The effect of ozone exposure on the release of eicosanoids in guinea-pig BAL fluid in relation to cellular damage and inflammation

The observed effects after ozone exposure strongly depend on ozone concentration and exposure time. We hypothesized that depending on the O3 exposure protocol, mainly either an oxidant damage or an inflammation will determine the O3 toxicity. We compared two different ozone exposure protocols: an acute exposure (3 ppm 2 h) for studying the oxidant damage and an exposure (1 ppm 12 h) where an inflammatory component is also probably involved. We measured LDH activity and protein and albumin exudation as markers for cellular damage. After the acute exposure an increase in LDH activity was measured and after exposure to 1 ppm ozone for 12 h the exudation of protein and albumin was also enhanced. The histological examinations showed a neutrophilic inflammatory response only after exposure to 1 ppm ozone for 12 h. The acute exposure protocol resulted in an increased release of PGE2, PGD2, PGF2α and 6-ketoPGF1α whereas exposure to 1 ppm ozone for 12 h led to an additional release of LTB4. No effects were measured on the release of TxB2 and LTC4/D4/E4. These changed amounts of eicosanoids will probably contribute to the ozone-induced lung function changes

In-gas-cell laser ionization spectroscopy in the vicinity of 100Sn: Magnetic moments and mean-square charge radii of N=50-54 Ag

In-gas-cell laser ionization spectroscopy studies on the neutron deficient 97-101Ag isotopes have been performed with the LISOL setup. Magnetic dipole moments and mean-square charge radii have been determined for the first time with the exception of 101Ag, which was found in good agreement with previous experimental values. The reported results allow tentatively assigning the spin of 97,99Ag to 9/2 and confirming the presence of an isomeric state in these two isotopes, whose collapsed hyperfine structure suggests a spin of 1/2 . The effect of the N=50 shell closure is not only manifested in the magnetic moments but also in the evolution of the mean-square charge radii of the isotopes investigated, in accordance with the spherical droplet model predictions

Low-energy Coulomb excitation of 62^{62}Fe and 62^{62}Mn following in-beam decay of 62^{62}Mn

Sub-barrier Coulomb-excitation was performed on a mixed beam of $^{62}$Mn and $^{62}$Fe, following in-trap $\beta^{-}$ decay of $^{62}$Mn at REX-ISOLDE, CERN. The trapping and charge breeding times were varied in order to alter the composition of the beam, which was measured by means of an ionisation chamber at the zero-angle position of the Miniball array. A new transition was observed at 418~keV, which has been tentatively associated to a $(2^{+},3^{+})\rightarrow1^{+}_{g.s.}$ transition. This fixes the relative positions of the $\beta$-decaying $4^{+}$ and $1^{+}$ states in $^{62}$Mn for the first time. Population of the $2^{+}_{1}$ state was observed in $^{62}$Fe and the cross-section determined by normalisation to the $^{109}$Ag target excitation, confirming the $B(E2)$ value measured in recoil-distance lifetime experiments.Comment: 9 pages, 10 figure

Monitoring recently acquired HIV infections in Amsterdam, The Netherlands:The attribution of test locations

Background:  Surveillance of recent HIV infections (RHI) using an avidity assay has been implemented at Dutch sexual health centres (SHC) since 2014, but data on RHI diagnosed at other test locations is lacking. Setting:  Implementation of the avidity assay in HIV treatment clinics for the purpose of studying RHI among HIV patients tested at different test locations. Methods: We retrospectively tested leftover specimens from newly diagnosed HIV patients in care in 2013–2015 in Amsterdam. Avidity Index (AI) values ≤0.80 indicated recent infection (acquired ≤6 months prior to diagnosis), and AI > 0.80 indicated established infection (acquired >6 months prior to diagnosis). An algorithm for RHI was applied to correct for false recency. Recency based on this algorithm was compared with recency based on epidemiological data only. Multivariable logistic regression analysis was used to identify factors associated with RHI among men who have sex with men (MSM).Results: We tested 447 specimens with avidity; 72% from MSM. Proportions of RHI were 20% among MSM and 10% among heterosexuals. SHC showed highest proportions of RHI (27%), followed by GPs (15%), hospitals (5%), and other/unknown locations (11%) (p < 0.001). Test location was the only factor associated with RHI among MSM. A higher proportion of RHI was found based on epidemiological data compared to avidity testing combined with the RHI algorithm. Conclusion:  SHC identify more RHI infections compared to other test locations, as they serve high-risk populations and offer frequent HIV testing. Using avidity-testing for surveillance purposes may help targeting prevention programs, but the assay lacks robustness and its added value may decline with improved, repeat HIV testing and data collection

Improved Precision Measurement of the Casimir Force

We report an improved precision measurement of the Casimir force. The force is measured between a large Al coated sphere and flat plate using an Atomic Force Microscope. The primary experimental improvements include the use of smoother metal coatings, reduced noise, lower systematic errors and independent measurement of surface separations. Also the complete dielectric spectrum of the metal is used in the theory. The average statistical precision remains at the same 1% of the forces measured at the closest separation

Immune Responses 6 Months After mRNA-1273 COVID-19 Vaccination and the Effect of a Third Vaccination in Patients with Inborn Errors of Immunity

