Exploiting Term Hiding to Reduce Run-time Checking Overhead

One of the most attractive features of untyped languages is the flexibility in term creation and manipulation. However, with such power comes the responsibility of ensuring the correctness of these operations. A solution is adding run-time checks to the program via assertions, but this can introduce overheads that are in many cases impractical. While static analysis can greatly reduce such overheads, the gains depend strongly on the quality of the information inferred. Reusable libraries, i.e., library modules that are pre-compiled independently of the client, pose special challenges in this context. We propose a technique which takes advantage of module systems which can hide a selected set of functor symbols to significantly enrich the shape information that can be inferred for reusable libraries, as well as an improved run-time checking approach that leverages the proposed mechanisms to achieve large reductions in overhead, closer to those of static languages, even in the reusable-library context. While the approach is general and system-independent, we present it for concreteness in the context of the Ciao assertion language and combined static/dynamic checking framework. Our method maintains the full expressiveness of the assertion language in this context. In contrast to other approaches it does not introduce the need to switch the language to a (static) type system, which is known to change the semantics in languages like Prolog. We also study the approach experimentally and evaluate the overhead reduction achieved in the run-time checks.Comment: 26 pages, 10 figures, 2 tables; an extension of the paper version accepted to PADL'18 (includes proofs, extra figures and examples omitted due to space reasons

The fully differential hadronic production of a Higgs boson via bottom quark fusion at NNLO

The fully differential computation of the hadronic production cross section of a Higgs boson via bottom quarks is presented at NNLO in QCD. Several differential distributions with their corresponding scale uncertainties are presented for the 8 TeV LHC. This is the first application of the method of non-linear mappings for NNLO differential calculations at hadron colliders.Comment: 27 pages, 13 figures, 1 lego plo

Regulation of accretion by its outflow in a symbiotic star: the 2016 outflow fast state of MWC 560

How are accretion discs affected by their outflows? To address this question for white dwarfs accreting from cool giants, we performed optical, radio, X-ray, and ultraviolet observations of the outflow-driving symbiotic star MWC 560 (=V694 Mon) during its 2016 optical high state. We tracked multi-wavelength changes that signalled an abrupt increase in outflow power at the initiation of a months-long outflow fast state, just as the optical flux peaked: (1) an abrupt doubling of Balmer absorption velocities; (2) the onset of a $20$ $\mu$Jy/month increase in radio flux; and (3) an order-of-magnitude increase in soft X-ray flux. Juxtaposing to prior X-ray observations and their coeval optical spectra, we infer that both high-velocity and low-velocity optical outflow components must be simultaneously present to yield a large soft X-ray flux, which may originate in shocks where these fast and slow absorbers collide. Our optical and ultraviolet spectra indicate that the broad absorption-line gas was fast, stable, and dense ($\gtrsim10^{6.5}$ cm$^{-3}$) throughout the 2016 outflow fast state, steadily feeding a lower-density ($\lesssim10^{5.5}$ cm$^{-3}$) region of radio-emitting gas. Persistent optical and ultraviolet flickering indicate that the accretion disc remained intact. The stability of these properties in 2016 contrasts to their instability during MWC 560's 1990 outburst, even though the disc reached a similar accretion rate. We propose that the self-regulatory effect of a steady fast outflow from the disc in 2016 prevented a catastrophic ejection of the inner disc. This behaviour in a symbiotic binary resembles disc/outflow relationships governing accretion state changes in X-ray binaries

Large variability in plasma efavirenz concentration in Papua New Guinea HIV/AIDS patients associated with high frequency of CYP2B6 516T allele

First published: 20 August 2021Papua New Guinea (PNG) has a high HIV/AIDS prevalence and very high frequency of the CYP2B6 c.516G>T (rs3745274) variant. We have conducted the first investigation of the impact of c.516G>T and patient demographics on plasma efavirenz (EFV) and 8-hydroxyefavirenz (8OH-EFV) concentrations, metabolic ratio (8OH-EFV/EFV) (MR), and their association with adverse effects, in PNG patients with HIV/AIDS. For 156 PNG patients with HIV/AIDS taking EFV 600 mg/day (for 3-156 months), plasma EFV and 8OH-EFV concentrations were quantified, CYP2B6 c.516G>T genotyped, and demographic and self-reported adverse effects data recorded. Genotype differences in EFV and 8OH-EFV concentrations, MR, and percent within therapeutic range (1000-4000 ng/ml) were examined, in addition to EFV and 8OH-EFV concentration differences between patients experiencing adverse effects. CYP2B6 c.516T allele frequency was 53%. Plasma EFV (p < 0.0001), 8OH-EFV (p < 0.01), and MR (p < 0.0001) differed significantly between genotypes, with genotype explaining 38%, 10%, and 50% of variability, respectively. Plasma EFV concentrations were significantly higher in T/T (median = 5168 ng/ml) than G/G (1036 ng/ml, post hoc p < 0.0001) and G/T (1502 ng/ml, p < 0.0001) genotypes, with all patients above therapeutic range (n = 23) being T/T genotype (p < 0.0001). EFV and 8OH-EFV concentrations were not significantly higher in patients experiencing adverse effects. In PNG HIV/AIDS population where the 516T frequency is very high, it explains a substantial portion of variability (38%) in EFV disposition; however, at least for the patients receiving EFV long term, this does not translate into significant side effects.Natália Bordin Andriguetti, Helena Katherina Van Schalkwyk, Daniel Thomas Barratt, Joseph Tucci, Paul Pumuye, Andrew Alexander Somogy

