Human Kallikrein 4 signal peptide induces cytotoxic T cell responses in healthy donors and prostate cancer patients.

Immunotherapy is a promising new treatment for patients with advanced prostate and ovarian cancer, but its application is limited by the lack of suitable target antigens that are recognized by CD8+ cytotoxic T lymphocytes (CTL). Human kallikrein 4 (KLK4) is a member of the kallikrein family of serine proteases that is significantly overexpressed in malignant versus healthy prostate and ovarian tissue, making it an attractive target for immunotherapy. We identified a naturally processed, HLA-A*0201-restricted peptide epitope within the signal sequence region of KLK4 that induced CTL responses in vitro in most healthy donors and prostate cancer patients tested. These CTL lysed HLA-A*0201+ KLK4 + cell lines and KLK4 mRNA-transfected monocyte-derived dendritic cells. CTL specific for the HLA-A*0201-restricted KLK4 peptide were more readily expanded to a higher frequency in vitro compared to the known HLA-A*0201-restricted epitopes from prostate cancer antigens; prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA) and prostatic acid phosphatase (PAP). These data demonstrate that KLK4 is an immunogenic molecule capable of inducing CTL responses and identify it as an attractive target for prostate and ovarian cancer immunotherapy.

A practical signal processing approach for condition monitoring of low speed machinery using Peak-Hold-Down-Sample algorithm

A simple and effective down-sample algorithm, Peak-Hold-Down-Sample (PHDS) algorithm is developed in this paper to enable a rapid and efficient data transfer in remote condition monitoring applications. The algorithm is particularly useful for high frequency Condition Monitoring (CM) techniques, and for low speed machine applications since the combination of the high sampling frequency and low rotating speed will generally lead to large unwieldy data size. The effectiveness of the algorithm was evaluated and tested on four sets of data in the study. One set of the data was extracted from the condition monitoring signal of a practical industry application. Another set of data was acquired from a low speed machine test rig in the laboratory. The other two sets of data were computer simulated bearing defect signals having either a single or multiple bearing defects. The results disclose that the PHDS algorithm can substantially reduce the size of data while preserving the critical bearing defect information for all the data sets used in this work even when a large down-sample ratio was used (i.e., 500 times down-sampled). In contrast, the down-sample process using existing normal down-sample technique in signal processing eliminates the useful and critical information such as bearing defect frequencies in a signal when the same down-sample ratio was employed. Noise and artificial frequency components were also induced by the normal down-sample technique, thus limits its usefulness for machine condition monitoring applications.

Signal patterns of piston slap of a four-cylinder diesel engine

This paper presents an experimental study on the vibration signal patterns associated with a simulated piston slap test of a four-cylinder diesel engine. It is found that a simulated worn-off piston results in an increase in vibration RMS peak amplitudes associated with the major mechanical events of the corresponding cylinder (i.e., inlet and exhaust valve closing and combustion of Cylinder 1). This then led to an increase of overall vibration amplitude of the time domain statistical features such as RMS, Crest Factor, Skewness and Kurtosis in all loading conditions. The simulated worn-off piston not only increased the impact amplitude of piston slap during the engine combustion, it also produced a distinct impulse response during the air induction stroke of the cylinder attributing to an increase of lateral impact force as a result of piston reciprocating motion and the increased clearance between the worn-off piston and the cylinder. The unique signal patterns of piston slap disclosed in this paper can be utilized to assist in the development of condition monitoring tools for automated diagnosis of similar diesel engine faults in practical applications.

Signal transduction mechanisms underlying growth hormone receptor action

Our understanding of the mechanisms of action of GH and its receptor, the GHR, has advanced significantly in the last decade and has provided some important surprises. It is now clear that the GH-GHR axis activates a number of inter-related signalling pathways, not all of which are dependent on the intracellular tyrosine kinase, JAK2 as originally postulated. JAK2-independent pathways, mediated via the Src family kinases, together with a number of negative regulators of GH signalling and emerging cross-talk mechanisms with other growth factor receptors, provide a complex array of mechanisms that are capable of fine-tuning responses to GH in a cell context dependent manner. Additionally, it is also now clear that GH and the GHR can translocate to the nucleus of target cells and initiate, as yet not well defined, nuclear responses. Continued emphasis on elucidation of these complex mechanisms is critical to provide further insights into the diverse physiological and pathophysiological effects of GH.

