Coagulation Signaling through PAR1 as a Therapeutic Target in Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal disease with a 5-year survival rate of less than 10% following diagnosis. The aggressive and invasive properties of pancreatic cancer tumors coupled with poor diagnostic options contribute to the high mortality rate since most patients present with late-stage disease. Accordingly, PDAC is linked to the highest rate of cancer-associated venous thromboembolic disease of all solid tumor malignancies. However, in addition to promoting clot formation, recent studies suggest that the coagulation system in PDAC mediates a reciprocal relationship, whereby coagulation proteases and receptors promote PDAC tumor progression and dissemination. Here, upregulation of tissue factor (TF) by tumor cells can drive local generation of the central coagulation protease thrombin that promotes cell signaling activity through protease-activated receptors (PARs) expressed by both tumor cells and multiple stromal cell subsets. Moreover, the TF-thrombin-PAR1 signaling axis appears to be a major mechanism of cancer progression in general and PDAC in particular. Here, we summarize the current literature regarding the role of PAR1 in PDAC and review possibilities for pharmacologically targeting PAR1 as a PDAC therapeutic approach.     

Plasma Metabolomics Analysis of Polyvinyl Chloride Workers Identifies Altered Processes and Candidate Biomarkers for Hepatic Hemangiosarcoma and Its Development

Background: High-level occupational vinyl chloride (VC) exposures have been associated with hepatic hemangiosarcoma, which typically develops following a long latency period. Although VC is genotoxic, a more comprehensive mode of action has not been determined and diagnostic biomarkers have not been established. The purpose of this study is to address these knowledge gaps through plasma metabolomics. Methods: Plasma samples from polyvinyl chloride polymerization workers who developed hemangiosarcoma (cases, n = 15) and VC exposure-matched controls (n = 17) underwent metabolomic analysis. Random forest and bioinformatic analyses were performed. Results: Cases and controls had similar demographics and routine liver biochemistries. Mass spectroscopy identified 606 known metabolites. Random forest analysis had an 82% predictive accuracy for group classification. 60 metabolites were significantly increased and 44 were decreased vs. controls. Taurocholate, bradykinin and fibrin degradation product 2 were up-regulated by greater than 80-fold. The naturally occurring anti-angiogenic phenol, 4-hydroxybenzyl alcohol, was down-regulated 5-fold. Top affected ontologies involved: (i) metabolism of bile acids, taurine, cholesterol, fatty acids and amino acids; (ii) inflammation and oxidative stress; and (iii) nicotinic cholinergic signaling. Conclusions: The plasma metabolome was differentially regulated in polyvinyl chloride workers who developed hepatic hemangiosarcoma. Ontologies potentially involved in hemangiosarcoma pathogenesis and candidate biomarkers were identified.     

Static and dynamic studies of phase composition in a polydisperse system

We have conducted a study of the phase compositions of a ternary solution containing dextran/polyethylene glycol (PEG)/water using UV-visible spectrometry to study the equilibrium behaviour and confocal microscopy to study the dynamic behaviour observed when the system undergoes phase separation driven by the loss of water. Such a study of phase compositions using confocal microscopy is a new development of the technique. In the static experiments, we find a cloud curve, which lies above the coexistence curve on the PEG rich side of the phase diagram, this is found to be in qualitative agreement with calculations of the phase behaviour for a model polydisperse system. In the dynamic experiments, we are able to measure the phase composition using confocal microscopy in the late stages of separation. Here, the compositions lie well inside the coexistence curve at lower drying rates but converge with it at higher drying rates. This is linked to a change in phase morphology: at low rates, a droplet morphology is observed throughout the process whilst at high drying rates a gross phase separation into two layers is observed to occur even at the earliest times probed by the experiment.     

The ageing Australian firefighter: an argument for age-based recruitment and fitness standards for urban fire services

Currently, there is no enforcement of physical standards within Australian fire services post-recruitment, possibly leading to inappropriate fitness and body composition. This study evaluated the impacts of ageing on physical standards of Australian firefighters. Seventy-three firefighters from three different 10-year age groups [25–34 years (n = 27), 35–44 years (n = 27), 45–54 years (n = 19)] volunteered for physical testing using dual-energy X-ray analysis and existing fitness tests used for recruitment by an Australian fire service. Older (45–54 years) participants demonstrated significantly poorer physical standards compared with younger participants including cardiovascular fitness (p < 0.05), strength (p = 0.001) and simulated operational power testing tasks (p < 0.001). Age-related body composition changes were also observed independent of body mass index. Minimum recruitment standards and fitness programs need to account for age-related declines in physical capabilities to ensure that the minimum standard is maintained regardless of age.

