Intrinsic capacity

To obtain an increased intrinsic capacity to transgress biological membranes, a number of different modifications have been introduced to PNA. These modifications include conjugation of PNA to Hpophilic moieties [51, 97, 98], conjugation of PNA to certain so-caUed ceU-penetrating peptides [49, 55, 56, 66, 99-102] and conjugation to different moieties, which are supposed to be internahzed by specific cellular receptors [48, 103-105]. The work on cellular dehvery of PNA is, like the related work on ex vivo and in vivo effects of PNA, very difficult to summarize conclusively. First of all, the pronounced diversity of the reporter systems employed makes it impossible to directly compare the studies. Secondly, the widespread use of fluorescence studies in spite of the many inherent pitfalls of this technique makes it sometimes difficult to judge even qualitatively whether a presented result actually indicates cellular uptake. We have recently published a comprehensive review on cellular dehvery of PNA [82], with a more detailed assessment of the PNA dehvery hterature. 

We have seen that many different factors can contribute to chemical hazard in the workplace. The degree of hazard, however, is fundamentally determined by two factors the basic toxicity of the agent concerned, that is, its intrinsic capacity to damage or affect biological tissue and the severity of the exposure, or what is sometimes called the dose-response relationship. The duration of the exposure, of course, must also be considered. 

Kaczur, V., Puskas, L. G., Takacs, M., et al. (2003) Evolution of the thyrotropin receptor a G protein coupled receptor with an intrinsic capacity to dimerize. Mol. Genet. Metab. 78, 275-290. 

Other important parameters for the correlation between GJJ and GJ include the ductility or the failure strain, particularly the non-linear strain (Jordan and Bradley, 1988 Jordan et al., 1989) of the matrix resin, the bond strength of the fiber-matrix interface (Jordan and Bradley, 1987 Bradley 1989a, b), and the fiber V and their distributions in the composites (Hunston et al., 1987). A high failure strain promotes the intrinsic capacity of the resin to permit shear deformation, and is shown to increase the G and G. values almost linearly, the rate of increase being steeper for G j than for Gf. ... 

When the pH of a suspension of microspheres of acidic proteinoid is raised by 1-2 units, diffusion of material from the interior to the exterior, fission into two particles, and the appearance of a double layer in the boundary are observed 2 Proteinoid microspheres shrink or swell on transfer to hypertonic or to hypotonic solutions respectively. Some experiments show that polysaccharides are retained under conditions in which monosaccharides diffuse out2. Some proteinoid microspheres possess the intrinsic capacity to grow by accretion, to proliferate through budding, and to form junctions 2). The morphology and other characteristics of proteinoid microspheres are altered by the inclusion of other materials such as polynucleotides, lipids or salts. 

Capsaicin causes transient bronchoconstriction and induces coughing, especially in individual with severe asthma, potentially triggering fatal crises [37]. These adverse respiratory effects are probably due to the limited capacity of respiratory tissues to metabolize capsaicin (see Section 4.3) [38], and are a major problem with the use of pepper sprays as antiriot agents [37]. Smokers are less sensitive to the respiratory effects of capsaicin, but asthmatic patients should avoid chilies and hot cuisine, as should people using drugs such as ACE-inhibitors, which have an intrinsic capacity to induce cough. 

Wentworth AD, Jones LH, Wentworth P Jr, Janda KD, Lemer RA. Antibodies have the intrinsic capacity to destroy antigens. Proc. Natl. Acad. Sci. U.S.A. 2000 97(20) 10930-10935. Wentworth P Jr, Jones LH, Wentworth AD, Zhu X, Larsen NA, Wilson lA, Xu X, Goddard WA III, Janda, KD, Eschenmoser, A, Lemer, RA. Antibody catalysis of the oxidation of water. Science 2001 293(5536) 1806-1811. 

