A synchronous program algebra: a basis for reasoning about shared-memory and event-based concurrency

This research started with an algebra for reasoning about rely/guarantee concurrency for a shared memory model. The approach taken led to a more abstract algebra of atomic steps, in which atomic steps synchronise (rather than interleave) when composed in parallel. The algebra of rely/guarantee concurrency then becomes an instantiation of the more abstract algebra. Many of the core properties needed for rely/guarantee reasoning can be shown to hold in the abstract algebra where their proofs are simpler and hence allow a higher degree of automation. The algebra has been encoded in Isabelle/HOL to provide a basis for tool support for program verification. In rely/guarantee concurrency, programs are specified to guarantee certain behaviours until assumptions about the behaviour of their environment are violated. When assumptions are violated, program behaviour is unconstrained (aborting), and guarantees need no longer hold. To support these guarantees a second synchronous operator, weak conjunction, was introduced: both processes in a weak conjunction must agree to take each atomic step, unless one aborts in which case the whole aborts. In developing the laws for parallel and weak conjunction we found many properties were shared by the operators and that the proofs of many laws were essentially the same. This insight led to the idea of generalising synchronisation to an abstract operator with only the axioms that are shared by the parallel and weak conjunction operator, so that those two operators can be viewed as instantiations of the abstract synchronisation operator. The main differences between parallel and weak conjunction are how they combine individual atomic steps; that is left open in the axioms for the abstract operator.Comment: Extended version of a Formal Methods 2016 paper, "An algebra of synchronous atomic steps

Additional file 6: Software. of Intraspecific rearrangement of mitochondrial genome suggests the prevalence of the tandem duplication-random loss (TDLR) mechanism in Quasipaa boulengeri

The Perl script mtGordV0.5.pl with its readme file and example input and output files. (ZIP 5.35 kb

A comparative analysis of the Irish post-graduate geriatric medicine training scheme with the European post-graduate curriculum in geriatric medicine

Purpose: Minimum training recommendations to become a specialist geriatrician in the EU have been published and in this study we compared these recommendations with content from the post-graduate training scheme in Geriatric Medicine in Ireland. Methods: We examined the content of didactic study-day lectures delivered during Geriatric medicine training in Ireland. We compared how both the formal Irish curriculum and the content of the study days match up with the 36 items that are identified as core knowledge content areas. Results: The Irish geriatric medicine curriculum outlined that 30 of the 36 knowledge areas from the European curriculum should be covered. Formal teaching was delivered on 33 of the 36 knowledge components that are outlined in the European curriculum. 24 of 36 topics were covered at least twice. Conclusion: There was a high concordance between the content of the Irish and European post-graduate curriculum in Geriatric medicine.</p

Docking and Free Energy Perturbation Studies of Ligand Binding in the Kappa Opioid Receptor

The kappa opioid receptor (KOR) is an important target for pain and depression therapeutics that lack harmful and addictive qualities of existing medications. We present a model for the binding of morphinan ligands and JDTic to the JDTic/KOR crystal structure based on an atomic level description of the water structure within its active site. The model contains two key interaction motifs that are supported by experimental evidence. The first is the formation of a salt bridge between the ligand and Asp 138^3.32 in transmembrane domain (TM) 3. The second is the stabilization by the ligand of two high energy, isolated, and ice-like waters near TM5 and TM6. This model is incorporated via energetic terms into a new empirical scoring function, WScore, designed to assess interactions between ligands and localized water in a binding site. Pairing WScore with the docking program Glide discriminates known active KOR ligands from large sets of decoy molecules much better than Glide’s older generation scoring functions, SP and XP. We also use rigorous free energy perturbation calculations to provide evidence for the proposed mechanism of interaction between ligands and KOR. The molecular description of ligand binding in KOR should provide a good starting point for future drug discovery efforts for this receptor

Vaccination roll-out:a time to develop and maintain trust in science and health care

Many countries are facing a new phase of the pandemic where COVID-19 vaccine roll-out and uptake takes centre stage. Vaccine hesitancy poses a real challenge in pursuit of this goal. Indeed, the World Health Organization (WHO) listed vaccine hesitancy as one of the top 10 threats to global health.1 The need to understand and support uptake of COVID-19 vaccinations is now imperative. To achieve herd immunity, the virus transmission rate, R, and the performance of the vaccine must be taken into account.2 Given higher transmissibility of new variants, and an optimistic estimate of efficacy of .80, reducing the risk of vaccine recipients getting the disease by 80%, herd immunity may require entire populations to be immunised

