HIV-1 down-modulates γ signaling chain of FcγR in human macrophages : a possible mechanism for inhibition of phagocytosis

HIV-1 infection impairs a number of macrophage effector functions, thereby contributing to development of opportunistic infections and the pathogenesis of AIDS. FcγR-mediated phagocytosis by human monocyte-derived macrophages (MDM) is inhibited by HIV-1 infection in vitro, and the underlying mechanism was investigated in this study. Inhibition of phagocytosis directly correlated with the multiplicity of HIV-1 infection. Expression of surface FcγRs was unaffected by HIV-1 infection, suggesting that inhibition of phagocytosis occurred during or after receptor binding. HIV-1 infection of MDM markedly inhibited tyrosine phosphorylation of the cellular proteins, which occurs following engagement of FcγRs, suggesting a defect downstream of initial receptor activation. FcγR-mediated phagocytosis in HIV-infected MDM was associated with inhibition of phosphorylation of tyrosine kinases from two different families, Hck and Syk, defective formation of Syk complexes with other tyrosine-phosphorylated proteins, and inhibition of paxillin activation. Down-modulation of protein expression but not mRNA of the γ signaling subunit of FcγR (a docking site for Syk) was observed in HIV-infected MDM. Infection of MDM with a construct of HIV-1 in which nef was replaced with the gene for the γ signaling subunit augmented FcγR-mediated phagocytosis, suggesting that down-modulation of γ-chain protein expression in HIV-infected MDM caused the defective FcγR-mediated signaling and impairment of phagocytosis. This study is the first to demonstrate a specific alteration in phagocytosis signal transduction pathway, which provides a mechanism for the observed impaired FcγR-mediated phagocytosis in HIV-infected macrophages and contributes to the understanding of how HIV-1 impairs cell-mediated immunity leading to HIV-1 disease progression.

The War Memoirs: Some origins of the thought of W.R. Bion

The work of W. R. Bion changed the shape of psychoanalytic theory in fundamental ways, one of the most important of which was Bion's insight into the nature of normal projective identification. No other psychoanalytic theorist has Bion's ability to represent the horrors of psychic abandonment and the converse, the absolute necessity of the presence of another mind for psychic survival. Through a discussion of Bion's War Memoirs 1917-1919 (Bion, 1997), Attacks on linking and A theory of thinking (1993), this paper explores the link between war, masculinity, the maternal and Bion's sensitivity to the significance of everyday interpersonal contact. It is argued that Bion's apocalyptic experiences as a teenage tank commander gave him shattering insight into the extent to which mind is inter-mind, self is inter-self. Bion's life writing has the quality of survivor insight: 'And only I am escaped alone to tell thee' (Job 1: 14-19), as he returns repeatedly to the events of the day when he 'died ', 8 August 1918. His insight into the elemental passions nature of love, hate and mindlessness are borne of his experiences on the battlefield, and exquisitely crystallized in his repeated explorations of an encounter with a dying soldier.

Game of Tropes: the Orientalist tradition in the Works of G.R.R. Martin

George R.R. Martin's A Song of Ice and Fire novels (and their television adaption, Game of Thrones) have become arguably the most well known fantasy epic of the last decade. However, the world of A Song of Ice and Fire conforms to many of the same Orientalist tropes that have dominated Western literature since the popularisation of the 'Arabian fantasy' in the 18th and 19th centuries and its subsequent perpetuation in film and television. Derivative imaginings of the real world Middle East are commonly reflected in non-Earthly fantasy worlds and Martin's work incorporates this standard vision of the Eastern Other. Owing to its popularity, the A Song of Ice and Fire series represents a significant reinforcement of Orientalist stereotypes and proves that fantasy locations have significant power to cement these ideas in the popular imagination. Moreover, the negative portyal of the East in these works supports Said's argument that the Orient is an invention of the West, and that our depiction of the Other is a means of framing our own cultural superiority.

