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Consensus PCR assays that can be used to sensitively detect several herpesvirus (HV) species across the different subfamilies were developed in this study. Primers containing degenerate bases were designed to amplify regions of the DNA polymerase (DPOL) gene of alpha- and gamma-HVs, and the glycoprotein B (gB) gene of beta-HVs in a singleplex, non-nested touchdown PCR format. The singleplex touchdown consensus PCR (STC-PCR) was used to amplify the DNA of eight human and 24 animal HVs. The assay was able to detect the lowest DNA dilution of 10−5 for alpha-HVs and 10−3 for beta- and gamma-HVs. In comparison, lowest detection limits of 10−5, 10−3, and 10−2 were obtained for alpha-, beta-, and gamma-HVs respectively when a nested PCR was used. The findings in this study suggest that the STC-PCR assays can be employed for the molecular surveys and clinical detection of novel and known HVs.

Most of our understanding of the ecology and evolution of avian influenza A virus (AIV) in wild birds is derived from studies conducted in the northern hemisphere on waterfowl, with a substantial bias towards dabbling ducks. However, relevant environmental conditions and patterns of avian migration and reproduction are substantially different in the southern hemisphere. Through the sequencing and analysis of 333 unique AIV genomes collected from wild birds collected over 15 years we show that Australia is a global sink for AIV diversity and not integrally linked with the Eurasian gene pool. Rather, AIV are infrequently introduced to Australia, followed by decades of isolated circulation and eventual extinction. The number of co-circulating viral lineages varies per subtype. AIV haemagglutinin (HA) subtypes that are rarely identified at duck-centric study sites (H8-12) had more detected introductions and contemporary co-circulating lineages in Australia. Combined with a lack of duck migration beyond the Australian-Papuan region, these findings suggest introductions by long-distance migratory shorebirds. In addition, we found no evidence of directional or consistent patterns in virus movement across the Australian continent. This feature corresponds to patterns of bird movement, whereby waterfowl have nomadic and erratic rainfall-dependant distributions rather than consistent intra-continental migratory routes. Finally, we detected high levels of virus gene segment reassortment, with a high diversity of AIV genome constellations across years and locations. These data, in addition to those from other studies in Africa and South America, clearly show that patterns of AIV dynamics in the Southern Hemisphere are distinct from those in the temperate north.Author SummaryA result of the ever-growing poultry industry is a dramatic global increase in the incidence of high pathogenicity avian influenza virus outbreaks. In contrast, wild birds are believed to be the main reservoir for low pathogenic avian influenza A virus. Due to intensive research and surveillance of AIV in waterfowl in the Northern Hemisphere, we have a better understanding of AIV ecology and evolution in that region compared to the Southern Hemisphere, which are characterised by different patterns of avian migration and ecological conditions. We analysed 333 unique AIV genomes collected from wild birds in Australia to understand how Australia fits into global AIV dynamics and how viruses are maintained and dispersed within the continent of Australia. We show that the Southern Hemisphere experiences differing evolutionary dynamics to those seen in Northern Hemisphere with Australia representing a global sink for AIV.

When polymer melt is subjected to stress, molecular chains become aligned along the elongation direction. However, when polyethylene film crystallizes under stress, molecular chains frequently align perpendicular to the elongation direction. In this paper we investigate why this happens. Evaluating metallocene LLDPE film we show that under the stress lamellae rotate to accommodate geometrical changes. Quantitative analysis of SAXS data explains the mechanism of this rotation. The lamellae rotation presents an opportunity to reexamine the strain-induced structure and crystallization mechanism. For the first time we apply 3D visualization to shish-kebab like structure in bulk samples and support visualization with Fourier analysis to relate the microscopy data to large body of evidence reported earlier by SAXS. Obtained evidence reveals that our samples do not contain extended chain precursors. Reevaluation of the equatorial streak, frequently interpreted as evidence of extended chain precursors or voids, suggests that in our sample the streak originates from rotated lamellae. Our findings indicate that strain-induced crystallization does not have to rely on the existence of extended chains precursors, as is widely assumed. While the major findings from this work are derived from microscopy investigations we supplement these with limited amount of SAXS and WAXS experiments to help elucidate the rotation mechanism and crystalline orientation. The insight dervied from this study reconciles seemingly contradictory SAXS, WAXS, TEM and optical microscopy data collected from polyethylene film.

