Polyvariant Analysis of the Untyped Lambda Calculus

We present a polyvariant closure, safety, and binding time analysis for the untyped lambda calculus. The innovation is to analyze each abstraction afresh at all syntactic application points. This is achieved by a semantics-preserving program transformation followed by a novel monovariant analysis, expressed using type constraints. The constraints are solved in cubic time by a single fixed-point computation.Safety analysis is aimed at determining if a term will cause an error during evaluation. We have recently proved that the monovariant safety analysis accepts strictly more terms than simple type inference. This paper demonstrates that the polyvariant transformation makes even more terms acceptable, even some without higher-order polymorphic types. Furthermore, polyvariant binding time analysis can improve the partial evaluators that base a polyvariant specialization on only monovariant binding time analysis

Invariant expansion for the trigonal band structure of graphene

We present a symmetry analysis of the trigonal band structure in graphene, elucidating the transformational properties of the underlying basis functions and the crucial role of time-reversal invariance. Group theory is used to derive an invariant expansion of the Hamiltonian for electron states near the K points of the graphene Brillouin zone. Besides yielding the characteristic k-linear dispersion and higher-order corrections to it, this approach enables the systematic incorporation of all terms arising from external electric and magnetic fields, strain, and spin-orbit coupling up to any desired order. Several new contributions are found, in addition to reproducing results obtained previously within tight-binding calculations. Physical ramifications of these new terms are discussed.Comment: 10 pages, 1 figure; expanded version with more details and additional result

Projection-Based Program Analysis

Projection-based program analysis techniques are remarkable for their ability to give highly detailed and useful information not obtainable by other methods. The first proposed projection-based analysis techniques were those of Wadler and Hughes for strictness analysis, and Launchbury for binding-time analysis; both techniques are restricted to analysis of first-order monomorphic languages. Hughes and Launchbury generalised the strictness analysis technique, and Launchbury the binding-time analysis technique, to handle polymorphic languages, again restricted to first order. Other than a general approach to higher-order analysis suggested by Hughes, and an ad hoc implementation of higher-order binding-time analysis by Mogensen, neither of which had any formal notion of correctness, there has been no successful generalisation to higher-order analysis. We present a complete redevelopment of monomorphic projection-based program analysis from first principles, starting by considering the analysis of functions (rather than programs) to establish bounds on the intrinsic power of projection-based analysis, showing also that projection-based analysis can capture interesting termination properties. The development of program analysis proceeds in two distinct steps: first for first-order, then higher order. Throughout we maintain a rigorous notion of correctness and prove that our techniques satisfy their correctness conditions. Our higher-order strictness analysis technique is able to capture various so-called data-structure-strictness properties such as head strictness-the fact that a function may be safely assumed to evaluate the head of every cons cell in a list for which it evaluates the cons cell. Our technique, and Hunt's PER-based technique (originally proposed at about the same time as ours), are the first techniques of any kind to capture such properties at higher order. Both the first-order and higher-order techniques are the first projection-based techniques to capture joint strictness properties-for example, the fact that a function may be safely assumed to evaluate at least one of several arguments. The first-order binding-time analysis technique is essentially the same as Launchbury's; the higher-order technique is the first such formally-based higher-order generalisation. Ours are the first projection-based termination analysis techniques, and are the first techniques of any kind that are able to detect termination properties such as head termination-the fact that termination of a cons cell implies termination of the head. A notable feature of the development is the method by which the first-order analysis semantics are generalised to higher-order: except for the fixed-point constant the higher-order semantics are all instances of a higher-order semantics parameterised by the constants defining the various first-order semantics

Comparison of manual and semi-automated delineation of regions of interest for radioligand PET imaging analysis