Effect of data length and bin numbers on distribution entropy (DistEn) measurement in analyzing healthy aging

Complexity analysis of a given time series is executed using various measures of irregularity, the most commonly used being Approximate entropy (ApEn), Sample entropy (SampEn) and Fuzzy entropy (FuzzyEn). However, the dependence of these measures on the critical parameter of tolerance `r' leads to precarious results, owing to random selections of r. Attempts to eliminate the use of r in entropy calculations introduced a new measure of entropy namely distribution entropy (DistEn) based on the empirical probability distribution function (ePDF). DistEn completely avoids the use of a variance dependent parameter like r and replaces it by a parameter M, which corresponds to the number of bins used in the histogram to calculate it. When tested for synthetic data, M has been observed to produce a minimal effect on DistEn as compared to the effect of r on other entropy measures. Also, DistEn is said to be relatively stable with data length (N) variations, as far as synthetic data is concerned. However, these claims have not been analyzed for physiological data. Our study evaluates the effect of data length N and bin number M on the performance of DistEn using both synthetic and physiologic time series data. Synthetic logistic data of `Periodic' and `Chaotic' levels of complexity and 40 RR interval time series belonging to two groups of healthy aging population (young and elderly) have been used for the analysis. The stability and consistency of DistEn as a complexity measure as well as a classifier have been studied. Experiments prove that the parameters N and M are more influential in deciding the efficacy of DistEn performance in the case of physiologic data than synthetic data. Therefore, a generalized random selection of M for a given data length N may not always be an appropriate combination to yield good performance of DistEn for physiologic data.

The use of injury surveillance databases to identify emerging injury hazards

Among the many valuable uses of injury surveillance is the potential to alert health authorities and societies in general to emerging injury trends, facilitating earlier development of prevention measures. Other than road safety, to date, few attempts to forecast injury data have been made, although forecasts have been made of other public health issues. This may in part be due to the complex pattern of variance displayed by injury data. The profile of many injury types displays seasonality and diurnal variance, as well as stochastic variance. The authors undertook development of a simple model to forecast injury into the near term. In recognition of the large numbers of possible predictions, the variable nature of injury profiles and the diversity of dependent variables, it became apparent that manual forecasting was impractical. Therefore, it was decided to evaluate a commercially available forecasting software package for prediction accuracy against actual data for a set of predictions. Injury data for a 4-year period (1996 to 1999) were extracted from the Victorian Emergency Minimum Dataset and were used to develop forecasts for the year 2000, for which data was also held. The forecasts for 2000 were compared to the actual data for 2000 by independent t-tests, and the standard errors of the predictions were modelled by stepwise hierarchical multiple regression using the independent variables of the standard deviation, seasonality, mean monthly frequency and slope of the base data (R = 0.93, R² = 0.86, F_{(3, 27)} = 55.2, p < 0.0001). Significant contributions to the model included the SD (β = 1.60, p < 0.001), mean monthly frequency (β =  - 0.72, p < 0.002), and the seasonality of the data (β = 0.16, p < 0.02). It was concluded that injury data could be reliably forecast and that commercial software was adequate for the task. Variance in the data was found to be the most important determinant of prediction accuracy. Importantly, automated forecasting may provide a vehicle for identifying emerging trends.

Assessing the economic benefits of starling detection and control to Western Australia

The common starling (Sturnus vulgaris) has a proven invasion history in many countries, and at a continental scale in North America and Australasia. In Australia, starlings are firmly established throughout the eastern states and Tasmania. Incursions of starlings into Western Australia (WA) represent a significant threat to this State’s agricultural, public amenity and biodiversity assets. We present models of starling population dynamics that incorporate environmental and control effort variability. We incorporate knowledge of starling ecology with economic data to assess the potential economic cost of starlings establishing in WA, evaluating the cost–benefits for each management scenario. We calculated starling population size will approach carrying capacity in WA within as little as 30 years if left unchecked. A population of this size could cost the WA economy up to $43.7 million annually in 2011/2012 dollars. Over a 50 year horizon, the conservative benefit–cost ratio for ongoing detection and control at the current level of expenditure is 6.03:1. However, even under current levels of control, starling numbers are projected to increase to almost 11 million by 2061. Further improvements in the efficiency of starling detection and control and/or an increased level of expenditure on detection and control are required.