Polymer insulators have been in production for over 50 years. There are numerous benefits to the use of polymer insulators that may not be well understood in the industry. This paper presents the laboratory and field-based experience and results of polymer insulator performance over the last 50 years that demonstrates the benefits and superior performance of this product to others available in the industry. These advantages are related to the design and construction of the transmission line as well other benefits of polymer insulators and their superior performance in contamination, flashover, and reducing system losses. All of these advantages can lead to significant cost savings for high voltage transmission projects. From contractors and construction crews to transmission line design engineers, owners, and operators, polymer insulators are a proven technology that can provide tremendous advantages

Avian A(H7N9) infections in humans have been reported in China since 2013 and are of public health concern due to their severity and pandemic potential. Oseltamivir and peramivir are neuraminidase inhibitors (NAIs) routinely used for the treatment of A(H7N9) infections, but variants with reduced sensitivity to these drugs can emerge in patients during treatment. Zanamivir and laninamivir are NAIs that are used less frequently. Herein, we performed in vitro serial passaging experiments with recombinant viruses, containing the neuraminidase (NA) from influenza A/Anhui/1/13 (H7N9) virus, in the presence of each NAI, to determine whether variants with reduced sensitivity would emerge. NA substitutions were characterized for their effect on the NA enzymatic activity and surface expression of the A/Anhui/1/13 (Anhui/1) NA, as well as NAs originating from contemporary A(H7N9) viruses of the Yangtze River Delta and Pearl River Delta lineages. In vitro passage in the presence of oseltamivir, peramivir and laninamivir selected for substitutions associated with reduced sensitivity (E119D, R292K and R152K), whereas passage in the presence of zanamivir did not select for any viruses with reduced sensitivity. All the NA substitutions significantly reduced activity, but not the expression of the Anhui/1 NA. In contemporary N9 NAs, all substitutions tested significantly reduced NA enzyme function in the Yangtze River lineage background, but not in the Pearl River Delta lineage background. Overall, these findings suggest that zanamivir may be less likely than the other NAIs to select for resistance in A(H7N9) viruses and that the impact of substitutions that reduce NAI susceptibility or enzyme function may be less in A(H7N9) viruses from the Pearl River lineage.

Through accumulation of genetic mutations in the neuraminidase gene, the influenza virus can become resistant to antiviral drugs such as oseltamivir. Quantifying the fitness of emergent drug-resistant influenza viruses, relative to contemporary circulating viruses, provides valuable information to complement existing efforts in the surveillance of drug-resistance. We have previously developed a co-infection based method for the assessment of the relative in vivo fitness of two competing viruses. We have also introduced a model of within-host co-infection dynamics that enables relative within-host fitness to be quantified in these competitive-mixtures experiments. The model assumed that fitness differences between co-infecting strains were mediated by strain-dependent viral production rates from infected epithelial cells. Here we extend the model to enable a more complete exploration of biological processes that may differ between virus pairs and hence generate fitness differences. We use the extended model to re-analyse data from competitive-mixtures experiments that investigated the fitness of oseltamivir-resistant (OR) H1N1 pandemic 2009 ("H1N1pdm09") viruses that emerged during a community outbreak in Australia in 2011. Results are consistent with those of our previous analysis, suggesting that the within-host replication fitness of these OR viruses is not compromised relative to that of related oseltamivir-susceptible (OS) strains, and that potentially permissive mutations in the neuraminidase gene (V241I and N369K) significantly enhance the fitness of H1N1pdm09 OR viruses. These results are consistent regardless of the hypothesised biological cause of fitness difference.

