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.     

Plaque-type blue nevus

Blue nevus may rarely appear in plaque form. It seems to be a benign and asymptomatic lesion, but because of its rarity, no definite prognosis can be given. Only through reporting of additional cases and their follow-up will the prognosis become clear.     

The Role of the Mizar Mathematical Library for Interactive Proof Development in Mizar

The Mizar system is one of the pioneering systems aimed at supporting mathematical proof development on a computer that have laid the groundwork for and eventually have evolved into modern interactive proof assistants. We claim that an important milestone in the development of these systems was the creation of organized libraries accumulating all previously available formalized knowledge in such a way that new works could effectively re-use all previously collected notions. In the case of Mizar, the turning point of its development was the decision to start building the Mizar Mathematical Library as a centrally-managed knowledge base maintained together with the formalization language and the verification system. In this paper we show the process of forming this library, the evolution of its design principles, and also present some data showing its current use with the modern version of the Mizar proof checker, but also as a rich corpus of semantically linked mathematical data in various areas including web-based and natural language proof presentation, maths education, and machine learning based automated theorem proving.     

Statistical shape modelling for expression-invariant face analysis and recognition

Paper introduces a 3-D shape representation scheme for automatic face analysis and identification, and demonstrates its invariance to facial expression. The core of this scheme lies on the combination of statistical shape modelling and non-rigid deformation matching. While the former matches 3-D faces with facial expression, the latter provides a low-dimensional feature vector that controls the deformation of model for matching the shape of new input, thereby enabling robust identification of 3-D faces. The proposed scheme is also able to handle the pose variation without large part of missing data. To assist the establishment of dense point correspondences, a modified free-form-deformation based on B-spline warping is applied with the help of extracted landmarks. The hybrid iterative closest point method is introduced for matching the models and new data. The feasibility and effectiveness of the proposed method was investigated using standard publicly available Gavab and BU-3DFE datasets, which contain faces with expression and pose changes. The performance of the system was compared with that of nine benchmark approaches. The experimental results demonstrate that the proposed scheme provides a competitive solution for face recognition.     

Structure-based design of inhibitors specific for bacterial thymidylate synthase

Thymidylate synthase is an attractive target for antiproliferative drug design because of its key role in the synthesis of DNA. As such, the enzyme has been widely targeted for anticancer applications. In principle, TS should also be a good target for drugs used to fight infectious disease. In practice, TS is highly conserved across species, and it has proven to be difficult to develop inhibitors that are selective for microbial TS enzymes over the human enzyme. Using the structure of TS from Lactobacillus casei in complex with the nonsubstrate analogue phenolphthalein, inhibitors were designed to take advantage of features of the bacterial enzyme that differ from those of the human enzyme. Upon synthesis and testing, these inhibitors were found to be up to 40-fold selective for the bacterial enzyme over the human enzyme. The crystal structures of two of these inhibitors in complex with TS suggested the design of further compounds. Subsequent synthesis and testing showed that these second-round compounds inhibit the bacterial enzyme at sub-micromolar concentrations, while the human enzyme was not inhibited at detectable levels (selectivities of 100-1000-fold or greater). Although these inhibitors share chemical similarities, X-ray crystal structures reveal that the analogues bind to the enzyme in substantially different orientations. Site-directed mutagenesis experiments suggest that the individual inhibitors may adopt multiple configurations in their complexes with TS.