Multi-output regression with structurally incomplete target labels: A case study of modelling global vegetation cover

Weakly-supervised learning has recently emerged in the classification context where true labels are often scarce or unreliable. However, this learning setting has not yet been extensively analyzed for regression problems, which are typical in macroecology. We further define a novel computational setting of structurally noisy and incomplete target labels, which arises, for example, when the multi-output regression task defines a distribution such that outputs must sum up to unity. We propose an algorithmic approach to reduce noise in the target labels and improve predictions. We evaluate this setting with a case study in global vegetation modelling, which involves building a model to predict the distribution of vegetation cover from climatic conditions based on global remote sensing data. We compare the performance of the proposed approach to several incomplete target baselines. The results indicate that the error in the targets can be reduced by our proposed partial-imputation algorithm. We conclude that handling structural incompleteness in the target labels instead of using only complete observations for training helps to better capture global associations between vegetation and climate.     

Biotin reagents for antibody pretargeting. 7. Investigation of chemically inert biotinidase blocking functionalities for synthetic utility

An investigation was conducted to evaluate three biotin derivatives designed to block biotinidase cleavage of the biotinamide bond. Difficulties in multistep syntheses of molecules containing tert-butyl protected hydroxymethyl and carboxylate groups positioned alpha to a biotinamide bond led to the investigation of alternative biotinidase-blocking moieties that do not require protection and deprotection. The targeted biotin derivatives contained serine-O-methyl ether, 2-aminobutyric acid, and valine moieties conjugated to the biotin carboxylate functionality. Those derivatives were further modified with a radioiodinated aryl ring to study their biotinidase stability. As a comparison to previously studied biotin derivatives, radioiodinated versions of biotin conjugates that contained (a) no biotinidase stabilizing group, (b) an N-methyl (sarcosine) stabilizing group, (c) an alpha-carboxylate (aspartate) stabilizing group and hydroxymethyl (serine) stabilizing group were also prepared and tested. When tested in human serum, all of the radioiodinated biotinidase-stabilized biotin derivatives had <1% biotinamide cleavage. Thus, under the conditions studied, all of the tested biotinidase blocking moieties appeared to be equal with regards to protection from biotinidase cleavage. Further testing of the biotin derivatives included a HPLC assay to determine their relative dissociation from recombinant streptavidin (rSAv). The dissociation of cyanocobalamin (CN-Cbl) adducts of biotin-serine-O-methyl ether, biotin-aminobutyric acid, and biotin-valine were compared with the CN-Cbl adduct of biotin-sarcosine. The relative rates of dissociation found were biotin-sarcosine-CN-Cbl > biotin-valine-CN-Cbl > biotin-serine-O-methyl ether-CN-Cbl > biotin-aminobutyric acid-CN-Cbl. Due to the high cost of serine-O-ethyl ether (and its N-Boc derivative) and difficulty in syntheses of its biotin derivatives, that adduct is not an attractive candidate for application to compounds used in vivo. The higher lipophilicity and diminished binding of the biotin-valine adduct also makes its use in vivo less attractive. Thus, the biotin-aminobutyric acid adduct appears to be the best candidate for incorporation into biotin derivatives used in vivo, as it simplifies the synthetic procedures, has low cost, and provides effective blocking of biotinidase while retaining high binding affinity.     

Production and characterization of an iminoimidazolidine specific monoclonal antibody using para-aminoclonidine as antigen.

Para-aminoclonidine coupled to hemocyanin was used to produce mouse monoclonal antibodies directed against clonidine. The properties of one of these, called mFE7, secreted by a clone of hybrid myeloma, are described. This antibody displayed total crossreactivity with imidazolidines and no crossreactivity at all with catecholamines or other known naturally occurring substances tested. A liquid phase radioimmunoassay permitted the detection of immunoreactivity in human brain extracts. The mFE7 antibody could be useful for immunopurifying the endogenous ligand of Imidazolines Preferring Receptors (IPR) which are catecholamines insensitive.     

The utility of repeated presence data as a surrogate for counts: a case study using butterflies

Abundance data are widely used to monitor long-term population trends for management and conservation of species of interest. Programs that collect count data are often prohibitively expensive and time intensive, limiting the number of species that can be simultaneously monitored. Presence data, on the other hand, can often be collected in less time and for multiple species simultaneously. We investigate the relationship of counts to presence using 49 butterfly species across 4 sites over 9 years, and then compare trends produced from each index. We also employed simulated datasets to test the effect of reduced sampling on the relationship of counts to presence data and to investigate changes in each index’s power to reveal population trends. Presence and counts were highly correlated for most species tested, and population trends based on each index were concordant for most species. The effect of reduced sampling was species-specific, but on a whole, sensitivity of both indices to detect population trends was reduced. Common and rare species, as well as those with a range of life-history and behavioral traits performed equally well. The relationship between presence and count data may break down in cases of very abundant and widespread species with extended flight seasons. Our results suggest that when used cautiously, presence data has the potential to be used as a surrogate for counts. Collection of presence data may be useful for multi-species monitoring or to reduce the duration of monitoring visits without fully sacrificing the ability to infer population trends.     

