ArguCast: a system for online multi-forecasting with gradual argumentation

Judgmental forecasting is a form of forecasting which employs (human) users to make predictions about specied future events. Judgmental forecasting has been shown to perform better than quantitative methods for forecasting, e.g. when historical data is unavailable or causal reasoning is needed. However, it has a number of limitations, arising from users’ irrationality and cognitive biases. To mitigate against these phenomena, we leverage on computational argumentation, a eld which excels in the representation and resolution of conicting knowledge and human-like reasoning, and propose novel ArguCast frameworks (ACFs) and the novel online system ArguCast, integrating ACFs. ACFs and ArguCast accommodate multi-forecasting, by allowing multiple users to debate on multiple forecasting predictions simultaneously, each potentially admitting multiple outcomes. Finally, we propose a novel notion of user rationality in ACFs based on votes on arguments in ACFs, allowing the ltering out of irrational opinions before obtaining group forecasting predictions by means commonly used in judgmental forecasting

The Time Machine: A Simulation Approach for Stochastic Trees

In the following paper we consider a simulation technique for stochastic trees. One of the most important areas in computational genetics is the calculation and subsequent maximization of the likelihood function associated to such models. This typically consists of using importance sampling (IS) and sequential Monte Carlo (SMC) techniques. The approach proceeds by simulating the tree, backward in time from observed data, to a most recent common ancestor (MRCA). However, in many cases, the computational time and variance of estimators are often too high to make standard approaches useful. In this paper we propose to stop the simulation, subsequently yielding biased estimates of the likelihood surface. The bias is investigated from a theoretical point of view. Results from simulation studies are also given to investigate the balance between loss of accuracy, saving in computing time and variance reduction.Comment: 22 Pages, 5 Figure

Down-regulation of Delta by proteolytic processing

Notch signaling regulates cell fate decisions during development through local cell interactions. Signaling is triggered by the interaction of the Notch receptor with its transmembrane ligands expressed on adjacent cells. Recent studies suggest that Delta is cleaved to release an extracellular fragment, DlEC, by a mechanism that involves the activity of the metalloprotease Kuzbanian; however, the functional significance of that cleavage remains controversial. Using independent functional assays in vitro and in vivo, we examined the biological activity of purified soluble Delta forms and conclude that Delta cleavage is an important down-regulating event in Notch signaling. The data support a model whereby Delta inactivation is essential for providing the critical ligand/receptor expression differential between neighboring cells in order to distinguish the signaling versus the receiving partner

Death and transfiguration in static staphylococcus epidermidis cultures

The overwhelming majority of bacteria live in slime embedded microbial communities termed biofilms, which are typically adherent to a surface. However, when several Staphylococcus epidermidis strains were cultivated in static liquid cultures, macroscopic aggregates were seen floating within the broth and also sedimented at the test tube bottom. Light- and electron microscopy revealed that early-stage aggregates consisted of bacteria and extracellular matrix, organized in sheetlike structures. Perpendicular under the sheets hung a network of periodically arranged, bacteria-associated strands. During the extended cultivation, the strands of a subpopulation of aggregates developed into cross-connected wall-like structures, in which aligned bacteria formed the walls. The resulting architecture had a compartmentalized appearance. In late-stage cultures, the wall-associated bacteria disintegrated so that, henceforth, the walls were made of the coalescing remnants of lysed bacteria, while the compartment-like organization remained intact. At the same time, the majority of strand containing aggregates with associated culturable bacteria continued to exist. These observations indicate that some strains of Staphylococcus epidermidis are able to build highly sophisticated structures, in which a subpopulation undergoes cell lysis, presumably to provide continued access to nutrients in a nutrient-limited environment, whilst maintaining structural integrity

(un)Doing standards in education with actor-network theory

Recent critiques have drawn important attention to the depoliticized consensus and empty promises embedded in network discourses of educational policy. While acceding this critique, this discussion argues that some forms of network analysis – specifically those adopting actor-network theory (ANT) approaches - actually offer useful theoretical resources for policy studies. Drawing from ANT-inspired studies of policy processes associated with educational standards, the article shows the ambivalences and contradictions as well as the possibilities that can be illuminated by ANT analysis of standards as networks. The discussion outlines the diverse network conceptions, considerations and sensibilities afforded by ANT approaches. Then it shows four phenomena that have been highlighted by ANT studies of educational standards: ordering (and rupturing) practice through ‘immutable mobiles’, local universality, tensions among networks of prescription and networks of negotiation, and different co-existing ontological forms of the same standards. The conclusion suggests starting points, drawing from these ANT-inspired network analyses, for examining policy processes associated with educational standards

