Lost in translation: data integration tools meet the Semantic Web (experiences from the Ondex project)

More information is now being published in machine processable form on the web and, as de-facto distributed knowledge bases are materializing, partly encouraged by the vision of the Semantic Web, the focus is shifting from the publication of this information to its consumption. Platforms for data integration, visualization and analysis that are based on a graph representation of information appear first candidates to be consumers of web-based information that is readily expressible as graphs. The question is whether the adoption of these platforms to information available on the Semantic Web requires some adaptation of their data structures and semantics. Ondex is a network-based data integration, analysis and visualization platform which has been developed in a Life Sciences context. A number of features, including semantic annotation via ontologies and an attention to provenance and evidence, make this an ideal candidate to consume Semantic Web information, as well as a prototype for the application of network analysis tools in this context. By analyzing the Ondex data structure and its usage, we have found a set of discrepancies and errors arising from the semantic mismatch between a procedural approach to network analysis and the implications of a web-based representation of information. We report in the paper on the simple methodology that we have adopted to conduct such analysis, and on issues that we have found which may be relevant for a range of similar platformsComment: Presented at DEIT, Data Engineering and Internet Technology, 2011 IEEE: CFP1113L-CD

A tunable macroscopic quantum system based on two fractional vortices

We propose a tunable macroscopic quantum system based on two fractional vortices. Our analysis shows that two coupled fractional vortices pinned at two artificially created \kappa\ discontinuities of the Josephson phase in a long Josephson junction can reach the quantum regime where coherent quantum oscillations arise. For this purpose we map the dynamics of this system to that of a single particle in a double-well potential. By tuning the \kappa\ discontinuities with injector currents we are able to control the parameters of the effective double-well potential as well as to prepare a desired state of the fractional vortex molecule. The values of the parameters derived from this model suggest that an experimental realisation of this tunable macroscopic quantum system is possible with today's technology.Comment: We updated our manuscript due to a change of the focus from qubit to macroscopic quantum effect

Plasma arginine vasopressin concentrations in epileptics under monotherapy

Plasma arginine vasopressin concentrations were determined by radio-immunoassay in 112 adult epileptics who were taking carbamazepine, phenytoin, primidone, or sodium valproate in long-term monotherapy, and in 19 controls. No significant difference was found between the groups, but some epileptics taking carbamazepine and primidone showed low values. Serum concentrations of carbamazepine did not correlate with the concentrations of plasma arginine vasopressin. In conclusion, there was no evidence of a stimulating effect of chronic carbamazepine medication or a special inhibiting effect of phenytoin on the release of vasopressin arginine from the posterior pituitary

Inflammatory measures in depressed patients with and without a history of adverse childhood experiences

Background: Major depressive disorder (MDD) is a complex psychiatric condition with different subtypes and etiologies. Exposure to adverse childhood experiences (ACE) is an important risk factor for the development of MDD later in life. Evidence suggests that pro-inflammatory processes may convey this risk as both MDD and ACE have been related to increased levels of inflammation. In the present study, we aimed to disentangle the effects of MDD and ACE on inflammation levels. Methods: Markers of inflammation (plasma interleukin(IL)-6 and high sensitive C-reactive protein (hsCRP) concentrations, white blood cell (WBC) count and a composite inflammation score (CIS) combining all three) were assessed in 23 MDD patients with ACE, 23 MDD patients without ACE, 21 healthy participants with ACE, and 21 healthy participants without ACE (mean age: 35 +/- 11 (SD) years). None of the patients and participants was taking psychotropic medication. ACE was assessed with the Early Trauma Inventory (ETI) and was defined as moderate to severe exposure to sexual or physical abuse. Results: Group differences in the different inflammatory measures were observed. MDD patients with ACE showed significantly higher IL-6 concentrations (p = 0.018), higher WBC counts (p = 0.003) and increased general inflammation levels as indicated by the CIS (p = 0.003) compared to healthy controls. In contrast, MDD patients without ACE displayed similar inflammation levels to the control group (p = 0.93). Conclusion: We observed elevated inflammation in MDD patients with a history of ACE, which could indicate a subtype of "inflammatory depression". Accordingly, MDD patients with ACE might potentially benefit from anti-inflammatory therapies

