Formalising the pi-calculus using nominal logic

We formalise the pi-calculus using the nominal datatype package, based on ideas from the nominal logic by Pitts et al., and demonstrate an implementation in Isabelle/HOL. The purpose is to derive powerful induction rules for the semantics in order to conduct machine checkable proofs, closely following the intuitive arguments found in manual proofs. In this way we have covered many of the standard theorems of bisimulation equivalence and congruence, both late and early, and both strong and weak in a uniform manner. We thus provide one of the most extensive formalisations of a process calculus ever done inside a theorem prover. A significant gain in our formulation is that agents are identified up to alpha-equivalence, thereby greatly reducing the arguments about bound names. This is a normal strategy for manual proofs about the pi-calculus, but that kind of hand waving has previously been difficult to incorporate smoothly in an interactive theorem prover. We show how the nominal logic formalism and its support in Isabelle accomplishes this and thus significantly reduces the tedium of conducting completely formal proofs. This improves on previous work using weak higher order abstract syntax since we do not need extra assumptions to filter out exotic terms and can keep all arguments within a familiar first-order logic.Comment: 36 pages, 3 figure

Handbok för skötsel och restaurering av rikkärr

Rikkärr är en våtmarkstyp som är unik för sin stora artmångfald av ovanliga arter varav orkidéerna är de mest kända. Rikkärren är hotade av utdikning, upphörd hävd och vergödning. Följderna har blivit olika grader av torrläggning, vegetationsförändringar och igenväxning och i värsta fall oåterkalleligen degenererade rikkärr. Minskningen av rikkärren har gjort att naturtypen och dess arter har dålig eller ogynnsam bevarandestatus. Dessutom adderas nu även den stress på rikkärren som orsakas av klimatförändringarna. För att motverka försämringen startade Naturvårdsverket ett åtgärdsprogram för rikkärr 2006. Mycket arbete har sedan starten 2006 gjorts inom ramen för åtgärdsprogrammet för bevarande av rikkärr. Denna handbok ger en sammanställning av några av de erfarenheter som har förvärvats under arbetet inom åtgärdsprogrammet, men sammanfattar även annan litteratur och andra erfarenheter från skötsel och restaurering av rikkärr samt andra områden med liknande problematik. Behovet av att restaurera rikkärr för att bevara naturtypen och rädda dess artmångfald är fortfarande stort; likaså behovet av kunskap för att lyckas med detta. Det som har varit centralt i arbetet med denna handbok har varit att ta fram ett dokument med samlad kunskap som är specifikt riktat mot just de naturvårdsåtgärder som vanligen kan vara aktuella för rikkärr. Trots detta kan delar av handboken även användas för åtgärder i andra våtmarkstyper. Handboken för skötsel och restaurering av rikkärr ger en beskrivning av hur man kan bedriva projekt i rikkärrsmiljöer från planering till uppföljning och utvärdering. Delar som särskilt berörs är restaurering och skötsel av rikkärr genom slåtter, bete, röjning av igenväxningsvegetation, hydrologisk restaurering, tuvoch stubbfräsning, schaktning av övergödd ytjord och återutsättning av växter och djur. En del om lagstiftningen runt åtgärder som görs i rikkärr tas också upp. Handboken är ett tidsdokument över hur långt vi hittills har kommit med metoder och lärdomar från arbete med rikkärr. Efterhand kommer erfarenheterna att bli fler och förutsättningarna kommer att förändras. Huvudsyftet med boken är att öka den allmänna kunskapsnivån med åtgärder för rikkärr, vilket förhoppningsvis både kan katalysera fortsatt inhämtande av ny kunskap, och att underlätta arbetet med den unika livsmiljö som rikkärren utgör. Att arbeta med praktisk naturvård är ett ständigt lärande och är därför både stimulerande och utmanande

Opioid-induced constipation, use of laxatives, and health-related quality of life

