Dynamic Characteristics of Neuron Models and Active Areas in Potential Functions

AbstractWe present a simple neuron model that shows a rich property in spite of the simple structure derived from a simplification of the Hindmarsh-Rose, the Morris-Lecar, and the Hodgkin-Huxley models. The model is a typical example whose characteristics can be discussed through the concept of potential with active areas. A potential function is able to provide a global landscape for dynamics of a model, and the dynamics is explained in connection with the disposition of the active areas on the potential, and hence we are able to discuss the global dynamic behaviors and the common properties among these realistic models

Fluctuation-induced traffic congestion in heterogeneous networks

In studies of complex heterogeneous networks, particularly of the Internet, significant attention was paid to analyzing network failures caused by hardware faults or overload, where the network reaction was modeled as rerouting of traffic away from failed or congested elements. Here we model another type of the network reaction to congestion -- a sharp reduction of the input traffic rate through congested routes which occurs on much shorter time scales. We consider the onset of congestion in the Internet where local mismatch between demand and capacity results in traffic losses and show that it can be described as a phase transition characterized by strong non-Gaussian loss fluctuations at a mesoscopic time scale. The fluctuations, caused by noise in input traffic, are exacerbated by the heterogeneous nature of the network manifested in a scale-free load distribution. They result in the network strongly overreacting to the first signs of congestion by significantly reducing input traffic along the communication paths where congestion is utterly negligible.Comment: 4 pages, 3 figure

Shaking Table Tests and Numerical Simulation of Seismic Response of The Seawall

Shaking table tests of a caisson seawall model were conducted to investigate sliding phenomena of the seawall. The response characteristics of the caisson placed on the mound which was fixed to the shaking table were investigated in the six series of experiments with varying the situation of the model; with or without backfill, wave breaking works and water. These test results were utilized to validate a two-dimensional FEM analysis method with joint elements. The numerical model with the finer mesh division and joint elements showed fairly close results with the series of test results, resulting the better representation of the characteristics of sliding and plastic deformation nature of the seawall model

A novel mutation in the tyrosine kinase domain of ERBB2 in hepatocellular carcinoma

BACKGROUND: Several studies showed that gain-of-function somatic mutations affecting the catalytic domain of EGFR in non-small cell lung carcinomas were associated with response to gefitinib and erlotinib, both EGFR-tyrosine kinase inhibitors. In addition, 4% of non-small cell lung carcinomas were shown to have ERBB2 mutations in the kinase domain. In our study, we sought to determine if similar respective gain-of-function EGFR and ERBB2 mutations were present in hepatoma and/or biliary cancers. METHODS: We extracted genomic DNA from 40 hepatoma (18) and biliary cancers (22) samples, and 44 adenocarcinomas of the lung, this latter as a positive control for mutation detection. We subjected those samples to PCR-based semi-automated double stranded nucleotide sequencing targeting exons 18–21 of EGFR and ERBB2. All samples were tested against matched normal DNA. RESULTS: We found 11% of hepatoma, but no biliary cancers, harbored a novel ERBB2 H878Y mutation in the activating domain. CONCLUSION: These newly described mutations may play a role in predicting response to EGFR-targeted therapy in hepatoma and their role should be explored in prospective studies

Involvement of promoter methylation in the regulation of Pregnane X receptor in colon cancer cells

