Asymptotics for the Wiener sausage among Poissonian obstacles

We consider the Wiener sausage among Poissonian obstacles. The obstacle is called hard if Brownian motion entering the obstacle is immediately killed, and is called soft if it is killed at certain rate. It is known that Brownian motion conditioned to survive among obstacles is confined in a ball near its starting point. We show the weak law of large numbers, large deviation principle in special cases and the moment asymptotics for the volume of the corresponding Wiener sausage. One of the consequence of our results is that the trajectory of Brownian motion almost fills the confinement ball.Comment: 19 pages, Major revision made for publication in J. Stat. Phy

Oral-Nasopharyngeal Dendritic Cells Mediate T Cell-Independent IgA Class Switching on B-1 B Cells

Native cholera toxin (nCT) as a nasal adjuvant was shown to elicit increased levels of T-independent S-IgA antibody (Ab) responses through IL-5- IL-5 receptor interactions between CD4+ T cells and IgA+ B-1 B cells in murine submandibular glands (SMGs) and nasal passages (NPs). Here, we further investigate whether oral-nasopharyngeal dendritic cells (DCs) play a central role in the induction of B-1 B cell IgA class switch recombination (CSR) for the enhancement of T cell-independent (TI) mucosal S-IgA Ab responses. High expression levels of activation-induced cytidine deaminase, Iα-Cμ circulation transcripts and Iμ-Cα transcripts were seen on B-1 B cells purified from SMGs and NPs of both TCRβ−/− mice and wild-type mice given nasal trinitrophenyl (TNP)-LPS plus nCT, than in the same tissues of mice given nCT or TNP-LPS alone. Further, DCs from SMGs, NPs and NALT of mice given nasal TNP-LPS plus nCT expressed significantly higher levels of a proliferation-inducing ligand (APRIL) than those in mice given TNP-LPS or nCT alone, whereas the B-1 B cells in SMGs and NPs showed elevated levels of transmembrane activator and calcium modulator cyclophilin ligand interactor (TACI) expression. Interestingly, high frequencies of IgA+ B-1 B cells were induced when peritoneal IgA− IgM+ B cells were stimulated with mucosal DCs from mice given nasal TNP-LPS plus nCT. Taken together, these findings show that nasal nCT plays a key role in the enhancement of mucosal DC-mediated TI IgA CSR by B-1 B cells through their interactions with APRIL and TACI

CANGAROO-III Observation of TeV Gamma Rays from the vicinity of PSR B1 706-44

Observation by the CANGAROO-III stereoscopic system of the Imaging Cherenkov Telescope has detected extended emission of TeV gamma rays in the vicinity of the pulsar PSR B1706$-$44. The strength of the signal observed as gamma-ray-like events varies when we apply different ways of emulating background events. The reason for such uncertainties is argued in relevance to gamma-rays embedded in the "off-source data", that is, unknown sources and diffuse emission in the Galactic plane, namely, the existence of a complex structure of TeV gamma-ray emission around PSR B1706$-$44.Comment: 10 pages, 13 figures, to be published in Ap

CANGAROO-III observation of TeV gamma rays from the unidentified gamma-ray source HESS J1614-518

We report the detection, with the CANGAROO-III imaging atmospheric Cherenkov telescope array, of a very high energy gamma-ray signal from the unidentified gamma-ray source HESS J1614-518, which was discovered in the H.E.S.S. Galactic plane survey. Diffuse gamma-ray emission was detected above 760 GeV at the 8.9 sigma level during an effective exposure of 54 hr from 2008 May to August. The spectrum can be represented by a power-law: 8.2+-2.2_{stat}+-2.5_{sys}x10^{-12}x (E/1TeV)^{-Gamma} cm^{-2} s^{-1} TeV^{-1} with a photon index Gamma of 2.4+-0.3_{stat}+-0.2_{sys}, which is compatible with that of the H.E.S.S. observations. By combining our result with multi-wavelength data, we discuss the possible counterparts for HESS J1614-518 and consider radiation mechanisms based on hadronic and leptonic processes for a supernova remnant, stellar winds from massive stars, and a pulsar wind nebula. Although a leptonic origin from a pulsar wind nebula driven by an unknown pulsar remains possible, hadronic-origin emission from an unknown supernova remnant is preferred.Comment: 9 pages, 7 figures, accepted for publication in Ap

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Functional transforming growth factor-β receptor type II expression by CD4+ T cells in Peyer's patches is essential for oral tolerance induction.

Our previous studies have shown that Peyer's patches (PPs) play a key role in the induction of oral tolerance. Therefore, we hypothesized that PPs are an important site for Transforming Growth Factor (TGF)-β signaling and sought to prove that this tissue is of importance in oral tolerance induction. We found that expression of TGF-β type II receptor (TGFβRII) by CD4(+) T cells increases and persists in the PPs of normal C57BL/6 mice after either high- or low-dose feeding of OVA when compared to mesenteric lymph nodes (MLNs) and spleen. Approximately one-third of these TGFβRII(+) CD4(+) T cells express the transcription factor Foxp3. Interestingly, the number of TGFβRII(+) CD4(+) T cells in PPs decreased when OVA-fed mice were orally challenged with OVA plus native cholera toxin (CT). In contrast, numbers of TGFβRII(+) CD4(+) T cells were increased in the intestinal lamina propria (iLP) of these challenged mice. Further, these PP CD4(+) TGFβRII(+) T cells upregulated Foxp3 within 2 hours after OVA plus CT challenge. Mice fed PBS and challenged with OVA plus CT did not reveal any changes in TGFβRII expression by CD4(+) T cells. In order to test the functional property of TGFβRII in the induction of oral tolerance, CD4dnTGFβRII transgenic mice, in which TGFβRII signaling is abrogated from all CD4(+) T cells, were employed. Importantly, these mice could not develop oral tolerance to OVA. Our studies show a critical, dose-independent, role for TGFβRII expression and function by CD4(+) T cells in the gut-associated lymphoid tissues, further underlining the vital role of PPs in oral tolerance