Rule-based transit signal priority control method using a real-time transit travel time prediction model

An advanced rule-based Transit Signal Priority (TSP) control method is presented in this paper. An on-line transit travel time prediction model is the key component of the proposed method, which enables the selection of the most appropriate TSP plans for the prevailing traffic and transit condition. The new method also adopts a priority plan re-development feature that enables modifying or even switching the already implemented priority plan to accommodate changes in the traffic conditions. The proposed method utilizes conventional green extension and red truncation strategies and also two new strategies including green truncation and queue clearance. The new method is evaluated against a typical active TSP strategy and also the base case scenario assuming no TSP control in microsimulation. The evaluation results indicate that the proposed method can produce significant benefits in reducing the bus delay time and improving the service regularity with negligible adverse impacts on the non-transit street traffic.

Small signal stability analysis of a DFIG based wind power system with tuned damping controller under super/sub-synchronous mode of operation

This paper focuses on the super/sub-synchronous operation of the doubly fed induction generator (DFIG) system. The impact of a damping controller on the different modes of operation for the DFIG based wind generation system is investigated. The co-ordinated tuning of the damping controller to enhance the damping of the oscillatory modes using bacteria foraging (BF) technique is presented. The results from eigenvalue analysis are presented to elucidate the effectiveness of the tuned damping controller in the DFIG system. The robustness issue of the damping controller is also investigated

Social signal processing for pain monitoring using a hidden conditional random field

utomatic pain monitoring has the potential to greatly improve patient diagnosis and outcomes by providing a continuous objective measure. One of the most promising methods is to do this via automatically detecting facial expressions. However, current approaches have failed due to their inability to: 1) integrate the rigid and non-rigid head motion into a single feature representation, and 2) incorporate the salient temporal patterns into the classification stage. In this paper, we tackle the first problem by developing a “histogram of facial action units” representation using Active Appearance Model (AAM) face features, and then utilize a Hidden Conditional Random Field (HCRF) to overcome the second issue. We show that both of these methods improve the performance on the task of pain detection in sequence level compared to current state-of-the-art-methods on the UNBC-McMaster Shoulder Pain Archive.

Optimized strategy for integrated traffic and transit signal control

This paper proposes a unique and innovative approach to integrate transit signal priority control into a traffic adaptive signal control strategy. The proposed strategy was named OSTRAC (Optimized Strategy for integrated TRAffic and TRAnsit signal Control). The cornerstones of OSTRAC include an online microscopic traffic f low prediction model and a Genetic Algorithm (GA) based traffic signal timing module. A sensitivity analysis was conducted to determine the critical GA parameters. The developed traffic f low model demonstrated reliable prediction results through a test. OSTRAC was evaluated by comparing its performance to three other signal control strategies. The evaluation results revealed that OSTRAC efficiently and effectively reduced delay time of general traffic and also transit vehicles.

Spectrum sensing optimisation for dynamic primary user signal

We propose a multi-layer spectrum sensing optimisation algorithm to maximise sensing efficiency by computing the optimal sensing and transmission durations for a fast changing, dynamic primary user. Dynamic primary user traffic is modelled as a random process, where the primary user changes states during both the sensing period and transmission period to reflect a more realistic scenario. Furthermore, we formulate joint constraints to correctly reflect interference to the primary user and lost opportunity of the secondary user during the transmission period. Finally, we implement a novel duty cycle based detector that is optimised with respect to PU traffic to accurately detect primary user activity during the sensing period. Simulation results show that unlike currently used detection models, the proposed algorithm can jointly optimise the sensing and transmission durations to simultaneously satisfy the optimisation constraints for the considered primary user traffic.

