The MyD88+ phenotype is an adverse prognostic factor in epithelial ovarian cancer

The prognosis of epithelial ovarian cancer is poor in part due to the high frequency of chemoresistance. Recent evidence points to the Toll-like receptor-4 (TLR4), and particularly its adaptor protein MyD88, as one potential mediator of this resistance. This study aims to provide further evidence that MyD88 positive cancer cells are clinically significant, stem-like and reproducibly detectable for the purposes of prognostic stratification. Expression of TLR4 and MyD88 was assessed immunohistochemically in 198 paraffin-embedded ovarian tissues and in an embryonal carcinoma model of cancer stemness. In parallel, expression of TLR4 and MyD88 mRNA and regulatory microRNAs (miR-21 and miR-146a) was assessed, as well as in a series of chemosensitive and resistant cancer cells lines. Functional analysis of the pathway was assessed in chemoresistant SKOV-3 ovarian cancer cells. TLR4 and MyD88 expression can be reproducibly assessed via immunohistochemistry using a semi-quantitative scoring system. TLR4 expression was present in all ovarian epithelium (normal and neoplastic), whereas MyD88 was restricted to neoplastic cells, independent of tumour grade and associated with reduced progression-free and overall survival, in an immunohistological specific subset of serous carcinomas, p<0.05. MiR-21 and miR-146a expression was significantly increased in MyD88 negative cancers (p<0.05), indicating their participation in regulation. Significant alterations in MyD88 mRNA expression were observed between chemosensitive and chemoresistant cells and tissue. Knockdown of TLR4 in SKOV-3 ovarian cells recovered chemosensitivity. Knockdown of MyD88 alone did not. MyD88 expression was down-regulated in differentiated embryonal carcinoma (NTera2) cells, supporting the MyD88+ cancer stem cell hypothesis. Our findings demonstrate that expression of MyD88 is associated with significantly reduced patient survival and altered microRNA levels and suggest an intact/functioning TLR4/MyD88 pathway is required for acquisition of the chemoresistant phenotype. Ex vivo manipulation of ovarian cancer stem cell (CSC) differentiation can decrease MyD88 expression, providing a potentially valuable CSC model for ovarian cancer.

The Catlin Seaview Survey – kilometre-scale seascape assessment, and monitoring of coral reef ecosystems

1.Marine ecosystems provide critically important goods and services to society, and hence their accelerated degradation underpins an urgent need to take rapid, ambitious and informed decisions regarding their conservation and management. 2.The capacity, however, to generate the detailed field data required to inform conservation planning at appropriate scales is limited by time and resource consuming methods for collecting and analysing field data at the large scales required. 3.The ‘Catlin Seaview Survey’, described here, introduces a novel framework for large-scale monitoring of coral reefs using high-definition underwater imagery collected using customized underwater vehicles in combination with computer vision and machine learning. This enables quantitative and geo-referenced outputs of coral reef features such as habitat types, benthic composition, and structural complexity (rugosity) to be generated across multiple kilometre-scale transects with a spatial resolution ranging from 2 to 6 m2. 4.The novel application of technology described here has enormous potential to contribute to our understanding of coral reefs and associated impacts by underpinning management decisions with kilometre-scale measurements of reef health. 5.Imagery datasets from an initial survey of 500 km of seascape are freely available through an online tool called the Catlin Global Reef Record. Outputs from the image analysis using the technologies described here will be updated on the online repository as work progresses on each dataset. 6.Case studies illustrate the utility of outputs as well as their potential to link to information from remote sensing. The potential implications of the innovative technologies on marine resource management and conservation are also discussed, along with the accuracy and efficiency of the methodologies deployed.

Primary and substance-induced psychotic disorders in methamphetamine users

This study investigates the rates of primary psychotic disorders (PPD) and substance induced psychotic disorders (SIPDs) in methamphetamine (MA) users accessing needle and syringe programs (NSPs). The aim was to determine if there are systematic differences in the characteristics of MA users with PPDs and SIPDs compared to those with no psychotic disorder. Participants were 198 MA users reporting use in the previous month. Diagnosis was determined using the Psychiatric Research Interview for DSM-IV Substance and Mental Disorders (PRISM-IV). Current psychiatric symptoms and substance use were also measured. Just over half (N=101) of participants met DSM-IV criteria for a lifetime psychotic disorder, including 81 (80%) with a SIPD and 20 (20%) with a PPD. Those with a younger age of onset of weekly MA use were at increased risk of a lifetime SIPD. A current psychotic disorder was found in 62 (39%), comprising 49 SIPDs (79%) and 13 PPDs (21%). MA users with a current PPD were more likely to have received psychiatric treatment in the past month than those with a current SIPD, despite a similar level of psychotic symptom severity. A high proportion of MA users accessing NSPs have psychotic disorders, the majority of which are substance-induced.

