Two novel mutations and a previously unreported intronic polymorphism in the NOTCH3 gene

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary disease of small vessel caused by mutations in the NOTCH3 gene (NCBI Gene ID: 4854) located on chromosome 19p13.1. NOTCH3 consists of 33 exons which encode a protein of 2321 amino acids. Exons 3 and 4 were found to be mutation hotspots, containing more than 65% of all CADASIL mutations. We performed direct sequencing on an ABI 3130 Genetic Analyser to screen for mutations and polymorphisms on 300 patients who were clinically suspected to have CADASIL. First, exons 3 and 4 were screened in NOTCH3 and if there were no variations found, then extended CADASIL testing (exons 2, 11, 18 and 19) was offered to patients. Here we report two novel non-synonymous mutations identified in the NOTCH3 gene. The first mutation, located in exon 4 was found in a 49-year-old female and causes an alanine to valine amino acid change at position 202 (605C > T). The second mutation, located in exon 11, was found in a 66-year-old female and causes a cysteine to arginine amino acid change at position 579 (1735T > C). We also report a 46-year-old male with a known polymorphism Thr101Thr (rs3815188) and an unreported polymorphism NM_000435.2:c.679+60G>A observed in intron 4 of the NOTCH3 gene. Although Ala202Ala (rs1043994) is a common polymorphism in the NOTCH3 gene, our reported novel mutation (Ala202Val) causes an amino acid change at the same locus. Our other reported mutation (Cys579Arg) correlates well with other known mutations in NOTCH3, as the majority of the CADASIL-associated mutations in NOTCH3 generally occur in the EGF-like (epidermal growth factor-like) repeat domain, causing a change in the number of cysteine residues. The intronic polymorphism NM_000435.2:c.679+60G>A lies close to the intron–exon boundary and may affect the splicing mechanism in the NOTCH3 gene.

Constitutive production of IL-13 promotes early-life Chlamydia respiratory infection and allergic airway disease

Deleterious responses to pathogens during infancy may contribute to infection and associated asthma. Chlamydia respiratory infections in early life are common causes of pneumonia and lead to reduced lung function and asthma. We investigated the role of interleukin-13 (IL-13) in promoting early-life Chlamydia respiratory infection, infection-induced airway hyperresponsiveness (AHR), and severe allergic airway disease (AAD). Infected infant Il13−/− mice had reduced infection, inflammation, and mucus-secreting cell hyperplasia. Surprisingly, infection of wild-type (WT) mice did not increase IL-13 production but reduced IL-13Rα2 decoy receptor levels compared with sham-inoculated controls. Infection of WT but not Il13−/− mice induced persistent AHR. Infection and associated pathology were restored in infected Il13−/− mice by reconstitution with IL-13. Stat6−/− mice were also largely protected. Neutralization of IL-13 during infection prevented subsequent infection-induced severe AAD. Thus, early-life Chlamydia respiratory infection reduces IL-13Rα2 production, which may enhance the effects of constitutive IL-13 and promote more severe infection, persistent AHR, and AAD.

A population genomics overview of the neuronal nitric oxide synthase (nNOS) gene and its relationship to migraine susceptibility

The ubiquitous chemical messenger molecule nitric oxide (NO) has been implicated in a diverse range of biological activities including neurotransmission, smooth muscle motility and mediation of nociception. Endogenous synthesis of NO by the neuronal isoform of the nitric oxide synthase gene family has an essential role within the central and peripheral nervous systems in addition to the autonomic innervation of cerebral blood vessels. To investigate the potential role of NO and more specifically the neuronal nitric oxide synthase (nNOS) gene in migraine susceptibility, we investigated two microsatellite repeat variants residing within the 5′ and 3′ regions of the nNOS gene. Population genomic evaluation of the two nNOS repeat variants indicated significant linkage disequilibrium between the two loci. Z-DNA conformational sequence structures within the 5′ region of the nNOS gene have the potential to enhance or repress gene promoter activity. We suggest that genetic analysis of this 5′ repeat variant is the more functional variant expressing gene wide information that could affect endogenous NO synthesis and potentially result in diseased states. However, no association with migraine (with or without aura) was seen in our extensive case-control cohort (n = 579 affected with matched controls), when both the 5′ and 3′ genetic variants were investigated.

