On value-laden science

Philosophical work on values in science is held back by widespread ambiguity about how values bear on scientific choices. Here, I disambiguate several ways in which a choice can be value-laden and show that this disambiguation has the potential to solve and dissolve philosophical problems about values in science. First, I characterize four ways in which values relate to choices: values can motivate, justify, cause, or be impacted by the choices we make. Next, I put my proposed taxonomy to work, using it to clarify one version of the argument from inductive risk. The claim that non-epistemic values must play a role in scientific choices that run inductive risk makes most sense as a claim about values being needed to justify such choices. The argument from inductive risk is not unique: many philosophical arguments about values in science can be more clearly understood and assessed by paying close attention to how values and choices are related.     

Effects of artificial shading on distribution and abundance of juvenile chinook salmon ( Oncorhynchus tshawytscha )

The influence of artificial shade on the distribution and abundance of juvenile chinook salmon was studied in a side channel of the South Fork Salmon River, Idaho. Fish biomass and abundance were greater in shaded than in unshaded areas when compared to both cumulative incident light reaching the study sections during the 72-hour test runs and instantaneous incident light conditions at the end of the 72-hour test runs. Because conditions may be atypical at the time of instantaneous light measurement, we prefer cumulative incident light for relating light and shade conditions to daytime distribution (abundance and biomass) of juvenile chinook salmon.     

Spatial pattern and interference in pi?on-juniper woodlands of northwest Colorado

The local spatial arrangement of the coniferous trees Pinus edulis and Juniperus osteosperma was mapped in two woodland stands and measured in two shrub-dominated stands in the semiarid Piceance Basin of northwest Colorado. In the woodlands, small trees were often clumped, while medium and large trees were either randomly or uniformly dispersed. Significant regressions were obtained between a tree?s basal area or canopy area and the area of its Dirichlet domain (the region closer to it than to any other tree). Both findings from the woodland stands accord with results obtained by other workers in other vegetation. Like earlier workers, we interpret these patterns to indicate density-dependent mortality and density-dependent depression of growth rates among the trees in the woodlands. In contrast, the trees in the shrub-dominated stands are located at random with respect to each other. However, they are strongly associated with shrub cover. Apparently tree seeds arrive in these stands primarily by long-distance dispersal, and the establishment of seedlings is more likely in the shade of shrubs.     

Evaluation of wildlife response to a retained mine highwall in south central Wyoming

From 1984 through 1985 a study was made of the influence of a retained mine highwall on a wildlife community in south central Wyoming. Vegetation species richness and diversity were greater near the highwall compared with two adjacent sites 150 m in front of and behind the highwall. However, vegetation abundance (cover) was greater on the two adjacent sites. Small mammal abundance, richness, and diversity were greater on the highwall than on the two adjacent sites. Male bird abundance, richness, and diversity were greatest in front of the highwall (+ 50 m to + 350 m) compared with the highwall and the area behind the highwall.     

IDH mutation impairs histone demethylation and results in a block to cell differentiation

Recurrent mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 have been identified in gliomas, acute myeloid leukaemias (AML) and chondrosarcomas, and share a novel enzymatic property of producing 2-hydroxyglutarate (2HG) from α-ketoglutarate. Here we report that 2HG-producing IDH mutants can prevent the histone demethylation that is required for lineage-specific progenitor cells to differentiate into terminally differentiated cells. In tumour samples from glioma patients, IDH mutations were associated with a distinct gene expression profile enriched for genes expressed in neural progenitor cells, and this was associated with increased histone methylation. To test whether the ability of IDH mutants to promote histone methylation contributes to a block in cell differentiation in non-transformed cells, we tested the effect of neomorphic IDH mutants on adipocyte differentiation in vitro. Introduction of either mutant IDH or cell-permeable 2HG was associated with repression of the inducible expression of lineage-specific differentiation genes and a block to differentiation. This correlated with a significant increase in repressive histone methylation marks without observable changes in promoter DNA methylation. Gliomas were found to have elevated levels of similar histone repressive marks. Stable transfection of a 2HG-producing mutant IDH into immortalized astrocytes resulted in progressive accumulation of histone methylation. Of the marks examined, increased H3K9 methylation reproducibly preceded a rise in DNA methylation as cells were passaged in culture. Furthermore, we found that the 2HG-inhibitable H3K9 demethylase KDM4C was induced during adipocyte differentiation, and that RNA-interference suppression of KDM4C was sufficient to block differentiation. Together these data demonstrate that 2HG can inhibit histone demethylation and that inhibition of histone demethylation can be sufficient to block the differentiation of non-transformed cells.     

Binding activities of a repertoire of single immunoglobulin variable domains secreted from Escherichia coli

In antibodies, a heavy and a light chain variable domain, VH and VL, respectively, pack together and the hypervariable loops on each domain contribute to binding antigen. We find, however, that isolated VH domains with good antigen-binding affinities can also be prepared. Using the polymerase chain reaction, diverse libraries of VH genes were cloned from the spleen genomic DNA of mice immunized with either lysozyme or keyhole-limpet haemocyanin. From these libraries, VH domains were expressed and secreted from Escherichia coli. Binding activities were detected against both antigens, and two VH domains were characterized with affinities for lysozyme in the 20 nM range. Isolated variable domains may offer an alternative to monoclonal antibodies and serve as the key to building high-affinity human antibodies. We suggest the name 'single domain antibodies (dAbs)' for these antigen binding demands.