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Surface flow and water transport models of a northern small scale region on Mars have been developed with two main objectives, (1) to locally resolve water vapor transport in a shallow regolith, and (2) to introduce a method for calculating water vapor flux to the atmosphere by means of a non-dimensional interfacial Sherwood number. This number can be used to provide improved boundary conditions for atmospheric general circulation models. The near surface atmospheric flow and water transport models were three dimensional, capable of resolving complex terrain geometries, and included a layer of porous regolith. The models were used to simulate two different local atmospheric flows, the near surface thermal convection caused by early morning solar heating, and horizontal dry winds. Using these models, analyses were performed to study the effects of several parameters on the water transport process. For the simulations in this study, the NASA Phoenix Mars Lander landing site was selected. Variable parameters were regolith thickness, ambient pressure and temperature, imposed wind velocity and surface temperature. Results of the numerical simulations were summarized by means of the interfacial Sherwood number that can be used to readily calculate water flux from the regolith to the atmosphere.

Background The monoclonal antibody NNC0215-0384 blocks the complement factor 5a receptor (C5aR), mainly expressed on leukocytes, and thereby inhibits the proinflammatory signaling mediated via C5aR, which is thought to play an important role in rheumatoid arthritis (RA).1 NNC0215-0384 is currently in clinical development as a 2nd generation compound, modified from the 1st generation compound NNC0151-0000,2 to ensure a reduced potential of inducing Fc-mediated depletion of C5aR-expressing cells and anti-drug antibodies (ADAs). Objectives The objective of this trial was to investigate the safety and tolerability of NNC0215-0384 in patients with RA. Methods 36 adults with active RA (DAS28-CRP >3.2) on stable background methotrexate treatment (7.5–25 mg/week for ≥16 weeks) were randomised in a 3:1 manner to receive a single dose of NNC0215-0384 or placebo by either intravenous (i.v. [n=24]) or subcutaneous (s.c. [n=12]) administration. Six increasing i.v. dose levels (0.02, 0.08, 0.3, 1, 3 and 10 mg/kg) and three increasing s.c. dose levels (0.2, 0.8 and 4 mg/kg) were investigated. Patients were followed for 9 weeks, and the primary outcome measure was the incidence of adverse events (AEs). ADAs were also evaluated, along with pharmacokinetic (PK) and pharmacodynamic (PD) properties and efficacy measures. Clinicaltrials.gov: NCT01611688. Results All patients (n=36) were included in the analysis. In total, 35 AEs were reported in 22 patients (61%): i.v. group, NNC0215-0384 vs. placebo: 24 AEs in 13 patients (72%) vs. 4 AEs in 4 patients (67%); s.c. group: 7 AEs in 5 patients (56%) vs. 0 AEs. The most frequently reported AEs were nasopharyngitis and headache, with more events reported with NNC0215-0384 vs. placebo in both routes of administration. No dose-dependent increase in AEs was apparent with either route of administration. No serious AEs were observed with NNC0215-0384. ADAs were detected in low titres in 1 i.v. patient (6%) and 3 s.c. patients (33%), with no neutralising activity measured in vitro. No clinically relevant changes in vital signs, electrocardiogram or laboratory safety parameters (including leukocyte-, lymphocyte-, and neutrophil counts) were observed in any of the dose groups. NNC0215-0384 showed nonlinear PK due to target-mediated disposition. Mean C5aR occupancy, measured in peripheral blood, increased with increasing dose levels. Full mean occupancy (>90%) was maintained for 4.3 weeks (i.v. 10 mg/kg) and 1.8 weeks (s.c. 4 mg/kg), respectively. No statistically significant differences were seen between single doses of NNC0215-0384 and placebo for both routes of administration in any of the efficacy measures, including DAS28-CRP and Vectra® DA score. Conclusions In this first-in-human trial, NNC0215-0384 was well tolerated in patients with RA at increasing doses up to 10 mg/kg i.v. and 4 mg/kg s.c. This trial provided initial information on the safety, PK and PD of NNC0215-0384. The safety data support further clinical development of the NNC0215-0384 compound for use in patients with RA. References Jose et al. Ann Rheum Dis 1990; 49(10):747-752 Clinicaltrials.gov: NCT01223911 Disclosure of Interest F. Wagner: None declared, C. F. Lange Shareholder of: Novo Nordisk A/S, Employee of: Novo Nordisk A/S, M. Nowak Shareholder of: Novo Nordisk A/S, Employee of: Novo Nordisk A/S, S. Ignatenko: None declared DOI 10.1136/annrheumdis-2014-eular.2156

Antisera to the streptococcal cell membrane (SCM) were evaluated for their reactivity to murine glomerular basement membrane (GBM) in four strains of mice. Animals were studied on a daily basis from birth through 3 months and weekly thereafter through 18 months. Paired animals were compared for in vivo binding of antibody versus an indirect fluorescent antibody technique on fresh kidney sections. The findings demonstrated a granular type GBM staining for all anti-SCM which were positive. Nonspecific background staining accompanied most of the indirect fluorescent antibody sections tested while being totally absent for the direct fluorescent test on tissue from in vivo challenge of the primary antibody. The in vitro testing showed tissue from young mice (0–6 days old) to be most reactive, while the strongest reactivity was seen in the age group of 10–20 days for in vivo testing. These cross-reactive antibodies, i.e., GBM-binding anti-SCM, are best evaluated by in vivo methods where tissue is taken 4 days after antiserum injection. Animals of the age range 6–8 weeks were often negative, indicating that this age range selected for many studies may not be the most favorable one via either in vitro or in vivo studies.

Urinary proteoses isolated from patients with glomerulonephritis have been shown by physical chemical studies to be distinct glycoproteins with α1-globulin mobilities. These proteoses have been shown to contain up to 45 % carbohydrate composed of neutral sugars, hexosamine, sialic acid, but no uronic acids; their amino acid composition is distinct. Analytical ultracentrifugation has shown them to have sedimentation values in the range of 2.57–2.63. Extinction coefficients in the range of 5.0–7.4 have been found for most of the isolates. A distinctive feature is their lack of reactivity with goat anti whole human serum on immunoelectrophoresis and double diffusion agar analysis. The converse also obtains, that is, specific anti proteose antisera will not visualize serum components on immunoelectrophoresis or in double diffusion agar analysis.

Streptococcal cell membrane (SCM) antiserum injected mice show a significant thickening of glomerular basement membrane (GBM) and an increase in mesangial matrix within 4 to 24 hours of antiserum administration (1,2,3). This study was undertaken to evaluate the incorporation of 3H proline into glomerular cells and GBM under normal and anti-SCM induced conditions. Mice were administered, intraperitoneally, 0.1 ml of normal or anti-SCM serum followed by a 10 µC/g body weight injection of 3H proline. Details of the preparation of anti-SCM (Group A type 12 streptococcal pyogenes) and other sera and injection protocol have been described elsewhere (2). After 15 minutes of isotope injection a chase of cold proline was given and animal sacrificed at 20 minutes, 1,2,4,8,24 and 48 hours. One of the removed kidneys was processed for immunofluorescence, light and electron microscopic radioautographic studies; second kidney was used for GBM isolation and aminoacid analysis.