AbstractBackground and aimsReal-life data on laxative use in patients suffering from opioid-induced constipation (OIC) are very limited, and many OIC patients are only using over the counter laxatives to resolve their constipation. Our aim was to describe laxative utilization and quality of life in participants in Norway who ever experienced OIC.MethodsThis was a cross-sectional online survey conducted between 27th of June and 3rd of July 2014 among participants above 18 years with self-reported OIC and who had agreed to receive information from the pharmacy chain (Boots A/S, Norway). The questionnaire comprised a series of multiple choice, close-ended, and free text questions on abdominal symptoms, laxative use and health-related quality of life.ResultsA total of 417 participants met the study eligibility criteria: (1) treated with opioid for a minimum of 4 weeks, (2) actively accepted participation, and (3) confirmed ever experiencing OIC and in addition completed the survey. Among the eligible participants, 86% were females, 85% were younger than 60 years of age, and 57% were currently suffering OIC. More than half of the currently constipated participants were experiencing moderate to very severe abdominal bloating (63%), abdominal pain (55%) and/or pain during bowel movement (50%). Less than every fourth participant (23%) had consulted health care professionals (HCPs) about their constipation. Up to 39% reported that they handled their OIC by self-management, e.g., bought laxative, reduced the dose and/or changed opioid without consulting HCP or pharmacy. Less than half (48%) of the laxative users were satisfied with the laxative they were using to relieve their constipation. The EQ-5D health-related quality of life score was mean (SD): 0.587 (0.272). Although not statistically significant (p=0.067), there was a tendency of lower quality of life among the participants who were currently constipated compared with those not currently constipated (difference of mean EQ-5D: 0.629–0.555=0.074). A significantly lower (p=0.001) quality of life was found among participants who were dissatisfied with their laxative [mean (SD): 0.424 (0.350)] than among those who were satisfied or neither satisfied nor dissatisfied [mean (SD): 0.628 (0.235) and 0.673 (0.155), respectively].ConclusionsThe results suggest a high degree of moderate to very severe abdominal symptoms, a high degree of self-management of opioid-induced constipation, a low degree of satisfaction with laxative, and low health-related quality of life of patients suffering from chronic pain necessitating long-term opioid treatment, subsequent constipation and laxatives use.ImplicationsPatients suffering from OIC with low quality of life and remaining symptoms despite use of two or more laxatives are a vulnerable patient group in need of optimized healthcare management, who also might benefit from more specific and innovative therapy

Pharmacologically relevant doses of valproate upregulate CD20 expression in three diffuse large B-cell lymphoma patients in vivo.

Epigenetic code modifications by histone deacetylase inhibitors (HDACi) have been proposed as potential new therapies for lymphoid malignancies. Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive lymphoma for which standard first line treatment is the chemotherapy regimen CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) combined with the monoclonal anti-CD20 antibody rituximab (R-CHOP). The HDACi valproate, which has for long been utilized in anti-convulsive therapy, has been shown to sensitize to chemotherapy in vitro. Valproate upregulates expression of CD20 in lymphoma cell lines; therefore, 48 hour pre-treatment with valproate before first line R-CHOP in DLBCL stages II-IV is evaluated in the phase I clinical trial VALFRID; Valproate as First line therapy in combination with Rituximab and CHOP in Diffuse large B-cell lymphoma

Psi-calculi: a framework for mobile processes with nominal data and logic

The framework of psi-calculi extends the pi-calculus with nominal datatypes for data structures and for logical assertions and conditions. These can be transmitted between processes and their names can be statically scoped as in the standard pi-calculus. Psi-calculi can capture the same phenomena as other proposed extensions of the pi-calculus such as the applied pi-calculus, the spi-calculus, the fusion calculus, the concurrent constraint pi-calculus, and calculi with polyadic communication channels or pattern matching. Psi-calculi can be even more general, for example by allowing structured channels, higher-order formalisms such as the lambda calculus for data structures, and predicate logic for assertions. We provide ample comparisons to related calculi and discuss a few significant applications. Our labelled operational semantics and definition of bisimulation is straightforward, without a structural congruence. We establish minimal requirements on the nominal data and logic in order to prove general algebraic properties of psi-calculi, all of which have been checked in the interactive theorem prover Isabelle. Expressiveness of psi-calculi significantly exceeds that of other formalisms, while the purity of the semantics is on par with the original pi-calculus.Comment: 44 page

Ancient genomes reveal a high diversity of Mycobacterium leprae in medieval Europe.