Research assessment exercises covering universities in the United Kingdom were established to produce quality ratings as a basis for allocating much of the research funding from central government. They represent some of the largest research management exercises ever undertaken. Amongst other aspects of university performance, the publications of all ‘research active’ UK academics are evaluated. This paper describes the way in which quality was assessed and funds were allocated as a result of the 1992, 1996 and 2001 exercises. It looks at how the exercises might continue to evolve and the value of a further exercise. The strategies adopted by universities to maximise their ratings and their income are also considered. Universities have improved their research performance and their reporting methods in response to changes in the criteria and weightings used in the exercise. In parallel the HEFC (Higher Education Funding Council) has changed the ways in which funds have been distributed once the level of research performance has been determined. The exercises have received much criticism as well as an acceptance that they have changed the culture of academic research. This paper considers the parallel evolution of trends in the management of R&D in business with trends in the management of university research via these exercises. There are underlying assumptions that seem to influence the transfer of policy design principles and management lessons between the two sectors.

Antivirals against influenza first became available in the 1960s when an adamantane compound, amantadine, was approved for the treatment and prophylaxis of influenza A viruses. Rimantadine, another...

Objectives The burden of disease due to influenza B is often underestimated. Clinical studies have shown that oseltamivir, a widely used neuraminidase inhibitor (NAI) antiviral drug, may have reduced effectiveness against influenza B viruses. Therefore, it is important to study the effect of neuraminidase mutations in influenza B viruses that may further reduce NAI susceptibility, and to determine whether these mutations have the same effect in the two lineages of influenza B viruses that are currently circulating (B/Yamagata-like and B/Victoria-like). Methods We characterized the effect of 16 amino acid substitutions across five framework residues and four monomeric interface residues on the susceptibility to four different NAIs (oseltamivir, zanamivir, peramivir and laninamivir). Results Framework residue mutations E117A and E117G conferred highly reduced inhibition to three of the four NAIs, but substantially reduced neuraminidase activity, whereas other framework mutations retained a greater level of NA activity. Mutations E105K, P139S and G140R of the monomeric interface were also found to cause highly reduced inhibition, but, interestingly, their effect was substantially greater in a B/Victoria-like neuraminidase than in a B/Yamagata-like neuraminidase, with some susceptibility values being up to 1000-fold different between lineages. Conclusions The frequency and the effect of key neuraminidase mutations on neuraminidase activity and NAI susceptibility can differ substantially between the two influenza B lineages. Therefore, future surveillance, analysis and interpretation of influenza B virus NAI susceptibility should consider the B lineage of the neuraminidase in the same manner as already occurs for different influenza A neuraminidase subtypes.

