Diffusions on a space of interval partitions: The two-parameter model

We study interval partition diffusions with Poisson--Dirichlet$(\alpha,\theta)$ stationary distribution for parameters $\alpha\in(0,1)$ and $\theta\ge 0$. This extends previous work on the cases $(\alpha,0)$ and $(\alpha,\alpha)$ and builds on our recent work on measure-valued diffusions. We work on spaces of interval partitions with $\alpha$-diversity. These processes can be viewed as diffusions on the boundary of a branching graph of integer compositions. The additional order and diversity structure of such interval partitions is essential for applications to continuum random tree models such as stable CRTs and limit structures of other regenerative tree growth processes, where intervals correspond to masses of spinal subtrees (or spinal bushes) in spinal order and diversities give distances between any two spinal branch points. We further show that our processes can be extended to enter continuously from the Hausdorff completion of our state space and that, in contrast to the measure-valued setting, these extensions are Feller processes.Comment: 34 pages, 7 figures. Version 2: the Feller property in Theorem 1.8 is adde

A two-parameter family of measure-valued diffusions with Poisson-Dirichlet stationary distributions

We give a pathwise construction of a two-parameter family of purely-atomic-measure-valued diffusions in which ranked masses of atoms are stationary with the Poisson-Dirichlet$(\alpha,\theta)$ distributions, for $\alpha\in (0,1)$ and $\theta\ge 0$. This resolves a conjecture of Feng and Sun (2010). We build on our previous work on $(\alpha,0)$- and $(\alpha,\alpha)$-interval partition evolutions. Indeed, we first extract a self-similar superprocess from the levels of stable processes whose jumps are decorated with squared Bessel excursions and distinct allelic types. We complete our construction by time-change and normalisation to unit mass. In a companion paper, we show that the ranked masses of the measure-valued processes evolve according to a two-parameter family of diffusions introduced by Petrov (2009), extending work of Ethier and Kurtz (1981). These ranked-mass diffusions arise as continuum limits of up-down Markov chains on Chinese restaurant processes.Comment: 57 pages, 5 figure

A study of certain accommodative findings under constant illumination with two different wavelengths of light

A study of certain accommodative findings under constant illumination with two different wavelengths of ligh

Neuroendocrine tumor of the pancreas causing biliary obstruction in a 12 year-old girl: A case report and literature review

Pancreatic tumors are uncommon in children and rarely result in biliary obstruction. A previously well 12-year old female presented with a one-week history of fatigue, pruritis, and painless jaundice. Abdominal ultrasound demonstrated a mass in the pancreatic head associated with dilation of the common bile duct. Further workup included abdominal MRI, CT and endoscopic retrograde pancreaticogram (ERCP) with biliary stenting. Octreotide scan did not reveal uptake in the pancreatic tumor. Percutaneous biopsies were consistent with a grade 2 pancreatic neuroendocrine tumor (NET). Preoperative imaging demonstrated involvement of the portal vein. The patient was brought the operating room for a pancreaticoduodenectomy and portal vein resection. Final pathology revealed a T3N1M0 pancreatic NET. The patient recovered uneventfully

Blast in Context: The Neuropsychological and Neurocognitive Effects of Long-Term Occupational Exposure to Repeated Low-Level Explosives on Canadian Armed Forces\u27 Breaching Instructors and Range Staff

Currently, there is strong interest within the military to better understand the effects of long-term occupational exposure to repeated low-level blast on health and performance. To gain traction on the chronic sequelae of blast, we focused on breaching—a tactical technique for gaining entry into closed/blocked spaces by placing explosives and maintaining a calculated safe distance from the detonation. Using a cross-sectional design, we compared the neuropsychological and neurocognitive profiles of breaching instructors and range staff to sex- and age-matched Canadian Armed Forces (CAF) controls. Univariate tests demonstrated that breaching was associated with greater post-concussive symptoms (Rivermead Post Concussion Symptoms Questionnaire) and lower levels of energy (RAND SF-36). In addition, breaching instructors and range staff were slower on a test that requires moving and thinking simultaneously (i.e., cognitive-motor integration). Next, using a multivariate approach, we explored the impact of other possible sources of injury, including concussion and prior war-zone deployment on the same outcomes. Concussion history was associated with higher post-concussive scores and musculoskeletal problems, whereas deployment was associated with higher post-concussive scores, but lower energy and greater PTSD symptomatology (using PCL-5). Our results indicate that although breaching, concussion, and deployment were similarly correlated with greater post-concussive symptoms, concussion history appears to be uniquely associated with altered musculoskeletal function, whereas deployment history appears to be uniquely associated with lower energy and risk of PTSD. We argue that the broader injury context must, therefore, be considered when studying the impact of repetitive low-level explosives on health and performance in military members

Multi-omics analysis of severe fever with thrombocytopenia syndrome virus infection in Rhipicephalus microplus cells reveals antiviral tick factors.

