Multiscale cell-based coarsening for discontinuous problems

Whether tracking the eye of a storm, the leading edge of a wildfire, or the front of a chemical reaction, one finds that significant change occurs at the thin edge of an advancing line. The tracking of such change-fronts comes in myriad forms with a wide variety of applications expressible as PDEs. Expanding on Ami Harten’s ideas, we construct an alternative to wavelet-based grid refinement, a multiresolution coarsening method that is capable of capturing sharp gradients across different scales, thus improving PDE-based simulations by concentrating computational resources where the solution varies sharply. We present this alternative grid coarsening method and compare its performance to other multiresolution methods by means of several examples.     

Accelerated fluid bed drying using NIR monitoring and phenomenological modeling

A “fast-drying” method to accelerate the fluid bed drying process is presented. It relies on concepts of heat and mass transfer with real-time near-infrared (NIR) monitoring of moisture. Triplicate trials show that fast drying can reduce granulation drying time by half over single-temperature cycles. The product is equivalent in every way tested to material made using a conventional cycle even though the inlet temperature throughout the constant-rate stage was higher than the melting point of the compound. Tablets made from the fast-dried granulation exhibit equivalent physical characteristics to tablets made from granulations dried at a single, lower temperature.     

The locomotion of dairy cows on concrete floors that are dry, wet, or covered with a slurry of excreta

Six dairy cows were trained to individually walk down a concrete aisle for a food reward. Their locomotion was then examined in a switchback experiment as the floor surface of the aisle was changed from dry to wetted concrete or concrete covered by shallow (5 cm) or deep (12.5 cm) slurry from cattle excreta. The static and dynamic frictional coefficients were measured by a tribometer, but did not give a clear indication of the risk of slipping. Cow locomotion was measured over the second half of the aisle, and limb angles recorded as the cow passed a video camera. Wetting the floor did not affect the walking or stepping rate, but it reduced the arc made by the joints of the hindlimb during the supporting phase. Slurry caused the cows to keep their legs more vertical at the end of the support phase, probably to aid lifting the limb out of the slurry. It also caused the cows to place their forelimbs down less vertically at the start of the support phase, probably because of the reduced risk of slip in the slurry. When the floor was covered with either the deep or, to a lesser extent, the shallow slurry, the cows' walking and stepping rates were reduced, and on the floor covered with deep slurry their step length was increased. Therefore slurry reduces the cow's walking speed and alters limb angles during the support phase, producing a different walking pattern from cows on dry or wetted concrete.     

Pitx2 participates in the late phase of the pathway controlling left-right asymmetry

BACKGROUND: We have studied the role of the different MHC (RT1) subregions in acute natural killer (NK) cell-mediated bone marrow allograft rejection in lethally irradiated, bone marrow cell (BMC) reconstituted rats. METHODS: We employed a series of MHC congenic and intra-MHC recombinant rat strains so that effects of mismatches in defined RT1 subregions could be studied systematically. BMC allograft survival was measured as 125IUdR uptake in the spleen between day 5 and day 7 after irradiation and BMC reconstitution. RESULTS: We found that in certain RT1 haplotype combinations, nonclassical RT1.C disparities by themselves could determine graft rejection (i.e., in the u/av1 recombinant haplotypes), whereas in another combination (between the av1 and c haplotypes) a mismatch for an isolated classical RT1.A region was decisive for engraftment. Thus, PVG.R1 BMC failed to proliferate in PVG rats, differing in the RT1.A region only, whereas in PVG.1U rats rejection could be determined by isolated differences in the RT1.C region (LEW.1WR1). Also, RT1 homozygous rats (RT1.U) rejected semi-allogeneic F1 hybrid BMC. The acute rejection of BMC was mediated by NK cells, as athymic nude rats, lacking alloreactive T cells but with normal alloreactive NK cells, showed the same patterns of rejection as did normal rats. Nude rats also rejected allogeneic lymphocytes, a previously documented NK-mediated phenomenon, with identical requirements of MHC disparity. CONCLUSIONS: This investigation shows that rat effector NK cells are radioresistant, independent of the thymus, and capable of recognizing and rejecting MHC mismatched transplanted BMC on the basis of mismatches in both classical and nonclassical class I regions in vivo. The studies underline the importance also of NK cells in determining BMC allograft survival.     

Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program

PURPOSE: The CD20 antigen is expressed on more than 90% of B-cell lymphomas. It is appealing for targeted therapy, because it does not shed or modulate. A chimeric monoclonal antibody more effectively mediates host effector functions and is itself less immunogenic than are murine antibodies. PATIENTS AND METHODS: This was a multiinstitutional trial of the chimeric anti-CD20 antibody, IDEC-C2B8. Patients with relapsed low grade or follicular lymphoma received an outpatient treatment course of IDEC-C2B8 375 mg/m2 intravenously weekly for four doses. RESULTS: From 31 centers, 166 patients were entered. Of this intent-to-treat group, 48% responded. With a median follow-up duration of 11.8 months, the projected median time to progression for responders is 13.0 months. Serum antibody levels were sustained longer after the fourth infusion than after the first, and were higher in responders and in patients with lower tumor burden. The majority of adverse events occurred during the first infusion and were grade 1 or 2; fever and chills were the most common events. Only 12% of patients had grade 3 and 3% grade 4 toxicities. A human antichimeric antibody was detected in only one patient. CONCLUSION: The response rate of 48% with IDEC-C2B8 is comparable to results with single-agent cytotoxic chemotherapy. Toxicity was mild. Attention needs to be paid to the rate of antibody infusion, with titration according to toxicity. Further investigation of this agent is warranted, including its use in conjunction with standard chemotherapy.     

Assessment of the biodistribution and metabolism of 5-fluorouracil as monitored by 18F PET and 19F MRI: a comparative animal study

The effective clinical use of the anticancer drug 5-fluorouracil (5-FU) requires the non-invasive assessment of its transport and metabolism, particularly in the tumor and the liver, where the drug is catabolized to alpha-fluoro-beta-alanine (FBAL). In this study, the potentials and limitations of dynamic 18F PET and metabolic 19F MRI examinations for noninvasive 5-FU monitoring were investigated in ACI and Buffalo rats with transplanted MH3924A and TC5123 Morris hepatomas, respectively. Selective 5-[19F]FU and [19F]FBAL MR images were acquired 5 and 70 min after 5-FU injection using a CHESS MRI sequence. After administration of 5-[18F]FU, the kinetics of the regional 5-[18F]FU uptake were measured by dynamic PET scanning over 120 min. To allow a comparison between PET and MRI data, standardized uptake values (SUV) were computed at the same points in time. The TC5123 hepatoma showed a significantly (p < 0.002) higher mean SUV at 5 and 70 min post-5-FU injection than the MH3924A cell lines, whereas there were no significant differences between the mean SUV measured in the liver of both animal populations. In contrast to the PET data, no significant differences in the mean 5-[19F]FU and [19F]FBAL MR signal values in the tumor of both models were observed. The MR images, however, yielded the additional information that 5-FU is converted to FBAL only in the liver and not in the hepatomas.