Compositional Explanation of Types and Algorithmic Debugging of Type Errors

The type systems of most typed functional programming languages are based on the Hindley-Milner type system. A practical problem with these type systems is that it is often hard to understand why a program is not type correct or a function does not have the intended type. We suggest that at the core of this problem is the difficulty of explaining why a given expression has a certain type. The type system is not defined compositionally. We propose to explain types using a variant of the Hindley-Milner type system that defines a compositional type explanation graph of principal typings. We describe how the programmer understands types by interactive navigation through the explanation graph. Furthermore, the explanation graph can be the foundation for algorithmic debugging of type errors, that is, semi-automatic localisation of the source of a type error without even having to understand the type inference steps. We implemented a prototype of a tool to explore the usefulness of the proposed methods

HLA-A, -B, -C, -DRB1, DRB3, DRB4, DRB5 and DQB1 polymorphism detected by PCR-SSP in a semi-urban HIV-positive Ugandan population.

PCR-SSP was used to HLA-type a cohort of Ugandan HIV-positive individuals. The results represent a more comprehensive description of HLA in an African population than previously described and are in concordance with data from a general Black population. Substantial differences exist between this population and Caucasoid populations in which immunological responses to HIV have been investigated; this emphasises that the main HLA-restrictive elements for HIV-specific cytotoxic T lymphocytes will most likely be different for each population

Social effects of territorial neighbours on the timing of spring breeding in North American red squirrels

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordOrganisms can affect one another’s phenotypes when they socially interact. Indirect genetic effects occur when an individual’s phenotype is affected by genes expressed in another individual. These heritable effects can enhance or reduce adaptive potential, thereby accelerating or reversing evolutionary change. Quantifying these social effects is therefore crucial for our understanding of evolution, yet estimates of indirect genetic effects in wild animals are limited to dyadic interactions. We estimated indirect phenotypic and genetic effects, and their covariance with direct effects, for the date of spring breeding in North American red squirrels (Tamiasciurus hudsonicus) living in an array of territories of varying spatial proximity. Additionally, we estimated indirect effects and the strength of selection at low and high population densities. Social effects of neighbours on the date of spring breeding were different from zero at high population densities but not at low population densities. Indirect phenotypic effects accounted for a larger amount of variation in the date of breeding than differences attributable to the among-individual variance, suggesting social interactions are important for determining breeding dates. The genetic component to these indirect effects was however not statistically significant. We therefore showcase a powerful and flexible method that will allow researchers working in organisms with a range of social systems to estimate indirect phenotypic and genetic effects, and demonstrate the degree to which social interactions can influence phenotypes, even in a solitary species

Optimisation of impact pile driving using optical fibre Bragg grating measurements

This paper reports the use of optical Fibre Bragg Grating (FBG) sensors to monitor the stress waves generated below ground during pile driving, combined with measurements using conventional pile driving analyzer (PDA) sensors mounted at the pile head. Fourteen tubular steel piles with a diameter of 508 mm and embedded length to diameter ratios of 6 to 20 were impact driven at an established chalk test site in Kent, UK. The pile shafts were instrumented with multiple FBG strain gauges and pile head PDA sensors, which monitored the piles’ responses under each hammer blow. A high frequency (5kHz) fibre optic interrogator allowed a previously unseen resolution of the stress wave propagation along the pile. Estimates of the base soil resistances to driving and distributions of shaft shear resistances were found through signal matching that compared time series of pile head PDA measurements and FBG strains measured below ground surface. Numerical solutions of the onedimensional wave equation were optimised by taking account of the data from multiple FBG gauges, leading to significant advantages that have potential for widespread application in cases where high resolution strain measurements are made

Genetic variation of a bacterial pathogen within individuals with cystic fibrosis provides a record of selective pressures

Advances in sequencing have enabled the identification of mutations acquired by bacterial pathogens during infection1-10. However, it remains unclear whether adaptive mutations fix in the population or lead to pathogen diversification within the patient11,12. Here, we study the genotypic diversity of Burkholderia dolosa within people with cystic fibrosis by re-sequencing individual colonies and whole populations from single sputum samples. Extensive intra-sample diversity reveals that mutations rarely fix within a patient's pathogen population—instead, diversifying lineages coexist for many years. When strong selection is acting on a gene, multiple adaptive mutations arise but neither sweeps to fixation, generating lasting allele diversity that provides a recorded signature of past selection. Genes involved in outer-membrane components, iron scavenging and antibiotic resistance all showed this signature of within-patient selection. These results offer a general and rapid approach for identifying selective pressures acting on a pathogen in individual patients based on single clinical samples

Evolved Gas Analyses of Sedimentary Materials in Gale Crater, Mars: Results of the Curiosity Rover's Sample Analysis at Mars (SAM) Instrument from Yellowknife Bay to the Stimson Formation

The Sample Analysis at Mars (SAM) instrument aboard the Mars Science Laboratory rover has analyzed 10 samples from Gale Crater. All SAM evolved gas analyses have yielded a multitude of volatiles (e.g, H2O, SO2, H2S, CO2, CO, NO, O2, HC1). The objectives of this work are to 1) Characterize the evolved H2O, SO2, CO2, and O2 gas traces of sediments analyzed by SAM through sol 1178, 2) Constrain sediment mineralogy/composition based on SAM evolved gas analysis (SAM-EGA), and 3) Discuss the implications of these results releative to understanding the geochemical history of Gale Crater

T Cell Recognition of the Dominant I-Ak–Restricted Hen Egg Lysozyme Epitope: Critical Role for Asparagine Deamidation

Type-B T cells raised against the immunodominant peptide in hen egg lysozyme (HEL48–62) do not respond to whole lysozyme, and this has been thought to indicate that peptide can bind to l-Ak in different conformations. Here we demonstrate that such T cells recognize a deamidated form of the HEL peptide and not the native peptide. The sequence of the HEL epitope facilitates rapid and spontaneous deamidation when present as a free peptide or within a flexible domain. However, this deamidated epitope is not created within intact lysozyme, most likely because it resides in a highly structured part of the protein. These findings argue against the existence of multiple conformations of the same peptide–MHC complex and have important implications for the design of peptide-based vaccines. Furthermore, as the type-B T cells are known to selectively evade induction of tolerance when HEL is expressed as a transgene, these results suggest that recognition of posttranslationally modified self-antigen may play a role in autoimmunity

Mineralogical and Geochemical Trends of the Murray Mudstones, Gale Crater: A Combined Sample Analysis at Mars-Evolved Gas Analyzer and Chemistry and Mineralogy Instrument Assessment

The Murray formation is predominantly composed of lacustrine mudstone that forms the basal layer of Aeolis Mons (informally Mt. Sharp) in Gale Crater, Mars. The Murray formation has distinct iron and sulfur mineralogical variation within its stratigraphy detectable by the Chemistry Mineralogy (Che-Min) instrument consisting of magnetite/hematite in the lower Murray and higher hematite, CaSO4, and smectite content in the upper Murray. The objectives of this work were to evaluate the Sample Analysis at Mars Evolved Gas Analyzer (SAM-EGA) data to 1) Determine what SAM-EGA-detectable phases correlate or do not correlate with the Murray mineralogical composition detected by CheMin and 2) Utilize CheMin/SAM results to propose possible formation scenarios for the observed Murray mudstone mineralogy