Examining gender differences in drivers' thoughts and feelings about different outcomes of speeding: Implications for future anti-speeding messages

Speeding remains a pervasive road safety problem, increasing both crash frequency and severity. Advertising countermeasures which aim to change individuals’ attitudes and behaviours are a key component in the array of countermeasures aimed at reducing this risky behaviour. Enhancing individuals’ perceptions of the personal relevance of such messages is important for increasing persuasiveness. This study examined what males and females reported as the most concerning aspects associated with (i) receiving a speeding fine, (ii) losing one’s license, and (iii) being involved in a crash. For each of these outcomes, a range of specific and appropriate aspects were assessed. For instance, in relation to receiving a fine, individuals reported the extent to which they would, for example, feel concerned about losing demerit points and paying more in insurance premiums. An online survey of 751 drivers (579 males; 16-79 years) was administered. When controlling for age, overall significant gender differences were found in relation to two of the three outcomes; receiving a fine and being in a crash. Follow-up tests of univariate effects revealed that females consistently reported being significantly more concerned than males on all aspects. Thus, for being fined, females were significantly more concerned with, for example, being caught and receiving a ticket in the mail; while, for being in a crash, specific aspects included, for example, injuring/killing oneself and seeing oneself as not a good/safe driver. The findings are discussed in terms of their implications for developing well-targeted messages aimed at discouraging drivers from speeding.

RNA silencing platforms in plants

Since the discovery of RNAi, its mechanism in plants and animals has been intensively studied, widely exploited as a research tool, and used for a number of potential commercial applications. In this article, we discuss the platforms for delivering RNAi in plants. We provide a brief background to these platforms and concentrate on discussing the more recent advances, comparing the RNAi technologies used in plants with those used in animals, and trying to predict the ways in which RNAi technologies may further develop. © 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Neutrophil counts in leptospirosis patients infected with different serovars

In leptospirosis patients, haematological abnormalities have been reported. The aim of this study was to determine if neutrophil counts were different between patients known to be infected with a range of leptospiral serovars. The study retrospectively compared the neutrophil counts from the first blood samples taken from 210 leptospirosis patients at first presentation to a Queensland Health hospital. Significant differences (p <0.001) were observed in neutrophil counts across the 11 different infecting serovars. These findings suggest that neutrophil counts may be useful in the development of an algorithm determining the infecting serovar in suspected leptospirosis patients. Further studies are required to delineate host cytokine responses which may suggest the underlying aetiology of the observed differences in neutrophil counts. Such studies would also provide valuable therapeutic insights into treating the disease.

Acticoat™ : A cost-effective and evidence-based dressing strategy [Letter to the Editor]

We thank Dr. Burd et al. for taking an interest in our paper [1]. The retrospective cohort study was performed and published for two reasons. Firstly, we wished to compare and contrast the use of Acticoat™ and Silvazine™, and secondly we wished to demonstrate how one's practice can be dramatically altered by a change in dressing used. We found that Acticoat™ was safe and easy to use, caused less trauma to patients, required less frequent dressing changes and enabled treatment to be conducted on an outpatient, rather than an inpatient basis. During the period of Acticoat™ treatment we also saw a dramatic reduction in grafting requirements and also in the need for long-term scar management. Burd et al. correctly state that silver-based dressings are now more widely available, however many burn centres in the world continue to use silver sulphadiazine with daily baths. We therefore feel that a comparison is very relevant and useful. Prospective, randomised clinical trials of a range of silver-based dressings would indeed be useful, and hopefully Dr. Burd and colleagues will take up their own suggestion and perform these studies...