Oseltamivir is relied upon worldwide as the drug of choice for the treatment of human influenza infection. Surveillance for oseltamivir resistance is routinely performed to ensure the ongoing efficacy of oseltamivir against circulating viruses. Since the emergence of the pandemic 2009 A(H1N1) influenza virus (A(H1N1)pdm09), the proportion of A(H1N1)pdm09 viruses that are oseltamivir resistant (OR) has generally been low. However, a cluster of OR A(H1N1)pdm09 viruses, encoding the neuraminidase (NA) H275Y oseltamivir resistance mutation, was detected in Australia in 2011 amongst community patients that had not been treated with oseltamivir. Here we combine a competitive mixtures ferret model of influenza infection with a mathematical model to assess the fitness, both within and between hosts, of recent OR A(H1N1)pdm09 viruses. In conjunction with data from in vitro analyses of NA expression and activity we demonstrate that contemporary A(H1N1)pdm09 viruses are now more capable of acquiring H275Y without compromising their fitness, than earlier A(H1N1)pdm09 viruses circulating in 2009. Furthermore, using reverse engineered viruses we demonstrate that a pair of permissive secondary NA mutations, V241I and N369K, confers robust fitness on recent H275Y A(H1N1)pdm09 viruses, which correlated with enhanced surface expression and enzymatic activity of the A(H1N1)pdm09 NA protein. These permissive mutations first emerged in 2010 and are now present in almost all circulating A(H1N1)pdm09 viruses. Our findings suggest that recent A(H1N1)pdm09 viruses are now more permissive to the acquisition of H275Y than earlier A(H1N1)pdm09 viruses, increasing the risk that OR A(H1N1)pdm09 will emerge and spread worldwide., Author Summary Antimicrobial resistance is an increasing problem for the treatment of infectious diseases. In 2007–2008 human seasonal A(H1N1) influenza viruses rapidly acquired resistance to the most commonly used anti-influenza drug oseltamivir, via a H275Y amino acid mutation within the neuraminidase (NA) protein. In 2009 the oseltamivir sensitive A(H1N1)pdm09 virus (encoding NA 275H) emerged in the human population, rapidly replacing the oseltamivir resistant seasonal A(H1N1) virus. However, there is increasing concern that currently circulating A(H1N1)pdm09 viruses may similarly acquire oseltamivir resistance (via the NA H275Y mutation) and become widespread. Here we demonstrate that two novel amino acid changes present in virtually all recent A(H1N1)pdm09 viruses (NA V241I and N369K) enable the acquisition of the NA H275Y oseltamivir resistance mutation without compromising viral fitness. As such recent A(H1N1)pdm09 viruses are now one step closer to acquiring widespread oseltamivir resistance.

The experiment examined Monroe's Motivated Sequence, an organizational pattern commonly taught in basic speech courses for its effects on attitude change and ratings of comprehensibility of messages. Treatment groups of 21, 23, and 24 participants read one of three versions of a persuasive message that advocated a $50 fee increase to improve parking facilities on campus. One version represented Monroe's five-step sequence, a second version reversed the five steps, and a third randomly ordered the steps. A control group of 22 read a message unrelated to the parking issue. Analysis showed no differences in attitude change across the four groups. The Monroe sequence condition did produce significantly higher ratings of comprehensibility on one of four comparisons.

Sum~nary.-The experiment examined the adage that material should never be given members of an audience during a speech presentation. 45 students enrolled in speech fundamentals courses were exposed to one of three versions of a speech, which informed students of an impending $50 fee increase to improve university parking facilities. The speaker, allegedly a representative from Parking Services, discussed four main benefits of the fee increase. In one version, he began by distributing a handout listing four main benefirs to the he increase. A second version listed four benefits different from those identified in the speech, while a control condition received no handout. The control condition established the receivers' dominant cognitive response as negative. This negauve response was accentuated when the handout repeared the four main points but was less when the handout provided a competing me\sdgc lo the form of information not contained in the speech. Results were discussed u.~th reference to previous research on distraction theory and repetition of a message. Virtually all speech fundamentals texts devote space to the issue of visual aids. Their usual approach is to cite a series of "dos and don'ts" along with the perspective that use of visual aids are of potential benefit to speakers' success. Often repeated in popular textbooks is a study by Linkugel and Berg (1970) who reported that, when knowledge was imparted by telling alone, recall was 70% 3 hr. later and only 10% three days later. When imparted by showing alone, recall was 72% after 3 hr., 35% after three days. When information was imparted by tehg and showing, recall was 85% 3 hr. later, 65% three days later. Also, Bohn and Jabusch (1982) tested various methods of instruction, concluding that the visually aided presentations significantly enhanced message retention. According to White (1978, p. 158), "Experimental, as well as practical, experience demonstrates that most of our learning is acquired by means of the eye rather than the ear and that we learn more quickly, remember better and are more deeply impressed when both of these senses are uthzed." Speech textbook authors typically rely on findings he those above to support an array of generalizations about the use of visual aids and may go beyond the hits of reasonable inference. For example, one commonly cited prescription is a taboo about handing out visual aid material during a presentation. According to the popular view, to