Studying ancient DNA allows us to retrace the evolutionary history of human pathogens, such as Mycobacterium leprae, the main causative agent of leprosy. Leprosy is one of the oldest recorded and most stigmatizing diseases in human history. The disease was prevalent in Europe until the 16th century and is still endemic in many countries with over 200,000 new cases reported annually. Previous worldwide studies on modern and European medieval M. leprae genomes revealed that they cluster into several distinct branches of which two were present in medieval Northwestern Europe. In this study, we analyzed 10 new medieval M. leprae genomes including the so far oldest M. leprae genome from one of the earliest known cases of leprosy in the United Kingdom-a skeleton from the Great Chesterford cemetery with a calibrated age of 415-545 C.E. This dataset provides a genetic time transect of M. leprae diversity in Europe over the past 1500 years. We find M. leprae strains from four distinct branches to be present in the Early Medieval Period, and strains from three different branches were detected within a single cemetery from the High Medieval Period. Altogether these findings suggest a higher genetic diversity of M. leprae strains in medieval Europe at various time points than previously assumed. The resulting more complex picture of the past phylogeography of leprosy in Europe impacts current phylogeographical models of M. leprae dissemination. It suggests alternative models for the past spread of leprosy such as a wide spread prevalence of strains from different branches in Eurasia already in Antiquity or maybe even an origin in Western Eurasia. Furthermore, these results highlight how studying ancient M. leprae strains improves understanding the history of leprosy worldwide

Testing macroecological abundance patterns: The relationship between local abundance and range size, range position and climatic suitability among European vascular plants

Aim: A fundamental question in macroecology centres around understanding the relationship between species' local abundance and their distribution in geographical and climatic space (i.e. the multi‐dimensional climatic space or climatic niche). Here, we tested three macroecological hypotheses that link local abundance to the following range properties: (a) the abundance-range size relationship, (b) the abundance-range centre relationship and (c) the abundance-suitability relationship. Location: Europe. Taxon: Vascular plants. Methods: Distribution range maps were extracted from the Chorological Database Halle to derive information on the range and niche sizes of 517 European vascular plant species. To estimate local abundance, we assessed samples from 744,513 vegetation plots in the European Vegetation Archive, where local species' abundance is available as plant cover per plot. We then calculated the 'centrality', that is, the distance between the location of the abundance observation and each species' range centre in geographical and climatic space. The climatic suitability of plot locations was estimated using coarse‐grain species distribution models (SDMs). The relationships between centrality or climatic suitability with abundance was tested using linear models and quantile regression. We summarized the overall trend across species' regression slopes from linear models and quantile regression using a meta‐analytical approach. Results: We did not detect any positive relationships between a species' mean local abundance and the size of its geographical range or climatic niche. Contrasting yet significant correlations were detected between abundance and centrality or climatic suitability among species. Main conclusions: Our results do not provide unequivocal support for any of the relationships tested, demonstrating that determining properties of species' distributions at large grains and extents might be of limited use for predicting local abundance, including current SDM approaches. We conclude that environmental factors influencing individual performance and local abundance are likely to differ from those factors driving plant species' distribution at coarse resolution and broad geographical extents

Structure and Stability of the Spinach Aquaporin SoPIP2;1 in Detergent Micelles and Lipid Membranes

Background: SoPIP2;1 constitutes one of the major integral proteins in spinach leaf plasma membranes and belongs to the aquaporin family. SoPIP2;1 is a highly permeable and selective water channel that has been successfully overexpressed and purified with high yields. In order to optimize reconstitution of the purified protein into biomimetic systems, we have here for the first time characterized the structural stability of SoPIP2;1. Methodology/Principal Finding: We have characterized the protein structural stability after purification and after reconstitution into detergent micelles and proteoliposomes using circular dichroism and fluorescence spectroscopy techniques. The structure of SoPIP2;1 was analyzed either with the protein solubilized with octyl-beta-D-glucopyranoside (OG) or reconstituted into lipid membranes formed by E. coli lipids, diphytanoylphosphatidylcholine (DPhPC), or reconstituted into lipid membranes formed from mixtures of 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPE), 1-palmitoyl-2-oleoyl-phosphatidylethanolamine (POPE), 1-palmitoyl-2-oleoyl-phosphatidylserine (POPS), and ergosterol. Generally, SoPIP2;1 secondary structure was found to be predominantly a-helical in accordance with crystallographic data. The protein has a high thermal structural stability in detergent solutions, with an irreversible thermal unfolding occurring at a melting temperature of 58 degrees C. Incorporation of the protein into lipid membranes increases the structural stability as evidenced by an increased melting temperature of up to 70 degrees C. Conclusion/Significance: The results of this study provide insights into SoPIP2;1 stability in various host membranes and suggest suitable choices of detergent and lipid composition for reconstitution of SoPIP2;1 into biomimetic membranes for biotechnological applications