Extraction Rates. The design of large-scale solvent extraction vessels must accommodate the rate at which equilibrium is attained between the free miscella flowing past the solid particles and the miscella absorbed within the solids. Attainment of equilibrium may be quite slow, particularly as the oil content of the solid material drops to low levels. Investigations show that the rate at which equilibrium is approached (in effect, the extraction rate) is influenced by many factors, including the intrinsic capacity for diffusion of solvent and oil, which is determined primarily by the viscosities of the two the size, the shape, and the internal structure of the solid particles and, at low oil levels in the solids, the rate at which the solvent dissolves nontriglyceride substances that are soluble but dissolve less readily than the triglycerides. 

The ability to bind actin is an intrinsic capacity of coronin proteins (reviewed in refs. 1, 2). In some family members, it is ofren hard to define the bona fide actin binding domain because most parts of the molecule possess actin binding properties. There is at least one family member, however, which until to date has not been shown to physically interact or colocalizc with actin. Although it is quite possible that future research will reveal specific conditions, processes or cell types where mammalian coronin 7 (CRN7 current official symbol C0R07) associates with actin cytoskeleton, the current data surest that this family member is unique in that its function is irrelevant to the regulation of the cytoskeleton. 

CSA have an intrinsic capacity to stimulate direct contraction of animal and human mesangial cells, smooth vascular cells and resistance vessels with obvious consequence for renal function and hemodynamics. These effects are associated to augmented intracellular influx of calcium, impaired relaxation response of vascular wall to vasodilatory stimuli and endothelin-1 [16, 20, 91, 223, 244-249]. CSA-induced cultured mesangial cell contraction was prevented by mycophenolic acid [250]. 

Studies have been made where the intrinsic capacity of A. annua to produce artemisinin under various environmental conditions was explored. Ram et al. [83] undertook a study in which A. annua was grown with varying plant densities during the winter-summer season of one year in a semiarid-subtropical climate with no interculture and no fertilization. At a population... 

Clinically overt nephrotoxicity is the result of the intrinsic capacity of a toxin to damage renal cells or tissue, the susceptibility of the patient, and changes in disposition of the toxin fhat result in increased delivery to the target organ or tissue. In this chapter we will examine the latter aspect of nephrotoxicity and will focus on (i) drug interactions that potentially lead to nephrotoxicity and (ii) changes in drug disposition induced by renal failure. 

In addition to allosteric regulation of PKC activity by membrane phospholipids, it has become apparent that phosphorylation of the kinase itself is an important regulatory mechanism. Using site-directed mutagenesis approaches, phosphorylation of PKCa on Thr 97 (Cazaubon etal., 1994) or PKC(3II on Thr (Orr and Newton, 1994) has been shown to be essential for catalytic activity. The catalytic subunit of protein phosphatase 1 specifically dephosphorylates this site, resulting in an inactive kinase that has no intrinsic capacity to rephosphorylate and activate when phosphatase is removed (Dutil et al., 1994). Based on this, and an analysis of the sequence around this site, it has been hypothesized that fransphosphorylation of Thr is catalyzed by an unidentified proline-directed protein... 

On the other hand, data so far indicate that the latter possess an intrinsic capacity to reduce local edema, attributable to their biological transformation by hydrolysis in the corresponding alcohols. This claim is sup-... 

This information affords a bird s eye view of the overall landscape. Once the intrinsic capacity to cause injury to a specific target organ or system has been characterized, some measure of the potency of the substance is essential, preferably in the form of dose-response data in appropriate test systems. Thus the potential for neurotoxicity, myelotoxicity, mutagenicity or carcinogenicity is spelled out in terms of a specific bracket within the range of 10 of possible potency. Naturally this definition applies only to a given set of experimental circumstances particular species, strain, sex and age of animals derived from a particular stock at a particular source, housed under particular defined conditions, and given a diet of specified composition. 

For a given protein the intrinsic capacity factor, k, is determined by the overall equilibrium constant, K, for its distribution between the stationary phase and the... 

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