Study of tumour suppressor genes in malignant tumours of liver, pancreas and biliary system

The importance of tumour suppressor gene inactivation by gene deletion and/or mutation in tumour development has been established. Loss of heterozygosity (LOH), or allele loss, in tumour DNA is thought to represent the loss of such genes. Detection of LOH in particular tumours has been widely used for searching for the loci of tumour suppressor genes in the tumours. Few studies on tumour suppressor genes in tumours of liver, pancreas and biliary system have been performed. The work in this thesis was undertaken to test the hypothesis that loss of tumour suppressor genes by LOH occurred in these tumours. Eighty-two such tumours (liver tumours: 53; carcinoma of the pancreas: 15 and cholangiocarcinoma: 14) were investigated to search for the consistent LOH. Paired normal and tumour DNA were analyzed by Southern hybridisation using a panel of restriction fragment length polymorphism (RFLP) DNA probes, previously assigned to different chromosomal regions. In informative patients, band losses in tumour DNA compared with bands of normal DNA on autoradiographs were scored as LOH or allele loss. In hepatocellular carcinoma (HCC) without liver cirrhosis, LOH in the chromosome region 5q35-qter was found in 6 out of 6 informative patients detected by the probe ?MS8, and the loss was distinct from the adenomatous polyposis coli (APC) locus in the region of 5q21-22. The results strongly suggested that a putative tumour suppressor gene for HCC without liver cirrhosis was located in the region 5q35-qter. A high frequency of loss was also found in 17p13, the chromosome region encompassing the p53 tumour suppressor gene. HCC with liver cirrhosis had no loss in the region of 5q35-qter, but in 1q42-43, 5p and 17p13. LOH occurred at a low frequency in fibrolamellar carcinomas and in none of the hepatocellular adenomas studied. In contrast, multiple allelic losses were found in two sarcomatoid liver carcinomas. Cholangiocarcinoma had a similar LOH pattern to that in HCC without liver cirrhosis, ie, losses in 5q35-qter and 17p13. Liver metastases from colorectal cancers showed a high incidence of allele loss on chromosomes 5q21-22, 17p13 and 18q. In carcinoma of the pancreas, LOH was detected in 1p33-35, 6q27 and 11q13. An extensive pilot study was performed to isolate the putative tumour suppressor gene in chromosomal region 5q35-qter for HCC without liver cirrhosis and cholangiocarcinoma. Effort was made to isolate DNA sequences from chromosome 5 that were expressed in normal human liver tissue, on the assumption that tumour suppressor genes are transcribed in normal tissues. This was performed by cross-screening a human chromosome 5 genomic DNA library in phage Charon 21A with a normal human liver cDNA library. Twenty-one positive clones in phages were obtained after the third round of screening. These clones were recloned to plasmid Bluescript KS+ for further use since clones would be easier to use in plasmid vectors than in phages. A proposal to identify the putative tumour suppressor gene from these clones was made

Superspace Formulation in a Three-Algebra Approach to D=3, N=4,5 Superconformal Chern-Simons Matter Theories

We present a superspace formulation of the D=3, N=4,5 superconformal Chern-Simons Matter theories, with matter supermultiplets valued in a symplectic 3-algebra. We first construct an N=1 superconformal action, and then generalize a method used by Gaitto and Witten to enhance the supersymmetry from N=1 to N=5. By decomposing the N=5 supermultiplets and the symplectic 3-algebra properly and proposing a new super-potential term, we construct the N=4 superconformal Chern-Simons matter theories in terms of two sets of generators of a (quaternion) symplectic 3-algebra. The N=4 theories can also be derived by requiring that the supersymmetry transformations are closed on-shell. The relationship between the 3-algebras, Lie superalgebras, Lie algebras and embedding tensors (proposed in [E. A. Bergshoeff, O. Hohm, D. Roest, H. Samtleben, and E. Sezgin, J. High Energy Phys. 09 (2008) 101.]) is also clarified. The general N=4,5 superconformal Chern-Simons matter theories in terms of ordinary Lie algebras can be rederived in our 3-algebra approach. All known N=4,5 superconformal Chern-Simons matter theories can be recovered in the present superspace formulation for super-Lie-algebra realization of symplectic 3-algebras.Comment: 37 pages, minor changes, published in PR

PABO: Mitigating Congestion via Packet Bounce in Data Center Networks

In today's data center, a diverse mix of throughput-sensitive long flows and delay-sensitive short flows are commonly presented in shallow-buffered switches. Long flows could potentially block the transmission of delay-sensitive short flows, leading to degraded performance. Congestion can also be caused by the synchronization of multiple TCP connections for short flows, as typically seen in the partition/aggregate traffic pattern. While multiple end-to-end transport-layer solutions have been proposed, none of them have tackled the real challenge: reliable transmission in the network. In this paper, we fill this gap by presenting PABO -- a novel link-layer design that can mitigate congestion by temporarily bouncing packets to upstream switches. PABO's design fulfills the following goals: i) providing per-flow based flow control on the link layer, ii) handling transient congestion without the intervention of end devices, and iii) gradually back propagating the congestion signal to the source when the network is not capable to handle the congestion.Experiment results show that PABO can provide prominent advantage of mitigating transient congestions and can achieve significant gain on end-to-end delay

Cerebral hemodynamic characteristics of acute mountain sickness upon acute high-altitude exposure at 3,700 m in young Chinese men.

PURPOSE: We aimed at identifying the cerebral hemodynamic characteristics of acute mountain sickness (AMS). METHODS: Transcranial Doppler (TCD) sonography examinations were performed between 18 and 24 h after arrival at 3,700 m via plane from 500 m (n = 454). A subgroup of 151 subjects received TCD examinations at both altitudes. RESULTS: The velocities of the middle cerebral artery, vertebral artery (VA) and basilar artery (BA) increased while the pulsatility indexes (PIs) and resistance indexes (RIs) decreased significantly (all p < 0.05). Velocities of BA were higher in AMS (AMS+) individuals when compared with non-AMS (AMS-) subjects (systolic velocity: 66 ± 12 vs. 69 ± 15 cm/s, diastolic velocity: 29 ± 7 vs. 31 ± 8 cm/s and mean velocity, 42 ± 9 vs. 44 ± 10 cm/s). AMS was characterized by higher diastolic velocity [V d_VA (26 ± 4 vs. 25 ± 4, p = 0.013)] with lower PI and RI (both p = 0.004) in VA. Furthermore, the asymmetry index (AI) of VAs was significantly lower in the AMS + group [-5.7 % (21.0 %) vs. -2.5 % (17.8 %), p = 0.016]. The AMS score was closely correlated with the hemodynamic parameters of BA and the V d_VA, PI, RI and AI of VA. CONCLUSION: AMS is associated with alterations in cerebral hemodynamics in the posterior circulation rather than the anterior one, and is characterized by higher blood velocity with lower resistance. In addition, the asymmetry of VAs may be involved in AMS