Dynamic Controllability of Temporally-flexible Reactive Programs

In this paper we extend dynamic controllability of temporally-flexible plans to temporally-flexible reactive programs. We consider three reactive programming language constructs whose behavior depends on runtime observations; conditional execution, iteration, and exception handling. Temporally-flexible reactive programs are distinguished from temporally-flexible plans in that program execution is conditioned on the runtime state of the world. In addition, exceptions are thrown and caught at runtime in response to violated timing constraints, and handled exceptions are considered successful program executions. Dynamic controllability corresponds to a guarantee that a program will execute to completion, despite runtime constraint violations and uncertainty in runtime state. An algorithm is developed which frames the dynamic controllability problem as an AND/OR search tree over possible program executions. A key advantage of this approach is the ability to enumerate only a subset of possible program executions that guarantees dynamic controllability, framed as an AND/OR solution subtree

Video counselling and psychotherapy:a critical commentary on the evidence base

Pre-pandemic research has suggested that video counselling is as effective as face-to-face practice. However, the mass migration of therapy to the online video domain as a result of the COVID-19 pandemic makes it essential to interrogate the evidence base. This paper provides a critical commentary on how video therapy is defined/labelled, the current evidence about whether video therapy is effective, and whether the working alliance and therapeutic relationship functions differently in video counselling. The paper concludes that while the evidence to date is promising, it is limited in quantity and applicability and hence generalisability. Lack of evidence is not evidence that video therapy is ineffective, but the large gaps in understanding highlight the importance, both ethically and empirically, of further research in this area.</p

Video counselling and psychotherapy: : A critical commentary on the evidence base

Peer reviewe

Elevated Levels of Trace Elements in Cores of Otoliths and Their Potential for Use as Natural Tags

Variation in the chemical composition of fish otoliths has been used in recent years to address a range of ecological questions, including levels of stock mixing, variation in habitat use, and rates of larval exchange. While some of these questions have been answered with varying success, the degree to which discrete populations are connected via larval exchange remains unknown. To identify larval sources using natural variation in otolith chemistry, we must distinguish and measure the chemical composition of the otolith core, the portion of the otolith formed at the spawning site. Using laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS), we found that the core regions of otoliths from 6 different species of fishes were highly enriched in manganese (Mn), and elevated in magnesium (Mg) and barium (Ba), relative to adjacent regions of the otolith. These patterns were consistent for species drawn from different taxonomic groups, which inhabit temperate and tropical regions, are found in marine and freshwater, and utilize a variety of spawning modes. Variation among species in Mn concentration in the core also corresponds to maternal investment, measured by egg size. These data suggest that core enrichment may be a general characteristic of otoliths, and that the chemical composition of the otolith core is fundamentally different from other regions of the otolith. The localized elemental enrichment of the core underscores the importance of methods that analyze the core region in small, discrete samples if otolith chemistry is used to address questions of larval exchange among populations

The Role of Innate APOBEC3G and Adaptive AID Immune Responses in HLA-HIV/SIV Immunized SHIV Infected Macaques

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Cochlear implantation in patients with chronic otitis media: 7 years’ experience in Maastricht

The purpose of this paper is to propose management options for cochlear implantation in chronic otitis media (COM) based on our 7-year experience. Thirteen patients with COM who were candidates for cochlear implantation were identified. COM was divided in an inactive and an active form based on clinical and radiological findings. One major complications and one minor complication were identified in the study group. In case of an active infection or in case of a unstable cavity we advise cochlear implantation as a staged procedure. A single stage procedure is recommended in case of patients with COM presenting with a dry perforation or a stable cavity

Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation.

Induction of antigen-specific CD8(+) T cells offers the prospect of immunization against many infectious diseases, but no subunit vaccine has induced CD8(+) T cells that correlate with efficacy in humans. Here we demonstrate that a replication-deficient chimpanzee adenovirus vector followed by a modified vaccinia virus Ankara booster induces exceptionally high frequency T-cell responses (median >2400 SFC/10(6) peripheral blood mononuclear cells) to the liver-stage Plasmodium falciparum malaria antigen ME-TRAP. It induces sterile protective efficacy against heterologous strain sporozoites in three vaccinees (3/14, 21%), and delays time to patency through substantial reduction of liver-stage parasite burden in five more (5/14, 36%), P=0.008 compared with controls. The frequency of monofunctional interferon-γ-producing CD8(+) T cells, but not antibodies, correlates with sterile protection and delay in time to patency (P(corrected)=0.005). Vaccine-induced CD8(+) T cells provide protection against human malaria, suggesting that a major limitation of previous vaccination approaches has been the insufficient magnitude of induced T cells