Practitioner Summary: Using dual-energy X-ray analysis and established fitness testing protocols, this study aimed to gain an appreciation of the current standards of body composition and fitness of Australian firefighters and the effects of ageing on their physical abilities post-recruitment. The study demonstrated a significant decline in physical standards due to age.     

Switching to Directional Antennas with Constant Increase in Radius and Hop Distance

For any angle α<2π, we show that any connected communication graph that is induced by a set P of n transceivers using omni-directional antennas of radius 1, can be replaced by a strongly connected communication graph, in which each transceiver in P is equipped with a directional antenna of angle α and radius r _dir, for some constant r _dir=r _dir(α). Moreover, the new communication graph is a c-spanner of the original graph, for some constant c=c(α), with respect to number of hops.     

Efficient fault-tolerant collision-free data aggregation scheduling for wireless sensor networks

This paper investigates the design of fault-tolerant TDMA-based data aggregation scheduling (DAS) protocols for wireless sensor networks (WSNs). DAS is a fundamental pattern of communication in wireless sensor networks where sensor nodes aggregate and relay data to a sink node. However, any such DAS protocol needs to be cognisant of the fact that crash failures can occur. We make the following contributions: (i) we identify a necessary condition to solve the DAS problem, (ii) we introduce a strong and weak version of the DAS problem, (iii) we show several impossibility results due to the crash failures, (iv) we develop a modular local algorithm that solves stabilising weak DAS and (v) we show, through simulations and an actual deployment on a small testbed, how specific instantiations of parameters can lead to the algorithm achieving very efficient stabilisation.     

Context matters: The structure of task goals affects accuracy in multiple-target visual search

Career visual searchers such as radiologists and airport security screeners strive to conduct accurate visual searches, but despite extensive training, errors still occur. A key difference between searches in radiology and airport security is the structure of the search task: Radiologists typically scan a certain number of medical images (fixed objective), and airport security screeners typically search X-rays for a specified time period (fixed duration). Might these structural differences affect accuracy? We compared performance on a search task administered either under constraints that approximated radiology or airport security. Some displays contained more than one target because the presence of multiple targets is an established source of errors for career searchers, and accuracy for additional targets tends to be especially sensitive to contextual conditions. Results indicate that participants searching within the fixed objective framework produced more multiple-target search errors; thus, adopting a fixed duration framework could improve accuracy for career searchers.     

Exploration of Linked Anomalies in Sensor Data for Suspicious Behavior Detection

We present a visual analytics system to understand the operation data of a company, GAStech, from IEEE VAST Challenge 2016. The data include proximity data recording the locations and movements of employees, and heating, ventilation, and air conditioning (HVAC) data recording the environmental conditions in the building. Analyzing the data to detect the suspicious behaviors of some disgruntled employees is of special interest. Our system provides coordinated multiple views to visualize the proximity data and the HVAC data over time. Visual hints and comparisons are designed for users to identify abnormal patterns and compare them. Furthermore, the system automatically detects and correlates the anomalies in the data. We provide use cases to demonstrate the effectiveness of our system.     

Effect of Enameling on the Strength and Dynamic Fatigue of Soda–Lime–Silica Float Glass

The effect of a glass enamel coating on the strength and fatigue behavior of float glass was investigated. Commercially available enamel that was comprised of Cu₂Cr₂O₄ pigment particles in a bismuth-zinc borosilicate glass matrix was applied to a soda–lime–silica float glass via screen printing, followed by fusion at elevated temperature. Strengths of the enameled specimens were evaluated in biaxial flexure using a ring-on-ring (ROR) test geometry, and the data were analyzed using a conventional two-parameter Weibull distribution. Enameling was found to significantly degrade the strength of the float glass. There was no statistical difference in the characteristic strengths of samples enameled on the air side (66 MPa) compared with samples enameled on the tin side (61 MPa) of the float glass. Fractographic analysis revealed that the failures in the enameled float glass samples initiated at pores and pigment aggregates in the enamel, whereas failures in float glass samples initiated solely from surface flaws. Dynamic fatigue tests were performed on enameled float glass and indented float glass samples to determine the effect of the enamel on the stress corrosion behavior of the enameled components. There was no statistically significant difference between the stress corrosion exponents for the float glass and enameled float glass specimens.