Multicenter Phase 2 Trial of Sirolimus for Tuberous Sclerosis: Kidney Angiomyolipomas and Other Tumors Regress and VEGF- D Levels Decrease

Tuberous sclerosis (TSC) related tumors are characterized by constitutively activated mTOR signaling due to mutations in TSC1 or TSC2.We completed a phase 2 multicenter trial to evaluate the efficacy and tolerability of the mTOR inhibitor, sirolimus, for the treatment of kidney angiomyolipomas.36 adults with TSC or TSC/LAM were enrolled and started on daily sirolimus. The overall response rate was 44.4% (95% confidence intervals [CI] 28 to 61); 16/36 had a partial response. The remainder had stable disease (47.2%, 17/36), or were unevaluable (8.3%, 3/36). The mean decrease in kidney tumor size (sum of the longest diameters [sum LD]) was 29.9% (95% CI, 22 to 37; n = 28 at week 52). Drug related grade 1-2 toxicities that occurred with a frequency of >20% included: stomatitis, hypertriglyceridemia, hypercholesterolemia, bone marrow suppression (anemia, mild neutropenia, leucopenia), proteinuria, and joint pain. There were three drug related grade 3 events: lymphopenia, headache, weight gain. Kidney angiomyolipomas regrew when sirolimus was discontinued but responses tended to persist if treatment was continued after week 52. We observed regression of brain tumors (SEGAs) in 7/11 cases (26% mean decrease in diameter), regression of liver angiomyolipomas in 4/5 cases (32.1% mean decrease in longest diameter), subjective improvement in facial angiofibromas in 57%, and stable lung function in women with TSC/LAM (n = 15). A correlative biomarker study showed that serum VEGF-D levels are elevated at baseline, decrease with sirolimus treatment, and correlate with kidney angiomyolipoma size (Spearman correlation coefficient 0.54, p = 0.001, at baseline).Sirolimus treatment for 52 weeks induced regression of kidney angiomyolipomas, SEGAs, and liver angiomyolipomas. Serum VEGF-D may be a useful biomarker for monitoring kidney angiomyolipoma size. Future studies are needed to determine benefits and risks of longer duration treatment in adults and children with TSC.Clinicaltrials.gov NCT00126672

VLIW Processor Codesign for Video Processing

A codesign approach for complex video compression systems is presented. The system is based on a flexible and programmable VLIW (Very Long Instruction Word) architecture. The design approach can be subdivided into two phases: a quantitative analysis for deriving the main processor structure and a cosynthesis for generating the processor hardware and the compiler back-end. The analysis results of different video compression algorithms are summarized. This permits to adapt the processor to a set of related applications rather than to a particular task. A compiled instruction-set simulator for analyzing large data sets is presented. An HTML-based codesign framework is shown which documents and organizes the analysis data

A Fuzzy Online Handwriting REcognition System: FOHRES

In this paper we present a new fuzzy online recognition system (FOHRES) for handwritten characters. Our new approach uses the advantages of fuzzy set theory for the classification of handwritten characters at different processing stages. The proposed fuzzy online handwriting description language (FOHDEL) provide a flexible multiwriter environment which is extendable to various tasks like recognizing expressions or words. In the initial development phase we connect FOHRES to an optical formula recognition system (OFR).The hierarchical form of input formulae and the context dependent symbol interpretation make this application adequate for early experiments. 1. INTRODUCTION Some of the areas where handwritten character recognition can improve the quality of the interface between humans and machines are the handwritten input to a computer algebra system(CAS) (Fig. 1) or an online text processing and personal documentation system. The user draws a two dimensional formula or writes a piece..