Enrichment of pathogenic alleles in the brittle cornea gene, ZNF469, in keratoconus

Keratoconus, a common inherited ocular disorder resulting in progressive corneal thinning, is the leading indication for corneal transplantation in the developed world. Genome-wide association studies have identified common SNPs 100 kb upstream of ZNF469 strongly associated with corneal thickness. Homozygous mutations in ZNF469 and PR domain-containing protein 5 (PRDM5) genes result in brittle cornea syndrome (BCS) Types 1 and 2, respectively. BCS is an autosomal recessive generalized connective tissue disorder associated with extreme corneal thinning and a high risk of corneal rupture. Some individuals with heterozygous PRDM5 mutations demonstrate a carrier ocular phenotype, which includes a mildly reduced corneal thickness, keratoconus and blue sclera. We hypothesized that heterozygous variants in PRDM5 and ZNF469 predispose to the development of isolated keratoconus. We found a significant enrichment of potentially pathologic heterozygous alleles in ZNF469 associated with the development of keratoconus (P = 0.00102) resulting in a relative risk of 12.0. This enrichment of rare potentially pathogenic alleles in ZNF469 in 12.5% of keratoconus patients represents a significant mutational load and highlights ZNF469 as the most significant genetic factor responsible for keratoconus identified to date.

Enrichment of low-abundance proteins from bovine and porcine serum samples for proteomic studies

One of the main applications of serum proteomics is the identification of new biomarkers for animal disease or animal production. However, potential obstacles to these studies are the poor performance of affinity serum depletion methods based on human antigens when using animal samples, and loss of minor serum components bound to albumin and other proteins. In the present study, we have analyzed the efficiency and reproducibility of the ProteoMiner® beads with bovine and porcine serum samples, and compared to a traditional immunoaffinity-based albumin and IgG depletion system specific for human samples. The ProteoMiner kit is based on the use of a combinatorial peptide binding library and intends to enrich low-abundance proteins.

Analogies to semantic and syntactic mental labour in the Feist decision

The Supreme Court of the United States in Feist v. Rural (Feist, 1991) specified that compilations or databases, and other works, must have a minimal degree of creativity to be copyrightable. The significance and global diffusion of the decision is only matched by the difficulties it has posed for interpretation. The judgment does not specify what is to be understood by creativity, although it does give a full account of the negative of creativity, as ‘so mechanical or routine as to require no creativity whatsoever’ (Feist, 1991, p.362). The negative of creativity as highly mechanical has particularly diffused globally.

A recent interpretation has correlated ‘so mechanical’ (Feist, 1991) with an automatic mechanical procedure or computational process, using a rigorous exegesis fully to correlate the two uses of mechanical. The negative of creativity is then understood as an automatic computation and as a highly routine process. Creativity is itself is conversely understood as non-computational activity, above a certain level of routinicity (Warner, 2013).

The distinction between the negative of creativity and creativity is strongly analogous to an independently developed distinction between forms of mental labour, between semantic and syntactic labour. Semantic labour is understood as human labour motivated by considerations of meaning and syntactic labour as concerned solely with patterns. Semantic labour is distinctively human while syntactic labour can be directly humanly conducted or delegated to machine, as an automatic computational process (Warner, 2005; 2010, pp.33-41).

The value of the analogy is to greatly increase the intersubjective scope of the distinction between semantic and syntactic mental labour. The global diffusion of the standard for extreme absence of copyrightability embodied in the judgment also indicates the possibility that the distinction fully captures the current transformation in the distribution of mental labour, where syntactic tasks which were previously humanly performed are now increasingly conducted by machine.

The paper has substantive and methodological relevance to the conference themes. Substantively, it is concerned with human creativity, with rationality as not reducible to computation, and has relevance to the language myth, through its indirect endorsement of a non-computable or not mechanical semantics. These themes are supported by the underlying idea of technology as a human construction. Methodologically, it is rooted in the humanities and conducts critical thinking through exegesis and empirically tested theoretical development

References

Feist. (1991). Feist Publications, Inc. v. Rural Tel. Service Co., Inc. 499 U.S. 340.

Warner, J. (2005). Labor in information systems. Annual Review of Information Science and Technology. 39, 2005, pp.551-573.

Warner, J. (2010). Human Information Retrieval (History and Foundations of Information Science Series). Cambridge, MA: MIT Press.

Warner, J. (2013). Creativity for Feist. Journal of the American Society for Information Science and Technology. 64, 6, 2013, pp.1173-1192.

“Signal, image and video processing” special issue: Semantic representations for social behavior analysis in video surveillance systems

No abstract available

Interpretable semantic vectors from a joint model of brain-and text-based meaning

Vector space models (VSMs) represent word meanings as points in a high dimensional space. VSMs are typically created using a large text corpora, and so represent word semantics as observed in text. We present a new algorithm (JNNSE) that can incorporate a measure of semantics not previously used to create VSMs: brain activation data recorded while people read words. The resulting model takes advantage of the complementary strengths and weaknesses of corpus and brain activation data to give a more complete representation of semantics. Evaluations show that the model 1) matches a behavioral measure of semantics more closely, 2) can be used to predict corpus data for unseen words and 3) has predictive power that generalizes across brain imaging technologies and across subjects. We believe that the model is thus a more faithful representation of mental vocabularies.

Evaluating environmental enrichment options for commercial broiler chickens

Implications Provision of environmental enrichment in line with that required by welfare-based quality assurance schemesdoes not always appear to lead to clear improvements in broiler chicken welfare. This research perhaps serves to highlightthe deficit in information regarding the ‘real world’ implications of enrichment with perches, string and straw bales.

