RNAi include viral infection, neurological diseases and cancer therapy. The synthesis of dsRNA displaying the desired nucleotide sequence is straightforward. However, as in the case of additional nucleic-acid-based therapeutic approaches, major technical hurdles remain to be overcome before RNAi becomes a therapeutic reality. Naked unmodified siRNAs for example display a serum half-life of less than 1 min, due to serum nuclease degradation. Approaches to improve the RNAi pharmacokinetic profile include chemical modification of the nucleotide backbone, to render it nuclease resistant, and the use of viral or non-viral vectors, to achieve safe product delivery to cells. As such, the jury remains out in terms of the development and approval of RNAi-based medicines, in the short to medium term at least. 

Once a suitable crystal is obtained and the X-ray diffraction data are collected, the calculation of the electron density map from the data has to overcome a hurdle inherent to X-ray analysis. The X-rays scattered by the electrons in the protein crystal are defined by their amplitudes and phases, but only the amplitude can be calculated from the intensity of the diffraction spot. Different methods have been developed in order to obtain the phase information. Two approaches, commonly applied in protein crystallography, should be mentioned here. In case the structure of a homologous protein or of a major component in a protein complex is already known, the phases can be obtained by molecular replacement. The other possibility requires further experimentation, since crystals and diffraction data of heavy atom derivatives of the native crystals are also needed. Heavy atoms may be introduced by covalent attachment to cystein residues of the protein prior to crystallization, by soaking of heavy metal salts into the crystal, or by incorporation of heavy atoms in amino acids (e.g., Se-methionine) prior to bacterial synthesis of the recombinant protein. Determination of the phases corresponding to the strongly scattering heavy atoms allows successive determination of all phases. This method is called isomorphous replacement. 

This illustrates the general philosophy of taxometrics. For something to be deemed a taxon, it needs to clear several hurdles, which arguably makes taxometrics the most rigorous analytic approach to the study of taxonomy. The last two conditions (e and f) are external consistency tests and apply to all taxometric studies. On the other hand, a, b, c, and d are internal consistency tests. Some of them are specific to MAXCOV—other procedures have their own unique internal consistency tests—but a and b can be performed with any of the CCK methods. We will now consider the first three internal consistency tests (a, b, and c) in detail and postpone discussion of the distribution of taxon membership. 

The concept of inherently safer plant has been with us now for many years. But in spite of its clear potential benefits related to safety, health and the environment (SHE), as well as the costs, there has been few applications in chemical plant design. But as Kletz (1996) has written there are hurdles to be overcome. Inherently safer design requires a basic change in approach. Instead of assuming e.g. that we can keep large quantities of hazardous materials under control we have to try and remove them. Changes in belief and the corresponding actions do not come easily. 

The economic)technical approach focuses on the question of which occurrences can be extracted economically with today s technology. According to this approach, all occurrences that at present are economically extractable with existing available technology are classified as conventional, whereas occurrences that are not extract-able at present owing to economic or technical hurdles are considered unconventional. The physical properties of the oil are not taken into account. It is important to note that, in this approach, the boundary between conventional and unconventional crude oil is current, as it is subject to the market price of oil, the production cost and the available technology. 

In the mathematical optimization based approaches first a superstructure is created which has embedded a large number of alternative designs. Then mathematical techniques like MINLP are used to find the optimum process within the specified superstructure. For the products considered here there are two big hurdles preventing the large scale use of these techniques (Hill, 2004). Firstly a lot of the physico-chemical phenomena occurring are not completely understood. This makes rigorous modeling difficult. Secondly there is a lack of relevant property models for structured products. 

As discussed above there are several hurdles to overcome in attempting to enhance the delivery of the drug to the tumour cell. In addition to the use of high dose chemotherapy with concomitant protection of normal tissues, a number of other approaches have been developed. Local perfusion is used with significant benefit in some cancers. This technique is however limited to cancers localized to a single site, e.g. to one of the extremities. This approach will not be discussed here. 

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