A practical approach to monitoring nutrient supplement intake of Australian adults

The adoption, in mid-1995, of the revised food Standard A9, which permits the more liberal addition of nutrients to a range of food products, highlighted the need to obtain information on nutrient intake from supplements to complement the i 995 National Nutrition Survey data on nutrient intake from food. This paper describes the method used to obtain quantitative information on nutrient supplement intake and reports on the prevalence of supplement use in different subgroups of the Australian population. Information on supplement intake was obtained in two Australian Bureau of Statistics Population Survey Monitor surveys in August 1995 and February 1996 using the Therapeutic Goods Administration (TGA) registration numbers to identify individual products. Approximately 18% of men and 29% of women aged 18 years and over reported consuming a nutrient supplement on the day before the survey and these proportions increased to 25% and 35% respectively for consumption during the two weeks before the survey. The prevalence of supplement intake increased with age, education level, socioeconomic status, employment status and with fruit and vegetable intake. The substantial proportion of Australian adults who consume nutrient supplements, and the rapidly changing composition of the Australian food supply in response to changes in food regulation, indicate that there is a need for regular monitoring of nutrient intake from supplements. The use of TGA registration numbers to identify supplements provides a practical way to address this need.

A roadmap to Renewable Adaptive Recyclable Environmental (R.A.R.E.) architecture

R.A.R.E. stands for Renewable Adaptive Recyclable Environmental Architecture; the acronym expresses a demand that is becoming increasingly important today in the eyes of designers and clients. The paper draws on the contents and the pedagogical methods applied in a Building Technology Unit (SRT 450) – at forth year level – at the School of Architecture and Building, Deakin University, Australia. The unit is basically structured upon eight subjects derived as relevant to the research and development for a R.A.R.E. Architecture: Sustainable Site & Climate Analysis; Flexible & Adaptive Structural Systems; Renewable Adaptive & Environmental Building Materials; Modular Building Systems; Innovative Building Envelope Systems; Renewable or Non-conventional Energy Systems; Innovative Heating, Ventilation & Air Conditioning; Water Storage & Systems. The overall objective of the unit is to present a comprehensive overview of all these Sustainable Building Categories (SBCs) so that the students can produce a guide towards the design of a R.A.R.E. Architecture. The push towards a holistic and integrated approach will contribute to the definition of an innovative architecture, which is both progressive and sustainable.

Challenges of continuous global optimization in molecular structure prediction

The molecular geometry, the three dimensional arrangement of atoms in space, is a major factor determining the properties and reactivity of molecules, biomolecules and macromolecules. Computation of stable molecular conformations can be done by locating minima on the potential energy surface (PES). This is a very challenging global optimization problem because of extremely large numbers of shallow local minima and complicated landscape of PES. This paper illustrates the mathematical and computational challenges on one important instance of the problem, computation of molecular geometry of oligopeptides, and proposes the use of the Extended Cutting Angle Method (ECAM) to solve this problem.

ECAM is a deterministic global optimization technique, which computes tight lower bounds on the values of the objective function and fathoms those part of the domain where the global minimum cannot reside. As with any domain partitioning scheme, its challenge is an extremely large partition of the domain required for accurate lower bounds. We address this challenge by providing an efficient combinatorial algorithm for calculating the lower bounds, and by combining ECAM with a local optimization method, while preserving the deterministic character of ECAM.