Abstract The increasing prevalence of tick-borne arboviral infections worldwide necessitates advanced control strategies, particularly those targeting vectors, to mitigate the disease burden. However, the cellular interactions between arboviruses and ticks, especially for negative-strand RNA viruses, remain largely unexplored. Here, we employed a proteomics informed by transcriptomics approach to elucidate the cellular response of the Rhipicephalus microplus-derived BME/CTVM6 cell line to severe fever with thrombocytopenia syndrome virus (SFTSV) infection. We generated the first de novo transcriptomes and proteomes of SFTSV- and mock-infected tick cells, identifying key host responses and regulatory pathways. Additionally, interactome analysis of the viral nucleoprotein (N) integrated host responses with viral replication mechanisms. Finally, our dsRNA-mediated gene silencing screen revealed two novel anti-SFTSV effectors, the RNA helicases, DHX9 and UPF1. Collectively, our results provide new insights into the antiviral responses of Rhipicephalus microplus vector cells and highlight critical SFTSV restriction factors, while enriching transcriptomic and proteomic resources for future research.</p

Biomarkers of neurodegeneration and glial activation validated in Alzheimer’s disease assessed in longitudinal cerebrospinal fluid samples of Parkinson’s disease

Aim: Several pathophysiological processes are involved in Parkinson's disease (PD) and could inform in vivo biomarkers. We assessed an established biomarker panel, validated in Alzheimer's Disease, in a PD cohort. Methods: Longitudinal cerebrospinal fluid (CSF) samples from PPMI (252 PD, 115 healthy controls, HC) were analyzed at six timepoints (baseline, 6, 12, 24, 36, and 48 months follow-up) using Elecsys® electrochemiluminescence immunoassays to quantify neurofilament light chain (NfL), soluble TREM2 receptor (sTREM2), chitinase-3-like protein 1 (YKL40), glial fibrillary acidic protein (GFAP), interleukin-6 (IL-6), S100, and total α-synuclein (αSyn). Results: αSyn was significantly lower in PD (mean 103 pg/ml vs. HC: 127 pg/ml, p0.05) and none showed a significant difference longitudinally. We found significantly higher levels of all these markers between PD patients who developed cognitive decline during follow-up, except for αSyn and IL-6. Conclusion: Except for αSyn, the additional biomarkers did not differentiate PD and HC, and none showed longitudinal differences, but most markers predict cognitive decline in PD during follow-up

Human Antibodies that Slow Erythrocyte Invasion Potentiate Malaria-Neutralizing Antibodies.

The Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) is the leading target for next-generation vaccines against the disease-causing blood-stage of malaria. However, little is known about how human antibodies confer functional immunity against this antigen. We isolated a panel of human monoclonal antibodies (mAbs) against PfRH5 from peripheral blood B cells from vaccinees in the first clinical trial of a PfRH5-based vaccine. We identified a subset of mAbs with neutralizing activity that bind to three distinct sites and another subset of mAbs that are non-functional, or even antagonistic to neutralizing antibodies. We also identify the epitope of a novel group of non-neutralizing antibodies that significantly reduce the speed of red blood cell invasion by the merozoite, thereby potentiating the effect of all neutralizing PfRH5 antibodies as well as synergizing with antibodies targeting other malaria invasion proteins. Our results provide a roadmap for structure-guided vaccine development to maximize antibody efficacy against blood-stage malaria. Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved

Attenuation of lung fibrosis in mice with a clinically relevant inhibitor of glutathione-S-transferase π

Idiopathic pulmonary fibrosis (IPF) is a debilitating lung disease characterized by excessive collagen production and fibrogenesis. Apoptosis in lung epithelial cells is critical in IPF pathogenesis, as heightened loss of these cells promotes fibroblast activation and remodeling. Changes in glutathione redox status have been reported in IPF patients. S-glutathionylation, the conjugation of glutathione to reactive cysteines, is catalyzed in part by glutathione-S-transferase π (GSTP). To date, no published information exists linking GSTP and IPF to our knowledge. We hypothesized that GSTP mediates lung fibrogenesis in part through FAS S-glutathionylation, a critical event in epithelial cell apoptosis. Our results demonstrate that GSTP immunoreactivity is increased in the lungs of IPF patients, notably within type II epithelial cells. The FAS-GSTP interaction was also increased in IPF lungs. Bleomycin- and AdTGFβ-induced increases in collagen content, α-SMA, FAS S-glutathionylation, and total protein S-glutathionylation were strongly attenuated in Gstp(–/–) mice. Oropharyngeal administration of the GSTP inhibitor, TLK117, at a time when fibrosis was already apparent, attenuated bleomycin- and AdTGFβ-induced remodeling, α-SMA, caspase activation, FAS S-glutathionylation, and total protein S-glutathionylation. GSTP is an important driver of protein S-glutathionylation and lung fibrosis, and GSTP inhibition via the airways may be a novel therapeutic strategy for the treatment of IPF