Introduction Earlier work showed that provision of natural light and straw bales improved leg health in commercial broilerchickens (Bailie et al., 2013). This research aimed to determine if additional welfare benefits were shown in windowedhouses by increasing straw bale provision (Study 1), or by providing perches and string in addition to straw bales (Study 2).

Material and methods Commercial windowed houses in Northern Ireland containing ~23,000 broiler chickens (placed inhouses as hatched) were used in this research which took place in 2011. In Study 1 two houses on a single farm wereassigned to one of two treatments: (1) 30 straw bales per house (1 bale/44m2), or (2) 45 straw bales per house (1bale/29m2). Bales of wheat straw, each measuring 80cm x 40cm x 40cm were provided from day 10 of the rearing cycle,as in Bailie et al. (2013). Treatments were replicated over 6 production cycles (using 276,000 Ross 308 and Cobb birds),and were swapped between houses in each replicate. In Study 2, four houses on a single farm were assigned to 1 of 4treatments in a 2 x 2 factorial design. Treatments involved 2 levels of access to perches (present (24/house), or absent), and2 levels of access to string (present (24/house), or absent), and both types of enrichment were provided from the start of thecycle. Each perch consisted of a horizontal, wooden beam (300 cm x 5 cm x 5cm) with a rounded upper edge resting on 2supports (15 cm high). In the string treatment, 6 pieces of white nylon string (60 cm x 10 mm) were tied at their mid-pointto the wire above each of 4 feeder lines. Thirty straw bales were also provided per house from day 10. This study wasreplicated over 4 production cycles using 368,000 Ross 308 birds. In both studies behaviour was observed between 0900and 1800 hours in weeks 3-5 of the cycle. In Study 1, 8 focal birds were selected in each house each week, and generalactivity, exploratory and social behaviours recorded directly for 10 minutes. In Study 2, 10 minute video recordings weremade of 6 different areas (that did not contain enrichment) of each house each week. The percentage of birds engaged inlocomotion or standing was determined through scan sampling these recordings at 120 second intervals. Four perches andfour pieces of string were filmed for 25 mins in each house that contained these enrichments on one day per week. The totalnumber of times the perch or string was used was recorded, along with the duration of each bout. In both studies, gaitscores (0 (perfect) to 5 (unable to walk)) and latency to lie (measured in seconds from when a bird had been encouraged tostand) were recorded in 25 birds in each house each week. Farm and abattoir records were also used in both studies todetermine the number of birds culled for leg and other problems, mortality levels, slaughter weights, and levels of pododermatitis and hock burn. Data were analysed using SPSS (version 20.0) and treatment and age effects on behaviouralparameters were determined in normally distributed data using ANOVA (‘Straw bale density*week’, or‘string*perches*week’ as appropriate), and in non-normally distributed data using Kuskall-Wallace tests (P<0.05 forsignificance) . Treatment (but not age) effects on performance and health data were determined using the same testsdepending on normality of data.

Results Average slaughter weight, and levels of mortality, culling, hock burn and pododermatitis were not affected bytreatment in either study (P<0.05). In Study 1 straw bale (SB) density had no significant effect on the frequency orduration of behaviours including standing, walking, ground pecking, dust bathing, pecking at bales or aggression, or onaverage gait score (P>0.05). However, the average latency to lie was greater when fewer SB were provided (30SB 23.38s,45SB 18.62s, P<0.01). In Study 2 there was an interaction between perches (Pe) and age in lying behaviour, with higherpercentages of birds observed lying in the Pe treatment during weeks 4 and 5 (week 3 +Pe 77.0 -Pe 80.9, week 4 +Pe 79.5 -Pe 75.2, week 5 +Pe 78.4 -Pe 76.2, P<0.02). There was also a significant interaction between string (S) and age inlocomotory behaviour, with higher percentages of birds observed in locomotion in the string treatment during week 3 butnot weeks 4 and 5 (week 3 +S 4.9 -S 3.9, week 4 +S 3.3 -S 3.7, week 5 +S 2.6 -S 2.8, P<0.04). There was also aninteraction between S and age in average gait scores, with lower gait scores in the string treatment in weeks 3 and 5 (week3: +S 0.7, -S 0.9, week 4: +S 1.5, -S 1.4, week 5: +S 1.9, -S 2.0, P<0.05). On average per 25 min observation there were15.1 (±13.6) bouts of perching and 19.2 (±14.08) bouts of string pecking, lasting 117.4 (±92.7) and 4.2 (±2.0) s for perchesand string, respectively.

Conclusion Increasing straw bale levels from 1 bale/44m2 to 1 bale/29m2 floor space does not appear to lead to significantimprovements in the welfare of broilers in windowed houses. The frequent use of perches and string suggests that thesestimuli have the potential to improve welfare. Provision of string also appeared to positively influence walking ability.However, this effect was numerically small, was only shown in certain weeks and was not reflected in the latency to lie.Further research on optimum design and level of provision of enrichment items for broiler chickens is warranted. Thisshould include measures of overall levels of activity (both in the vicinity of, and away from, enrichment items).

A Compositional and Interpretable Semantic Space

Vector Space Models (VSMs) of Semantics are useful tools for exploring the semantics of single words, and the composition of words to make phrasal meaning. While many methods can estimate the meaning (i.e. vector) of a phrase, few do so in an interpretable way. We introduce a new method (CNNSE) that allows word and phrase vectors to adapt to the notion of composition. Our method learns a VSM that is both tailored to support a chosen semantic composition operation, and whose resulting features have an intuitive interpretation. Interpretability allows for the exploration of phrasal semantics, which we leverage to analyze performance on a behavioral task.