Morphine-induced receptor endocytosis in a novel knockin mouse reduces tolerance and dependence

Abstract Opioid drugs, such as morphine, are among the most effective analgesics available. However, their utility for the treatment of chronic pain is limited by side effects including tolerance and dependence. Morphine acts primarily through the mu-opioid receptor (MOP-R) , which is also a target of endogenous opioids. However, unlike endogenous ligands, morphine fails to promote substantial receptor endocytosis both in vitro, and in vivo. Receptor endocytosis serves at least two important functions in signal transduction. First, desensitization and endocytosis act as an "off" switch by uncoupling receptors from G protein. Second, endocytosis functions as an "on" switch, resensitizing receptors by recycling them to the plasma membrane. Thus, both the off and on function of the MOP-R are altered in response to morphine compared to endogenous ligands. To examine whether the low degree of endocytosis induced by morphine contributes to tolerance and dependence, we generated a knockin mouse that expresses a mutant MOP-R that undergoes morphine-induced endocytosis. Morphine remains an excellent antinociceptive agent in these mice. Importantly, these mice display substantially reduced antinociceptive tolerance and physical dependence. These data suggest that opioid drugs with a pharmacological profile similar to morphine but the ability to promote endocytosis could provide analgesia while having a reduced liability for promoting tolerance and dependence

Producing the intercultural citizen in the International Baccalaureate

The International Baccalaureate Diploma (IBD) is currently offered in 2,718 schools across 138 countries, and explicitly aims to produce ‘internationally-minded’ citizens with a sense of belonging to both the local and the global community. It thus offers an opportunity to enquire how a school curriculum might produce more intercultural or global dispositions, knowledge and skills, and the challenges inherent in such design. To frame this empirical enquiry, the chapter distinguishes between the fact of living together in difference as a life circumstance, and a range of ethical dispositions for such living together, including cosmopolitanism, internationalism, interculturality and global citizenship. These alternatives are understood as competing social imaginaries with different premises and logics. This chapter offers an empirical exploration of how the IBD’s curricular goal of ‘international-mindedness’ is interpreted firstly in current official documents, then reinterpreted by teachers and students in three case study schools in Australia. Traces of these overlapping but distinct discourses are found in the teachers’ recontextualisation of the IBD’s ‘internationalmindedness’ producing diffuse and contradictory versions of what ‘internationalmindedness’ means, and looks like in educational settings.

Demonstration of cellulosic ethanol production from sugarcane bagasse in Australia : the Mackay Renewable Biocommodities Pilot Plant

The ready availability of sugarcane bagasse at an existing industrial facility and the potential availability of extra fibre through trash collection make sugarcane fibre the best candidate for early stage commercialisation of cellulosic ethanol technologies. The commercialisation of cellulosic ethanol technologies in the sugar industry requires both development of novel technologies and the assessment of these technologies at a pre-commercial scale. In 2007, the Queensland University of Technology (QUT) received funding from the Australian and Queensland Governments to construct a pilot research and development facility for the production of bioethanol and other renewable biocommodities from biomass including sugarcane bagasse. This facility has been built on the site of the Racecourse Sugar Mill in Mackay, Queensland and is known as the Mackay Renewable Biocommodities Pilot Plant (MRBPP). This research facility is capable of processing cellulosic biomass by a variety of pretreatment technologies and includes equipment for enzymatic saccharification, fermentation and distillation to produce ethanol. Lignin and fermentation co-products can also be produced in the pilot facility.

A Bayesian approach for estimating detection times in horses : exploring the pharmacokinetics of a urinary acepromazine metabolite

We describe the population pharmacokinetics of an acepromazine (ACP) metabolite (2-(1-hydroxyethyl)promazine) (HEPS) in horses for the estimation of likely detection times in plasma and urine. Acepromazine (30 mg) was administered to 12 horses, and blood and urine samples were taken at frequent intervals for chemical analysis. A Bayesian hierarchical model was fitted to describe concentration-time data and cumulative urine amounts for HEPS. The metabolite HEPS was modelled separately from the parent ACP as the half-life of the parent was considerably less than that of the metabolite. The clearance ($Cl/F_{PM}$) and volume of distribution ($V/F_{PM}$), scaled by the fraction of parent converted to metabolite, were estimated as 769 L/h and 6874 L, respectively. For a typical horse in the study, after receiving 30 mg of ACP, the upper limit of the detection time was 35 hours in plasma and 100 hours in urine, assuming an arbitrary limit of detection of 1 $\mu$g/L, and a small ($\approx 0.01$) probability of detection. The model derived allowed the probability of detection to be estimated at the population level. This analysis was conducted on data collected from only 12 horses, but we assume that this is representative of the wider population.

Are alphabetic language-derived models of L2 reading relevant to L1 logographic background readers?

In this paper, we argue that second language (L2) reading research, which has been informed by studies involving first language (L1) alphabetic English reading, may be less relevant to L2 readers with non-alphabetic reading backgrounds, such as Chinese readers with an L1 logographic (Chinese character) learning history. We provide both neuroanatomical and behavioural evidence from Chinese language reading studies to support our claims. The paper concludes with an argument outlining the need for a universal L2 reading model which can adequately account for readers with diverse L1 orthographic language learning histories.

