Expression of Main Toll-Like Receptors in Patients with Different Types of Colorectal Polyps and Their Relationship with Gut Microbiota

Abnormal activation of Toll-like receptor (TLRs) signaling can result in colon cancer development. The aim of this study was to investigate the expression of important TLRs in different histological types of colorectal polyps and evaluate their relationship with intestinal microbiota. The expression levels of TLR2, 3, 4, and 5 were analyzed in intestinal biopsy specimens of 21 hyperplastic polyp (HP), 16 sessile serrated adenoma (SSA), 29 tubular adenoma (TA), 21 villous/tubulovillous (VP/TVP) cases, and 31 normal controls. In addition, selected gut bacteria including Streptococcus bovis, Enterococcus faecalis, Enterotoxigenic Bacteroides fragilis (ETBF), Fusobacterium nucleatum, Porphyromonas spp., Lactobacillus spp., Roseburia spp., and Bifidobacterium spp. were quantified in fecal samples using absolute qRT PCR, and, finally, the association between TLRs and these gut microbiota- was evaluated by Spearman’s correlation coefficient. Higher expression of TLR2 and TLR4 in VP/TVP and TA, and lower expression levels of TLR3 and TLR5 in all type of polyps were observed. The differences in TLR expression patterns was not only dependent on the histology, location, size, and dysplasia grade of polyps but also related to the intestinal microbiota patterns. TLR2 and TLR4 expression was directly associated with the F. nucleatum, E. faecalis, S. bovis, Porphyromonas, and inversely to Bifidobacterium, Lactobacillus, and Roseburia quantity. Furthermore, TLR3 and TLR5 expression was directly associated with Bifidobacterium, Roseburia, and Lactobacillus quantity. Our results suggest a possible critical role of TLRs during colorectal polyp progression. An abnormal regulation of TLRs in relation to gut microbial quantity may contribute to carcinogenesis.     

Profile-Driven Component Placement for Cluster-Based Online Services

The growth of the Internet and of various intranets has spawned a wealth of online services, most of which are implemented on local-area clusters using remote invocation (for example, remote procedure call/remote method invocation) among manually placed application components. Component placement can be a significant challenge for large-scale services, particularly when application resource needs are workload dependent. Automatic component placement has the potential to maximize overall system throughput. The key idea is to construct (offline) a mapping between input workload and individual-component resource consumption. Such mappings, called component profiles, then support high-performance placement. Preliminary results on an online auction benchmark based on J2EE (Java 2 Platform, Enterprise Edition) suggest that profile-driven tools can identify placements that achieve near-optimal overall throughput.     

Management gaps analysis: a case study of groundwater resource management in New Zealand

The primary objective of this project is to identify gaps, whether real or perceived, that hinder effective groundwater management in New Zealand. These gaps show as gaps in information, gaps in implementation, gaps in technological and management tools, and gaps in understanding of fundamental processes. The secondary objective is to propose a management strategy to close the identified gaps. Several methods are used to meet these objectives: surveys distributed to selected staff in each regional council; the review of various written reports; the analysis of land-use databases; and private consultation within each regional council. Results show that groundwater management in New Zealand is generally reactionary with the main gaps being in strategic planning and national guidelines. Most gaps appear to be predominantly information and implementation issues. In some cases there are gaps in the understanding of fundamental processes within an aquifer system, including the long-term effects of land-use on groundwater quality. An adaptive management approach is suggested as a means of closing these gaps.     

Interior symmetry and local bifurcation in coupled cell networks

A coupled cell system is a network of dynamical systems, or 'cells', coupled together. Such systems can be represented schematically by a directed graph whose nodes correspond to cells and whose edges represent couplings. A symmetry of a coupled cell system is a permutation of the cells and edges that preserves all internal dynamics and all couplings. It is well known that symmetry can lead to patterns of synchronized cells, rotating waves, multirhythms, and synchronized chaos. Recently, the introduction of a less stringent form of symmetry, the 'symmetry groupoid', has shown that global group-theoretic symmetry is not the only mechanism that can create such states in a coupled cell system. The symmetry groupoid consists of structure-preserving bijections between certain subsets of the cell network, the input sets. Here, we introduce a concept intermediate between the groupoid symmetries and the global group symmetries of a network: 'interior symmetry'. This concept is closely related to the groupoid structure, but imposes stronger constraints of a group-theoretic nature. We develop the local bifurcation theory of coupled cell systems possessing interior symmetries, by analogy with symmetric bifurcation theory. The main results are analogues for 'synchrony-breaking' bifurcations of the Equivariant Branching Lemma for steady-state bifurcation, and the Equivariant Hopf Theorem for bifurcation to time-periodic states.     

Prolonged tamoxifen exposure selects a breast cancer cell clone that is stable in vitro and in vivo

The effects of long-term tamoxifen exposure on cell growth and cell cycle kinetics were compared between oestrogen receptor (ER)-positive (MCF-7) and ER-negative (MDA-MB-231) cell lines. In the MCF-7 cell line, prolonged tamoxifen exposure (0.5 mumol/l for > 100 days) blocked cells in G0-G1 of the cell cycle, and slowed the doubling time of cells from 30 to 59 h. These effects corresponded to an increase in the cellular accumulation of tamoxifen over time [mean area under concentration curve (AUC) = 77.92 mumoles/10(6)/cells/day]. In contrast, in the MDA-MB-231 cell line, long-term tamoxifen exposure had no obvious effect on the doubling time, and reduced cellular tamoxifen accumulation (mean AUC = 50.50 mumoles/10(6)/cells/day) compared to the MCF-7 cells. Flow cytometric analysis of MDA-MB-231 cells demonstrated that a new tetraploid clone emerged following 56 days of tamoxifen exposure. Inoculation of the MDA-MB-231 tetraploid clone and MDA-MB-231 wildtype cells into the opposite flanks of athymic nude mice resulted in the rapid growth of tetraploid tumours. The tetraploid tumours maintained their ploidy following tamoxifen treatment for nine consecutive serial transplantations. Histological examination of the fifth transplant generation xenografts revealed that the tetraploid tumour had a 25-30 times greater mass, area of haemorrhage and necrosis, a slightly higher mitotic index and was more anaplastic than the control neoplasm. The control wildtype MDA-MB-231 tumours maintained a stable ploidy following tamoxifen treatment until the eighth and ninth transplantation, when a tetraploid population appeared, suggesting that tamoxifen treatment may select for this clone in vivo. These studies suggest that prolonged tamoxifen exposure may select for new, stable, fast growing cell clones in vitro as well as in vivo.     

NETWORKING WITH A HUMAN FACE Mentoring as a Career Strategy

Mentoring has been around for ages, often masquerading as the management club or the fast track. Among successful business unit managers, mentoring is a well-understood practice, and it's a career development strategy today's IS professional would be wise to consider.