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.     

A phase I-II study of paclitaxel, ifosfamide, and vinorelbine with filgrastim (rhG-CSF) support in advanced non-small-cell lung cancer

PURPOSE: We designed a phase I-II trial of three active agents, paclitaxel, ifosfamide, and vinorelbine, in advanced non-small-cell lung cancer (NSCLC) to: 1) define the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of paclitaxel with filgrastim (G-CSF) support; and 2) determine the overall response rate and median survival of patients treated on this regimen. PATIENTS AND METHODS: We treated cohorts of patients with stage IIIB or IV NSCLC with ifosfamide 1.2-1.6 g/m2/day x 3 and vinorelbine 20-25 mg/m2/day x 3 and escalating doses of paclitaxel at 100-175 mg/m2 on day 2 with G-CSF support on a 21-day cycle. One prior experimental single-agent chemotherapy regimen was allowed. RESULTS: Fifty-six patients, were enrolled on this trial: 27 on the phase I portion of the study and an additional 29 at the recommended phase II dose (RPTD). Thirteen patients had received prior chemotherapy. Paclitaxel doses of 175 mg/m2 and 150 mg/m2 produced dose-limiting myelosuppression, and the RPTD was determined to be paclitaxel 135 mg/m2 with ifosfamide 1.2 g/m2/day on days 1-3 and vinorelbine 20 mg/m2/ day on days 1-3 with G-CSF support. The overall response rate was 18%, with a median survival of 6.1 months. Six of 35 patients (17%) treated at the RPTD achieved a partial response to therapy. Grade IV neutropenia was observed in 19 of 35 patients at this dose, with eight patients suffering febrile neutropenia. CONCLUSIONS: This non-cisplatin-containing three-drug regimen has substantial toxicity and low activity in advanced NSCLC, and does not seem to improve on prior regimens. It is unclear whether the lack of efficacy relates to an antagonistic reaction between the specific drugs, administration schedule, or to subtherapeutic doses of the individual agents.     

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     

Effects of cocaine on dopamine receptor gene expression: a study in the postmortem human brain

The effects of chronic cocaine exposure on dopamine D1 and D2 receptor gene expression in the human brain were studied in postmortem samples from chronic cocaine abusing and matched control subjects. Using in situ hybridization of receptor autoradiography to examine messenger ribonucleic acid (RNA) and binding sites, respectively, neither D1 nor D2 receptor expression was found to be changed in the nucleus accumbens, caudate, putamen, or substantia nigra of the cocaine-exposed subjects. Although chronic cocaine exposure can produce alterations in dopaminergic neurotransmission, sustained compensatory changes in dopamine receptor expression do not appear to occur in the human.     

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     

A comparison of biofilms from macrophytes and rocks for taste and odour producers in the St. Lawrence river.

Given their widespread and prolific annual development in the St. Lawrence River (SLR), macrophytes (i.e. submerged aquatic plants) represent large surface areas for biofilm growth and potentially important sites for associated production of taste and odour (T&O) compounds. We therefore evaluated the importance of submerged macrophytes and their associated biofilms for production of T&O compounds, 2-methylisoborneol (MIB) and geosmin (GM), compared with biofilms from adjacent rocks. We also tested the hypothesis that production of these compounds would differ between macrophyte species, based on the premise that they are not inert substrates but directly influence the communities that colonise their surfaces. Samples collected from transects across the SLR between Kingston and Cornwall, ON were dominated by the flat-bladed Vallisneria spp., and the leafed Myriophyllum spicatum, Elodea canadensis, Chara spp., Potamgeton spp., and Ceratophyllum spp. Overall, MIB and GM levels in biofilms ranged widely between samples. Expressed per g dry weight of biofilm, median levels from macrophyte were 50 (range 1-5000) ng MIB g(-1) and 10 (<1 to 580) ng GM g(-1) compared with 50 (range 5-970) ng MIB g(-1) and 160 (1-1600) ng GM g(-1) from rocks. Based on non-parametric statistical analysis, levels of GM were higher on a g dry weight basis in biofilms from rocks than macrophytes (P = 0.02), but MIB levels were similar (P = 0.94). However, when normalised for differences in substrate surface area (i.e. ng cm(-2)), levels of both MIB and GM were higher in biofilms from rocks than from macrophytes (P < 0.01). There were no discernable differences in MIB and GM concentrations from biofilms of different macrophytes based on either g dry weight sample or surface area (P > 0.05). Overlying water (OLW) concentrations ranged between 2-45 ng L(-1) for MIB and 5-30 ng L(-1) for GM and were not correlated with levels in adjacent biofilms. However, OLW concentrations peaked in shallow, low energy embayments consistent with enhanced production and release of MIB and GM in nearshore areas. The results support our previous work showing the importance of biofilms on various surfaces (rocks, macrophytes and zebra mussels) for MIB and GM production in the SLR, but suggest that inert surfaces like rocks are more productive sites per unit surface area than macrophytes.