Granular size segregation in silos with and without inserts.

The storage of granular materials is a critical process in industry, which has driven research into flow in silos. Varying material properties, such as particle size, can cause segregation of mixtures. This work seeks to elucidate the effects of size differences and determine how using a flow-correcting insert mitigates segregation during silo discharge. A rotating table was used to collect mustard seeds discharged from a three-dimensional (3D)-printed silo. This was loaded with bidisperse mixtures of varying proportions. A 3D-printed biconical insert was suspended near the hopper exit to assess its effect on the flow. Samples were analysed to determine the mass fractions of small particle species. The experiments without the insert resulted in patterns consistent with segregation. Introducing the insert into the silo eliminated the observed segregation during discharge. Discrete element method simulations of silo discharge were performed with and without the insert. These results mirrored the physical experiment and, when complimented with coarse graining analysis, explained the effect of the insert. Most of the segregation occurs at the grain-air free surface and is driven by large velocity gradients. In the silo with an insert, the velocity gradient at the free surface is greatly reduced, hence, so is the degree of segregation.

The dynamics of granular flow from a silo with two symmetric openings.

The dynamics of granular flow in a rectangular silo with two symmetrically placed exit openings is investigated using particle image velocimetry (PIV), flow rate measurements and discrete element modelling (DEM). The flow of mustard seeds in a Perspex silo is recorded using a high-speed camera and the resulting image frames are analysed using PIV to obtain velocity, velocity divergence and shear rate plots. A change in flow structure is observed as the distance L between the two openings is varied. The mass flow rate is shown to be at a maximum at zero opening separation, decreasing as L is increased; it then reaches a minimum before rising to an equilibrium rate close to two times that of an isolated (non-interacting) opening. The flow rate experiment is repeated using amaranth and screened sand and similar behaviour is observed. Although this result is in contrast with some recent DEM and physical experiments in silo systems, this effect has been reported in an analogous system: the evacuation of pedestrians from a room through two doors. Our experimental results are replicated using DEM and we show that inter-particle friction controls the flow rate behaviour and explains the discrepancies in the literature results.

A novel immunosuppressant, FTY720, induces peripheral lymphodepletion of both T- and B cells and immunosuppression in baboons.

OBJECTIVE: FTY720, a new immunosuppressant active in transplantation models, modulates lymphocyte re-circulation, leading to peripheral lymphopenia and increased lymphocytes in lymph nodes and Peyer's patches. Here, we investigated the susceptibility of baboons to FTY720 as an introductory study to transplantation protocols. METHODS: FTY720 was administered orally to Chacma baboons at 0.3 or 0.1 mg/kg/day for 3 days or at 0.03 mg/kg/day for 10 days. Haematological parameters, lymphocyte phenotype (CD3, CD4, CD8, CD20), cell apoptosis, ex vivo blood cell proliferation in response to mitogens and drug blood levels were monitored during treatment and up to 4 weeks thereafter. MAIN FINDINGS: FTY720 administered p.o. in baboons at 0.3 mg/kg/day caused a marked decrease in circulating lymphocytes within 4 h of treatment, reaching 60-80% decrease within 24-48 h. The effect of FTY720 was seen both on T- and B cells, although it was slightly more rapid/pronounced on T cells. CD4+ cells were slightly more affected than CD8+ cells. The response onset was faster and the duration longer at higher dose, but the maximal peripheral lymphodepletion achieved was similar within the dose range 0.03-0.3 mg/kg tested. Ex vivo mitogen-induced lymphoproliferation was drastically decreased after FTY720 treatment, corresponding to the reduced blood lymphocyte counts. The blood drug levels measured after FTY720 administration correlated well with the dose applied but there was a poor correlation between FTY720 blood levels and the extent of peripheral lymphodepletion, suggestive of a high tissue distribution of the drug. When compared with cynomolgus monkeys treated in the same way, baboons had a lower initial exposure and a slightly lower response 24 h after one or two doses of FTY720 0.03-0.3 mg/kg. However, the stabilized drug blood levels and peripheral lymphodepletion achieved after 7 days of FTY720 0.03 mg/kg/day were similar in both nonhuman primate species. CONCLUSIONS: FTY720 was well tolerated and was effective in terms of peripheral T- and B lymphodepletion in baboons, indicating that it could be used in protocols of allo- and xenotransplantation. The pharmacokinetic and pharmacodynamic profiles of FTY720 in baboons suggest the use of high induction doses to optimize immediate response followed by a reduced dose regimen for drug maintenance.

