CD40 is constitutively expressed on platelets and provides a novel mechanism for platelet activation

CD40 is a 48-kDa phosphorylated transmembrane glycoprotein belonging to the TNF receptor superfamily. CD40 has been demonstrated on a range of cell types, and it has an important role in adaptive immunity and inflammation. CD40 has recently been described on platelets but platelet activation by CD40 has not been described. In the present study, we use flow cytometry and immunoblotting to confirm that platelets constitutively express surface CD40. CD40 mRNA was undetectable, suggesting that the protein is synthesized early in platelet differentiation by megakaryocytes. Ligation of platelet CD40 with recombinant soluble CD40L trimer (sCD40LT) caused increased platelet CD62P expression, -granule and dense granule release, and the classical morphological changes associated with platelet activation. CD40 ligation also caused ß3 integrin activation, although this was not accompanied by platelet aggregation. These actions were abrogated by the CD40L blocking antibody TRAP-1 and the CD40 blocking antibodies M2 and M3, showing that activation was mediated by CD40L binding to platelet CD40. ß3 integrin blockade with eptifibatide had no effect, indicating that outside-in signaling via IIbß3 was not contributing to these CD40-mediated effects. CD40 ligation led to enhanced platelet-leukocyte adhesion, which is important in the recruitment of leukocytes to sites of thrombosis or inflammation. Our results support a role for CD40-mediated platelet activation in thrombosis, inflammation, and atherosclerosis

The mediating role of parenting in the associations between household chaos and children’s representations of family dysfunction

Children’s drawings are thought to reflect their mental representations of self and their interpersonal relations within families. Household chaos is believed to disrupt key proximal processes related to optimal development. The present study examines the mediating role of parenting behaviors in the relations between two measures of household chaos, instability and disorganization, and how they may be evidenced in children’s representations of family dysfunction as derived from their drawings. The sample (N= 962) is from a longitudinal study of rural poverty exploring the ways in which child, family, and contextual factors shape development over time. Findings reveal that, after controlling for numerous factors including child and primary caregiver covariates, there were significant indirect effects from cumulative family disorganization, but not cumulative family instability, on children’s representation of family dysfunction through parenting behaviors. Results suggest that the proximal effects of daily disorganization outweigh the effects of periodic instability overtime

Pulsar timing arrays and the challenge of massive black hole binary astrophysics

Pulsar timing arrays (PTAs) are designed to detect gravitational waves (GWs) at nHz frequencies. The expected dominant signal is given by the superposition of all waves emitted by the cosmological population of supermassive black hole (SMBH) binaries. Such superposition creates an incoherent stochastic background, on top of which particularly bright or nearby sources might be individually resolved. In this contribution I describe the properties of the expected GW signal, highlighting its dependence on the overall binary population, the relation between SMBHs and their hosts, and their coupling with the stellar and gaseous environment. I describe the status of current PTA efforts, and prospect of future detection and SMBH binary astrophysics.Comment: 18 pages, 4 figures. To appear in the Proceedings of the 2014 Sant Cugat Forum on Astrophysics. Astrophysics and Space Science Proceedings, ed. C.Sopuerta (Berlin: Springer-Verlag

The energy spectrum of all-particle cosmic rays around the knee region observed with the Tibet-III air-shower array

We have already reported the first result on the all-particle spectrum around the knee region based on data from 2000 November to 2001 October observed by the Tibet-III air-shower array. In this paper, we present an updated result using data set collected in the period from 2000 November through 2004 October in a wide range over 3 decades between $10^{14}$ eV and $10^{17}$ eV, in which the position of the knee is clearly seen at around 4 PeV. The spectral index is -2.68 $\pm$ 0.02(stat.) below 1PeV, while it is -3.12 $\pm$ 0.01(stat.) above 4 PeV in the case of QGSJET+HD model, and various systematic errors are under study now.Comment: 12 pages, 7 figures, accepted by Advances in space researc

A single-center, observational study of 607 children & young people presenting with Differences in Sex Development (DSD)

Context Differences in sex development (DSD) represent a wide range of conditions presenting at different ages to various health professionals. Establishing a diagnosis, supporting the family and developing a management plan are important. Objective We aimed to better understand the presentation and prevalence of pediatric DSD. Design A retrospective, observational cohort study was undertaken of all children and young people (CYP) referred to a DSD multi-disciplinary team over 25 years (1995-2019). Setting A single tertiary paediatric center. Participants In total, 607 CYP (520 regional referrals) were included. Main Outcome Measures Data were analyzed for diagnosis, sex-assignment, age and mode of presentation, additional phenotypic features, mortality, and approximate point prevalence. Results Amongst the three major DSD categories, sex chromosome DSD was diagnosed in 11.2% (68/607) (most commonly 45, X/46, XY mosaicism), 46, XY DSD in 61.1% (371/607) (multiple diagnoses often with associated features), while 46, XX DSD occurred in 27.7% (168/607) (often 21-hydroxylase deficiency). Most children (80.1%) presented as neonates, usually with atypical genitalia, adrenal insufficiency, undescended testes or herniae. Those presenting later had diverse features. Rarely, the diagnosis was made antenatally (3.8%, n = 23) or following incidental karyotyping/family history (n = 14). Mortality was surprisingly high in 46, XY children, usually due to complex associated features (46, XY girls, 8.3%; 46, XY boys, 2.7%). The approximate point prevalence of neonatal referrals for investigation of DSD was 1 in 6,347 births, and 1 in 5,101 overall throughout childhood. Conclusions DSD represent a diverse range of conditions that can present at different ages. Pathways for expert diagnosis and management are important to optimize care

Moon Shadow by Cosmic Rays under the Influence of Geomagnetic Field and Search for Antiprotons at Multi-TeV Energies

We have observed the shadowing of galactic cosmic ray flux in the direction of the moon, the so-called moon shadow, using the Tibet-III air shower array operating at Yangbajing (4300 m a.s.l.) in Tibet since 1999. Almost all cosmic rays are positively charged; for that reason, they are bent by the geomagnetic field, thereby shifting the moon shadow westward. The cosmic rays will also produce an additional shadow in the eastward direction of the moon if cosmic rays contain negatively charged particles, such as antiprotons, with some fraction. We selected 1.5 x10^{10} air shower events with energy beyond about 3 TeV from the dataset observed by the Tibet-III air shower array and detected the moon shadow at $\sim 40 \sigma$ level. The center of the moon was detected in the direction away from the apparent center of the moon by 0.23$^\circ$ to the west. Based on these data and a full Monte Carlo simulation, we searched for the existence of the shadow produced by antiprotons at the multi-TeV energy region. No evidence of the existence of antiprotons was found in this energy region. We obtained the 90% confidence level upper limit of the flux ratio of antiprotons to protons as 7% at multi-TeV energies.Comment: 13pages,4figures; Accepted for publication in Astroparticle Physic