Supervising Offline Partial Evaluation of Logic Programs using Online Techniques

A major impediment for more widespread use of offline partial evaluation is the difficulty of obtaining and maintaining annotations for larger, realistic programs. Existing automatic binding-time analyses still only have limited applicability and annotations often have to be created or improved and maintained by hand, leading to errors. We present a technique to help overcome this problem by using online control techniques which supervise the specialisation process in order to help the development and maintenance of correct annotations by identifying errors. We discuss an implementation in the Logen system and show on a series of examples that this approach is effective: very few false alarms were raised while infinite loops were detected quickly. We also present the integration of this technique into a web interface, which highlights problematic annotations directly in the source code. A method to automatically fix incorrect annotations is presented, allowing the approach to be also used as a pragmatic binding time analysis. Finally we show how our method can be used for efficiently locating built-in errors in Prolog source code

The Ecce and Logen Partial Evaluators and their Web Interfaces

We present Ecce and Logen, two partial evaluators for Prolog using the online and offline approach respectively. We briefly present the foundations of these tools and discuss various applications. We also present new implementations of these tools, carried out in Ciao Prolog. In addition to a command-line interface new user-friendly web interfaces were developed. These enable non-expert users to specialise logic programs using a web browser, without the need for a local installation

A low-cost X-ray-transparent experimental cell for synchrotron-based X-ray microtomography studies under geological reservoir conditions

A new modular X-ray-transparent experimental cell enables tomographic investigations of fluid rock interaction under natural reservoir conditions (confining pressure up to 20 MPa, pore fluid pressure up to 15 MPa, temperature ranging from 296 to 473 K). The portable cell can be used at synchrotron radiation sources that deliver a minimum X-ray flux density of 109 photons mm−2s−1in the energy range 30–100 keV to acquire tomographic datasets in less than 60 s. It has been successfully used in three experiments at the bending-magnet beamline 2BM at the Advanced Photon Source. The cell can be easily machined and assembled from off-the-shelf components at relatively low costs, and its modular design allows it to be adapted to a wide range of experiments and lower-energy X-ray sources.</jats:p

Initial Conditions for Models of Dynamical Systems

The long-time behaviour of many dynamical systems may be effectively predicted by a low-dimensional model that describes the evolution of a reduced set of variables. We consider the question of how to equip such a low-dimensional model with appropriate initial conditions, so that it faithfully reproduces the long-term behaviour of the original high-dimensional dynamical system. Our method involves putting the dynamical system into normal form, which not only generates the low-dimensional model, but also provides the correct initial conditions for the model. We illustrate the method with several examples. Keywords: normal form, isochrons, initialisation, centre manifoldComment: 24 pages in standard LaTeX, 66K, no figure

Heitt Mjölnir: a heated miniature triaxial apparatus for 4D synchrotron microtomography

Third- and fourth-generation synchrotron light sources with high fluxes and beam energies enable the use of innovative X-ray translucent experimental apparatus. These experimental devices access geologically relevant conditions whilst enabling in situ characterization using the spatial and temporal resolutions accessible at imaging beamlines. Here, Heitt Mjölnir is introduced, a heated miniature triaxial rig based on the design of Mjölnir, but covering a wider temperature range and larger sample volume at similar pressure capacities. This device is designed to investigate coupled thermal, chemical, hydraulic and mechanical processes from grain to centimetre scales using cylindrical samples of 10 mm × 20 mm (diameter × length). Heitt Mjölnir can simultaneously reach confining (hydraulic) pressures of 30 MPa and 500 MPa of axial stress with independently controlled sample pore fluid pressure &lt; 30 MPa. This internally heated apparatus operates to temperatures up to 573 K with a minimal vertical thermal gradient in the sample of &lt;0.3 K mm−1. This new apparatus has been deployed in operando studies at the TOMCAT (Swiss Light Source), I12 JEEP (Diamond Light Source) and PSICHÉ (Synchrotron SOLEIL) beamlines for 4D X-ray microtomography with scan intervals of a few minutes. Heitt Mjölnir is portable and modular, allowing a wide range of 4D characterizations of low-grade metamorphism and deformational processes. It enables spatially and temporally resolved fluid–rock interaction studies at conditions of crustal reservoirs and is suitable for characterization of material properties in geothermal, carbonation or subsurface gas storage applications. Technical drawings and an operation guide are included in this publication

