Photo-assisted shot noise in Coulomb interacting systems

We consider the fluctuations of the electrical current (shot noise) in the presence of a voltage time-modulation. For a non-interacting metal, it is known that the derivative of the photo-assisted noise has a staircase behavior. In the presence of Coulomb interactions, we show that the photo-assisted noise presents a more complex profile, in particular for the two following systems: 1) a two-dimensional electron gas in the fractional quantum Hall regime for which we have obtained evenly spaced singularities in the noise derivative, with a spacing related to the filling factor and, 2) a carbon nanotube for which a smoothed staircase in the noise derivative is obtained.Comment: Proceedings of the 6th Rencontres du Vietnam, Hanoi (2006

Towards the convergent therapeutic potential of GPCRs in autism spectrum disorders

Changes in genetic and/or environmental factors to developing neural circuits and subsequent synaptic functions are known to be a causative underlying the varied socio-emotional behavioural patterns associated with autism spectrum disorders (ASD). Seven transmembrane G protein-coupled receptors (GPCRs) comprising the largest family of cell-surface receptors, mediate the transfer of extracellular signals to downstream cellular responses. Disruption of GPCR and their signalling have been implicated as a convergent pathologic mechanism of ASD. Here, we aim to review the literature about the 23 GPCRs that are genetically associated to ASD pathology according to Simons Foundation Autism Research Initiative (SFARI) database such as oxytocin (OXTR) and vasopressin (V1A, V1B) receptors, metabotropic glutamate (mGlu5, mGlu7) and gamma-aminobutyric acid (GABAB) receptors, dopamine (D1, D2), serotoninergic (5-HT1B and additionally included the 5-HT2A, 5-HT7 receptors for their strong relevance to ASD), adrenergic ($\beta$2) and cholinergic (M3) receptors, adenosine (A2A, A3) receptors, angiotensin (AT2) receptors, cannabinoid (CB1) receptors, chemokine (CX3CR1) receptors, orphan (GPR37, GPR85) and olfactory (OR1C1, OR2M4, OR2T10, OR52M1) receptors. We discussed the genetic variants, relation to core ASD behavioural deficits and update on pharmacological compounds targeting these 23 GPCRs. Of these OTR, V1A, mGlu5, D2, 5-HT2A, CB1, and GPR37 serve as the best therapeutic targets and have potential towards core domains of ASD pathology. With a functional crosstalk between different GPCRs and converging pharmacological responses, there is an urge to develop novel therapeutic strategies based on multiple GPCRs to reduce the socioeconomic burden associated with ASD and we strongly emphasize the need to prioritize the increased clinical trials targeting the multiple GPCRs

The SPES Laser Ion Source: Time Structure and Laser Enhancement Measurements with Sm+ beam

A two-step resonance photo-ionization scheme has been used to ionize samarium atoms in the SPES tantalum hot-cavity ion source. The effect of the ion load on the ion beam time structure and the laser enhancement of the ion yield has been studied at different ion source temperatures. Generally, the introduction of more positive ions (ion load) affects negatively the overall confinement of the laser ions inside the volume of the ion source. Possible enhancement of the laser ion confinement through the introduction of neutrals is observed as well. The ion load is also observed to affect the confinement in the transfer line much more than in the hot cavity. Measurement of the time structure with inverted polarity of the cavity DC heating supply confirmed the significance of the longitudinal potential for ion extraction. The laser enhancements of the ion yield are found to be sensitive to the ion load at low operating temperature of the ion source i.e. 1800°C, whereas at 2050°C and 2200°C, they are relatively stable till an ion load value of 1.2 μA

First laser ions at the CERN-MEDICIS facility

The CERN-MEDICIS facility aims to produce emerging medical radionuclides for the theranostics approach in nuclear medicine with mass separation of ion beams. To enhance the radioisotope yield and purity of collected samples, the resonance ionization laser ion source MELISSA was constructed, and provided the first laser ions at the facility in 2019. Several operational tests were accomplished to investigate its performance in preparation for the upcoming production of terbium radioisotopes, which are of particular interest for medical applications. © 2020, The Author(s).KU LeuvenHorizon 2020: 642889 MEDICIS-PROMED05P12UMCIA, 05P15UMCIAOpen Access funding provided by Projekt DEAL. We would like to acknowledge the help and assistance from the whole MEDICIS collaboration; from CERN-ISOLDE Technical and Physical groups. This research project has been supported by a Marie Skłodowska-Curie Innovative Training Network Fellowship of the European Commission’s Horizon 2020 Programme under contract number 642889 MEDICIS-PROMED; by the German Federal Ministry of Education and Research under the consecutive projects 05P12UMCIA and 05P15UMCIA; by the Research Foundation Flanders FWO (Belgium) and by a KU Leuven START grant

