The Universal Plausibility Metric (UPM) & Principle (UPP)

<p>Abstract</p> <p>Background</p> <p>Mere possibility is not an adequate basis for asserting scientific plausibility. A precisely defined universal bound is needed beyond which the assertion of <it>plausibility</it>, particularly in life-origin models, can be considered operationally falsified. But can something so seemingly relative and subjective as plausibility ever be quantified? Amazingly, the answer is, "Yes." A method of objectively measuring the plausibility of any chance hypothesis (The Universal Plausibility Metric [UPM]) is presented. A numerical inequality is also provided whereby any chance hypothesis can be definitively falsified when its UPM metric of ξ is < 1 (The Universal Plausibility Principle [UPP]). Both UPM and UPP pre-exist and are independent of any experimental design and data set.</p> <p>Conclusion</p> <p>No low-probability hypothetical plausibility assertion should survive peer-review without subjection to the UPP inequality standard of formal falsification (ξ < 1).</p

ALMA reveals a chemically evolved submillimeter galaxy at z=4.76

The chemical properties of high-z galaxies provide important information to constrain galaxy evolutionary scenarios. However, widely-used metallicity diagnostics based on rest-frame optical emission lines are not usable for heavily dust-enshrouded galaxies (such as Sub-Millimeter Galaxies; SMGs), especially at z>3. Here we focus on the flux ratio of the far-infrared fine-structure emission lines [NII]205um and [CII]158um to assess the metallicity of high-z SMGs. Through ALMA cycle 0 observations, we have detected the [NII]205um emission in a strongly [CII]-emitting SMG, LESS J033229.4-275619 at z=4.76. The velocity-integrated [NII]/[CII] flux ratio is 0.043 +/- 0.008. This is the first measurement of the [NII]/[CII] flux ratio in high-z galaxies, and the inferred flux ratio is similar to the ratio observed in the nearby universe (~0.02-0.07). The velocity-integrated flux ratio and photoionization models suggest that the metallicity in this SMG is consistent with solar, implying the chemical evolution has progressed very rapidly in this system at z=4.76. We also obtain a tight upper limit on the CO(12-11) transition, which translates into CO(12-11)/CO(2-1) <3.8 (3 sigma). This suggests that the molecular gas clouds in LESS J033229.4-275619 are not affected significantly by the radiation field emitted by the AGN in this system.Comment: 5 pages, 3 figures, accepted for publication in Astronomy and Astrophysics Letter

Open Design: Contributions, Solutions, Processes and Projects

Open design is a catchall term for various on- and offline design and making activities. It can be used to describe a type of design process that allows for (is open to) the participation of anybody (novice or professional) in the collaborative development of something. As well as this, it can mean the distribution and unrestricted use of design blueprints and documentation for the use by others. In this paper, the authors highlight various aspects of open and collaborative design and argue for the use of new terms that address what is open and when. A range of design projects and online platforms that have open attributes are then explored, whereby these terms are applied. In terms of design, the focus is specifically on the design of physical things rather than graphical, software or system design

Altered Microbiota, Impaired Quality of Life, Malabsorption, Infection, and Inflammation in CVID Patients With Diarrhoea

© Copyright © 2020 van Schewick, Nöltner, Abel, Burns, Workman, Symes, Guzman, Proietti, Bulashevska, Moreira, Soetedjo, Lowe and Grimbacher. Background: Diarrhoea is the commonest gastrointestinal symptom in patients with common variable immunodeficiency (CVID). Objective: The aim of this study was to describe the prevalence and clinical presentation of chronic and recurrent diarrhoea in the Royal-Free-Hospital (RFH) London CVID cohort, including symptoms, infections, level of inflammation, and microbial diversity. Methods: A cross-sectional study of adult CVID patients (139 out of 172 diagnosed with CVID completed the screening questionnaire). Those with diarrhoea ≥6 days/month had stool and blood samples analysed and completed the short Inflammatory Bowel Disease Questionnaire (sIBDQ). BMI, spleen-size, lymphocytes and gut-microbial diversity were compared. Due to logistical and clinical restraints, not all patients could be analysed on all measures. Results: 46/139 (33.1%) patients had current significant diarrhoea. In patients with past or present diarrhoea, BMI was lower (median 23.7 vs. 26, p = 0.005), malabsorption more common (57.97 vs. 35.71%, p = 0.011). CD4+ lymphocytes were higher in patients with diarrhoea (p = 0.028; n = 138), but CD4+ naïve lymphocytes were significantly higher in non-diarrhoea patients (p = 0.009, N = 28). Nine patients had confirmed or probable current gastrointestinal infections. Calprotectin was >60 μg/g in 13/29 with significant diarrhoea including 9 without infection. SIBDQ revealed a low median score of 4.74. Microbial alpha diversity was significantly lower in CVID patients compared to healthy household controls. There was no significant difference in alpha diversity in relation to antibiotic intake during the 6 weeks prior to providing samples. Conclusion: Patients with CVID and significant diarrhoea had infections, raised calprotectin, malabsorption, a lower BMI, an impaired quality of life (comparable to active IBD), and they differed from non-diarrhoea patients in their lymphocyte phenotyping. Furthermore, microbial diversity was altered. These findings strongly imply that there may be an inflammatory nature and a systemic predisposition to diarrhoea in CVID, which necessitates further investigation

