679 research outputs found
Applications of Quantum Algorithms to Partially Observable Markov Decision Processes
Abstract Due to the enormous processing gains that are theoretically achievable by using quantum algorithms instead of classical algorithms to solve rather generic classes of numerical problems, it makes sense that one should evaluate their potential applicability, appropriateness, and efficiency for solving virtually any computationally intensive task. Since many types of control and optimization problems may be couched in terms of partially observable Markov decision processes (POMDPs), and since solutions to these types of problems are invariably extremely difficult to obtain, the use of quantum algorithms to help solve POMDP problems is investigated here. Quantum algorithms are indeed found likely to provide significant efficiency improvements in several computationally intensive tasks associated with solving POMDPs, particularly in the areas of searching, optimization, and parameter optimization and estimation
Prognostic impact of proliferative index determined by quantitative image analysis and the International Prognostic Index in patients with mantle cell lymphoma
Background: The proliferative index (PI) is a powerful prognostic factor in mantle cell lymphoma (MCL); however, its utility is hampered by interobserver variability. The mantle cell international prognostic index (MIPI) has been reported to have prognostic importance. In this study, we determined the prognostic value of the PI as determined by quantitative image analysis in MCL
Characterization of 8p21.3 chromosomal deletions in B-cell lymphoma: TRAIL-R1 and TRAIL-R2 as candidate dosage-dependent tumor suppressor genes
Deletions of chromosome 8p are a recurrent event in B-cell non-Hodgkin lymphoma (B-NHL), suggesting the presence of a tumor suppressor gene. We have characterized these deletions using comparative genomic hybridization to microarrays, fluorescence in situ hybridization (FISH) mapping, DNA sequencing, and functional studies. A minimal deleted region (MDR) of 600 kb was defined in chromosome 8p21.3, with one mantle cell lymphoma cell line (Z138) exhibiting monoallelic deletion of 650 kb. The MDR extended from bacterial artificial chromosome (BAC) clones RP11-382J24 and RP11-109B10 and included the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor gene loci. Sequence analysis of the individual expressed genes within the MDR and DNA sequencing of the entire MDR in Z138 did not reveal any mutation. Gene expression analysis and quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) showed down-regulation of TRAIL-R1 and TRAIL-R2 receptor genes as a consistent event in B-NHL with 8p21.3 loss. Epigenetic inactivation was excluded via promoter methylation analysis. In vitro studies showed that TRAIL-induced apoptosis was dependent on TRAIL-R1 and/or -R2 dosage in most tumors. Resistance to apoptosis of cell lines with 8p21.3 deletion was reversed by restoration of TRAIL-R1 or TRAIL-R2 expression by gene transfection. Our data suggest that TRAIL-R1 and TRAIL-R2 act as dosage-dependent tumor suppressor genes whose monoallelic deletion can impair TRAIL-induced apoptosis in B-cell lymphoma
The Translation Factor eIF6 Is a Notch-Dependent Regulator of Cell Migration and Invasion
A growing body of evidence indicates that protein factors controlling translation play an important role in tumorigenesis. The protein known as eIF6 is a ribosome anti-association factor that has been implicated in translational initiation and in ribosome synthesis. Over-expression of eIF6 is observed in many natural tumours, and causes developmental and differentiation defects in certain animal models. Here we show that the transcription of the gene encoding eIF6 is modulated by the receptor Notch-1, a protein involved in embryonic development and cell differentiation, as well as in many neoplasms. Inhibition of Notch-1 signalling by γ-secretase inhibitors slowed down cell-cycle progression and reduced the amount of eIF6 in lymphoblastoid and ovarian cancer cell lines. Cultured ovarian cancer cell lines engineered to stably over-expressing eIF6 did not show significant changes in proliferation rate, but displayed an enhanced motility and invasive capacity. Inhibition of Notch-1 signalling in the cells over-expressing eIF6 was effective in slowing down the cell cycle, but did not reduce cell migration and invasion. On the whole, the results suggest that eIF6 is one of the downstream effectors of Notch-1 in the pathway that controls cell motility and invasiveness
Diagnostic and prognostic prediction using gene expression profiles in high-dimensional microarray data
Relevance of cyclin D1b expression and CCND1 polymorphism in the pathogenesis of multiple myeloma and mantle cell lymphoma
BACKGROUND: The CCND1 gene generates two mRNAs (cyclin D1a and D1b) through an alternative splicing at the site of a common A/G polymorphism. Cyclin D1a and b proteins differ in their C-terminus, a region involved in protein degradation and sub-cellular localization. Recent data have suggested that cyclin D1b could be a nuclear oncogene. The presence of cyclin D1b mRNA and protein has been studied in two hemopathies in which cyclin D1 could be present: multiple myeloma (MM) and mantle cell lymphoma (MCL). The A/G polymorphism of CCND1 has also been verified in a series of patients. METHODS: The expression of cyclin D1 mRNA isoforms has been studied by real-time quantitative PCR; protein isoforms expression, localization and degradation by western blotting. The CCND1 polymorphism was analyzed after sequencing genomic DNA. RESULTS: Cyclin D1 mRNA isoforms a and b were expressed in mantle cell lymphoma (MCL) and multiple myeloma (MM). Cyclin D1b proteins were present in MCL, rarely in MM. Importantly, both protein isoforms localized the nuclear and cytoplasmic compartments. They displayed the same short half-life. Thus, the two properties of cyclin D1b recognized as necessary for its transforming activity are missing in MCL. Moreover, CCND1 polymorphism at the exon/intron boundary had no influence on splicing regulation in MCL cells. CONCLUSION: Our results support the notion that cyclin D1b is not crucial for the pathogenesis of MCL and MM
Genome-wide miRNAprofiling of mantle cell lymphoma reveals a distinct subgroup with poor prognosis
miRNA deregulation has been implicated in the pathogenesis of mantle cell lymphoma (MCL). Using a high-throughput quantitative real-time PCR platform, we performed miRNA profiling on cyclin D1–positive MCL (n = 30) and cyclin D1–negative MCL (n =7) and compared them with small lymphocytic leukemia/ lymphoma (n =12), aggressive B-cell lymphomas (n =138), normal B-cell subsets, and stromal cells.We identified a 19-miRNA classifier that included 6 up-regulated miRNAs and 13 down regulated miRNA that was able to distinguish MCL from other aggressive lymphomas. Some of the up-regulated miRNAs are highly expressed in naive B cells. This miRNAclassifier showed consistent results in formalinfixed paraffin-embedded tissues and was able to distinguish cyclin D1–negative MCL from other lymphomas. A 26-miRNA classifier could distinguish MCL from small lymphocytic leukemia/lymphoma, dominated by 23 up-regulated miRNAs in MCL. Unsupervised hierarchical clustering of MCL patients demonstrated a cluster characterized by high expression of miRNAs from the polycistronic miR17-92 cluster and its paralogs, miR-106a-363 and miR-106b-25, and associated with high proliferation gene signature. The other clusters showed enrichment of stroma-associated miRNAs, and also had higher expression of stroma-associated genes. Our clinical outcome analysis in the present study suggested that miRNAs can serve as prognosticators
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