BACKGROUND As imaging centers produce higher resolution research scans, the number of man-hours required to process regional data has become a major concern. Comparison of automated vs. manual methodology has not been reported for functional imaging. We explored validation of using automation to delineate regions of interest on positron emission tomography (PET) scans. The purpose of this study was to ascertain improvements in image processing time and reproducibility of a semi-automated brain region extraction (SABRE) method over manual delineation of regions of interest (ROIs). METHODS We compared 2 sets of partial volume corrected serotonin 1a receptor binding potentials (BPs) resulting from manual vs. semi-automated methods. BPs were obtained from subjects meeting consensus criteria for frontotemporal degeneration and from age- and gender-matched healthy controls. Two trained raters provided each set of data to conduct comparisons of inter-rater mean image processing time, rank order of BPs for 9 PET scans, intra- and inter-rater intraclass correlation coefficients (ICC), repeatability coefficients (RC), percentages of the average parameter value (RM%), and effect sizes of either method. RESULTS SABRE saved approximately 3 hours of processing time per PET subject over manual delineation (p 0.8) for both methods. RC and RM% were lower for the manual method across all ROIs, indicating less intra-rater variance across PET subjects' BPs. CONCLUSION SABRE demonstrated significant time savings and no significant difference in reproducibility over manual methods, justifying the use of SABRE in serotonin 1a receptor radioligand PET imaging analysis. This implies that semi-automated ROI delineation is a valid methodology for future PET imaging analysis

Temperature Dependence of Backbone Dynamics in Human Ileal Bile Acid-Binding Protein: Implications for the Mechanism of Ligand Binding

Human ileal bile acid-binding protein (I-BABP), a member of the family of intracellular lipid binding proteins plays a key role in the cellular trafficking and metabolic regulation of bile salts. The protein has two internal and, according to a recent study, an additional superficial binding site and binds di- and trihydroxy bile salts with positive cooperativity and a high degree of site-selectivity. Previously, in the apo form, we have identified an extensive network of conformational fluctuations on the millisecond time scale, which cease upon ligation. Additionally, ligand binding at room temperature was found to be accompanied by a slight rigidification of picosecond-nanosecond (ps-ns) backbone flexibility. In the current study, temperature-dependent N-15 NMR spin relaxation measurements were used to gain more insight into the role of dynamics in human I-BABP-bile salt recognition. According to our analysis, residues sensing a conformational exchange in the apo state can be grouped into two clusters with slightly different exchange rates. The entropy-enthalpy compensation observed for both clusters suggests a disorder-order transition between a ground and a sparsely populated higher energy state in the absence of ligands. Analysis of the faster, ps-ns motion of N-15-H-1 bond vectors indicates an unusual nonlinear temperature-dependence for both ligation states. Intriguingly, while bile salt binding results in a more uniform response to temperature change throughout the protein, the temperature derivative of the generalized order parameter shows different responses to temperature increase for the two forms of the protein in the investigated temperature range. Analysis of both slow and fast motions in human I-BABP indicates largely different energy landscapes for the apo and halo states suggesting that optimization of binding interactions might be achieved by altering the dynamic behavior of specific segments in the protein

Aptamers against the β-conglutin allergen: Insights into the behavior of the shortest multimeric (intra)molecular dna gquadruplex

In previous work, a 93-mer aptamer was selected against the anaphylactic allergen, β-conglutin and truncated to an 11-mer, improving the affinity by two orders of magnitude, whilst maintaining the specificity. This 11-mer was observed to fold in a G-quadruplex, and preliminary results indicated the existence of a combination of monomeric and higher-order structures. Building on this previous work, in the current study, we aimed to elucidate a deeper understanding of the structural forms of this 11-mer and the effect of the structure on its binding ability. A battery of techniques including polyacrylamide gel electrophoresis, high-performance liquid chromatography in combination with electrospray ionization time-of-flight mass spectrometry, matrix-assisted laser desorption/ionization time-of-flight, thermal binding analysis, circular dichroism and nuclear magnetic resonance were used to probe the structure of both the 11-mer and the 11-mer flanked with TT- at either the 5′ or 3′ end or at both ends. The TT-tail at the 5′ end hinders stacking effects and effectively enforces the 11-mer to maintain a monomeric form. The 11-mer and the TT- derivatives of the 11-mer were also evaluated for their ability to bind its cognate target using microscale thermophoresis and surface plasmon resonance, and biolayer interferometry confirmed the nanomolar affinity of the 11-mer. All the techniques utilized confirmed that the 11-mer was found to exist in a combination of monomeric and higher-order structures, and that independent of the structural form present, nanomolar affinity was observed