Photon Radiation with MadDipole

We present the automation of a subtraction method for photon radiation using the dipole formalism within the MadGraph framework. The subtraction terms are implemented both in dimensional regularization and mass regularization for massless and massive cases and non-collinear-safe observables are accounted for.Comment: 23 pages, 2 figures, minor additions, references added, version published in JHE

Pharmacokinetics of tramadol after subcutaneous administration in a critically ill population and in a healthy cohort

BACKGROUND: Tramadol is an atypical centrally acting analgesic agent available as both oral and parenteral preparations. For patients who are unable to take tramadol orally, the subcutaneous route of administration offers an easy alternative to intravenous or intramuscular routes. This study aimed to characterise the absorption pharmacokinetics of a single subcutaneous dose of tramadol in severely ill patients and in healthy subjects. METHODS/DESIGN: Blood samples (5 ml) taken at intervals from 2 minutes to 24 hours after a subcutaneous dose of tramadol (50 mg) in 15 patients (13 male, two female) and eight healthy male subjects were assayed using high performance liquid chromatography. Pharmacokinetic parameters were derived using a non-compartmental approach. RESULTS: There were no statistically significant differences between the two groups in the following parameters (mean ± SD): maximum venous concentration 0.44 ± 0.18 (patients) vs. 0.47 ± 0.13 (healthy volunteers) mcg/ml (p = 0.67); area under the plasma concentration-time curve 177 ± 109 (patients) vs. 175 ± 75 (healthy volunteers) mcg/ml*min (p = 0.96); time to maximum venous concentration 23.3 ± 2 (patients) vs. 20.6 ± 18.8 (healthy volunteers) minutes (p = 0.73) and mean residence time 463 ± 233 (patients) vs. 466 ± 224 (healthy volunteers) minutes (p = 0.97). CONCLUSIONS: The similar time to maximum venous concentration and mean residence time suggest similar absorption rates between the two groups. These results indicate that the same dosing regimens for subcutaneous tramadol administration may therefore be used in both healthy subjects and severely ill patients. TRIAL REGISTRATION: ACTRN12611001018909.Neil M Dooney, Krishnaswamy Sundararajan, Tharapriya Ramkumar, Andrew A Somogyi, Richard N Upton, Jennifer Ong, Stephanie N O, Connor, Marianne J Chapman and Guy L Ludbroo

t2prhd: a tool to study the patterns of repeat evolution

BACKGROUND: The models developed to characterize the evolution of multigene families (such as the birth-and-death and the concerted models) have also been applied on the level of sequence repeats inside a gene/protein. Phylogenetic reconstruction is the method of choice to study the evolution of gene families and also sequence repeats in the light of these models. The characterization of the gene family evolution in view of the evolutionary models is done by the evaluation of the clustering of the sequences with the originating loci in mind. As the locus represents positional information, it is straightforward that in the case of the repeats the exact position in the sequence should be used, as the simple numbering according to repeat order can be misleading. RESULTS: We have developed a novel rapid visual approach to study repeat evolution, that takes into account the exact repeat position in a sequence. The "pairwise repeat homology diagram" visualizes sequence repeats detected by a profile HMM in a pair of sequences and highlights their homology relations inferred by a phylogenetic tree. The method is implemented in a Perl script (t2prhd) available for downloading at http://t2prhd.sourceforge.net and is also accessible as an online tool at http://t2prhd.brc.hu. The power of the method is demonstrated on the EGF-like and fibronectin-III-like (Fn-III) domain repeats of three selected mammalian Tenascin sequences. CONCLUSION: Although pairwise repeat homology diagrams do not carry all the information provided by the phylogenetic tree, they allow a rapid and intuitive assessment of repeat evolution. We believe, that t2prhd is a helpful tool with which to study the pattern of repeat evolution. This method can be particularly useful in cases of large datasets (such as large gene families), as the command line interface makes it possible to automate the generation of pairwise repeat homology diagrams with the aid of script