Absence of Inhibin Alpha and Retinoblastoma Protein Leads to Early Sertoli Cell Dysfunction

Sertoli cells, the support cells of mammalian spermatogenesis, are regulated by a number of nuclear factors and express retinoblastoma (RB) tumor suppressor protein. We hypothesized that RB is an important mediator of Sertoli cell tumorigenesis in inhibin α knockout (Inha KO) mice. In our previous mouse studies, we found that conditional knockout (cKO) of Rb in Sertoli cells caused progressive Sertoli cell dysfunction. Initially, loss of RB had no gross effect on Sertoli cell function as the mice were fertile with normal testis weights at 6 weeks of age, but by 10–14 weeks of age, mutant mice demonstrated severe Sertoli cell dysfunction and infertility. Although double knockout (dKO) of Rb and Inha did not result in exacerbation of the tumorigenic phenotype of Inha-null mice, we found that the dKO mice demonstrate an acceleration of Sertoli cell dysfunction compared to Rb cKO mice. Specifically, in contrast to Rb cKO mice, Inha/Rb dKO mice showed signs of Sertoli cell dysfunction as early as 4 weeks of age. These results demonstrate that RB is not essential for Sertoli cell tumorigenesis in Inha KO mice but that loss of Inha accelerates the infertility phenotype of Rb cKO mice

QTL linkage analysis of connected populations using ancestral marker and pedigree information

The common assumption in quantitative trait locus (QTL) linkage mapping studies that parents of multiple connected populations are unrelated is unrealistic for many plant breeding programs. We remove this assumption and propose a Bayesian approach that clusters the alleles of the parents of the current mapping populations from locus-specific identity by descent (IBD) matrices that capture ancestral marker and pedigree information. Moreover, we demonstrate how the parental IBD data can be incorporated into a QTL linkage analysis framework by using two approaches: a Threshold IBD model (TIBD) and a Latent Ancestral Allele Model (LAAM). The TIBD and LAAM models are empirically tested via numerical simulation based on the structure of a commercial maize breeding program. The simulations included a pilot dataset with closely linked QTL on a single linkage group and 100 replicated datasets with five linkage groups harboring four unlinked QTL. The simulation results show that including parental IBD data (similarly for TIBD and LAAM) significantly improves the power and particularly accuracy of QTL mapping, e.g., position, effect size and individuals’ genotype probability without significantly increasing computational demand

Gene and QTL detection in a three-way barley cross under selection by a mixed model with kinship information using SNPs

Quantitative trait locus (QTL) detection is commonly performed by analysis of designed segregating populations derived from two inbred parental lines, where absence of selection, mutation and genetic drift is assumed. Even for designed populations, selection cannot always be avoided, with as consequence varying correlation between genotypes instead of uniform correlation. Akin to linkage disequilibrium mapping, ignoring this type of genetic relatedness will increase the rate of false-positives. In this paper, we advocate using mixed models including genetic relatedness, or ‘kinship’ information for QTL detection in populations where selection forces operated. We demonstrate our case with a three-way barley cross, designed to segregate for dwarfing, vernalization and spike morphology genes, in which selection occurred. The population of 161 inbred lines was screened with 1,536 single nucleotide polymorphisms (SNPs), and used for gene and QTL detection. The coefficient of coancestry matrix was estimated based on the SNPs and imposed to structure the distribution of random genotypic effects. The model incorporating kinship, coancestry, information was consistently superior to the one without kinship (according to the Akaike information criterion). We show, for three traits, that ignoring the coancestry information results in an unrealistically high number of marker–trait associations, without providing clear conclusions about QTL locations. We used a number of widely recognized dwarfing and vernalization genes known to segregate in the studied population as landmarks or references to assess the agreement of the mapping results with a priori candidate gene expectations. Additional QTLs to the major genes were detected for all traits as well