Is meaning fraught with ought?

According to Normativism, what an expression means has immediate implications for how a subject should or may (not) employ that expression. Many view this thesis as imposing substantive constraints upon theories of linguistic meaning. In this paper, I shall not consider that view; instead, I shall address the prior issue of whether or not one should accept Normativism. Against certain recent prominent lines of attack common to a number of different anti-Normativist discussions, I shall defend both the Normativist thesis and an attempt to appeal to a certain platitude in its support

The Hypothesis of Locality and its Limitations

The hypothesis of locality, its origin and consequences are discussed. This supposition is necessary for establishing the local spacetime frame of accelerated observers; in this connection, the measurement of length in a rotating system is considered in detail. Various limitations of the hypothesis of locality are examined.Comment: LaTeX file, no figures, 14 pages, to appear in: "Relativity in Rotating Frames", edited by G. Rizzi and M.L. Ruggiero (Kluwer Academic Publishers, Dordrecht, 2003

Large-scale motif discovery using DNA Gray code and equiprobable oligomers

Motivation: How to find motifs from genome-scale functional sequences, such as all the promoters in a genome, is a challenging problem. Word-based methods count the occurrences of oligomers to detect excessively represented ones. This approach is known to be fast and accurate compared with other methods. However, two problems have hampered the application of such methods to large-scale data. One is the computational cost necessary for clustering similar oligomers, and the other is the bias in the frequency of fixed-length oligomers, which complicates the detection of significant words

The Caenorhabditis chemoreceptor gene families

Background: Chemoreceptor proteins mediate the first step in the transduction of environmental chemical stimuli, defining the breadth of detection and conferring stimulus specificity. Animal genomes contain families of genes encoding chemoreceptors that mediate taste, olfaction, and pheromone responses. The size and diversity of these families reflect the biology of chemoperception in specific species. Results: Based on manual curation and sequence comparisons among putative G-protein-coupled chemoreceptor genes in the nematode Caenorhabditis elegans, we identified approximately 1300 genes and 400 pseudogenes in the 19 largest gene families, most of which fall into larger superfamilies. In the related species C. briggsae and C. remanei, we identified most or all genes in each of the 19 families. For most families, C. elegans has the largest number of genes and C. briggsae the smallest number, suggesting changes in the importance of chemoperception among the species. Protein trees reveal family-specific and species-specific patterns of gene duplication and gene loss. The frequency of strict orthologs varies among the families, from just over 50% in two families to less than 5% in three families. Several families include large species-specific expansions, mostly in C. elegans and C. remanei. Conclusion: Chemoreceptor gene families in Caenorhabditis species are large and evolutionarily dynamic as a result of gene duplication and gene loss. These dynamics shape the chemoreceptor gene complements in Caenorhabditis species and define the receptor space available for chemosensory responses. To explain these patterns, we propose the gray pawn hypothesis: individual genes are of little significance, but the aggregate of a large number of diverse genes is required to cover a large phenotype space.JHT was supported by NIH grant RO1GM48700 and HMR by R01AI56081

The climate sensitivity of Norway spruce [Picea abies (L.) Karst.] in the southeastern European Alps

Tree ring chronologies were developed from trees growing at two sites in Slovenia which differed in their ecological and climatological characteristics. Ring width, maximum latewood density, annual height increment and latewood cellulose carbon isotope composition were developed at both sites and time-series verified against instrumental climate data over the period (AD 1960–AD 2002). Ring width sensitivity to summer temperature is site-dependent, with contrasting responses at alpine and lowland sites. Maximum density responds to September temperatures, suggesting lignification after cell division has ended for the season. Stable carbon isotopes have great potential, responding to summer temperature at oth alpine and lowland stands. Height increment appears relatively insensitive to climate, and is likely to be dominated by local stand dynamics

α-Synuclein Aggregation Inhibitory Prunolides and a Dibrominated β-Carboline Sulfamate from the Ascidian Synoicum prunum

Seven new polyaromatic bis-spiroketal-containing butenolides, the prunolides D–I (4–9) and cis-prunolide C (10), a new dibrominated β-carboline sulfamate named pityriacitrin C (11), alongside the known prunolides A–C (1–3) were isolated from the Australian colonial ascidian Synoicum prunum. The prunolides D–G (4–7) represent the first asymmetrically brominated prunolides, while cis-prunolide C (10) is the first reported with a cis-configuration about the prunolide’s bis-spiroketal core. The prunolides displayed binding activities with the Parkinson’s disease-implicated amyloid protein α-synuclein in a mass spectrometry binding assay, while the prunolides (1–5 and 10) were found to significantly inhibit the aggregation (>89.0%) of α-synuclein in a ThT amyloid dye assay. The prunolides A–C (1–3) were also tested for inhibition of pSyn aggregate formation in a primary embryonic mouse midbrain dopamine neuron model with prunolide B (2) displaying statistically significant inhibitory activity at 0.5 μM. The antiplasmodial and antibacterial activities of the isolates were also examined with prunolide C (3) displaying only weak activity against the 3D7 parasite strain of Plasmodium falciparum. Our findings reported herein suggest that the prunolides could provide a novel scaffold for the exploration of future therapeutics aimed at inhibiting amyloid protein aggregation and the treatment of numerous neurodegenerative diseases.Peer reviewe