Breit Hamiltonian and QED Effects for Spinless Particles

We describe a simplified derivation for the relativistic corrections of order $\alpha^4$ for a bound system consisting of two spinless particles. We devote special attention to pionium, the bound system of two oppositely charged pions. The leading quantum electrodynamic (QED) correction to the energy levels is of the order of $\alpha^3$ and due to electronic vacuum polarization. We analyze further corrections due to the self-energy of the pions, and due to recoil effects, and we give a complete result for the scalar-QED leading logarithmic corrections which are due to virtual loops involving only the scalar constituent particles (the pions); these corrections are of order $\alpha^5 \ln \alpha$ for S states.Comment: 12 pages, LaTeX; references added (J. Phys. B, in press

Monocyte Metabolic Reprogramming Promotes Pro-Inflammatory Activity and Staphylococcus Aureus Biofilm Clearance

Biofilm-associated prosthetic joint infections (PJIs) cause significant morbidity due to their recalcitrance to immune-mediated clearance and antibiotics, with Staphylococcus aureus (S. aureus) among the most prevalent pathogens. We previously demonstrated that S. aureus biofilm-associated monocytes are polarized to an anti-inflammatory phenotype and the adoptive transfer of pro-inflammatory macrophages attenuated biofilm burden, highlighting the critical role of monocyte/macrophage inflammatory status in dictating biofilm persistence. The inflammatory properties of leukocytes are linked to their metabolic state, and here we demonstrate that biofilm-associated monocytes exhibit a metabolic bias favoring oxidative phosphorylation (OxPhos) and less aerobic glycolysis to facilitate their anti-inflammatory activity and biofilm persistence. To shift monocyte metabolism in vivo and reprogram cells to a pro-inflammatory state, a nanoparticle approach was utilized to deliver the OxPhos inhibitor oligomycin to monocytes. Using a mouse model of S. aureus PJI, oligomycin nanoparticles were preferentially internalized by monocytes, which significantly reduced S. aureus biofilm burden by altering metabolism and promoting the pro-inflammatory properties of infiltrating monocytes as revealed by metabolomics and RT-qPCR, respectively. Injection of oligomycin alone had no effect on monocyte metabolism or biofilm burden, establishing that intracellular delivery of oligomycin is required to reprogram monocyte metabolic activity and that oligomycin lacks antibacterial activity against S. aureus biofilms. Remarkably, monocyte metabolic reprogramming with oligomycin nanoparticles was effective at clearing established biofilms in combination with systemic antibiotics. These findings suggest that metabolic reprogramming of biofilm-associated monocytes may represent a novel therapeutic approach for PJI

Multi-omics subtyping of hepatocellular carcinoma patients using a Bayesian network mixture model

Comprehensive molecular characterization of cancer subtypes is essential for predicting clinical outcomes and searching for personalized treatments. We present bnClustOmics, a statistical model and computational tool for multi-omics unsupervised clustering, which serves a dual purpose: Clustering patient samples based on a Bayesian network mixture model and learning the networks of omics variables representing these clusters. The discovered networks encode interactions among all omics variables and provide a molecular characterization of each patient subgroup. We conducted simulation studies that demonstrated the advantages of our approach compared to other clustering methods in the case where the generative model is a mixture of Bayesian networks. We applied bnClustOmics to a hepatocellular carcinoma (HCC) dataset comprising genome (mutation and copy number), transcriptome, proteome, and phosphoproteome data. We identified three main HCC subtypes together with molecular characteristics, some of which are associated with survival even when adjusting for the clinical stage. Cluster-specific networks shed light on the links between genotypes and molecular phenotypes of samples within their respective clusters and suggest targets for personalized treatments

Development of a Forced Oscillation System for Measuring Dynamic Derivatives of Fluidic Vehicles