Minocycline treatment inhibits microglial activation and alters spinal levels of endocannabinoids in a rat model of neuropathic pain

Activation of spinal microglia contributes to aberrant pain responses associated with neuropathic pain states. Endocannabinoids (ECs) are present in the spinal cord, and inhibit nociceptive processing; levels of ECs may be altered by microglia which modulate the turnover of endocannabinoids in vitro. Here, we investigate the effect of minocycline, an inhibitor of activated microglia, on levels of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG), and the related compound N-palmitoylethanolamine (PEA), in neuropathic spinal cord. Selective spinal nerve ligation (SNL) in rats resulted in mechanical allodynia and the presence of activated microglia in the ipsilateral spinal cord. Chronic daily treatment with minocycline (30 mg/kg, ip for 14 days) significantly reduced the development of mechanical allodynia at days 5, 10 and 14 post-SNL surgery, compared to vehicle-treated SNL rats (P < 0.001). Minocycline treatment also significantly attenuated OX-42 immunoreactivity, a marker of activated microglia, in the ipsilateral (P < 0.001) and contralateral (P < 0.01) spinal cord of SNL rats, compared to vehicle controls. Minocycline treatment significantly (P < 0.01) decreased levels of 2-AG and significantly (P < 0.01) increased levels of PEA in the ipsilateral spinal cord of SNL rats, compared to the contralateral spinal cord. Thus, activation of microglia affects spinal levels of endocannabinoids and related compounds in neuropathic pain states

Cannabinoid receptors in GtoPdb v.2023.1

Cannabinoid receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Cannabinoid Receptors [119]) are activated by endogenous ligands that include N-arachidonoylethanolamine (anandamide), N-homo-&#947;-linolenoylethanolamine, N-docosatetra-7,10,13,16-enoylethanolamine and 2-arachidonoylglycerol. Potency determinations of endogenous agonists at these receptors are complicated by the possibility of differential susceptibility of endogenous ligands to enzymatic conversion [5].There are currently three licenced cannabinoid medicines each of which contains a compound that can activate CB1 and CB2 receptors [111]. Two of these medicines were developed to suppress nausea and vomiting produced by chemotherapy. These are nabilone (Cesamet&#174;), a synthetic CB1/CB2 receptor agonist, and synthetic &#916;9-tetrahydrocannabinol (Marinol&#174;; dronabinol), which can also be used as an appetite stimulant. The third medicine, Sativex&#174;, contains mainly &#916;9-tetrahydrocannabinol and cannabidiol, both extracted from cannabis, and is used to treat multiple sclerosis and cancer pain

Experiences of using vedolizumab in the treatment of inflammatory bowel disease in the East Midlands UK – a retrospective observational study

PurposeClinical trials have demonstrated efficacy of vedolizumab in ulcerative colitis (UC) and Crohn’s disease (CD). Further real-world data is needed to inform clinical practice. The primary outcome was to assess corticosteroid-free and clinical remission after vedolizumab initiation. Secondary outcomes included effect on disease activity scores, biochemical markers, concomitant drug use, endoscopic remission, surgical intervention, hospital admissions and adverse events.Materials and methodsA multi-centre retrospective observational study was conducted with patients initiated on vedolizumab across seven UK hospitals 1/11/14-30/11/16. Clinical disease activity was assessed using the partial Mayo Scores (pMS) and Harvey Bradshaw Index (HBI). Clinical remission was defined as HBI [less than] 4 or pMS [less than]2 with a combined stool frequency and rectal bleeding sub score of [less than] 1. Clinical response was defined as ≥2-point decrease from baseline in pMS and ≥3-point decrease from baseline in HBI.ResultsOne hundred ninety-two patients were included in the final analysis. 45% of UC and 10% of CD patients were anti-TNF naive. Over the observation period corticosteroid-free remission rates for UC and CD were 46% and 45%, while clinical remission rates were 52% and 44%, respectively. Time to corticosteroid free remission for UC and CD was 17.6 [IQR: 8.7–29.6] and 14.1 [QR: 6.0–21.7] weeks, respectively. Time to clinical response for UC was 9.4 [IQR: 5.7–15.4] and CD was 9.5 [IQR: 6.1–18.2] weeks. There was a substantial decrease in the concomitant use of immunomodulators and a similar decrease in concomitant corticosteroid use over the study period. ConclusionsResults in this predominately anti-TNF experienced population mirror other published real-world data, demonstrating good clinical effectiveness and a comparable safety profile