Correlation of TACC3, FGFR3, MMSET and p21 expression with the t(4;14)(p16.3;q32) in multiple myeloma

The t(4;14)(p16;q32) translocation seen in c. 18% of newly diagnosed multiple myeloma (MM) cases, results in FGFR3 activation and creation of an IGH/MMSET fusion transcript. We have recently shown that FGFR3 is activated in only 75% of t(4;14)(+) cases, suggesting that alternative genes near the breakpoint may be involved in the transforming event. The gene, TACC3, located just 50 kb telomeric of FGFR3, with transforming capacity, therefore represented a candidate gene. Using a real-time quantitative polymerase chain reaction-based approach on a cohort of 54 patients, we found a statistically significant, twofold increase in TACC3 expression in t(4;14)(+) cases. TACC3, MMSET and p21 values were positively correlated in all cases and, of particular interest, six patient samples [three t(4;14)(-), three t(4;14)(+)] samples showed a joint up-regulation of TACC3, MMSET and p21. Although a poor prognosis is linked with elevated MMSET expression, an extended follow-up period will be required to evaluate the significance of elevated TACC3 and p21 expression in this subgroup of MM.

Glucose-potentiated chemotaxis in human vascular smooth muscle is dependent on cross-talk between the P13K and MAPK signalling pathways

Atheroma formation involves the movement of vascular smooth muscle cells (VSMC) into the subendothelial space. The aim of this study was to determine the involvement of PI3K and MAPK pathways and the importance of cross-talk between these pathways, in glucose-potentiated VSMC chemotaxis to serum factors. VSMC chemotaxis occurred in a serum gradient in 25 mmol/L glucose (but not in 5 mmol/L glucose) in association with increased phosphorylation (activation) of Akt and ERK1/2 in PI3K and MAPK pathways, respectively. Inhibitors of these pathways blocked chemotaxis, as did an mTOR inhibitor. VSMC expressed all class IA PI3K isoforms, but microinjection experiments demonstrated that only the p110beta isoform was involved in chemotaxis. ERK1/2 phosphorylation was reduced not only by MAPK pathway inhibitors but also by PI3K and mTOR inhibitors; when PI3K was inhibited, ERK phosphorylation could be induced by microinjected activated Akt, indicating important cross-talk between the PI3K and ERK1/2 pathways. Glucose-potentiated phosphorylation of molecules in the p38 and JNK MAPK pathways inhibited these pathways but did not affect chemotaxis. The statin, mevinolin, blocked chemotaxis through its effects on the MAPK pathway. Mevinolin-inhibited chemotaxis was restored by farnesylpyrophosphate but not by geranylgeranylpyrophosphate; in the absence of mevinolin, inhibition of farnesyltransferase reduced ERK phosphorylation and blocked chemotaxis, indicating a role for the Ras family of GTPases (MAPK pathway) under these conditions. In conclusion, glucose sensitizes VSMC to serum, inducing chemotaxis via pathways involving p110beta-PI3K, Akt, mTOR, and ERK1/2 MAPK. Cross-talk between the PI3K and MAPK pathways is necessary for VSMC chemotaxis under these conditions.

Evidence for altered ETB receptor characterisitics during development and progression of ventricular cardiomyocyte hypertrophy.

The hypothesis that endothelin (ET) receptor mechanisms are altered during development and progression of left ventricular hypertrophy (LVH) in vivo was tested using spontaneously hypertensive rats (SHRs). Ventricular cardiomyocytes were isolated from SHRs before onset (8 and 12 wk) and during progression (16, 20, and 24 wk) of LVH and compared with age-matched normotensive Wistar-Kyoto (WKY) rats. PreproET-1 mRNA expression was elevated in SHR (P

A VLSI Architecture for Variable Block Size Video Motion Estimation

With the advent of new video standards such as MPEG-4 part-10 and H.264/H.26L, demands for advanced video coding, particularly in the area of variable block size video motion estimation (VBSME), are increasing. In this paper, we propose a new one-dimensional (1-D) very large-scale integration architecture for full-search VBSME (FSVBSME). The VBS sum of absolute differences (SAD) computation is performed by re-using the results of smaller sub-block computations. These are distributed and combined by incorporating a shuffling mechanism within each processing element. Whereas a conventional 1-D architecture can process only one motion vector (MV), this new architecture can process up to 41 MV sub-blocks (within a macroblock) in the same number of clock cycles.

Tungsten Silicide Contacts to Polycrystalline Silicon and Silicon-Germanium Alloys

Novel CVD WSi2 technology with low series and contact resistance in SiGe HBTs was achieved. Specific contact resistance to Si1-xGex with 0

Modelling Vibrated Stone Colums in Soft Clay

The vibrated stone column technique is an economical and environmentally friendly process that treats weak ground to enable it to withstand low to moderate loading conditions. The performance of the treated ground depends on various parameters such as the strengths of the in-situ and backfill materials, and the spacing, length and diameter of the columns. In practice, vibrated stone columns are frequently used for settlement control. Studies have shown that columns can fail by bulging, bending, punching or shearing. These failure mechanisms are examined in this paper. The study involved a series of laboratory model tests on a consolidated clay bed. The tests were carried out using two different materials: (a) transparent material with ‘clay like’ properties, and (b) speswhite kaolin. The tests on the transparent material have, probably for the first time, permitted visual examination of deforming granular columns during loading. They have shown that bulging was significant in long columns, whereas punching was prominent in shorter columns. The presence of the columns also greatly improved the load-carrying capacity of the soft clay bed. However, columns longer than about six times their diameter did not lead to further increases in the load-carrying capacity. This suggests that there is an optimum column length for a given arrangement of stone columns beneath a rigid footing.