An extensible framework for analysing resource behaviour using event logs

Business processes depend on human resources and managers must regularly evaluate the performance of their employees based on a number of measures, some of which are subjective in nature. As modern organisations use information systems to automate their business processes and record information about processes’ executions in event logs, it now becomes possible to get objective information about resource behaviours by analysing data recorded in event logs. We present an extensible framework for extracting knowledge from event logs about the behaviour of a human resource and for analysing the dynamics of this behaviour over time. The framework is fully automated and implements a predefined set of behavioural indicators for human resources. It also provides a means for organisations to define their own behavioural indicators, using the conventional Structured Query Language, and a means to analyse the dynamics of these indicators. The framework's applicability is demonstrated using an event log from a German bank.

Adipose differentiation of bone marrow-derived mesenchymal stem cells using Pluronic F-127 hydrogel in vitro

Due to increasing clinical demand for adipose tissue, a suitable scaffold for engineering adipose tissue constructs is needed. In this study, we have developed a three-dimensional (3-D) culture system using bone marrow-derived mesenchymal stem cells (BM-MSC) and a Pluronic F-127 hydrogel scaffold as a step towards the in vitro tissue engineering of fat. BM-MSC were dispersed into a Pluronic F-127 hydrogel with or without type I collagen added. The adipogenic differentiation of the BM-MSC was assessed by cellular morphology and further confirmed by Oil Red O staining. The BM-MSC differentiated into adipocytes in Pluronic F-127 in the presence of adipogenic stimuli over a period of 2 weeks, with some differentiation present even in absence of such stimuli. The addition of type I collagen to the Pluronic F-127 caused the BM-MSC to aggregate into clumps, thereby generating an uneven adipogenic response, which was not desirable.

Modelling of arc welding : the importance of including the arc plasma in the computational domain

We present results of computational simulations of tungsten-inert-gas and metal-inert-gas welding. The arc plasma and the electrodes (including the molten weld pool when necessary) are included self-consistently in the computational domain. It is shown, using three examples, that it would be impossible to accurately estimate the boundary conditions on the weld-pool surface without including the arc plasma in the computational domain. First, we show that the shielding gas composition strongly affects the properties of the arc that influence the weld pool: heat flux density, current density, shear stress and arc pressure at the weld-pool surface. Demixing is found to be important in some cases. Second, the vaporization of the weld-pool metal and the diffusion of the metal vapour into the arc plasma are found to decrease the heat flux density and current density to the weld pool. Finally, we show that the shape of the wire electrode in metal-inert-gas welding has a strong influence on flow velocities in the arc and the pressure and shear stress at the weld-pool surface. In each case, we present evidence that the geometry and depth of the weld pool depend strongly on the properties of the arc.

Users’ perception of using web search engines and their impact on the perceived intention to reuse the systems

In today’s world of information-driven society, many studies are exploring usefulness and ease of use of the technology. The research into personalizing next-generation user interface is also ever increasing. A better understanding of factors that influence users’ perception of web search engine performance would contribute in achieving this. This study measures and examines how users’ perceived level of prior knowledge and experience influence their perceived level of satisfaction of using the web search engines, and how their perceived level of satisfaction affects their perceived intention to reuse the system. 50 participants from an Australian university participated in the current study, where they performed three search tasks and completed survey questionnaires. A research model was constructed to test the proposed hypotheses. Correlation and regression analyses results indicated a significant correlation between (1) users’ prior level of experience and their perceived level of satisfaction in using the web search engines, and (2) their perceived level of satisfaction in using the systems and their perceived intention to reuse the systems. A theoretical model is proposed to illustrate the causal relationships. The implications and limitations of the study are also discussed.