This paper describes the Network-Attached Secure Disk (NASD) storage architecture, prototype implementations oj NASD drives, array management for our architecture, and three, filesystems built on our prototype. NASD provides scalable storage bandwidth without the cost of servers used primarily, for transferring data from peripheral networks (e.g. SCSI) to client networks (e.g. ethernet). Increasing datuset sizes, new attachment technologies, the convergence of peripheral and interprocessor switched networks, and the increased availability of on-drive transistors motivate and enable this new architecture. NASD is based on four main principles: direct transfer to clients, secure interfaces via cryptographic support, asynchronous non-critical-path oversight, and variably-sized data objects. Measurements of our prototype system show that these services can be cost-effectively integrated into a next generation disk drive ASK. End-to-end measurements of our prototype drive andfilesysterns suggest that NASD cun support conventional distributed filesystems without performance degradation. More importantly, we show scaluble bandwidth for NASD-specialized filesystems. Using a parallel data mining application, NASD drives deliver u linear scaling of 6.2 MB/s per clientdrive pair, tested with up to eight pairs in our lab.

This study examined the relationship between scores on two personality characteristics, apprehension about communication and resilience, from 200 elementary school teachers from several counties who completed the Personal Report of Communication Apprehension and the Personal Resilience Questionnaire. Scores on the two measures correlated −.33, which accounts for 10% of the common variance.

Exposure of neutrophils to a variety of agonists including soluble chemoattractant peptides and cytokines results in degranulation and activation of the oxidative burst (effector functions) that are required for bacterial killing. At present, the signaling pathways regulating these important functions are incompletely characterized. Mitogen-activated protein (MAP) kinases (MAPK) as well as members of a family of "renaturable kinases" are rapidly activated in neutrophils in response to diverse physiological agonists, suggesting that they may regulate cell activation. Antagonists of phosphatidyl inositol-3-(OH) kinase (PI3-kinase) such as wortmannin (Wtmn) inhibit these effector responses as well as certain of the above-mentioned kinases, leading to the suggestion that these enzymes lie downstream of PI3-kinase in the pathway regulating the oxidative burst and granule secretion. However, an apparent discrepancy exists in that, while virtually obliterating activity of PI3-kinase and the oxidase at low concentrations (ID50 100 nM and approximately 75 nM, respectively). In contrast, Wtmn potently inhibited fMLP-induced activation of the 63 and 69 kDa renaturable kinases (ID50 approximately 5-10 nM). We speculate that the renaturable kinases may be involved in the regulation of the oxidative burst, whereas the MAPK pathway may play a role in other neutrophil functions such as granule secretion.

A minor viral population of oseltamivir-resistant A(H3N2) viruses (E119V neuraminidase mutation) was selected and maintained in a continually infected immunocompromised child following initial oseltamivir treatment. A subsequent course of oseltamivir given 7 weeks later rapidly selected for the E119V variant resulting in a near-pure population of the resistant virus. The study highlights the challenges of oseltamivir treatment of immunocompromised patients that are continually shedding virus and demonstrates the ability of the E119V oseltamivir-resistant virus to be maintained for prolonged periods even in the absence of drug-selective pressure.

A case-study of the R&D networking activities of Glaxo Group Research was carried out between June and November 1993. Different types of networking situation were identified using a simple 2times2 matrix –- the ‘networking uncertainty map’. This paper describes the background to Glaxo's R&D networking activities, introduces and illustrates the uncertainty map and then suggests the implications of each type of network. There are implications in general for R&D management and more specifically for the management of human resources in R&D. Managers might easily apply the uncertainty map to their own R&D networking situations.

A translated version of the Personal Report of Communication Apprehension was administered to 688 students at four Chinese colleges and universities. The data were compared with American norms established by McCroskey in 1982 and with the responses of 177 students at a large state university in Florida. The Chinese sample reported a significantly higher mean score on apprehension about communication than the Americans. The findings were discussed with reference to cultural differences.

