Overt repeats

The repeat sequences in solenoid proteins are often so imperfect that it is difficult to identify them without knowledge of the 3D structure or other supplementary information. In highly regular /1-solenoids, such as antifreeze proteins (Leinala et al., 2002 Liou et al., 2000) or YadA adhesin (Nummelin et al., 2004), the repeats are of the same length and sequence similarity between the repeats is discernible (so-called overt repeats). Frequently, however, the repeats in a given /1-solenoid vary in length because additional residues may be inserted at turn sites without disrupting the pattern of /1-strands that stabilizes the structure (Steinbacher et al., 1994 Yoder et al., 1993). In these cases, the structural repeats are not apparent as sequence repeats (covert repeats). 

Reports in the literature of animal studies show that nerve agents can be administered repeatedly with minimal overt neurobehavioral effects if care is taken in choosing the dose and the time between doses (Sterri et al, 1980, 1981). The... 

More and more patients seek advice on complementary medicine via the Internet. It is therefore important to monitor the validity of such advice. In one survey, most of the 13 most popular websites on complementary medicine for cancer recommended cancer therapies for which there was no evidence of efficacy (30). Three of the sites overtly discouraged cancer patients from using conventional therapies. When the study was repeated, this time focussing on HIV instead of cancer, the results were virtually identical (31). These findings were similar to those of another study of 61 popular websites on herbal medicines for cancer (32). Most of these sites were commercial by nature and claimed cancer cures through herbal medicines, with little regard for current regulations. 

With repeated exposures, acetylcholinesterase inhibition can persist without indications of toxicity. In most cases, cholinesterase inhibition is without overt effects. Methyl parathion cannot cause delayed neurotoxicity. 

Because the Mad Hatter in Alice in Wonderland exhibited some of the symptoms of erethism, he is sometimes held to be a model for the afflictions suffered by workers in the hat industry whether Lewis Carrol intended such a parallel is still disputed, but the resemblances are uncanny. Even in the absence of identifiable symptoms, psychological testing has revealed what could be called nascent erethism in workers exposed to mercury vapor but showing no overt signs of toxicity. Tests of coordination and reaction time reveal differences between exposed and unexposed workers. Performance on elements of adult intelligence tests, such as the ability to repeat strings of digits, also shows differences. 

A subsequent short pharmacodynamic study showed that a very close analog of 54, the tolyl derivative 55, corrected the frataxin deficiency in a Friedreich s ataxia mouse model [201]. These mice carry a homozygous (GAA)23o expansion in the first intron of the mouse FXN gene (KI/KI mice). Biochemical analysis revealed that these mice carry the same heterochromatin marks, close to the GAA repeat as those detected in patient cell lines and have mildly but significantly reduced frataxin mRNA and protein levels. However, they show no overt phenotype. Once a day treatment with compound 55 at 150 mg/kg subcutaneously for 3 days increased global brain tissue histone acetylation as well as histone acetylation close to the GAA repeat and restored frataxin levels in the nervous system and heart (determined by qPCR and semiquantitative western blot analysis). Reversion of other differentially expressed genes toward wild-type levels was also observed. The compound showed no apparent toxicity. 

No overt toxicity in repeat Availability required As follow-up for... 

Negotiations with Japan appear to be terminated to all practical purposes with only the barest possibility that the Japanese Government might come back and offer to continue. Japanese future action unpredictable but hostile action possible at any moment. If hostilities cannot, repeat cannot be avoided the United States desires that Japan commit the first overt act... Measures should be carried out so as not, repeat not, to alarm civil population or disclose intent. 

While bacterial and fungal contaminations represent an added concern, in most instances they are overt and easily detected, and therefore have less serious consequences than the more insidious contaminations by mycoplasma. That the presence of these microorganisms in cultured cell lines often negates research findings entirely has been stated repeatedly over the years (Barile et al., 1973 Hay et al., 1989). However, the difficulties of detection and prevalence of contaminated cultures in the research community suggest that the problem cannot be overemphasized. These and related difficulties associated with use of cell lines obtained from different sources can be avoided if one acquires stocks from a centralized cell banking agency which applies appropriate quality control (Hay, 1992). 

In some cases, it is important to periodically repeat the chest x-ray. This is particularly the case with systems which do not have lead impedance telemetry measurements or there is another concern such as a fracture of the retention wire as in the Accufix J lead which will not have any overt electrical manifestations. 

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