Decentralised bilateral trading, competition for bargaining partners and the “law of one price”

This paper analyses a model of price formation in a market with a finite number of non-identical agents engaging in decentralised bilateral interactions. We focus mainly on equal numbers of buyers and sellers, though we discuss other cases. All characteristics of agents are assumed to be common knowledge. Buyers simultaneously make targeted offers, which sellers can accept or reject. Acceptance leads to a pair exiting and rejection leads to the next period. Offers can be public, private or “ex ante public”. As the discount factor goes to 1, the price in all transactions converges to the same value

Combinations of Qualitative Winning for Stochastic Parity Games

We study Markov decision processes and turn-based stochastic games with parity conditions. There are three qualitative winning criteria, namely, sure winning, which requires all paths to satisfy the condition, almost-sure winning, which requires the condition to be satisfied with probability 1, and limit-sure winning, which requires the condition to be satisfied with probability arbitrarily close to 1. We study the combination of two of these criteria for parity conditions, e.g., there are two parity conditions one of which must be won surely, and the other almost-surely. The problem has been studied recently by Berthon et al. for MDPs with combination of sure and almost-sure winning, under infinite-memory strategies, and the problem has been established to be in NP cap co-NP. Even in MDPs there is a difference between finite-memory and infinite-memory strategies. Our main results for combination of sure and almost-sure winning are as follows: (a) we show that for MDPs with finite-memory strategies the problem is in NP cap co-NP; (b) we show that for turn-based stochastic games the problem is co-NP-complete, both for finite-memory and infinite-memory strategies; and (c) we present algorithmic results for the finite-memory case, both for MDPs and turn-based stochastic games, by reduction to non-stochastic parity games. In addition we show that all the above complexity results also carry over to combination of sure and limit-sure winning, and results for all other combinations can be derived from existing results in the literature. Thus we present a complete picture for the study of combinations of two qualitative winning criteria for parity conditions in MDPs and turn-based stochastic games

Genetic disorders of nuclear receptors.

Following the first isolation of nuclear receptor (NR) genes, genetic disorders caused by NR gene mutations were initially discovered by a candidate gene approach based on their known roles in endocrine pathways and physiologic processes. Subsequently, the identification of disorders has been informed by phenotypes associated with gene disruption in animal models or by genetic linkage studies. More recently, whole exome sequencing has associated pathogenic genetic variants with unexpected, often multisystem, human phenotypes. To date, defects in 20 of 48 human NR genes have been associated with human disorders, with different mutations mediating phenotypes of varying severity or several distinct conditions being associated with different changes in the same gene. Studies of individuals with deleterious genetic variants can elucidate novel roles of human NRs, validating them as targets for drug development or providing new insights into structure-function relationships. Importantly, human genetic discoveries enable definitive disease diagnosis and can provide opportunities to therapeutically manage affected individuals. Here we review germline changes in human NR genes associated with "monogenic" conditions, including a discussion of the structural basis of mutations that cause distinctive changes in NR function and the molecular mechanisms mediating pathogenesis

A Swift study of long-term changes in the X-ray flaring properties of Sagittarius A

The radiative counterpart of the supermassive black hole at the Galactic Centre, Sagittarius A∗, displays flaring emission in the X-ray band atop a steady, quiescent level. Flares are also observed in the near-infrared band. The physical process producing the flares is not fully understood and it is unclear if the flaring rate varies, although some recent works suggest it has reached unprecedented variability in recent years. Using over a decade of regular X-ray monitoring of Neil Gehrels Swift Observatory, we studied the variations in count rate of Sgr A∗ on time-scales of years. We decomposed the X-ray emission into quiescent and flaring emission, modelled as a constant and power-law process, respectively. We found that the complete, multiyear data set cannot be described by a stationary distribution of flare fluxes, while individual years follow this model better. In three of the ten studied years, the data is consistent with a purely Poissonian quiescent distribution, while for 5 yr, only an upper limit of the flare flux distribution parameter could be determined. We find that these possible changes cannot be explained fully by the different number of observations per year. Combined, these results are instead consistent with a changing flaring rate of Sgr A∗, appearing more active between 2006-2007 and 2017-2019, than between 2008-2012. Finally, we discuss this result in the context of flare models and the passing of gaseous objects, and discuss the extra statistical steps taken, for instance, to deal with the background in the Swift observations

Structure-Guided Approach to Relieving Transcriptional Repression in Resistance to Thyroid Hormone α

Mutations in thyroid hormone receptor a (TRα), a ligand-inducible transcription factor, cause resistance to thyroid hormone a (RTHα). This disorder is characterized by tissue-specific hormone refractoriness and hypothyroidism due to the inhibition of target gene expression by mutant TRa-corepressor complexes. Using biophysical approaches, we show that RTHa-associated TRa mutants devoid of ligand-dependent transcription activation function unexpectedly retain the ability to bind thyroid hormone. Visualization of the ligand T3 within the crystal structure of a prototypic TRa mutant validates this notion. This finding prompted the synthesis of different thyroid hormone analogues, identifying a lead compound, ES08, which dissociates corepressor from mutant human TRa more efficaciously than T3. ES08 rescues developmental anomalies in a zebrafish model of RTHa and induces target gene expression in TRa mutation-containing cells from an RTHa patient more effectively than T3. Our observations provide proof of principle for developing synthetic ligands that can relieve transcriptional repression by the mutant TRa-corepressor complex for treatment of RTHa.</p