Purpose: Patients with inborn errors of immunity (IEI) are at increased risk of severe coronavirus disease-2019 (COVID-19). Effective long-term protection against COVID-19 is therefore of great importance in these patients, but little is known about the decay of the immune response after primary vaccination. We studied the immune responses 6 months after two mRNA-1273 COVID-19 vaccines in 473 IEI patients and subsequently the response to a third mRNA COVID-19 vaccine in 50 patients with common variable immunodeficiency (CVID).Methods: In a prospective multicenter study, 473 IEI patients (including X-linked agammaglobulinemia (XLA) (N = 18), combined immunodeficiency (CID) (N = 22), CVID (N = 203), isolated or undefined antibody deficiencies (N = 204), and phagocyte defects (N = 16)), and 179 controls were included and followed up to 6 months after two doses of the mRNA-1273 COVID-19 vaccine. Additionally, samples were collected from 50 CVID patients who received a third vaccine 6 months after primary vaccination through the national vaccination program. SARS-CoV-2-specific IgG titers, neutralizing antibodies, and T cell responses were assessed.Results: At 6 months after vaccination, the geometric mean antibody titers (GMT) declined in both IEI patients and healthy controls, when compared to GMT 28 days after vaccination. The trajectory of this decline did not differ between controls and most IEI cohorts; however, antibody titers in CID, CVID, and isolated antibody deficiency patients more often dropped to below the responder cut-off compared to controls. Specific T cell responses were still detectable in 77% of controls and 68% of IEI patients at 6 months post vaccination. A third mRNA vaccine resulted in an antibody response in only two out of 30 CVID patients that did not seroconvert after two mRNA vaccines.Conclusion: A similar decline in IgG titers and T cell responses was observed in patients with IEI when compared to healthy controls 6 months after mRNA-1273 COVID-19 vaccination. The limited beneficial benefit of a third mRNA COVID-19 vaccine in previous non-responder CVID patients implicates that other protective strategies are needed for these vulnerable patients.</p

Coulomb excitation of 68^{68}Ni at safe energies

The $B(E2;0^+\to2^+)$ value in $^{68}$Ni has been measured using Coulomb excitation at safe energies. The $^{68}$Ni radioactive beam was post-accelerated at the ISOLDE facility (CERN) to 2.9 MeV/u. The emitted $\gamma$ rays were detected by the MINIBALL detector array. A kinematic particle reconstruction was performed in order to increase the measured c.m. angular range of the excitation cross section. The obtained value of 2.8$^{+1.2}_{-1.0}$ 10$^2$ e$^2$fm$^4$ is in good agreement with the value measured at intermediate energy Coulomb excitation, confirming the low $0^+\to2^+$ transition probability.Comment: 4 pages, 5 figure

Complete roughness and conductivity corrections for the recent Casimir force measurement

We consider detailed roughness and conductivity corrections to the Casimir force in the recent Casimir force measurement employing an Atomic Force Microscope. The roughness of the test bodies-a metal plate and a sphere- was investigated with the Atomic Force Microscope and the Scanning Electron Microscope respectively. It consists of separate crystals of different heights and a stochastic background. The amplitude of roughness relative to the zero roughness level was determined and the corrections to the Casimir force were calculated up to the fourth order in a small parameter (which is this amplitude divided by the distance between the two test bodies). Also the corrections due to finite conductivity were found up to the fourth order in relative penetration depth of electromagnetic zero point oscillations into the metal. The theoretical result for the configuration of a sphere above a plate taking into account both corrections is in excellent agreement with the measured Casimir force

Cyclopentenyl cytosine increases gemcitabine radiosensitisation in human pancreatic cancer cells

The deoxycytidine analogue 2′,2′-difluoro-2′-deoxycytidine (dFdC, gemcitabine) is a potent radiosensitiser, but has limited efficacy in combination with radiotherapy in patients with pancreatic cancer due to acute toxicity. We investigated whether cyclopentenyl cytosine (CPEC), targetting the ‘de novo' biosynthesis of cytidine triphosphate (CTP), could increase dFdC cytotoxicity alone or in combination with irradiation in a panel of human pancreatic cancer cells (Panc-1, Miapaca-2, BxPC-3). To investigate the role of deoxycytidine kinase (dCK), the rate-limiting enzyme in the activation of dFdC, human lung cancer cells without (dFdC-resistant SWg) and with an intact dCK gene (dFdC-sensitive SWp) were included. We found that CPEC (100–1000 nmol l−1) specifically reduced CTP levels in a dose-dependent manner that lasted up to 72 h in all cell lines. Preincubation with CPEC resulted in a dose-dependent increase in dFdC incorporated into the DNA only in dFdC-sensitive cells. Consequently, CPEC increased the effectiveness of dFdC (300 nmol l−1 for 4 h) only in dFdC-sensitive cells, which was accompanied by an increase in apoptosis. We also found that CPEC enhanced the radiosensitivity of cells treated with dFdC (30–300 nmol l−1 for 4 h). These results indicate that CPEC enhances the cytotoxicity of dFdC alone and in combination with irradiation in several human tumour cell lines with an intact dCK gene