Studies on the Restriction of Murine Leukemia Viruses by Mouse APOBEC3

APOBEC3 proteins function to restrict the replication of retroviruses. One mechanism of this restriction is deamination of cytidines to uridines in (−) strand DNA, resulting in hypermutation of guanosines to adenosines in viral (+) strands. However, Moloney murine leukemia virus (MoMLV) is partially resistant to restriction by mouse APOBEC3 (mA3) and virtually completely resistant to mA3-induced hypermutation. In contrast, the sequences of MLV genomes that are in mouse DNA suggest that they were susceptible to mA3-induced deamination when they infected the mouse germline. We tested the possibility that sensitivity to mA3 restriction and to deamination resides in the viral gag gene. We generated a chimeric MLV in which the gag gene was from an endogenous MLV in the mouse germline, while the remainder of the viral genome was from MoMLV. This chimera was fully infectious but its response to mA3 was indistinguishable from that of MoMLV. Thus, the Gag protein does not seem to control the sensitivity of MLVs to mA3. We also found that MLVs inactivated by mA3 do not synthesize viral DNA upon infection; thus mA3 restriction of MLV occurs before or at reverse transcription. In contrast, HIV-1 restricted by mA3 and MLVs restricted by human APOBEC3G do synthesize DNA; these DNAs exhibit APOBEC3-induced hypermutation

Evaluation of a co-culture of rapidly isolated chondrocytes and stem cells seeded on tri-layered collagen-based scaffolds in a caprine osteochondral defect model

Cartilage has poor regenerative capacity and thus damage to the joint surfaces presents a major clinical challenge. Recent research has focussed on the development of tissue-engineered and cell-based approaches for the treatment of cartilage and osteochondral injuries, with current clinically available cell-based approaches including autologous chondrocyte implantation and matrix-assisted autologous chondrocyte implantation. However, these approaches have significant disadvantages due to the requirement for a two-stage surgical procedure and an in vitro chondrocyte expansion phase which increases logistical challenges, hospital times and costs. In this study, we hypothesized that seeding biomimetic tri-layered scaffolds, with proven regenerative potential, with chondrocyte/infrapatellar fat pad stromal cell co-cultures would improve their regenerative capacity compared to scaffolds implanted cell-free. Rapid cell isolation techniques, without the requirement for long term in vitro culture, were utilised to achieve co-cultures of chondrocytes and stromal cells and thus overcome the limitations of existing cell-based techniques. Cell-free and cell-seeded scaffolds were implanted in osteochondral defects, created within the femoral condyle and trochlear ridge, in a translational large animal goat model. While analysis showed trends towards delayed subchondral bone healing in the cell-seeded scaffold group, by the 12 month timepoint the cell-free and cell-seeded groups yield cartilage and bone tissue with comparable quality and quantity. The results of the study reinforce the potential of the biomimetic tri-layered scaffold to repair joint defects but failed to demonstrate a clear benefit from the addition of the CC/FPMSC co-culture to this scaffold. Taking into consideration the additional cost and complexity associated with the cell-seeded scaffold approach, this study demonstrates that the treatment of osteochondral defects using cell-free tri-layered scaffolds may represent a more prudent clinical approach

Encapsidation of APOBEC3G into HIV-1 virions involves lipid raft association and does not correlate with APOBEC3G oligomerization

<p>Abstract</p> <p>Background</p> <p>The cellular cytidine deaminase APOBEC3G (A3G), when incorporated into the human immunodeficiency virus type 1 (HIV-1), renders viral particles non-infectious. We previously observed that mutation of a single cysteine residue of A3G (C100S) inhibited A3G packaging. In addition, several recent studies showed that mutation of tryptophan 127 (W127) and tyrosine 124 (Y124) inhibited A3G encapsidation suggesting that the N-terminal CDA constitutes a viral packaging signal in A3G. It was also reported that W127 and Y124 affect A3G oligomerization.</p> <p>Results</p> <p>Here we studied the mechanistic basis of the packaging defect of A3G W127A and Y124A mutants. Interestingly, cell fractionation studies revealed a strong correlation between encapsidation, lipid raft association, and genomic RNA binding of A3G. Surprisingly, the presence of a C-terminal epitope tag affected lipid raft association and encapsidation of the A3G W127A mutant but had no effect on wt A3G encapsidation, lipid raft association, and interaction with viral genomic RNA. Mutation of Y124 abolished A3G encapsidation irrespective of the presence or absence of an epitope tag. Contrasting a recent report, our co-immunoprecipitation studies failed to reveal a correlation between A3G oligomerization and A3G encapsidation. In fact, our W127A and Y124A mutants both retained the ability to oligomerize.</p> <p>Conclusion</p> <p>Our results confirm that W127 and Y124 residues in A3G are important for encapsidation into HIV-1 virions and our data establish a novel correlation between genomic RNA binding, lipid raft association, and viral packaging of A3G. In contrast, we were unable to confirm a role of W127 and Y124 in A3G oligomerization and we thus failed to confirm a correlation between A3G oligomerization and virus encapsidation.</p