Sarah J. Johnson

Prevalence of Ras mutations in thyroid neoplasia

Mutations at codons 12, 13 or 61 of ras which result in constitutive activation occur frequently in human malignancies. There have been varied reports on their prevalence and hence their likely significance in the pathogenesis of primary thyroid neoplasia. To address this, we have examined a large series of benign and malignant thyroid tumours for ras mutations.

A family of irregular LDPC codes with low encoding complexity

We consider irregular quasi-cyclic low-density parity-check (LDPC) codes derived from difference families. The resulting codes can be encoded with low complexity and perform well when iteratively decoded with the sum-product algorithm.

Regular low-density parity-check codes from combinatorial designs

Analytically constructed LDPC codes comprise only a very small subset of possible codes and as a result LDPC codes are still, for the most part, constructed randomly. This paper extends the class of LDPC codes that can be systematically generated by presenting a construction method for regular LDPC codes based on combinatorial designs known as Kirkman triple systems. We construct (3, /spl rho/)-regular codes whose Tanner graph is free of 4-cycles for any integer /spl rho/, and examine girth and minimum distance properties of several classes of LDPC codes obtained from combinatorial designs.

Hepatitis C virus: epidemiology and genotypes in the north east of England.

The epidemiology of hepatitis C virus (HCV) infection was studied in an English teaching hospital over an 18 month period. A total of 104 HCV antibody positive patients were referred for further investigation. They were divided into those diagnosed through screening (blood donors and intravenous drug abusers) and those diagnosed for other reasons, and their mean ages, known risk factors for HCV transmission, genotypes, and liver biopsy histology were analysed. Screened patients were significantly younger than the others. No significant difference in age was found between genotypes. Most patients genotyped (69%) were genotype 1. Intravenous drug abusers had a higher proportion of subtype 1a, and patients who acquired HCV through blood transfusion had a higher proportion of subtype 1b. Liver biopsy specimens were scored using a histological activity index for liver inflammation and fibrosis. Patients with subtype 1b had significantly more severe liver disease than other genotypes when the histological activity index scores for fibrosis were analysed (p < 0.05). Liver disease worsened significantly with age according to all three histological activity index scores (portal activity: p < 0.01, acinar activity: p < 0.001, fibrosis: p < 0.0001). Liver disease worsened with increased duration of infection (p < 0.002), and patients who also abused alcohol presented at a significantly younger age (cirrhosis, p < 0.05, hepatocellular carcinoma, p < 0.02).

Chronic stress-induced disruption of the astrocyte network is driven by structural atrophy and not loss of astrocytes

Chronic stress is well recognized to decrease the number of GFAP+ astrocytes within the prefrontal cortex (PFC). Recent research, however, has suggested that our understanding of how stress alters astrocytes may be incomplete. Specifically, chronic stress has been shown to induce a unique form of microglial remodelling, but it is not yet clear whether astrocytes also undergo similar structural modifications. Such alterations may be significant given the role of astrocytes in modulating synaptic function. Accordingly, in the current study we have examined changes in astrocyte morphology following exposure to chronic stress in adult rats, using three-dimensional digital reconstructions of astrocytes. Our analysis indicated that chronic stress produced profound atrophy of astrocyte process length, branching and volume. We additionally examined changes in astrocyte-specific S100β, which are both a putative astrocyte marker and a protein whose expression is associated with astrocyte distress. While we found that S100β levels were increased by stress, this increase was not correlated with atrophy. We further established that while chronic stress was associated with a decrease in astrocyte numbers when GFAP labelling was used as a marker, we could find no evidence of a decrease in the total number of cells, based on Nissl staining, or in the number of S100β+ cells. This finding suggests that chronic stress may not actually reduce astrocyte numbers and may instead selectively decrease GFAP expression. The results of the current study are significant as they indicate stress-induced astrocyte-mediated disturbances may not be due to a loss of cells but rather due to significant remodeling of the astrocyte network.

Construction of low-density parity-check codes from Kirkman triple systems

Gallager introduced low-density parity-check (LDPC) codes in 1962, presenting a construction method to randomly allocate bits in the parity-check matrix subject to certain structural constraints. Since then improvements have been made to Gallagers construction method and some analytic constructions for LDPC codes have been presented. However analytically constructed LDPC codes comprise only a very small subset of possible codes and as a result LDPC codes are still, for the most part, constructed randomly. This paper extends the class of LDPC codes that can be systematically generated by presenting a construction method for regular LDPC codes based on combinatorial designs known as Kirkman triple systems. That is, we construct (3, /spl rho/)-regular codes whose Tanner (1981) graph is free of 4-cycles for any integer /spl rho/.

