Determinant representation for some transition probabilities in the TASEP with second class particles

We study the transition probabilities for the totally asymmetric simple exclusion process (TASEP) on the infinite integer lattice with a finite, but arbitrary number of first and second class particles. Using the Bethe ansatz we present an explicit expression of these quantities in terms of the Bethe wave function. In a next step it is proved rigorously that this expression can be written in a compact determinantal form for the case where the order of the first and second class particles does not change in time. An independent geometrical approach provides insight into these results and enables us to generalize the determinantal solution to the multi-class TASEP.Comment: Minor revision; journal reference adde

Concentration Dependence of Superconductivity and Order-Disorder Transition in the Hexagonal Rubidium Tungsten Bronze RbxWO3. Interfacial and bulk properties

We revisited the problem of the stability of the superconducting state in RbxWO3 and identified the main causes of the contradictory data previously published. We have shown that the ordering of the Rb vacancies in the nonstoichiometric compounds have a major detrimental effect on the superconducting temperature Tc.The order-disorder transition is first order only near x = 0.25, where it cannot be quenched effectively and Tc is reduced below 1K. We found that the high Tc's which were sometimes deduced from resistivity measurements, and attributed to compounds with .25 < x < .30, are to be ascribed to interfacial superconductivity which generates spectacular non-linear effects. We also clarified the effect of acid etching and set more precisely the low-rubidium-content boundary of the hexagonal phase.This work makes clear that Tc would increase continuously (from 2 K to 5.5 K) as we approach this boundary (x = 0.20), if no ordering would take place - as its is approximately the case in CsxWO3. This behaviour is reminiscent of the tetragonal tungsten bronze NaxWO3 and asks the same question : what mechanism is responsible for this large increase of Tc despite the considerable associated reduction of the electron density of state ? By reviewing the other available data on these bronzes we conclude that the theoretical models which are able to answer this question are probably those where the instability of the lattice plays a major role and, particularly, the model which call upon local structural excitations (LSE), associated with the missing alkali atoms.Comment: To be published in Physical Review

Functional characterisation of the amyotrophic lateral sclerosis risk locus GPX3/TNIP1

Background Amyotrophic lateral sclerosis (ALS) is a complex, late-onset, neurodegenerative disease with a genetic contribution to disease liability. Genome-wide association studies (GWAS) have identified ten risk loci to date, including the TNIP1/GPX3 locus on chromosome five. Given association analysis data alone cannot determine the most plausible risk gene for this locus, we undertook a comprehensive suite of in silico, in vivo and in vitro studies to address this. Methods The Functional Mapping and Annotation (FUMA) pipeline and five tools (conditional and joint analysis (GCTA-COJO), Stratified Linkage Disequilibrium Score Regression (S-LDSC), Polygenic Priority Scoring (PoPS), Summary-based Mendelian Randomisation (SMR-HEIDI) and transcriptome-wide association study (TWAS) analyses) were used to perform bioinformatic integration of GWAS data (Ncases = 20,806, Ncontrols = 59,804) with ‘omics reference datasets including the blood (eQTLgen consortium N = 31,684) and brain (N = 2581). This was followed up by specific expression studies in ALS case-control cohorts (microarray Ntotal = 942, protein Ntotal = 300) and gene knockdown (KD) studies of human neuronal iPSC cells and zebrafish-morpholinos (MO). Results SMR analyses implicated both TNIP1 and GPX3 (p < 1.15 × 10−6), but there was no simple SNP/expression relationship. Integrating multiple datasets using PoPS supported GPX3 but not TNIP1. In vivo expression analyses from blood in ALS cases identified that lower GPX3 expression correlated with a more progressed disease (ALS functional rating score, p = 5.5 × 10−3, adjusted R2 = 0.042, Beffect = 27.4 ± 13.3 ng/ml/ALSFRS unit) with microarray and protein data suggesting lower expression with risk allele (recessive model p = 0.06, p = 0.02 respectively). Validation in vivo indicated gpx3 KD caused significant motor deficits in zebrafish-MO (mean difference vs. control ± 95% CI, vs. control, swim distance = 112 ± 28 mm, time = 1.29 ± 0.59 s, speed = 32.0 ± 2.53 mm/s, respectively, p for all < 0.0001), which were rescued with gpx3 expression, with no phenotype identified with tnip1 KD or gpx3 overexpression. Conclusions These results support GPX3 as a lead ALS risk gene in this locus, with more data needed to confirm/reject a role for TNIP1. This has implications for understanding disease mechanisms (GPX3 acts in the same pathway as SOD1, a well-established ALS-associated gene) and identifying new therapeutic approaches. Few previous examples of in-depth investigations of risk loci in ALS exist and a similar approach could be applied to investigate future expected GWAS findings

Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy

Developmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients’ primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy

Measurement of the cross section for isolated-photon plus jet production in pp collisions at √s=13 TeV using the ATLAS detector

The dynamics of isolated-photon production in association with a jet in proton–proton collisions at a centre-of-mass energy of 13 TeV are studied with the ATLAS detector at the LHC using a dataset with an integrated luminosity of 3.2 fb−1. Photons are required to have transverse energies above 125 GeV. Jets are identified using the anti- algorithm with radius parameter and required to have transverse momenta above 100 GeV. Measurements of isolated-photon plus jet cross sections are presented as functions of the leading-photon transverse energy, the leading-jet transverse momentum, the azimuthal angular separation between the photon and the jet, the photon–jet invariant mass and the scattering angle in the photon–jet centre-of-mass system. Tree-level plus parton-shower predictions from Sherpa and Pythia as well as next-to-leading-order QCD predictions from Jetphox and Sherpa are compared to the measurements