Measuring the effect of enhanced cleaning in a UK hospital : a prospective cross-over study

Increasing hospital-acquired infections have generated much attention over the last decade. There is evidence that hygienic cleaning has a role in the control of hospital-acquired infections. This study aimed to evaluate the potential impact of one additional cleaner by using microbiological standards based on aerobic colony counts and the presence of Staphylococcus aureus including meticillin-resistant S. aureus. We introduced an additional cleaner into two matched wards from Monday to Friday, with each ward receiving enhanced cleaning for six months in a cross-over design. Ten hand-touch sites on both wards were screened weekly using standardised methods and patients were monitored for meticillin-resistant S. aureus infection throughout the year-long study. Patient and environmental meticillin-resistant S. aureus isolates were characterised using molecular methods in order to investigate temporal and clonal relationships. Enhanced cleaning was associated with a 32.5% reduction in levels of microbial contamination at handtouch sites when wards received enhanced cleaning (P < 0.0001: 95% CI 20.2%, 42.9%). Near-patient sites (lockers, overbed tables and beds) were more frequently contaminated with meticillin-resistant S. aureus/S. aureus than sites further from the patient (P = 0.065). Genotyping identified indistinguishable strains from both handtouch sites and patients. There was a 26.6% reduction in new meticillin-resistant S. aureus infections on the wards receiving extra cleaning, despite higher meticillin-resistant S. aureus patient-days and bed occupancy rates during enhanced cleaning periods (P = 0.032: 95% CI 7.7%, 92.3%). Adjusting for meticillin-resistant S. aureus patient-days and based upon nine new meticillin-resistant S. aureus infections seen during routine cleaning, we expected 13 new infections during enhanced cleaning periods rather than the four that actually occurred. Clusters of new meticillin-resistant S. aureus infections were identified 2 to 4 weeks after the cleaner left both wards. Enhanced cleaning saved the hospital £30,000 to £70,000.Introducing one extra cleaner produced a measurable effect on the clinical environment, with apparent benefit to patients regarding meticillin-resistant S. aureus infection. Molecular epidemiological methods supported the possibility that patients acquired meticillin-resistant S. aureus from environmental sources. These findings suggest that additional research is warranted to further clarify the environmental, clinical and economic impact of enhanced hygienic cleaning as a component in the control of hospital-acquired infection

Policy windows for the environment: Tips for improving the uptake of scientific knowledge

© 2017 The Authors. Scientific knowledge is considered to be an important factor (alongside others) in environmental policy-making. However, the opportunity for environmentalists to influence policy can often occur within short, discrete time windows. Therefore, a piece of research may have a negligible or transformative policy influence depending on when it is presented. These ‘policy windows’ are sometimes predictable, such as those dealing with conventions or legislation with a defined renewal period, but are often hard to anticipate. We describe four ways that environmentalists can respond to policy windows and increase the likelihood of knowledge uptake: 1) foresee (and create) emergent windows, 2) respond quickly to opening windows, 3) frame research in line with appropriate windows, and 4) persevere in closed windows. These categories are closely linked; efforts to enhance the incorporation of scientific knowledge into policy need to harness mechanisms within each. We illustrate the main points with reference to nature conservation, but the principles apply widely.European Union Seventh Framework Programme EU Biodiversity Observation Network (No. 308454); Fondation Wiener Anspach, Belgium; Scriven fellowship; Natural Environment Research Council Cambridge Earth System Science NERC DTP [NE/L002507/1]; Natural Environment Research Council Industrial CASE studentship [NE/M010287/1]; Austrian Science Fund (FWF); Arcadia

Policy windows for the environment: Tips for improving the uptake of scientific knowledge

Scientific knowledge is considered to be an important factor (alongside others) in environmental policy-making. However, the opportunity for environmentalists to influence policy can often occur within short, discrete time windows. Therefore, a piece of research may have a negligible or transformative policy influence depending on when it is presented. These ‘policy windows’ are sometimes predictable, such as those dealing with conventions or legislation with a defined renewal period, but are often hard to anticipate. We describe four ways that environmentalists can respond to policy windows and increase the likelihood of knowledge uptake: 1) foresee (and create) emergent windows, 2) respond quickly to opening windows, 3) frame research in line with appropriate windows, and 4) persevere in closed windows. These categories are closely linked; efforts to enhance the incorporation of scientific knowledge into policy need to harness mechanisms within each. We illustrate the main points with reference to nature conservation, but the principles apply widely.(1) EU’s Seventh Framework Programme within the EU Biodiversity Observation Network (No. 308454) (2) Post-doctoral fellowship from Fondation Wiener Anspach, Belgium and the Scriven fellowship, (3) Cambridge Earth System Science NERC DTP [NE/L002507/1], (4) Austrian Science Fund (FWF), (5) Arcadia