Capacity Theorems for the AWGN multi-way relay channel

The L-user additive white Gaussian noise multi-way relay channel is considered, where multiple users exchange information through a single relay at a common rate. Existing coding strategies, i.e., complete-decode-forward and compress-forward are shown to be bounded away from the cut-set upper bound at high signal-to-noise ratios (SNR). It is known that the gap between the compress-forward rate and the capacity upper bound is a constant at high SNR, and that between the complete-decode-forward rate and the upper bound increases with SNR at high SNR. In this paper, a functional-decode-forward coding strategy is proposed. It is shown that for L ≥ 3, complete-decode-forward achieves the capacity when SNR ≤ 0 dB, and functional-decode-forward achieves the capacity when SNR ≥ 0 dB. For L = 2, functional-decode-forward achieves the capacity asymptotically as SNR increases.

Hepatitis C virus

The epidemiology of hepatitis C virus (HCV) infection was studied in an English teaching hospital over an 18 month period. A total of 104 HCV antibody positive patients were referred for further investigation. They were divided into those diagnosed through screening (blood donors and intravenous drug abusers) and those diagnosed for other reasons, and their mean ages, known risk factors for HCV transmission, genotypes, and liver biopsy histology were analysed. Screened patients were significantly younger than the others. No significant difference in age was found between genotypes. Most patients genotyped (69%) were genotype 1. Intravenous drug abusers had a higher proportion of subtype 1a, and patients who acquired HCV through blood transfusion had a higher proportion of subtype 1b. Liver biopsy specimens were scored using a histological activity index for liver inflammation and fibrosis. Patients with subtype 1b had significantly more severe liver disease than other genotypes when the histological activity index scores for fibrosis were analysed (p < 0.05). Liver disease worsened significantly with age according to all three histological activity index scores (portal activity: p < 0.01, acinar activity: p < 0.001, fibrosis: p < 0.0001). Liver disease worsened with increased duration of infection (p < 0.002), and patients who also abused alcohol presented at a significantly younger age (cirrhosis, p < 0.05, hepatocellular carcinoma, p < 0.02).

Resolvable 2-designs for regular low-density parity-check codes

This paper extends the class of low-density parity-check (LDPC) codes that can be algebraically constructed. We present regular LDPC codes based on resolvable Steiner 2-designs which have Tanner graphs free of four-cycles. The resulting codes are (3, /spl rho/)-regular or (4, /spl rho/)-regular for any value of /spl rho/ and for a flexible choice of code lengths.

Quantitative analysis of macrophages and perisinusoidal cells in primary biliary cirrhosis.

Immunohistochemistry and image analysis were used to quantify alterations in the Kupffer cell and ‘activated’ perisinusoidal cell populations in the different stages of primary biliary cirrhosis. Anti‐CD68 macrophage antibodies were used to detect Kupffer cells, and anti‐α‐smooth muscle actin (α‐SMA), PR 2D3 and anti‐desmin antibodies to detect perisinusoidal cells. Liver biopsy material was available from 26 patients with primary biliary cirrhosis and 23 patients with histologically normal liver. Increased Kupffer cell numbers were observed in periportal/periseptal zones of stage 3 primary biliary cirrhosis (n= 9), and in random parenchymal areas of stage 3 and stage 4 cases. Significantly increased ‘activated’ perisinusoidal cell numbers were seen only in periportal/periseptal zones of stage 3 and stage 4 primary biliary cirrhosis. Neither Kupffer cell nor perisinusoidal cell numbers altered significantly in stage 1 and 2 primary biliary cirrhosis (n= 6). PR 2D3 positivity and increased α‐SMA immunoreactivity by perisinusoidal cells in primary biliary cirrhosis support myofibroblastic differentiation of these cells. Human perisinusoidal cells, unlike their rodent counterparts, did not express desmin in primary biliary cirrhosis or control liver. Kupffer cell and ‘activated’ perisinusoidal cell accumulation in periportal/periseptal zones of the precirrhotic and cirrhotic primary biliary cirrhosis liver support the concept of Kupffer cell‐mediated stimulation of perisinusoidal cells. Furthermore, these findings indicate that Kupffer cell–perisinusoidal interactions play an important role in the development of liver fibrosis and cirrhosis in primary biliary cirrhosis.