Particularized protection: UNSC mandates and the protection of civilians in armed conflict

The protection of civilians at risk in armed conflict has, since the late 1990s, become institutionalized at the United Nations (UN), gaining acceptance as a normative rationale for UN peacekeeping. However, the bulk of civilians in need of protection in armed conflict are unlikely to attain it. The article develops an argument on ‘particularized protection’ - particularized in that UN Security Council (SC) mandates are formulated and adjusted over time to direct mission protection to specific subsets of civilian populations, that is, those relevant to the UN itself, the host state, other states, NGOs and the media, leaving most local civilians receiving little effective protection. Particularized protection, we argue, is a result of the institutional dynamics involving actors producing mandates - the UNSC - and those providing protection - peacekeeping missions - whereby mandates are specified to direct mission protection to selected, particularized groups. We demonstrate these dynamics in two cases, Côte d’Ivoire and Somalia

Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas

RNA polymerase II mediates the transcription of all protein-coding genes in eukaryotic cells, a process that is fundamental to life. Genomic mutations altering this enzyme have not previously been linked to any pathology in humans, which is a testament to its indispensable role in cell biology. On the basis of a combination of next-generation genomic analyses of 775 meningiomas, we report that recurrent somatic p.Gln403Lys or p.Leu438_His439del mutations in POLR2A, which encodes the catalytic subunit of RNA polymerase II (ref. 1), hijack this essential enzyme and drive neoplasia. POLR2A mutant tumors show dysregulation of key meningeal identity genes including WNT6 and ZIC1/ZIC4. In addition to mutations in POLR2A, NF2, SMARCB1, TRAF7, KLF4, AKT1, PIK3CA, and SMO4 we also report somatic mutations in AKT3, PIK3R1, PRKAR1A, and SUFU in meningiomas. Our results identify a role for essential transcriptional machinery in driving tumorigenesis and define mutually exclusive meningioma subgroups with distinct clinical and pathological features

A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies

Microtubule severing enzymes implement a diverse range of tissue-specific molecular functions throughout development and into adulthood. Although microtubule severing is fundamental to many dynamic neural processes, little is known regarding the role of the family member Katanin p60 subunit A-like 1, KATNAL1, in central nervous system (CNS) function. Recent studies reporting that microdeletions incorporating the KATNAL1 locus in humans result in intellectual disability and microcephaly suggest that KATNAL1 may play a prominent role in the CNS; however, such associations lack the functional data required to highlight potential mechanisms which link the gene to disease symptoms. Here we identify and characterise a mouse line carrying a loss of function allele in Katnal1. We show that mutants express behavioural deficits including in circadian rhythms, sleep, anxiety and learning/memory. Furthermore, in the brains of Katnal1 mutant mice we reveal numerous morphological abnormalities and defects in neuronal migration and morphology. Furthermore we demonstrate defects in the motile cilia of the ventricular ependymal cells of mutants, suggesting a role for Katnal1 in the development of ciliary function. We believe the data we present here are the first to associate KATNAL1 with such phenotypes, demonstrating that the protein plays keys roles in a number of processes integral to the development of neuronal function and behaviour.Molecular Psychiatry advance online publication, 4 April 2017; doi:10.1038/mp.2017.54

Loss of PTB or Negative Regulation of Notch mRNA Reveals Distinct Zones of Notch and Actin Protein Accumulation in Drosophila Embryo

Polypyrimidine Tract Binding (PTB) protein is a regulator of mRNA processing and translation. Genetic screens and studies of wing and bristle development during the post-embryonic stages of Drosophila suggest that it is a negative regulator of the Notch pathway. How PTB regulates the Notch pathway is unknown. Our studies of Drosophila embryogenesis indicate that (1) the Notch mRNA is a potential target of PTB, (2) PTB and Notch functions in the dorso-lateral regions of the Drosophila embryo are linked to actin regulation but not their functions in the ventral region, and (3) the actin-related Notch activity in the dorso-lateral regions might require a Notch activity at or near the cell surface that is different from the nuclear Notch activity involved in cell fate specification in the ventral region. These data raise the possibility that the Drosophila embryo is divided into zones of different PTB and Notch activities based on whether or not they are linked to actin regulation. They also provide clues to the almost forgotten role of Notch in cell adhesion and reveal a role for the Notch pathway in cell fusions