Functional characterization of generalized Langevin equations

We present an exact functional formalism to deal with linear Langevin equations with arbitrary memory kernels and driven by any noise structure characterized through its characteristic functional. No others hypothesis are assumed over the noise, neither the fluctuation dissipation theorem. We found that the characteristic functional of the linear process can be expressed in terms of noise's functional and the Green function of the deterministic (memory-like) dissipative dynamics. This object allow us to get a procedure to calculate all the Kolmogorov hierarchy of the non-Markov process. As examples we have characterized through the 1-time probability a noise-induced interplay between the dissipative dynamics and the structure of different noises. Conditions that lead to non-Gaussian statistics and distributions with long tails are analyzed. The introduction of arbitrary fluctuations in fractional Langevin equations have also been pointed out

Establishment of proximity-dependent biotinylation approaches in different plant model systems

Proximity labeling is a powerful approach for detecting protein-protein interactions. Most proximity labeling techniques use a promiscuous biotin ligase (PBL) or a peroxidase fused to a protein of interest, enabling the covalent biotin labelling of proteins and subsequent capture and identification of interacting and neighbouring proteins without the need for the protein complex to remain intact. To date, only few papers report on the use of proximity labeling in plants. Here, we present the results of a systematic study applying a variety of biotin-based proximity labeling approaches in several plant systems using various conditions and bait proteins. We show that TurboID is the most promiscuous variant in several plant model systems and establish protocols which combine Mass Spectrometry-based analysis with harsh extraction and washing conditions. We demonstrate the applicability of TurboID in capturing membrane-associated protein interactomes using Lotus japonicus symbiotically active receptor kinases as test-case. We further benchmark the efficiency of various PBLs in comparison with one-step affinity purification approaches. We identified both known as well as novel interactors of the endocytic TPLATE complex. We furthermore present a straightforward strategy to identify both non-biotinylated as well as biotinylated peptides in a single experimental setup. Finally, we provide initial evidence that our approach has the potential to infer structural information of protein complexes

Population III stars and the Long Gamma Ray Burst rate

Because massive, low-metallicity population III (PopIII) stars may produce very powerful long gamma-ray bursts (LGRBs), high-redshift GRB observations could probe the properties of the first stars. We analyze the correlation between early PopIII stars and LGRBs by using cosmological N-body/hydrodynamical simulations, which include detailed chemical evolution, cooling, star formation, feedback effects and the transition between PopIII and more standard population I/II (PopII/I) stars. From the Swift observed rate of LGRBs, we estimate the fraction of black holes that will produce a GRB from PopII/I stars to be in the range 0.028<f_{GRB}<0.140, depending on the assumed upper metallicity of the progenitor. Assuming that as of today no GRB event has been associated to a PopIII star, we estimate the upper limit for the fraction of LGRBs produced by PopIII stars to be in the range 0.006<f_{GRB}<0.022. When we apply a detection threshold compatible with the BAT instrument, we find that the expected fraction of PopIII GRBs (GRB3) is ~10% of the full LGRB population at z>6, becoming as high has 40% at z>10. Finally, we study the properties of the galaxies hosting our sample of GRB3. We find that the average metallicity of the galaxies hosting a GRB3 is typically higher than the critical metallicity used to select the PopIII stars, due to the efficiency in polluting the gas above such low values. We also find that the highest probability of finding a GRB3 is within galaxies with a stellar mass <10^7 Msun, independently from the redshift.Comment: 8 pages,3 figures. Submitted to MNRAS, revised version after referee's comment