The utility of a workplace injury instrument in prediction of workplace injury

Workplace injuries are common and destructive to persons, organisations, and society. Various instruments presently exist that are designed to assess the factors underlying workplace injury. The study reports on the construct and predictive validity of a 46-item instrument, the safety perception survey (SPS), currently used to assess safety climate in industrial organisations throughout Australia. Initially, factor analysis was conducted on the data from a sample of 1238 employees from nine organisations, which indicated a one-factor solution, was the best fit. A structural equation model (SEM) linking injury rates to the safety climate measure for 16 sub-groups of six industrial organisations indicated that the measure contributed just 23% of the variance in injury rates. Interestingly, the results indicated that the number of employees was a better and more significant predictor of injury (R² = 0.48). It is proposed that the SPS as is would need to be modified significantly from its current form to produce improvements in validity, as in its current form the survey is no more predictive of injury than organisational size. Future research into safety climate measures should incorporate predictive validity analysis on injury rates, as for many organisations; this is a performance outcome measure.

The evolution of an online community - a case study

This article reflects findings from a long term case study of an online community of practice established through a network for the professional education of teachers in Ontario, Canada. The Education Network of Ontario/Réseau éducatif de l'Ontario (ENO/REO) was created in 1992–1993 to support and connect teachers from kindergarten to grade 12 in the province of Ontario. Its mandate was to ensure that all teachers had free access to the Internet and to each other and to encourage the development of skills in the area of information and communication technology with the ultimate goal of using those skills to improve classroom practice. The study investigated whether information technology had the potential to connect teachers to each other in order to build the capacity to create networks where professional learning could take place in a cost-efficient and flexible time and/or place. It was found that participants were early adopters who enjoyed innovation, that online networkswere supportive for learning but hard to maintain over time, and though they supported the integration of technology in the classroom, other barriers within schools could challenge this effect.

Development and application of polymerase chain reaction-based assays for Rathayibacter Toxicus and a Bacteriophage associated with annual ryegrass (Lolium Rigidum) toxicity

Annual ryegrass toxicity (ARGT) is responsible for significant stock losses in South Australia and Western Australia. The toxicity is caused by corynetoxins produced by the bacterium Rathayibacter toxicus (with the possible involvement of a bacteriophage), which infects annual ryegrass (Lolium rigidum). Polymerase chain reaction (PCR)-based assays, compatible with an existing enzyme-linked immunosorbent assay for the corynetoxins, have been developed and used to screen L. rigidum for both the presence of R. toxicus and for the bacteriophage isolate NCPPB 3778. The results from analysing bacterially infected galls from toxic grain screenings showed a positive correlation between the presence of the bacterium and corynetoxins but not with the bacteriophage. Analysis of pasture-derived samples of annual ryegrass showed about a 50% correlation of corynetoxins with bacterial presence and about a 5% correlation of phage with the presence of the bacterium. These observations support the potential application of the PCR-based assays in providing a useful, complementary tool in the assessment of the likelihood of pasture and feed to cause ARGT and to enable a better understanding of the complex aetiology of ARGT.

Effect of carbohydrate ingestion on glucose kinetics during exercise in the heat

Six endurance-trained men [peak oxygen uptake (VO₂) = 4.58 ± 0.50 (SE) l/min] completed 60 min of exercise at a workload requiring 68 ± 2% peak VO₂ in an environmental chamber maintained at 35°C (<50% relative humidity) on two occasions, separated by at least 1 wk. Subjects ingested either a 6% glucose solution containing 1 µCi [3-³H]glucose/g glucose (CHO trial) or a sweet placebo (Con trial) during the trials. Rates of hepatic glucose production [HGP = glucose rate of appearance (R_a) in Con trial] and glucose disappearance (R_d), were measured using a primed, continuous infusion of [6,6-^₂H]glucose, corrected for gut-derived glucose (gut R_a) in the CHO trial. No differences in heart rate, VO₂, respiratory exchange ratio, or rectal temperature were observed between trials. Plasma glucose concentrations were similar at rest but increased (P < 0.05) to a greater extent in the CHO trial compared with the Con trial. This was due to the absorption of ingested glucose in the CHO trial, because gut R_a after 30 and 50 min (16 ± 5 µmol · kg^-1 · min^-1) was higher (P < 0.05) compared with rest, whereas HGP during exercise was not different between trials. Glucose R_d was higher (P < 0.05) in the CHO trial after 30 and 50 min (48.0 ± 6.3 vs 34.6 ± 3.8 µmol · kg^-1 · min^-1, CHO vs. Con, respectively). These results indicate that ingestion of carbohydrate, at a rate of ~1.0 g/min, increases glucose Rd but does not blunt the rise in HGP during exercise in the heat.