<p>Abstract</p> <p>Background</p> <p>Pregnane X receptor (PXR) is a key transcription factor that regulates drug metabolizing enzymes such as cytochrome P450 (CYP) 3A4, and plays important roles in intestinal first-pass metabolism. Although there is a large inter-individual heterogeneity with intestinal CYP3A4 expression and activity, the mechanism driving these differences is not sufficiently explained by genetic variability of PXR or CYP3A4. We examined whether epigenetic mechanisms are involved in the regulation of PXR/CYP3A4 pathways in colon cancer cells.</p> <p>Methods</p> <p>mRNA levels of PXR, CYP3A4 and vitamin D receptor (VDR) were evaluated by quantitative real-time PCR on 6 colon cancer cell lines (Caco-2, HT29, HCT116, SW48, LS180, and LoVo). DNA methylation status was also examined by bisulfite sequencing of the 6 cell lines and 18 colorectal cancer tissue samples. DNA methylation was reversed by the treatment of these cell lines with 5-aza-2'-deoxycytidine (5-aza-dC).</p> <p>Results</p> <p>The 6 colon cancer cell lines were classified into two groups (high or low expression cells) based on the basal level of PXR/CYP3A4 mRNA. DNA methylation of the CpG-rich sequence of the <it>PXR </it>promoter was more densely detected in the low expression cells (Caco-2, HT29, HCT116, and SW48) than in the high expression cells (LS180 and LoVo). This methylation was reversed by treatment with 5-aza-dC, in association with re-expression of PXR and CYP3A4 mRNA, but not VDR mRNA. Therefore, PXR transcription was silenced by promoter methylation in the low expression cells, which most likely led to downregulation of CYP3A4 transactivation. Moreover, a lower level of <it>PXR </it>promoter methylation was observed in colorectal cancer tissues compared with adjacent normal mucosa, suggesting upregulation of the PXR/CYP3A4 mRNAs during carcinogenesis.</p> <p>Conclusions</p> <p><it>PXR </it>promoter methylation is involved in the regulation of intestinal PXR and CYP3A4 mRNA expression and might be associated with the inter-individual variability of the drug responses of colon cancer cells.</p

MT1-MMP regulates urothelial cell invasion via transcriptional regulation of Dickkopf-3

Membrane type-1 matrix metalloproteinase (MT1-MMP) is a zinc-binding endopeptidase, which plays a crucial role in tumour growth, invasion and metastasis. We have shown previously that MT1-MMP has higher expression levels in the human urothelial cell carcinoma (UCC) tissue. We show here that siRNA against MT1-MMP blocks invasion in UCC cell lines. Invasion is also blocked by broad-spectrum protease and MMP inhibitors including tissue inhibitor of metalloproteinase-1 and -2. Membrane type-1-MMP can also regulate transcription. We have used expression arrays to identify genes that are differentially transcribed when siRNA is used to suppress MT1-MMP expression. Upon MT1-MMP knockdown, Dickkopf-3 (DKK3) expression was highly upregulated. The stability of DKK3 mRNA was unaffected under these conditions, suggesting transcriptional regulation of DKK3 by MT1-MMP. Dickkopf-3 has been previously shown to inhibit invasion. We confirm that the overexpression of DKK3 leads to decreased invasive potential as well as delayed wound healing. We show for the first time that the effects of MT1-MMP on cell invasion are mediated in part through changes in DKK3 gene transcription

Can the stroma provide the clue to the cellular basis for mammographic density?

Mammographic density is recognised as a useful phenotypic biomarker of breast cancer risk. Deeper understanding is needed of the cellular basis, but evidence is limited because of difficulty in designing studies to validate hypotheses. The ductal epithelial components do not adequately explain the physical and dynamic features observed. The stroma is thought to interact with ductal structures in cancer initiation. Stromal tissues might account for the mammographic features, and this interplay can be hypothesised to relate risk to density. In a paper in this issue of Breast Cancer Research, Alowami has shown a relationship between density and stromal proteins, which might provide useful insight into mammographic density

Elevated levels of Dickkopf-related protein 3 in seminal plasma of prostate cancer patients