Introduction Iowa research has provided much information about P and K management for corn and soybeans, but it has been mostly based on broadcast fertilization for tilled soils. No-till management results in little or no incorporation of residues and fertilizers with soil. Subsurface banding of phosphorus (P) and potassium (K) fertilizers with planter attachments or before planting could be more effective because both nutrients accumulate at or near the soil surface. A long-term study was initiated in 1994 at this farm and at other farms to evaluate P and K fertilizer placement for corn and soybeans managed with no-till and chisel-plow tillage.

The concepts we use to think about R&D must be refreshed and reinterpreted in the context of how businesses now operate, how industries are restructuring and how R&D activities are being organized to meet new requirements and promote new opportunities. The links between business strategy, technology strategy and R&D and innovation strategy are not fixed. Innovative businesses can exploit the dynamism of these relationships.

In some industries, the use of virtual reality (VR) technology is now firmly established and it is not difficult recognize its further potential across many sectors in a wide range of innovative applications. Since the technology is still emerging, and is evolving rapidly, any application of VR might be regarded as technologically innovative. This paper focuses on the organizational and networking benefits of the technology and the stimulation of entrepreneurial opportunities in design and development activities. In this paper, a business process model is presented by the authors in order to articulate and illustrate the benefits of using VR. The model can be used in several ways.

The paper describes two models of technology and innovation management that are relevant to all managers, not just technology managers. The first model puts innovation management into a learning organisation framework and can be used to monitor progress and manage projects. It can also be used to evaluate the implementation and improvement of technology management within an organisation, and across virtual organisations and networks. The second model integrates technology management into a multi-disciplinary business context and treats it and the business holistically. This model is compatible with business process thinking and regards innovation as an ongoing technology and business management responsibility rather than a discrete event or project. The two models are complementary but can be used independently. This paper discusses their educational value and practical application.

In recent years, much attention has been given to product introduction by managers, consultants and academics. Although many companies are actively improving their new product introduction processes, many are merely applying prescriptive techniques without fully understanding their processes. Very few companies use self-assessment techniques on the product introduction process because it is believed by many that product introduction is too complex and too diverse. This paper argues that self-assessment can be applied to global product introduction (the most complex operating scenario) and a framework for applying the technique is suggested.

A computer-morphing procedure was used to produce a “full cranial hair” photograph for comparisons of perceptions by 96 undergraduates of a photograph of a naturally bald 30-yr.-old man on 13 dependent measures derived from 30 semantic differential scales. Analysis showed the full-hair condition was rated significantly more dominant, dynamic, and masculine than the bald condition. While the model was also perceived as younger in the full-hair condition, there was no difference in mean ratings of attractiveness between photographs.

In 1992, a survey of over 40 UK companies was conducted to identify the progress being made in the implementation of quality management principles within R&D environments. Subsequently two workshops were organised to identify and explore areas of concern. The companies involved were selected because of their known interest in the subject. A variety of means were used to identify the "sample", including information from previous communications and studies by the R&D Research Unit, membership of TQM in R&D study groups, or mention in journals such as Total Quality Management. A telephone survey was conducted and thirteen companies were visited. Semi-structured interviews were conducted with R&D managers, quality managers and other employees. The companies visited were selected in order to illustrate a broad cross-section of experience in implementing quality management. The timing of their quality initiatives ranged from 1986 to embryonic stages in 1992. From the interviews and workshop discussions a model or framework was devised of the way in which TQM is implemented in R&D. This is presented in the paper with a recommendation that it be used to guide companies already in progress, or those companies still about to start.

The response of R and D to the Health and Safety at Work Act is discussed and the factors which may stimulate or impede further action are described. Evidence cited includes that from a 1976 survey of R and D managers in the chemical industry.

Butler, J., Ball, D.F. and Pearson, A.W., 1978. Plant insurance and health and safety at work. Journal of Occupational Accidents , 1: 297–309. The potential role of insurance in improving health and safety in the chemical industry has been investigated as part of a wider study of the influence of recent health and safety legislation on the pattern of research and development in the industry.