Glutaraldehyde detoxification of aortic wall tissue: a promising perspective for emerging bioprosthetic valve concepts.

BACKGROUND AND AIMS OF THE STUDY: Due to its superb crosslinking activity, glutaraldehyde (GA) is still the most widely used fixative for bioprosthetic heart valves. At the same time, however, GA is also believed to be partly responsible for tissue calcification and the lack of surface re-endothelialization, both of which may contribute to valve degeneration. Although excess GA has previously been extracted from thin leaflet tissue, this treatment proved insufficient for the detoxification of thick aortic wall tissue of stentless valves or root prostheses. METHODS: In order to establish a detoxification procedure which thoroughly extracts biologically active GA from aortic wall tissue, we used a highly sensitive bioassay where endothelial cells were seeded onto glutaraldehyde-fixed aortic wall discs following various detoxification procedures. Absolute cell numbers and morphologic shape were correlated with shrinkage temperature and shrinkage extent of the tissue to determine the potential of the treatments to reverse crosslinks. To optimize treatment conditions, pH (3.2 versus 4.5), temperature (22 degrees C versus 37 degrees C) and incubation time (48 h versus one week) were varied. In order to identify an optimal detoxification agent, 12 different amino-reagents from four chemical groups were compared: low pKa aromatic amines, amino acids, low pKa N-heterocyclic compounds and amino sugars. RESULTS: Amino-reagent treatment required warm temperature (37 degrees C), prolonged reaction time (one week) and a pH of 4.5 to achieve long-term cell growth on glutaraldehyde-fixed aortic wall. All 12 amino-reagents were able to detoxify aortic tissue satisfactorily; and all mildly reversed crosslinks, although there were differences between candidates. When summarized data were ranked correlating cell growth and quality with shrinkage temperature and shrinkage extent, seven reagents had a rank sum above the overall mean value, and five below with statistically significant differences between candidates. The additional stabilization of the detoxification reaction through borohydride-reduction had no further effect on tissue biocompatibility and crosslinks. CONCLUSIONS: Efficient detoxification of thick aortic wall tissue is possible if a one-week incubation in an acetic acid buffer-based amino-reagent is carried out at 37 degrees C.

T cell depletion by exposure to Campath-1G in vitro prevents graft-versus-host disease.

Campath-1G is an immunosuppressive monoclonal antibody directed against human lymphocytes. Its effectiveness in preventing graft-versus-host disease (GVHD) by simple opsonisation of bone marrow T-cells has been studied in 36 consecutive allografts: in 17 for leukaemia, one for essential thrombocytosis and four for myeloma this was the sole means of GVHD prophylaxis. A further eight patients with aplastic anaemia received 3 months post-transplantation cyclosporin A (CsA) for this purpose whereas in the ninth and tenth the preparative regimen has been modified with this immunosuppressive agent now discontinued. Nucleated cells were harvested and after quantitative recovery of the mononuclear population on the Cobe 2997 separator they were exposed to 20 mg Campath-1G for 30 min at room temperature and then infused. Following standard conditioning, which included total lymphoid irradiation, the median days to reach 0.5 and 1.0 x 10(9)/l neutrophils were respectively 18 (range 9-34) and 28 (range 10-59); to 25 and 100 x 10(9)/l platelets the corresponding times were 17 days (range 5-32 days) and 27 days (range 13-127 days). In all, the day 14 trephine biopsy showed engraftment. At median follow-up of 20 months (range 5-44 months) only one patient has developed possible grade I cutaneous GVHD that responded promptly to corticosteroids: no chronic GVHD or CMV pneumonitis has been encountered. Of those with haematological malignancy transplanted in remission only two with acute leukaemia have relapsed. In aplastic anaemia graft loss initially occurred but this has been overcome by adding Campath-1G in vivo and omitting CsA.(ABSTRACT TRUNCATED AT 250 WORDS)