Digital social signal processing - theorectical underpinning and research agenda

Organizations make increasingly use of social media in order to compete for customer awareness and improve the quality of their goods and services. Multiple techniques of social media analysis are already in use. Nevertheless, theoretical underpinnings and a sound research agenda are still unavailable in this field at the present time. In order to contribute to setting up such an agenda, we introduce digital social signal processing (DSSP) as a new research stream in IS that requires multi-facetted investigations. Our DSSP concept is founded upon a set of four sequential activities: sensing digital social signals that are emitted by individuals on social media; decoding online data of social media in order to reconstruct digital social signals; matching the signals with consumers’ life events; and configuring individualized goods and service offerings tailored to the individual needs of customers. We further contribute to tying loose ends of different research areas together, in order to frame DSSP as a field for further investigation. We conclude with developing a research agenda.

A novel immunodeficiency disorder characterized by genetic amplification of interleukin 25

Many primary immunodeficiency disorders of differing etiologies have been well characterized, and much understanding of immunological processes has been gained by investigating the mechanisms of disease. Here, we have used a whole-genome approach, employing single-nucleotide polymorphism and gene expression microarrays, to provide insight into the molecular etiology of a novel immunodeficiency disorder. Using DNA copy number profiling, we define a hyperploid region on 14q11.2 in the immunodeficiency case associated with the interleukin (IL)-25 locus. This alteration was associated with significantly heightened expression of IL25 following T-cell activation. An associated dominant type 2 helper T cell bias in the immunodeficiency case provides a mechanistic explanation for recurrence of infections by pathogens met by Th1-driven responses. Furthermore, this highlights the capacity of IL25 to alter normal human immune responses.

IS-RT-PCR assay detection of MT-MMP in a human breast cancer cell line

The in situ-reverse transcription-polymerase chain reaction (IS-RT-PCR) is a method that allows the direct localisation of gene expression. The method utilises the dual buffer mediated activity of the enzyme rTth DNA polymerase enabling both reverse transcription and DNA amplification. Labelled nucleoside triphosphates allow the site of expression to be labelled, rather than the PCR primers themselves, giving a more accurate localisation of transcript expression and decreased background than standard in situ hybridisation (ISH) assays. The MDA-MB-231 human breast carcinoma (HBC) cell line was assayed via the IS-RT-PCR technique, using primers encoding MT-MMP (membrane-type matrix metalloproteinase) and human β-actin. Our results clearly indicate baseline expression of MT-MMP in the relatively invasive MDA-MB-231 cell line at a signal intensity similar to the housekeeping gene β-actin, and results following induction with Concanavalin A (Con A) are consistent with our previous results obtained via Northern blotting.

MMP-9 and the epidermal growth factor signal pathway in non-small cell lung cancer

Background Matrix metalloproteinase (MMP)-9 is an endopeptidase that digests basement membrane type-IV collagen. Enhanced expression has been related to tumour progression in a number of systems. The control of MMP expression is complex, but recently epidermal growth actor receptor (EGFR) activity has been implicated in up-regulation of MMP-9 in tumour cells in vitro. Aims To evaluate interrelations between MMP-9 and EGFR expression in non-small cell lung cancer (NSCLC) and to assess the impact of expression on survival. Methods This is a retrospective study of 152 patients who underwent resection for stage I-IIIa NSCLC with a post-operative survival >60 days. Minimum follow-up was 2 years. Standard ABC immunohistochemistry was performed on 4μm paraffin-embedded sections from the tumour periphery using monoclonal antibodies to MMP-9 and EGFR. Results: MMP-9 was expressed in the tumour cells of 79/152 (52%) cases. EGFR expression was found in 86/152 (57%) cases [membranous 51/152 (34%), cytoplasmic 35/152 (23%)]. MMP-9 expression was associated with poor outcome (p=0.04). Membranous, cytoplasmic and overall EGFR expression were not associated with outcome (p=0.29, p=0.85 and p=0.41 respectively). There was a strong correlation between MMP-9 expression and EGFR expression (p=0.001) and EGFR membranous expression (p=0.01) but not with cytoplasmic EGFR expression (p=0.28). Co-expression of MMP-9 and EGFR (36%) conferred a worse prognosis (p=0.003). Subset analysis revealed only MMP-9 and membranous EGFR co-expression (22%) was associated with poor outcome (p=0.008). Conclusions Our results show that MMP-9 and EGFR are co-expressed in NSCLC. This finding suggests the EGFR signalling pathway may play an important role in the invasive behaviour of NSCLC via specific upregulation of MMP-9. The co-expression of these markers also confers a poor prognosis.

