Objective prior for the number of degrees of freedom of a t distribution

In this paper, we construct an objective prior for the degrees of freedom of a t distribution, when the parameter is taken to be discrete. This parameter is typically problematic to estimate and a problem in objective Bayesian inference since improper priors lead to improper posteriors, whilst proper priors may dom- inate the data likelihood. We find an objective criterion, based on loss functions, instead of trying to define objective probabilities directly. Truncating the prior on the degrees of freedom is necessary, as the t distribution, above a certain number of degrees of freedom, becomes the normal distribution. The defined prior is tested in simulation scenarios, including linear regression with t-distributed errors, and on real data: the daily returns of the closing Dow Jones index over a period of 98 days

Liquidity in second tier equity markets: evidence from London's Alternative Investment Market (AIM)

This paper studies liquidity provision in the Alternative Investment Market (AIM) of the London Stock Exchange. Our analysis shows that it is possible to generate sufficient liquidity in a small company market. Indeed, a small group of AIM stocks are found to trade frequently, exposing the investor to minimal execution risk. At the same time, we find that the majority of AIM stocks trade infrequently, with trades often clustered around a few days. We find the latter group to be further characterised by higher price volatility and wider spreads, indicating that for the majority of AIM stocks, immediacy risk is an issue of concern. When studying AIM stocks that were transferred from the Rule 4.2. market, we report a significant increase in trading activity, but surprisingly little change in liquidity as measured by either price volatility or trading costs. Finally, we develop a statistical model to identify the main determinants of liquidity. We find that a higher market capitalisation and a higher free float both contribute to a larger number of trades, lower trade concentration, lower price volatility and lower effective spreads. There also seems to be a technology effect, in that technology firms are more actively traded and enjoy lower trading costs, in the form of lower average effective spreads. At the same time, our empirical evidence seems to indicate that there is no "average" AIM stock, and that liquidity is therefore difficult to predict

On a Class of Objective Prior from Scoring Rules

Objective prior distributions represent an important tool that allows one to have the advantages of using a Bayesian framework even when information about the parameters of a model is not available. The usual objective approaches work off the chosen statistical model and in the majority of cases the resulting prior is improper, which can pose limitations to a practical implementation, even when the complexity of the model is moderate. In this paper we propose to take a novel look at the construction of objective prior distributions, where the connection with a chosen sampling distribution model is removed. We explore the notion of defining objective prior distributions which allow one to have some degree of flexibility, in particular in exhibiting some desirable features, such as being proper, or log-concave, convex etc. The basic tool we use are proper scoring rules and the main result is a class of objective prior distributions that can be employed in scenarios where the usual model based priors fail, such as mixture models and model selection via Bayes factors. In addition, we show that the proposed class of priors is the result of minimising the information it contains, providing solid interpretation to the method

Parkin-independent mitophagy controls chemotherapeutic response in cancer cells

Mitophagy is an evolutionarily conserved process that selectively targets impaired mitochondria for degradation. Defects in mitophagy are often associated with diverse pathologies, including cancer. Because the main known regulators of mitophagy are frequently inactivated in cancer cells, the mechanisms that regulate mitophagy in cancer cells are not fully understood. Here, we identified an E3 ubiquitin ligase (ARIH1/HHARI) that triggers mitophagy in cancer cells in a PINK1-dependent manner. We found that ARIH1/HHARI polyubiquitinates damaged mitochondria, leading to their removal via autophagy. Importantly, ARIH1 is widely expressed in cancer cells, notably in breast and lung adenocarcinomas; ARIH1 expression protects against chemotherapy-induced death. These data challenge the view that the main regulators of mitophagy are tumor suppressors, arguing instead that ARIH1-mediated mitophagy promotes therapeutic resistance

Targeting multi-loop integrals with neural networks

Numerical evaluations of Feynman integrals often proceed via a deformation of the integration contour into the complex plane. While valid contours are easy to construct, the numerical precision for a multi-loop integral can depend critically on the chosen contour. We present methods to optimize this contour using a combination of optimized, global complex shifts and a normalizing flow. They can lead to a significant gain in precision

Immune checkpoint inhibitors in cancer therapy: Review of orofacial adverse events and role of the oral healthcare provider

Immune checkpoint inhibitors (ICIs) are a revolutionary class of antineoplastic therapy that restore anti-tumor immunity. Consequences of this enhanced immune response include a multitude of immune related adverse events (irAEs) that can affect any body system, including the mouth. Orofacial irAEs reproduce features of numerous immune-mediated conditions, including oral lichen planus, mucous membrane pemphigoid, and Sjögren syndrome, among others. The aim of this review is to summarize known orofacial irAEs and to familiarize oral healthcare providers with how to identify and manage these toxicities as part of the care team for patients treated with ICIs

Structure-activity analysis of CJ-15,801 analogues that interact with Plasmodium falciparum pantothenate kinase and inhibit parasite proliferation

Survival of the human malaria parasite Plasmodium falciparum is dependent on pantothenate (vitamin B5), a precursor of the fundamental enzyme cofactor coenzyme A. CJ-15,801, an enamide analogue of pantothenate isolated from the fungus Seimatosporium sp. CL28611, was previously shown to inhibit P. falciparum proliferation in vitro by targeting pantothenate utilization. To inform the design of next generation analogues, we set out to synthesize and test a series of synthetic enamide-bearing pantothenate analogues. We demonstrate that conservation of the R-pantoyl moiety and the trans-substituted double bond of CJ-15,801 is important for the selective, on-target antiplasmodial effect, while replacement of the carboxyl group is permitted, and, in one case, favored. Additionally, we show that the antiplasmodial potency of CJ-15,801 analogues that retain the R-pantoyl and trans-substituted enamide moieties correlates with inhibition of P. falciparum pantothenate kinase (PfPanK)-catalyzed pantothenate phosphorylation, implicating the interaction with PfPanK as a key determinant of antiplasmodial activity.C.S. was funded by an NHMRC Overseas Biomedical Fellowship (1016357). EPSRC and Syngenta provided postgraduate support (MJV) and a Leadership Fellowship (RM). Additional support was provided by Dr. Ian Sword, the EPSRC (grant EP/H005692/1) and the COST Action CM0801