A new Forced Oscillation System (FOS) has been designed and built at NASA Langley Research Center that provides new capabilities for aerodynamic researchers to investigate the dynamic derivatives of vehicle configurations. Test vehicles may include high performance and general aviation aircraft, re-entry spacecraft, submarines and other fluidic vehicles. The measured data from forced oscillation testing is used in damping characteristic studies and in simulation databases for control algorithm development and performance analyses. The newly developed FOS hardware provides new flexibility for conducting dynamic derivative studies. The design is based on a tracking principle where a desired motion profile is achieved via a fast closed-loop positional controller. The motion profile for the tracking system is numerically generated and thus not limited to sinusoidal motion. This approach permits non-traditional profiles such as constant velocity and Schroeder sweeps. Also, the new system permits changes in profile parameters including nominal offset angle, waveform, and associated parameters such as amplitude and frequency. Most importantly, the changes may be made remotely without halting the FOS and the tunnel. System requirements, system analysis, and the resulting design are addressed for a new FOS in the 12-Foot Low-Speed Wind Tunnel (LSWT). The overall system including mechanical, electrical, and control subsystems is described. The design is complete, and the FOS has been built and installed in the 12-Foot LSWT. System integration and testing have verified design intent and safe operation. Currently it is being validated for wind-tunnel operations and aerodynamic testing. The system is a potential major enhancement to forced oscillation studies. The productivity gain from the motion profile automation will shorten the testing cycles needed for control surface and aircraft control algorithm development. The new motion capabilities also will serve as a test bed for researchers to study and to improve and/or alter future forced oscillation testing techniques

Stigma against mental health disorders in Nepal conceptualised with a 'what matters most' framework: a scoping review.

Stigma related to mental disorders is a barrier to quality mental healthcare. This scoping review aimed to synthesise literature on stigma related to mental disorders in Nepal to understand stigma processes. The anthropological concept of 'what matters most' to understand culture and stigma was used to frame the literature on explanatory models, manifestations, consequences, structural facilitators and mitigators, and interventions. We conducted a scoping review with screening guided by the Preferred Reporting Items for Systematic Review and Meta-analysis Extension for Scoping Reviews (PRISMA-ScR). A structured search was done using three international databases (PsycINFO, Medline and Web of Science), one Nepali database (NepJol) and cross-referencing for publications from 1 January 2000 through 24 June 2020. The search was repeated to include structural stigma-related terms. Quality of quantitative studies was assessed using the Systematic Assessment of Quality in Observational Research (SAQOR) tool. The review was registered through the Open Science Framework (OSF) (osf.io/u8jhn). The searches yielded 57 studies over a 20-year period: 19 quantitative, 19 qualitative, nine mixed methods, five review articles, two ethnographies and three other types of studies. The review identified nine stigma measures used in Nepal, one stigma intervention, and no studies focused on adolescent and child mental health stigma. The findings suggest that 'what matters most' in Nepali culture for service users, caregivers, community members and health workers include prestige, productivity, privacy, acceptance, marriage and resources. Cultural values related to 'what matters most' are reflected in structural barriers and facilitators including lack of policies, programme planning and resources. Most studies using quantitative tools to assess stigma did not describe cultural adaptation or validation processes, and 15 out of the 18 quantitative studies were 'low-quality' on the SAQOR quality rating. The review revealed clear gaps in implementation and evaluation of stigma interventions in Nepal with only one intervention reported, and most stigma measures not culturally adapted for use. As stigma processes are complex and interlinked in their influence on 'what matters most' and structural barriers and facilitators, more studies are required to understand this complexity and establish effective interventions targeting multiple domains. We suggest that stigma researchers should clarify conceptual models to inform study design and interpretations. There is a need to develop procedures for the systematic cultural adaptation of stigma assessment tools. Research should be conducted to understand the forms and drivers of structural stigma and to expand intervention research to evaluate strategies for stigma reduction

Random noise in Diffusion Tensor Imaging, its Destructive Impact and Some Corrections

The empirical origin of random noise is described, its influence on DTI variables is illustrated by a review of numerical and in vivo studies supplemented by new simulations investigating high noise levels. A stochastic model of noise propagation is presented to structure noise impact in DTI. Finally, basics of voxelwise and spatial denoising procedures are presented. Recent denoising procedures are reviewed and consequences of the stochastic model for convenient denoising strategies are discussed