Molecular characteristics and gene segment usage in IGH gene rearrangements in multiple myeloma.

BACKGROUND AND OBJECTIVES: Analysis of IgH rearrangements in B-cell malignancies has provided clinical researchers with a wide range of information during the last few years. However, only a few studies have contributed to the characterization of these features in multiple myeloma (MM), and they have been focused on the analysis of the expressed IgH allele only. Comparison between the expressed and the non-functional IgH alleles allows further characterizion of the selection processes to which pre-myeloma cells are submitted. DESIGN AND METHODS: We analyzed a cohort of 84 untreated MM patients in order to characterize their functional VDJH and non-functional DJH rearrangements. The pattern of mutations and gene segment usage for both types of rearrangements was analyzed by polymerase chain reaction and sequencing. RESULTS: VH3 and VH1 family members were over- and under-represented, respectively. VH3-30 and VH3-15 segments were the most frequently used, whereas VH4-34 was found only in non-functional or heavily mutated VDJH rearrangements. DH2 and DH3 family members were over-represented in both VDJH and DJH repertoires, while the DH1 family was under-represented only in the productive VDJH rearrangements. Finally, DH3-22 and DH2-21 gene segments were found to be over-represented in the functional repertoire while segments commonly used by less mature B-cell malignancies, such as DH6-19 or DH3-3, were under-represented. INTERPRETATION AND CONCLUSIONS: Data reported here help to identify the clonogenic MM cell as a post-germinal center B cell that has undergone selection processes during the germinal center reaction.

A low overhead error confinement method based on application statistical characteristics

Reliability has emerged as a critical design constraint especially in memories. Designers are going to great lengths to guarantee fault free operation of the underlying silicon by adopting redundancy-based techniques, which essentially try to detect and correct every single error. However, such techniques come at a cost of large area, power and performance overheads which making many researchers to doubt their efficiency especially for error resilient systems where 100% accuracy is not always required. In this paper, we present an alternative method focusing on the confinement of the resulting output error induced by any reliability issues. By focusing on memory faults, rather than correcting every single error the proposed method exploits the statistical characteristics of any target application and replaces any erroneous data with the best available estimate of that data. To realize the proposed method a RISC processor is augmented with custom instructions and special-purpose functional units. We apply the method on the proposed enhanced processor by studying the statistical characteristics of the various algorithms involved in a popular multimedia application. Our experimental results show that in contrast to state-of-the-art fault tolerance approaches, we are able to reduce runtime and area overhead by 71.3% and 83.3% respectively.