Experiencing archives at universities : archivists, librarians, understanding, and collaboration

Collaboration is one of the top trends in academic librarianship in the United States as noted by the Association of College and Research Libraries (ACRL), and is likely to be a growing trend in other countries as well (Association of College and Research Libraries [ACRL] Research Planning and Review Committee, 2014). While ACRL is focusing on library participation in various initiatives and projects on campus that are external to the library, this trend can be broadened to include the possibility for further collaboration within many academic libraries between the librarians and archivists.

Emotion as a boost to metacognition : how worry enhances the quality of confidence

Emotion and cognition are known to interact during human decision processes. In this study we focus on a specific kind of cognition, namely metacognition. Our experiment induces a negative emotion, worry, during a perceptual task. In a numerosity task subjects have to make a two alternative forced choice and then reveal their confidence in this decision. We measure metacognition in terms of discrimination and calibration abilities. Our results show that metacognition, but not choice, is affected by the level of worry anticipatedbefore the decision. Under worry individuals tend to have better metacognition in terms of the two measures. Furthermore understanding the formation of confidence is better explained with taking into account the level of worry in the model. This study shows the importance of an emotional component in the formation and the quality of the subjective probabilities.

Targeting and transport : how microtubules control focal adhesion dynamics

Directional cell migration requires force generation that relies on the coordinated remodeling of interactions with the extracellular matrix (ECM), which is mediated by integrin-based focal adhesions (FAs). Normal FA turnover requires dynamic microtubules, and three members of the diverse group of microtubule plus-end-tracking proteins are principally involved in mediating microtubule interactions with FAs. Microtubules also alter the assembly state of FAs by modulating Rho GTPase signaling, and recent evidence suggests that microtubule-mediated clathrin-dependent and -independent endocytosis regulates FA dynamics. In addition, FA-associated microtubules may provide a polarized microtubule track for localized secretion of matrix metalloproteases (MMPs). Thus, different aspects of the molecular mechanisms by which microtubules control FA turnover in migrating cells are beginning to emerge.

A sensitivity analysis of train speed and its effect on railway capacity

Increasing train speeds is conceptually a simple and straight forward method to expand railway capacity, for example in comparison to other more extensive and elaborate alternatives. In this article an analytical capacity model has been investigated as a means of performing a sensitivity analysis of train speeds. The results of this sensitivity analysis can help improve the operation of this railway system and to help it cope with additional demands in the future. To test our approach a case study of the Rah Ahane Iran (RAI) national railway network has been selected. The absolute capacity levels for this railway network have been determined and the analysis shows that increasing trains speeds may not be entirely cost effective in all circumstances.

Side Channel Analysis of Some Hash Based MACs: A Response to SHA-3 Requirements

The forthcoming NIST’s Advanced Hash Standard (AHS) competition to select SHA-3 hash function requires that each candidate hash function submission must have at least one construction to support FIPS 198 HMAC application. As part of its evaluation, NIST is aiming to select either a candidate hash function which is more resistant to known side channel attacks (SCA) when plugged into HMAC, or that has an alternative MAC mode which is more resistant to known SCA than the other submitted alternatives. In response to this, we perform differential power analysis (DPA) on the possible smart card implementations of some of the recently proposed MAC alternatives to NMAC (a fully analyzed variant of HMAC) and HMAC algorithms and NMAC/HMAC versions of some recently proposed hash and compression function modes. We show that the recently proposed BNMAC and KMDP MAC schemes are even weaker than NMAC/HMAC against the DPA attacks, whereas multi-lane NMAC, EMD MAC and the keyed wide-pipe hash have similar security to NMAC against the DPA attacks. Our DPA attacks do not work on the NMAC setting of MDC-2, Grindahl and MAME compression functions.

A follow up sample of first time drink driving offenders : how many drink drive post offence?

Background Drink driving remains an important issue to address in terms of health and injury prevention even though research shows that over time there has been a steady decline in drink driving. This has been attributed to the introduction of countermeasures such as random breath testing (RBT), changing community attitudes and norms leading to less acceptance of the behaviour and, to a lesser degree, the implementation of programs designed to deter offenders from engaging in drink driving. Most of the research to date has focused on the hard core offenders - those with high blood alcohol content at the time of arrest, and those who have more than one offence. Aims There has been little research on differences within the first offender population or on factors contributing to second offences. This research aims to fill the gap by reporting on those factors in a sample of offenders. Methods This paper reports on a study that involved interviewing 198 first offenders in court and following up this group 6-8 months post offence. Of these original participants, 101 offenders were able to be followed up, with 88 included in this paper on the basis that they had driven a vehicle since the offence. Results Interestingly, while the rate of reported apprehended second offences was low in that time frame (3%), a surprising number of offenders reported that they had driven under the influence at a much higher rate (27%). That is a large proportion of first offenders were willing to risk the much larger penalties associated with a second offence in order to engage in drink driving. Discussion and conclusions Key characteristics of this follow up group are examined to inform the development of a evidence based brief intervention program that targets first time offenders with the goal of decreasing the rate of repeat drink driving.

