Eosinophils Are Important for Protection, Immunoregulation and Pathology during Infection with Nematode Microfilariae

Eosinophil responses typify both allergic and parasitic helminth disease. In helminthic disease, the role of eosinophils can be both protective in immune responses and destructive in pathological responses. To investigate whether eosinophils are involved in both protection and pathology during filarial nematode infection, we explored the role of eosinophils and their granule proteins, eosinophil peroxidase (EPO) and major basic protein-1 (MBP-1), during infection with Brugia malayi microfilariae. Using eosinophil-deficient mice (PHIL), we further clarify the role of eosinophils in clearance of microfilariae during primary, but not challenge infection in vivo. Deletion of EPO or MBP-1 alone was insufficient to abrogate parasite clearance suggesting that either these molecules are redundant or eosinophils act indirectly in parasite clearance via augmentation of other protective responses. Absence of eosinophils increased mast cell recruitment, but not other cell types, into the broncho-alveolar lavage fluid during challenge infection. In addition absence of eosinophils or EPO alone, augmented parasite-induced IgE responses, as measured by ELISA, demonstrating that eosinophils are involved in regulation of IgE. Whole body plethysmography indicated that nematode-induced changes in airway physiology were reduced in challenge infection in the absence of eosinophils and also during primary infection in the absence of EPO alone. However lack of eosinophils or MBP-1 actually increased goblet cell mucus production. We did not find any major differences in cytokine responses in the absence of eosinophils, EPO or MBP-1. These results reveal that eosinophils actively participate in regulation of IgE and goblet cell mucus production via granule secretion during nematode-induced pathology and highlight their importance both as effector cells, as damage-inducing cells and as supervisory cells that shape both innate and adaptive immunity

Lambda production near threshold in central nucleus-nucleus collisions

Lambda 's produced in central collisions of 40Ar+KC1 at 1.8-GeV/u incident energy were detected in a streamer chamber by their charged-particle decay. For central collisions with impact parameters b<2.4 fm the Lambda production cross section is 7.6±2.2 mb. A calculation in which Lambda production occurs in the early stage of the collision qualitatively reproduces the results but underestimates the transverse momenta. An average Lambda polarization of -0.10±0.05 is observed. PACS numbers: 25.70 B

Energy dependence of multi-pion production in high-energy nucleus-nucleus collisions

Exclusive pi - and charged-particle production in collisions of Ar+KCl is studied at incident energies from 0.4 to 1.8 GeV/u. Complete disintegration of both nuclei is observed. The correlation between pi - and total charge multiplicity shows no islands of anomalous pion production. For constant numbers of proton participants the pi - multiplicity distributions are Poissons. For central collisions increases smoothly and to first order linearly with the c.m. energy. Disagreement with the firestreak model is found. Pacs numbers: 25.70.Hi, 24.10.D

Charged-particle exclusive analysis of central Ar + KCl and Ar + Pb reactions at 1.8 and 0.8 GeV/nucleon

An event by event analysis is carried out for all charged particles observed in central collisions of 40Ar + KCl and 40Ar + Pb at 1.808 and 0.772 GeV/nucleon, respectively. Total transverse energy is used for impact parameter selection within the central trigger condition. The central Ar + KCl reaction exhibits a forward-backward oriented momentum flux. The flux distribution of the most central Ar + Pb events is approximately isotropic in the fireball center of mass

Stopping power and collective flow of nuclear matter in the reaction Ar+Pb at 0.8 GeV/u

Charged-particle exclusive data for Ar+Pb collisions at 0.772 GeV/u are analyzed in terms of collective variables for the event shapes in momentum space. Semicentral collisions lead to sidewards flow whereas nearly head-on collisions have spherical shapes in the c.m. frame, resulting from complete stopping of projectile motion. The hydrodynamical model predictions agree qualitatively with the data whereas the standard cascade model disagrees, lacking in stopping power and collective flow

Collective motion in nucleus-nucleus collisions at 800 MeV/nucleon

Semicentral Ar+KCl, La+La, and Ar+Pb collisions at 800 MeV/nucleon were studied using a streamer chamber. The results are analyzed in the framework of the transverse momentum analysis and in terms of the average sphericity matrix. A critical examination of the analysis procedures, both experimental and theoretical, is given. New procedures are described to account for overall momentum conservation in the reaction, and to correct for azimuthal variations in the detection efficiency. Average transverse momenta per nucleon in the reaction plane are presented for deuterons emitted in the forward hemisphere, as these provide the most reliable information. A Vlasov-Uehling-Uhlenbeck calculation with a stiff equation of state gives a good fit to the momenta in the Ar+Pb reaction. Flow effects parametrized further using the sphericity tensor are found stronger than in the cascade model and consistently weaker than predicted by hydrodynamics. Parameters from the sphericity tensor exhibit a larger variation as a function of multiplicity than do the average momenta per nucleon

Compression effects in relativistic nucleus-nucleus collisions

The negative-pion multiplicity is measured for central collisions of 40Ar with KCl at eight energies from 0.36 to 1.8 GeV/nucleon and for 4He on KCl and 40Ar on BaI2 at 977 and 772 MeV/nucleon, respectively. A systematic discrepancy with a cascade-model calculation which fits proton- and pion-nucleus cross sections but omits potential-energy effects is used to derive the energy going into bulk compression of the system. A value of the incompressibility constant of K=240 MeV is extracted in a parabolic form of the nuclear-matter equation of state

Irinotecan plus folinic acid/continuous 5-fluorouracil as simplified bimonthly FOLFIRI regimen for first-line therapy of metastatic colorectal cancer

BACKGROUND: Combination therapy of irinotecan, folinic acid (FA) and 5-fluorouracil (5-FU) has been proven to be highly effective for the treatment of metastatic colorectal cancer. However, in light of safety and efficacy concerns, the best combination regimen for first-line therapy still needs to be defined. The current study reports on the bimonthly FOLFIRI protocol consisting of irinotecan with continuous FA/5-FU in five German outpatient clinics, with emphasis on the safety and efficiency, quality of life, management of delayed diarrhea, and secondary resection of regressive liver metastases. METHODS: A total of 35 patients were treated for metastatic colorectal cancer. All patients received first-line treatment according to the FOLFIRI regimen, consisting of irinotecan (180 mg/m(2)), L-FA (200 mg/m(2)) and 5-FU bolus (400 mg/m(2)) on day 1, followed by a 46-h continuous infusion 5-FU (2400 mg/m(2)). One cycle contained three fortnightly administrations. Staging was performed after 2 cycles. Dosage was reduced at any time if toxicity NCI CTC grade III/IV was observed. Chemotherapy was administered only to diarrhea-free patients. RESULTS: The FOLFIRI regimen was generally well tolerated. It was postponed for one-week in 51 of 415 applications (12.3%). Dose reduction was necessary in ten patients. Grade III/IV toxicity was rare, with diarrhea (14%), nausea/vomiting (12%), leucopenia (3%), neutropenia (9%) and mucositis (3%). The overall response rate was 31% (4 CR and 7 PR), with disease control in 74%. After primary chemotherapy, resection of liver metastases was achieved in three patients. In one patient, the CR was confirmed pathologically. Median progression-free and overall survival were seven and 17 months, respectively. CONCLUSIONS: The FOLFIRI regimen proved to be safe and efficient. Outpatient treatment was well tolerated. Since downstaging was possible, combinations of irinotecan and continuous FA/5-FU should further be investigated in neoadjuvant protocols

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13