<p>Abstract</p> <p>Background</p> <p>Expression of Dkk-3, a secreted putative tumor suppressor, is altered in age-related proliferative disorders of the human prostate. We now investigated the suitability of Dkk-3 as a diagnostic biomarker for prostate cancer (PCa) in seminal plasma (SP).</p> <p>Methods</p> <p>SP samples were obtained from 81 patients prior to TRUS-guided prostate biopsies on the basis of elevated serum prostate-specific antigen (PSA; > 4 ng/mL) levels and/or abnormal digital rectal examination. A sensitive indirect immunoenzymometric assay for Dkk-3 was developed and characterized in detail. SP Dkk-3 and PSA levels were determined and normalized to total SP protein. The diagnostic accuracies of single markers including serum PSA and multivariate models to discriminate patients with positive (N = 40) and negative (N = 41) biopsy findings were investigated.</p> <p>Results</p> <p>Biopsy-confirmed PCa showed significantly higher SP Dkk-3 levels (100.9 ± 12.3 vs. 69.2 ± 9.4 fmol/mg; <it>p </it>= 0.026). Diagnostic accuracy (AUC) of SP Dkk-3 levels (0.633) was enhanced in multivariate models by including serum PSA (model A; AUC 0.658) or both, serum and SP PSA levels (model B; AUC 0.710). In a subpopulation with clinical follow-up > 3 years post-biopsy to ensure veracity of negative biopsy status (positive biopsy N = 21; negative biopsy N = 25) AUCs for SP Dkk-3, model A and B increased to 0.667, 0.724 and 0.777, respectively.</p> <p>Conclusions</p> <p>In multivariate models to detect PCa, inclusion of SP Dkk-3 levels, which were significantly elevated in biopsy-confirmed PCa patients, improved the diagnostic performance compared with serum PSA only.</p

Enabling connectivity for tactical networks in mountainous areas by aerial relays

A general modeling framework for realistic performance evaluations of tactical mobile ad-hoc networks deployed in mountainous areas is presented. The framework is easily extensible, and can be eventually automated. It can be also used to generate data for other network simulators. The framework utilizes the freely downloadable high resolution 3D terrain data to define time dependent trajectories of network nodes. The node speeds and directions are linked to the terrain profile which extends the previously proposed mobility models. The path-loss analysis along the node trajectories revealed the need for aerial relays to enable full network connectivity at all times. The network consisting of 5 cluster heads and a single stationary relay is considered as a case study. The relay location and its antenna height are optimized to achieve the line-of-sight connectivity over the whole mission duration. The antenna radiation pattern at the relay is incorporated in the analysis. The resulting star network topology is used by the cluster heads to broadcast their packets to all other cluster heads. Several relaying schemes including the amplify-and-forward and the decode-and-forward relaying are studied together with the go-back-N retransmissions to achieve the reliable data transfer

Serum galectin-9 levels are elevated in the patients with type 2 diabetes and chronic kidney disease

Background: Galectin-9 (Gal-9) induces apoptosis in activated T helper 1 (T(H)1) cells as a ligand for T cell immunoglobulin mucin-3 (Tim-3). Gal-9 also inhibits the G1 phase cell cycle arrest and hypertrophy in db/db mice, the hallmark of early diabetic nephropathy, by reversing the high glucose-induced up-regulation of cyclin dependent kinase inhibitors such as p27(Kip1) and p21(Cip1). Methods: We investigated the serum levels of Gal-9 in the patients with type 2 diabetes and various stages of chronic kidney disease (CKD) (n = 182). Results: Serum Gal-9 levels in the patients with type 2 diabetes were 131.9 +/- 105.4 pg/ml and Log(10)Gal-9 levels significantly and positively correlated with age (r = 0.227, p = 0.002), creatinine (r = 0.175, p = 0.018), urea nitrogen (r = 0.162, p = 0.028) and osmotic pressure (r = 0.187, p = 0.014) and negatively correlated with estimated glomerular filtration rate (eGFR) (r = -0.188, p = 0.011). Log(10)Gal-9 levels increased along with the progression of GFR categories of G1 to G4, and they were statistically significant by Jonckheere-Terpstra test (p = 0.012). Log(10)Gal-9 levels remained similar levels in albuminuria stages of A1 to A3. Conclusion: The elevation of serum Gal-9 in the patients with type 2 diabetes is closely linked to GFR and they may be related to the alteration of the immune response and inflammation of the patients with type 2 diabetes and CKD