RNAseq Analyses Identify Tumor Necrosis Factor-Mediated Inflammation as a Major Abnormality in ALS Spinal Cord

ALS is a rapidly progressive, devastating neurodegenerative illness of adults that produces disabling weakness and spasticity arising from death of lower and upper motor neurons. No meaningful therapies exist to slow ALS progression, and molecular insights into pathogenesis and progression are sorely needed. In that context, we used high-depth, next generation RNA sequencing (RNAseq, Illumina) to define gene network abnormalities in RNA samples depleted of rRNA and isolated from cervical spinal cord sections of 7 ALS and 8 CTL samples. We aligned \u3e50 million 2X150 bp paired-end sequences/sample to the hg19 human genome and applied three different algorithms (Cuffdiff2, DEseq2, EdgeR) for identification of differentially expressed genes (DEG’s). Ingenuity Pathways Analysis (IPA) and Weighted Gene Co-expression Network Analysis (WGCNA) identified inflammatory processes as significantly elevated in our ALS samples, with tumor necrosis factor (TNF) found to be a major pathway regulator (IPA) and TNFα-induced protein 2 (TNFAIP2) as a major network “hub” gene (WGCNA). Using the oPOSSUM algorithm, we analyzed transcription factors (TF) controlling expression of the nine DEG/hub genes in the ALS samples and identified TF’s involved in inflammation (NFkB, REL, NFkB1) and macrophage function (NR1H2::RXRA heterodimer). Transient expression in human iPSC-derived motor neurons of TNFAIP2 (also a DEG identified by all three algorithms) reduced cell viability and induced caspase 3/7 activation. Using high-density RNAseq, multiple algorithms for DEG identification, and an unsupervised gene co-expression network approach, we identified significant elevation of inflammatory processes in ALS spinal cord with TNF as a major regulatory molecule. Overexpression of the DEG TNFAIP2 in human motor neurons, the population most vulnerable to die in ALS, increased cell death and caspase 3/7 activation. We propose that therapies targeted to reduce inflammatory TNFα signaling may be helpful in ALS patients

Knowledge formalization in experience feedback processes : an ontology-based approach

Because of the current trend of integration and interoperability of industrial systems, their size and complexity continue to grow making it more difficult to analyze, to understand and to solve the problems that happen in their organizations. Continuous improvement methodologies are powerful tools in order to understand and to solve problems, to control the effects of changes and finally to capitalize knowledge about changes and improvements. These tools involve suitably represent knowledge relating to the concerned system. Consequently, knowledge management (KM) is an increasingly important source of competitive advantage for organizations. Particularly, the capitalization and sharing of knowledge resulting from experience feedback are elements which play an essential role in the continuous improvement of industrial activities. In this paper, the contribution deals with semantic interoperability and relates to the structuring and the formalization of an experience feedback (EF) process aiming at transforming information or understanding gained by experience into explicit knowledge. The reuse of such knowledge has proved to have significant impact on achieving themissions of companies. However, the means of describing the knowledge objects of an experience generally remain informal. Based on an experience feedback process model and conceptual graphs, this paper takes domain ontology as a framework for the clarification of explicit knowledge and know-how, the aim of which is to get lessons learned descriptions that are significant, correct and applicable

The Paradox of Power in CSR: A Case Study on Implementation

Purpose Although current literature assumes positive outcomes for stakeholders resulting from an increase in power associated with CSR, this research suggests that this increase can lead to conflict within organizations, resulting in almost complete inactivity on CSR. Methods A single in-depth case study, focusing on power as an embedded concept. Results Empirical evidence is used to demonstrate how some actors use CSR to improve their own positions within an organization. Resource dependence theory is used to highlight why this may be a more significant concern for CSR. Conclusions Increasing power for CSR has the potential to offer actors associated with it increased personal power, and thus can attract opportunistic actors with little interest in realizing the benefits of CSR for the company and its stakeholders. Thus power can be an impediment to furthering CSR strategy and activities at the individual and organizational level