Herceptest: HER2 expression and gene amplification in non-small cell lung cancer

HER2 is an erbB/HER type I tyrosine kinase receptor that is frequently over-expressed in malignant epithelial tumours. Herceptin, a humanised mouse monoclonal antibody to HER2, is proven therapeutically in the management of metastatic breast cancer, significantly prolonging survival when combined with cytotoxic chemotherapeutic agents. Immunohistochemical studies suggest that non-small-cell lung cancer (NSCLC) tumours may over-express HER2. Our aim was to evaluate HER2 gene amplification and semi-quantitative immuno-expression in NSCLC. A total of 344 NSCLC cases were immunostained for HER2 expression in 2 centres using the HercepTest. Fluorescence in situ hybridisation (FISH) analysis for HER2 gene amplification was performed on most positive cases and a subset of negative cases. Fifteen cases (4.3%) demonstrated 2+ or 3+ membranous HER2 immuno-expression. There was no correlation between immuno-expression and tumour histology or grade. Tumours from higher-stage disease were more often HercepTest-positive (p < 0.001). All 4 HercepTest 3 + cases demonstrated gene amplification. One of the 5 2+ cases tested for gene amplification showed areas of borderline amplification and areas of polyploidy. None of the 19 HercepTest-negative cases demonstrated gene amplification or polyploidy (p < 0.001). Gene amplification was demonstrated in all HercepTest 3+ scoring NSCLC cases. Unlike breast cancer, gene amplification and HER2 protein over-expression assessed by the HercepTest appeared to be uncommon in NSCLC. Herceptin may therefore target only a small proportion of NSCLC tumours and be of limited clinical value in this disease, particularly in the adjuvant setting. © 2001 Wiley-Liss, Inc.

An extracellular signal-regulated kinase 2 survival pathway mediates resistance of human mesothelioma cells to asbestos-induced injury

We hypothesized that normal human mesothelial cells acquire resistance to asbestos-induced toxicity via induction of one or more epidermal growth factor receptor (EGFR) - linked survival pathways (phosphoinositol-3-kinase/AKT/ mammalian target of rapamycin and extracellular signal - regulated kinase [ERK] 1/2) during simian virus 40 (SV40) transformation and carcinogenesis. Both isolated HKNM-2 mesothelial cells and a telomerase-immortalized mesothelial line (LP9/TERT-1) were more sensitive to crocidolite asbestos toxicity than an SV40 Tag-immortalized mesothelial line (MET5A) and malignant mesothelioma cell lines (HMESO and PPM Mill). Whereas increases in phosphorylation of AKT (pAKT) were observed in MET5A cells in response to asbestos, LP9/TERT-1 cells exhibited dose-related decreases in pAKT levels. Pretreatment with an EGFR phosphorylation or mitogen-activated protein kinase kinase 1/2 inhibitor abrogated asbestos-induced phosphorylated ERK (pERK) 1/2 levels in both LP9/TERT-1 and MET5A cells as well as increases in pAKT levels in MET5A cells. Transient transfection of small interfering RNAs targeting ERK1, ERK2, or AKT revealed that ERK1/2 pathways were involved in cell death by asbestos in both cell lines. Asbestos-resistant HMESO or PPM Mill cells with high endogenous levels of ERKs or AKT did not show dose-responsive increases in pERK1/ERK1, pERK2/ERK2, or pAKT/AKT levels by asbestos. However, small hairpin ERK2 stable cell lines created from both malignant mesothelioma lines were more sensitive to asbestos toxicity than shERK1 and shControl lines, and exhibited unique, tumor-specific changes in endogenous cell death - related gene expression. Our results suggest that EGFR phosphorylation is causally linkedto pERK and pAKT activation by asbestos in normal and SV40 Tag - immortalized human mesothelial cells. They also indicate that ERK2 plays a role in modulating asbestos toxicity by regulating genes critical to cell injury and survival that are differentially expressed in human mesotheliomas.