Effects of ovariectomy and estrogen on ischemia-reperfusion injury in hindlimbs of female rats

The effects of estrogen and ovariectomy on indexes of muscle damage after 2 h of complete hindlimb ischemia and 2 h of reperfusion were investigated in female Sprague-Dawley rats. The rats were assigned to one of three experimental groups: ovariectomized with a 17-estradiol pellet implant (OE), ovariectomized with a placebo pellet implant (OP), or control with intact ovaries (R). It was hypothesized that following ischemia-reperfusion (I/R), muscle damage indexes [serum creatine kinase (CK) activity, calpain-like activity, inflammatory cell infiltration, and markers of lipid peroxidation (thiobarbituric-reactive substances)] would be lower in the OE and R rats compared with the OP rats due to the protective effects of estrogen. Serum CK activity following I/R was greater (P < 0.01) in the R rats vs. OP rats and similar in the OP and OE rats. Calpain-like activity was greatest in the R rats (P < 0.01) and similar in the OP and OE rats. Neutrophil infiltration was assessed using the myeloperoxidase (MPO) assay and immunohistochemical staining for CD43-positive (CD43+) cells. MPO activity was lower (P < 0.05) in the OE rats compared with any other group and similar in the OP and R rats. The number of CD43+ cells was greater (P < 0.01) in the OP rats compared with the OE and R rats and similar in the OE and R rats. The OE rats had lower (P < 0.05) thiobarbituric-reactive substance content following I/R compared with the R and OP rats. Indexes of muscle damage were consistently attenuated in the OE rats but not in the R rats. A 10-fold difference in serum estrogen content may mediate this. Surprisingly, serum CK activity and muscle calpain-like activity were lower (P < 0.05) in the OP rats compared with the R rats. Increases in serum insulin-like growth factor-1 content (P < 0.05) due to ovariectomy were hypothesized to account for this finding. Thus both ovariectomy and estrogen supplementation have differential effects on indexes of I/R muscle damage.

The impact of RICS education reform on building surveying

Purpose – It is of major concern to the surveying profession that the seven years between 1994 and 2001 witnessed a decline in the numbers of UK student surveyors of nearly 50 per cent. This was significant, especially when considered in the context of rising student numbers overall. The RICS decided to implement an education policy with the aim of increasing graduate quality. Changes were introduced in UK universities from September 2001. A number of universities saw their professionally accredited courses withdrawn as the RICS imposed  academic entry standards and research output based on the UK Government's Research Assessment Exercise (RAE) criteria on which to base their “partnership” relationships. Figures released by the RICS in 2003 indicated that surveying student numbers increased by 17 per cent in all areas except building surveying, where they fell by just under 25 per cent to 445 in 2001. The paper seeks to answer a number of questions. Why were building surveying courses failing to recruit students whereas other surveying courses have increased their numbers? If the figures continue to decline or remain at these low levels, what is the future for the BS? In short, could building surveying become an endangered profession?
Design/methodology/approach – All UK university BS course leaders were approached by questionnaire and approximately half responded. The study was partly funded by the RICS Education Trust.
Findings – The small amount of quantitative data collected suggests that recruitment is static at a time when other built environment courses are recruiting well. Course leaders expressed strong views about the impact of the education reforms.
Research limitations/implications – Failure by some BS course leaders to provide some statistical data prevented completion of the quantitative part of the study.
Originality/value – Key recommendations have been made to the BS Faculty Board of the RICS about the future of BS education.