Degradable 3D-Printed Hydrogels Based on Star-Shaped Copolypeptides

We present a star copolypeptide-based hydrogel ink capable of structural microfabrication using 3D extrusion printing. The material comprises an amphiphilic block copolymer structure of poly­(benzyl-l-glutamate)-<i>b</i>-oligo­(l-valine), which spontaneously forms hydrogels through hydrophobic interactions. The chemical design allows the bulk phase of the hydrogel to remain intact after application of shear due to its self-recovery behavior. It is demonstrated that the composition of the materials is ideally suited for 3D printing with scaffolds capable of maintaining structural cohesion after extrusion. Post extrusion UV-triggered fixation of the printed structures is carried out, resulting in stable hydrogel constructs. The constructs were found to be degradable, exhibited favorable release of encapsulated molecular cargo, and do not appear to affect the metabolic health of the commonly used fibroblastic cell line Balb/3T3 in the absence of the reactive diluent <i>N</i>,<i>N</i>′-methylenebis­(acrylamide). The star copolypeptide inks allow for rapid prototyping enabling the fabrication of defined intricate microstructures, providing a platform for complex scaffold development that would otherwise be unattainable with other processing techniques such as molding or casting

Supplementary Materials

1.Appendix Showing collecting locality, latitude, longitude, field number, sequence ID, lineage, and GenBank accession numbers for all individuals used in this study.Primer information is shown in Supplementary Table 1

Degradable 3D-Printed Hydrogels Based on Star-Shaped Copolypeptides

We present a star copolypeptide-based hydrogel ink capable of structural microfabrication using 3D extrusion printing. The material comprises an amphiphilic block copolymer structure of poly­(benzyl-l-glutamate)-<i>b</i>-oligo­(l-valine), which spontaneously forms hydrogels through hydrophobic interactions. The chemical design allows the bulk phase of the hydrogel to remain intact after application of shear due to its self-recovery behavior. It is demonstrated that the composition of the materials is ideally suited for 3D printing with scaffolds capable of maintaining structural cohesion after extrusion. Post extrusion UV-triggered fixation of the printed structures is carried out, resulting in stable hydrogel constructs. The constructs were found to be degradable, exhibited favorable release of encapsulated molecular cargo, and do not appear to affect the metabolic health of the commonly used fibroblastic cell line Balb/3T3 in the absence of the reactive diluent <i>N</i>,<i>N</i>′-methylenebis­(acrylamide). The star copolypeptide inks allow for rapid prototyping enabling the fabrication of defined intricate microstructures, providing a platform for complex scaffold development that would otherwise be unattainable with other processing techniques such as molding or casting

Additional file 2: Figure S2. of Cytosolic phospholipase A2 contributes to innate immune defense against Candida albicans lung infection

Expression of cytokines and chemokines in lung tissue from cPLA2α+/+ and cPLA2α−/− mice during C. albicans infection. Real-time PCR was carried out using the Mouse Cytokines & Chemokines RT2 Profiler PCR Array to compare expression in lungs of cPLA2α−/− (KO) and cPLA2α+/+ (WT) mice challenged with saline or 106 C. albicans (CA) for 12 and 24 h (n = 6-10 mice/group in 3–5 experiments). *P < 0.05 compared to WT saline control; ϕ P < 0.05 compared to WT saline control, # P < 0.05 compared to KO saline control; **P < 0.05 compared to WT with CA. (TIF 859 kb

Additional file 1: Figure S1. of Cytosolic phospholipase A2 contributes to innate immune defense against Candida albicans lung infection

Flow cytometry gating strategy for cell identification in lung digests from cPLA2α+/+ (WT) and cPLA2α−/− (KO) mice challenged with C. albicans for 24 h. Cells were isolated from enzymatically digested mouse lungs, and after exclusion of doublets and debris, immune cells were identified by CD45 staining. A sequential gating strategy was used to identify populations expressing specific markers: a alveolar macrophages (AM) (CD45+ CD24− CD11b− SiglecF+), (b) tissue macrophages (TM) (CD45+ CD24− CD11b+), (c) neutrophils (PMN) (CD45+ CD11b+ Ly6G+) and (d) CD11b+ dendritic cells (CD11b+ DCs) (CD45+ MHCII+ CD11c+ CD11b+). (TIF 954 kb