Glycosylation in Indolent,Significant and Aggressive Prostate Cancer by Automated High-Throughput N-Glycan Profiling

The diagnosis and treatment of prostate cancer (PCa) is a major health-care concern worldwide. This cancer can manifest itself in many distinct forms and the transition from clinically indolent PCa to the more invasive aggressive form remains poorly understood. It is now universally accepted that glycan expression patterns change with the cellular modifications that accompany the onset of tumorigenesis. The aim of this study was to investigate if differential glycosylation patterns could distinguish between indolent, significant, and aggressive PCa. Whole serum N-glycan profiling was carried out on 117 prostate cancer patients’ serum using our automated, high-throughput analysis platform for glycan-profiling which utilizes ultra-performance liquid chromatography (UPLC) to obtain high resolution separation of N-linked glycans released from the serum glycoproteins. We observed increases in hybrid, oligomannose, and biantennary digalactosylated monosialylated glycans (M5A1G1S1, M8, and A2G2S1), bisecting glycans (A2B, A2(6)BG1) and monoantennary glycans (A1), and decreases in triantennary trigalactosylated trisialylated glycans with and without core fucose (A3G3S3 and FA3G3S3) with PCa progression from indolent through significant and aggressive disease. These changes give us an insight into the disease pathogenesis and identify potential biomarkers for monitoring the PCa progression, however these need further confirmation studies.     

GOLPH3 Regulates EGFR in T98G Glioblastoma Cells by Modulating Its Glycosylation and Ubiquitylation

Protein trafficking is altered when normal cells acquire a tumor phenotype. A key subcellular compartment in regulating protein trafficking is the Golgi apparatus, but its role in carcinogenesis is still not well defined. Golgi phosphoprotein 3 (GOLPH3), a peripheral membrane protein mostly localized at the trans-Golgi network, is overexpressed in several tumor types including glioblastoma multiforme (GBM), the most lethal primary brain tumor. Moreover, GOLPH3 is currently considered an oncoprotein, however its precise function in GBM is not fully understood. Here, we analyzed in T98G cells of GBM, which express high levels of epidermal growth factor receptor (EGFR), the effect of stable RNAi-mediated knockdown of GOLPH3. We found that silencing GOLPH3 caused a significant reduction in the proliferation of T98G cells and an unexpected increase in total EGFR levels, even at the cell surface, which was however less prone to ligand-induced autophosphorylation. Furthermore, silencing GOLPH3 decreased EGFR sialylation and fucosylation, which correlated with delayed ligand-induced EGFR downregulation and its accumulation at endo-lysosomal compartments. Finally, we found that EGF failed at promoting EGFR ubiquitylation when the levels of GOLPH3 were reduced. Altogether, our results show that GOLPH3 in T98G cells regulates the endocytic trafficking and activation of EGFR likely by affecting its extent of glycosylation and ubiquitylation.     

Blood pressure estimation and beliefs among normotensives and hypertensives.

14 medicated hypertensive, 15 nonmedicated mild hypertensive, 39 normotensive, and 13 hypotensive adults participated in a 1–2 hr laboratory experiment that assessed each S's symptoms, moods, and estimates of systolic blood pressure (SBP) relative to actual SBP levels. Several self-reports and autonomic measures were collected during and after each of 22 tasks. Within-S correlations indicated that all Ss could estimate SBP at levels greater than chance. Further, 68% of the Ss evidenced at least 1 significant symptom–SBP correlation. Although medicated hypertensives believed they could estimate their BP more accurately than other groups, they were actually no more accurate than the other Ss. They also evidenced far fewer empirically derived symptom–SBP and emotion–SBP correlations than any other group. Overall, blood pressure (BP) beliefs were largely inaccurate. If these erroneous beliefs can be eliminated, Ss may be able to estimate BP fluctuations more accurately. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

GUIDELINES FOR DESIGNING EIS INTERFACES Meeting Executives' Information Needs

For users of an executive information system (EIS), the EIS interface is the system and is crucial to the EIS's success. These guidelines for designing EIS interfaces are based on studies of actual EIS interfaces that meet the unique information needs of executives.     

Afterburner [network-independent card for protocols]

Many current implementations of protocols such as the Transmission Control Protocol/Internet Protocol (TCP/IP) are inefficient because data are often accessed more frequently than necessary. Three techniques that reduce the need for memory bandwidth are proposed. The techniques are copy-on-write, page remapping, and single-copy. Afterburner, a network-independent card that provides the services that are necessary for a single-copy protocol stack, is described. The card has 1 MByte of local buffers and provides a simple interface to a variety of network link adapters, including HIPPI and asynchronous transfer mode (ATM). Afterburner can support transfers to and from the link adapter card at rates up to 1 Gbit/s. An implementation of TCP/IP that uses the features provided by Afterburner to reduce the movement of data to a single copy is discussed. Measurements of the end-to-end performance of Afterburner and the single-copy implementation of TCP/IP are presented     

Improvements to the instrumentation of a laboratory demonstration surge tank

The instrumentation described in this paper is designed to provide a relatively cheap and simple method of recording the changing water level during the operation of a laboratory surge tank. The method detects the passage of the water surface past a number of pairs of electrodes fitted into the side of the surge tank. One of each pair is supplied with a low D.C. voltage, so that when the pair is immersed in water, a small current flows. This signal is amplified and encoded before being used by a VELA datalogger acting as a timing device. The data is later transferred to a microcomputer for presentation in graphical and printed form. The method copes accurately both with the initial rapid large change in water level and the subsequent slowly decaying oscillations. It can also be used for automatic calibration of other methods of recording changing water levels.     

Detecting delaminations in a composite beam using anti-optimization

The present study proposes a detection technique for delaminations in a laminated beam. The proposed technique optimizes the spatial distribution of harmonic excitation so as to magnify the difference in response between the delaminated and intact beam. The technique is evaluated by numerical simulation of two-layered aluminum beams. Effects of measurement and geometric noise are included in the analysis. A finite element model for a delaminated composite, based on a layer-wise laminated plate theory is used in conjunction with a step function to simulate delaminations     

Off flavours in large waterbodies: physics, chemistry and biology in synchrony.

The Laurentian Great Lakes of North America are a drinking water source for millions of Canadian and US consumers. These waterbodies have undergone extensive change over the past century as a result of widespread degradation and remediation. Many of the Lakes are prone to taste and odour (T&O), and although these outbreaks have been poorly monitored, evidence suggests that they are increasing in frequency. Tracing and controlling T&O in such large systems presents a challenging task, due to their physical size and complexity. This paper presents an overview of recent investigative and management approaches to T&O in Lake Ontario and its outflow, the St. Lawrence River. We have identified three distinct patterns of T&O in these source-waters, caused by geosmin and 2-methylisoborneol and differing in their planktonic and benthic sources, and temporal and spatial dynamics. Each pattern has required a different approach by scientists and management, in partnership with the water industry. We have shown these T&O outbreaks are caused and moderated by physical, chemical and biological mechanisms over a spectrum of spatial and temporal scales. Canadian municipalities affected by these outbreaks have been key to the investigation of the links between T&O and ecosystem processes with the aim to develop more proactive water treatment and long-term management.