High-resolution GNSS-tracked drifter for studying surface dispersion in shallow water

The use of GNSS tracked Lagrangian drifters allows more realistic quantification of fluid motion and dispersion coefficients than Eulerian techniques because such drifters are analogues of particles that are relevant to flow field characterisation and pollutant dispersion. Using the fast growing Real Time Kinematic (RTK) positioning technique derived from Global Satellite Navigation Systems (GNSS), drifters are developed for high frequency (10 Hz) sampling with position estimates to centimetre accuracy. The drifters are designed with small size and less direct wind drag to follow the sub-surface flow which characterizes dispersion in shallow waters. An analysis of position error from stationary observation indicates that the drifter can efficiently resolve motion up to 1 Hz. The result of the field deployments of the drifter in conjunction with acoustic Eulerian devices shows higher estimate of the drifter streamwise velocities. Single particle statistical analysis of field deployments in a shallow estuarine zone yielded dispersion coefficients estimate comparable to those of dye tracer studies. The drifters capture the tidal elevation during field studies in a tidal estuary.

Valé Bunny Watson? Law librarians, law libraries, and legal research in the post-internet era

Katharine Hepburn’s entertaining portrayal of reference librarian Bunny Watson in Desk Set (1957) moves her character from apprehension about new technology to an understanding that it is simply another tool. This article outlines the impact of technology on academic legal research. It examines the nature of legal research and the doctrinal method, the importance of law libraries (and librarians) in legal research, and the roles and implications of the Internet and web search engines on legal research methods and education.

Translating road safety research on night-time visibility to the context of mining

In recent years a significant amount of research has been undertaken in collision avoidance and personnel location technology in order to reduce the number of incidents involving pedestrians and mobile plant equipment which are a high risk in underground coal mines. Improving the visibility of pedestrians to drivers would potentially reduce the likelihood of these incidents. In the road safety context, a variety of approaches have been used to make pedestrians more conspicuous to drivers at night (including vehicle and roadway lighting technologies and night vision enhancement systems). However, emerging research from our group and others has demonstrated that clothing incorporating retroreflective markers on the movable joints as well as the torso can provide highly significant improvements in pedestrian visibility in reduced illumination. Importantly, retroreflective markers are most effective when positioned on the moveable joints creating a sensation of “biological motion”. Based only on the motion of points on the moveable joints of an otherwise invisible body, observers can quickly recognize a walking human form, and even correctly judge characteristics such as gender and weight. An important and as yet unexplored question is whether the benefits of these retroreflective clothing configurations translate to the context of mining where workers are operating under low light conditions. Given that the benefits of biomotion clothing are effective for both young and older drivers, as well as those with various eye conditions common in those >50 years reinforces their potential application in the mining industry which employs many workers in this age bracket. This paper will summarise the visibility benefits of retroreflective markers in a biomotion configuration for the mining industry, highlighting that this form of clothing has the potential to be an affordable and convenient way to provide a sizeable safety benefit. It does not involve modifications to vehicles, drivers, or infrastructure. Instead, adding biomotion markings to standard retroreflective vests can enhance the night-time conspicuity of mining workers by capitalising on perceptual capabilities that have already been well documented.

The role of institutional pressures and top management support in the intention to adopt cloud computing solutions

Purpose – While many studies have predominantly looked at the benefits and risks of cloud computing, little is known whether and to what extent institutional forces play a role in cloud computing adoption. The purpose of this paper is to explore the role of institutional factors in top management team’s (TMT’s) decision to adopt cloud computing services. Design/methodology/approach – A model is developed and tested with data from an Australian survey using the partial least squares modeling technique. Findings – The results suggest that mimetic and coercive pressures influence TMT’s beliefs in the benefits of cloud computing. The results also show that TMT’s beliefs drive TMT’s participation, which in turn affects the intention to increase the adoption of cloud computing solutions. Research limitations/implications – Future studies could incorporate the influences of local actors who might also press for innovation. Practical implications – Given the influence of institutional forces and the plethora of cloud-based solutions on the market, it is recommended that TMTs exercise a high degree of caution when deciding for the types of applications to be outsourced as organizational requirements in terms of performance and security will differ. Originality/value – The paper contributes to the growing empirical literature on cloud computing adoption and offers the institutional framework as an alternative lens with which to interpret cloud-based information technology outsourcing.