Low expression, poor solubility, and polyspecificity are significant obstacles that have impeded the development of antibodies discovered from in vitro display libraries. Current biophysical characterization tools that identify these 'developability' problems are typically only applied after the discovery process, and thus limited to perhaps a few hundred candidates. We report a flow cytometric assay using a polyspecificity reagent (PSR) that allows for the identification and counter selection of polyspecific antibodies both during and after the selection process. The reported assay correlates well with cross-interaction chromatography, a surrogate for antibody solubility, as well as a baculovirus particle enzyme-linked immunosorbent assay, a surrogate for in vivo clearance. However, unlike these assays, PSR labeling is compatible both with screening of individual antibodies as well as selections of large antibody libraries. To this end, we demonstrate the ability to counter-select against polyspecificity while enriching for antigen affinity from a diverse antibody library, which enables simultaneous evolution of both antigen binding and superior non-target-related properties during the discovery process.
SUMMARY.
As susceptible varieties of potato are still widely cultivated and sporadic outbreaks of Wart Disease are a serious menace, it is imperative to find a method whereby the winter sporangia of Synchytrium endobioticum in contaminated soil may be killed. Previous studies and the unusual difficulties presented by the problem are discussed. Results of experiments extending over four years are recorded.
During 1920–2 pot experiments were carried out to test various chemicals alone and in conjunction with steam. Steaming the soil proved effective. but offered little hope of being economically possible as a field treatment. The amount of disease was reduced by sulphur. calcium and potassium polysulphides. formaldehyde, dichlorcrrsol. chlordinitro‐benzene and nitrobenzene. Satisfactory infection was not obtained in pot experiments; this method was therefore abandoned in favour of field experiments.
The incorporation of chemicals with the soil in the field was carried out with the Simar Rotary Tiller, great care being taken to ensure very thorough and even distribution. Results suggest that the efficiency of the treatment depends on this thoroughness of incorporation. During 1922 a selection of the chemicals tried in 1921 and others were tested. From these sulphur was selected in 1923 for more extensive study as being the most hopeful, because of its efficiency and cheapness.
In 1924, a year of very heavy disease, it was proved at Ormskirk that when the dose of ground sulphur was increased through 1, 2, 3, 4, 5, 10 cwts. per acre the degree of infection was reduced in direct ratio from 73 per cent., the value for untreated soil, to 8 per cent. for an application of 10 cwts. per acre. Doses greater than the latter did not completely eradicate the disease; but there are reasons for thinking that the small amount of disease in certain of the plots was due to recontamination of those plots later in the season. When the results are represented in graphical form the straight line of nearest fit to the experimental values cuts the horizontal axis at a point representing 11.2 cwts. per acre of sulphur; and, in the absence of recontamination, this quantity of sulphur should be slightly more than the minimum necessary to free the Ormskirli soil of disease.
On the heavy clay soil at Hatfield it was found necessary to use much heavier applications of sulphur (about 40 cwts. per acre) to ensure absolutely clean plots.
Gasworks spent oxides, tried as an alternative source of sulphur, proved rather less effective than ground sulphur when equal quantities of sulphur were applied in each case. The result was probably due to the unsatisfactory state of division of our sample of spent oxides.
Sulphur inoculated with Thiobacillus thiooxydans showed no increased efficiency over uninoculated sulphur on Ormskirk soils and appeared less effective than the latter on the Hatfield clay.
The elimination of Wart Disease in the field by sulphur and sulphur compounds is not a simple function of the final soil reaction and it would appear that so...
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