Combustion enhancement in a scramjet engine using oxygen enrichment and porous fuel injection

This paper reports on the experimental testing of oxygen-enriched porous fuel injection in a scramjet engine. Fuel was injected via inlet mounted, oxide-based ceramic matrix composite (CMC) injectors on both flow path surfaces that covered a total of 9.2 % of the intake surface area. All experiments were performed at an enthalpy of 3.93−4.25±3.2% MJ kg−1, flight Mach number 9.2–9.6 and an equivalence ratio of 0.493±3%. At this condition, the engine was shown to be on the verge of achieving appreciable combustion. Oxygen was then added to the fuel prior to injection such that two distinct enrichment levels were achieved. Combustion was found to increase, by as much as 40 % in terms of combustion-induced pressure rise, over the fuel-only case with increasing oxygen enrichment. Further, the onset of combustion was found to move upstream with increasing levels of oxygen enrichment. Thrust, both uninstalled and specific, and specific impulse were found to be improved with oxygen enrichment. Enhanced fuel–air mixing due to the pre-mixing of oxygen with the fuel together with the porous fuel injection are believed to be the main contributors to the observed enhanced performance of the tested engine.

Impact of real-time traffic characteristics on freeway crash occurrence: Systematic review and meta-analysis

The development of methods for real-time crash prediction as a function of current or recent traffic and roadway conditions is gaining increasing attention in the literature. Numerous studies have modeled the relationships between traffic characteristics and crash occurrence, and significant progress has been made. Given the accumulated evidence on this topic and the lack of an articulate summary of research status, challenges, and opportunities, there is an urgent need to scientifically review these studies and to synthesize the existing state-of-the-art knowledge. This paper addresses this need by undertaking a systematic literature review to identify current knowledge, challenges, and opportunities, and then conducts a meta-analysis of existing studies to provide a summary impact of traffic characteristics on crash occurrence. Sensitivity analyses were conducted to assess quality, publication bias, and outlier bias of the various studies; and the time intervals used to measure traffic characteristics were also considered. As a result of this comprehensive and systematic review, issues in study designs, traffic and crash data, and model development and validation are discussed. Outcomes of this study are intended to provide researchers focused on real-time crash prediction with greater insight into the modeling of this important but extremely challenging safety issue.

Achieving intention-centric BPM through automated planning

As a result of the more distributed nature of organisations and the inherently increasing complexity of their business processes, a significant effort is required for the specification and verification of those processes. The composition of the activities into a business process that accomplishes a specific organisational goal has primarily been a manual task. Automated planning is a branch of artificial intelligence (AI) in which activities are selected and organised by anticipating their expected outcomes with the aim of achieving some goal. As such, automated planning would seem to be a natural fit to the BPM domain to automate the specification of control flow. A number of attempts have been made to apply automated planning to the business process and service composition domain in different stages of the BPM lifecycle. However, a unified adoption of these techniques throughout the BPM lifecycle is missing. As such, we propose a new intention-centric BPM paradigm, which aims on minimising the specification effort by exploiting automated planning techniques to achieve a pre-stated goal. This paper provides a vision on the future possibilities of enhancing BPM using automated planning. A research agenda is presented, which provides an overview of the opportunities and challenges for the exploitation of automated planning in BPM.

Retaining a diverse workforce: The impact of gender-focused human resource management

Demography theory suggests that high gender diversity leads to high turnover. As turnover is costly, we tested the following: a main effect prediction derived from demography theory, and a moderating effect prediction derived from the relational framework. Data on 198 publicly listed organizations were collected through a human resources decision maker survey and archival databases. The results indicate that higher gender diversity leads to lower turnover in organizations with many gender-focused policies and practices. Findings suggest that organizations can lower their turnover rates by increasing their gender diversity and by implementing gender-focused policies and practices.

Genentech and the stolen gene: Patent law and pioneer inventions

This paper evaluates the litigation over the biotechnology patent dispute between the University of California and Genentech. First it outlines the scientific work behind the cloning of the human growth hormone, and looks at the patent office, and its treatment of biotechnological inventions. Second, it considers the court room dispute, and the legal case of the University of California and the biotechnology company in this dispute. Finally, it considers the implications of this dispute for policy reform in respect of patent law and biotechnology.