Identification of Bacteroides fragilis by co-agglutination, using a specific monoclonal antibody

A monoclonal antibody, mAbC3 (IgG(2b)), specific for the Bacteroides fragilis lipopolysaccharide (LPS) was produced and found to react with a common epitope in most strains within the species. mAbC3 was adsorbed to Staphylococcus aureus Cowan I strain and used in a co-agglutination assay for identification of B. fragilis. Almost 98% of the B. fragilis strains were positive in co-agglutination. Among the 283 non-B. fragilis only two strains showed false positive reaction. These results show that the mAbC3 has a high specificity and can be used for the rapid identification of the B. fragilis species.     

The use of base pair specific DNA binding agents as affinity labels for the study of mammalian chromosomes

The fluorochromes Hoechst 33258 and olivomycin are base pair specific DNA binding agents. The fluorescence enhancement of Hoechst 33258 and olivomycin in the presence of DNA can be directly related to the A-T and G-C content of the interacting DNA respectively. Cytological observations of metaphase chromosomes treated with these two compounds suggest that the fluorescent banding patterns produced are the reverse of one another. —Non-fluorescent base pair specific DNA binding agents have been used as counterstains in chromosome preparations to enhance the contrast of the banding patterns produced by the base specific fluorochromes. The non-fluorescent G-C specific antibiotic actinomycin-D enhanced the resolution of fluorescent bands produced by the A-T specific fluorochrome Hoechst 33258. Similarly the non-fluorescent A-T specific antibiotic netropsin was found to enhance resolution of the bands produced by the G-C specific fluorochrome olivomycin. Netropsin was also found to increase the differential fluorescent enhancement of complexes of olivomycin with DNAs of various base composition in solution. These findings suggest that counterstaining agents act through a base sequence dependent inhibition of subsequent binding by base pair specific fluorochromes.—The base specific DNA binding agents have been used to differentiate different types of constitutive heterochromatin in mammalian species, and to facilitate chromosome identification in somatic cell hybrids.     

Human protease nexin-I. Further characterization using a highly specific polyclonal antibody

We have used purified protease nexin-I (PN-I) from human fibroblasts to develop a polyclonal antibody that specifically blocks the PN-I-mediated cellular binding of thrombin and urokinase. Anti-PN-I IgG did not inhibit the binding of 125I-epidermal growth factor-binding protein to fibroblasts, which is mediated by protease nexin-II, another cell-secreted, serine protease inhibitor that is distinct from PN-I. This furthers the belief that the protease nexins are distinct from one another. In addition, while anti-PN-I IgG immunoprecipitated PN-I X thrombin complexes, it did not do so with antithrombin-III X thrombin. Metabolically labeled PN-I was also immunoprecipitated by IgG, indicating that the protein can be labeled in vivo. The antibody also recognized primarily one band on Western transfers of conditioned medium from fibroblast cultures. These results suggest that anti-PN-I will be useful in probing the physiological role of PN-I as well as its biosynthesis.     

Inhibition of malate dehydrogenase by thyroxine and structurally related compounds.

The inhibition of pig heart mitochondrial malate dehydrogenase (L-malate: NAD+ oxidoreductase, EC 1.1.1.37) by the thyroxine and structurally related compounds was studied to resolve a longstanding question about the exact nature of the inhibition. Thyroxine, in freshly prepared solution, was found to be a "pure" competitive inhibitor relative to the nucleotide cofactor. Upon standing in diffuse daylight, solutions of thyroxine showed increased ability to inhibit the enzyme, presumably as a result of oxidation of enzyme sulfhydryl groups by free iodine that is released photochemically. This behavior probably accounts for earlier reports of irreversible inactivation by thyroxine. Comment is made on the implications of these findings to the mechanism of thyroid hormmone action.     

Detection of Ki-ras proto-oncogene protein by a specific monoclonal antibody.

We have used a commercially available mouse monoclonal antibody and shown it to bind specifically to cellular Ki-ras p21 proteins and not to cellular N- and Ha-ras p21 proteins. In conjunction with electrophoresis and Western blotting, this antibody can be used, with further detailing, to assess levels of the cellular Ki-ras p21 against a background of total p21s.     

Conformational analysis of thioredoxin using organoarsenical reagents as probes. A time-resolved fluorescence anisotropy and size exclusion chromatography study

Reduced thioredoxin was subjected to chemical modification studies employing organoarsenical reagents specific for "spatially close" thiols. Modification was monitored by the loss in the free thiol content, by the percent incorporation of radiolabelled organoarsenical reagents, and by observing the changes in the amounts of the various thioredoxins by size exclusion chromatography. The rate of modification depends upon the polarity, rigidity, and size of the reagents. Small nonpolar organoarsenical reagents readily modified reduced thioredoxin, whereas polar and large reagents do not. Modifications resulted in the formation of stable 15-membered cyclodithioarsenite ring structures with no apparent changes in the secondary structure of the protein. Modification was reversed by the extrusion of the arsenical moiety by addition of 2,3-dimercaptopropanol. We have further characterized the oxidized, reduced, and modified thioredoxins by size exclusion chromatography and fluorescence anisotropy decay measurements. Both techniques show an increase in the hydrated volume of the protein upon reduction. Upon modification, the hydrodynamic volume of the protein further swells. Fluorescence anisotropy decay reveals that with modification there is loosening of the protein so that a "domain" containing the fluorophores can relax independently of the whole protein structure.