Prediction and measurement of multiuser MIMO-OFDM channel in rural Australia

Commonwealth Scientific and Industrial Research Organization (CSIRO) has recently conducted a technology demonstration of a novel fixed wireless broadband access system in rural Australia. The system is based on multi user multiple-input multiple-output orthogonal frequency division multiplexing (MU-MIMO-OFDM). It demonstrated an uplink of six simultaneous users with distances ranging from 10 m to 8.5 km from a central tower, achieving 20 bits s/Hz spectrum efficiency. This paper reports on the analysis of channel capacity and bit error probability simulation based on the measured MUMIMO-OFDM channels obtained during the demonstration, and their comparison with the results based on channels simulated by a novel geometric optics based channel model suitable for MU-MIMO OFDM in rural areas. Despite its simplicity, the model was found to predict channel capacity and bit error rate probability accurately for a typical MU-MIMO-OFDM deployment scenario.

Quantitative studies of lower motor neuron degeneration in amyotrophic lateral sclerosis : Evidence for exponential decay of motor unit numbers and greatest rate of loss at the site of onset

Objective: To use our Bayesian method of motor unit number estimation (MUNE) to evaluate lower motor neuron degeneration in ALS. Methods: In subjects with ALS we performed serial MUNE studies. We examined the repeatability of the test and then determined whether the loss of MUs was fitted by an exponential or Weibull distribution. Results: The decline in motor unit (MU) numbers was well-fitted by an exponential decay curve. We calculated the half life of MUs in the abductor digiti minimi (ADM), abductor pollicis brevis (APB) and/or extensor digitorum brevis (EDB) muscles. The mean half life of the MUs of ADM muscle was greater than those of the APB or EDB muscles. The half-life of MUs was less in the ADM muscle of subjects with upper limb than in those with lower limb onset. Conclusions: The rate of loss of lower motor neurons in ALS is exponential, the motor units of the APB decay more quickly than those of the ADM muscle and the rate of loss of motor units is greater at the site of onset of disease. Significance: This shows that the Bayesian MUNE method is useful in following the course and exploring the clinical features of ALS. 2012 International Federation of Clinical Neurophysiology.

Analysis of indirect message injection for MAC generation using stream ciphers

This paper presents a model for generating a MAC tag with a stream cipher using the input message indirectly. Several recent proposals represent instances of this model with slightly different options. We investigate the security of this model for different options, and identify cases which permit forgery attacks. Based on this, we present a new forgery attack on version 1.4 of 128-EIA3. Design recommendations to enhance the security of proposals following this general model are given.

An investigation into factors affecting electron density calibration for a megavoltage cone-beam CT system

There is a growing interest in the use of megavoltage cone-beam computed tomography (MV CBCT) data for radiotherapy treatment planning. To calculate accurate dose distributions, knowledge of the electron density (ED) of the tissues being irradiated is required. In the case of MV CBCT, it is necessary to determine a calibration-relating CT number to ED, utilizing the photon beam produced for MV CBCT. A number of different parameters can affect this calibration. This study was undertaken on the Siemens MV CBCT system, MVision, to evaluate the effect of the following parameters on the reconstructed CT pixel value to ED calibration: the number of monitor units (MUs) used (5, 8, 15 and 60 MUs), the image reconstruction filter (head and neck, and pelvis), reconstruction matrix size (256 by 256 and 512 by 512), and the addition of extra solid water surrounding the ED phantom. A Gammex electron density CT phantom containing EDs from 0.292 to 1.707 was imaged under each of these conditions. The linear relationship between MV CBCT pixel value and ED was demonstrated for all MU settings and over the range of EDs. Changes in MU number did not dramatically alter the MV CBCT ED calibration. The use of different reconstruction filters was found to affect the MV CBCT ED calibration, as was the addition of solid water surrounding the phantom. Dose distributions from treatment plans calculated with simulated image data from a 15 MU head and neck reconstruction filter MV CBCT image and a MV CBCT ED calibration curve from the image data parameters and a 15 MU pelvis reconstruction filter showed small and clinically insignificant differences. Thus, the use of a single MV CBCT ED calibration curve is unlikely to result in any clinical differences. However, to ensure minimal uncertainties in dose reporting, MV CBCT ED calibration measurements could be carried out using parameter-specific calibration measurements.

Cloud computing for healthcare research information sharing

With the widespread application of healthcare Information and Communication Technology (ICT), constructing a stable and sustainable data sharing circumstance has attracted rapidly growing attention in both academic research area and healthcare industry. Cloud computing is one of long dreamed visions of Healthcare Cloud (HC), which matches the need of healthcare information sharing directly to various health providers over the Internet, regardless of their location and the amount of data. In this paper, we discuss important research tool related to health information sharing and integration in HC and investigate the arising challenges and issues. We describe many potential solutions to provide more opportunities to implement EHR cloud. As well, we introduce the development of a HC related collaborative healthcare research example, thus illustrating the prospective of applying Cloud Computing in the health information science research.

Linear adaptive channel equalization for multiuser MIMO-OFDM systems

Linear adaptive channel equalization using the least mean square (LMS) algorithm and the recursive least-squares(RLS) algorithm for an innovative multi-user (MU) MIMOOFDM wireless broadband communications system is proposed. The proposed equalization method adaptively compensates the channel impairments caused by frequency selectivity in the propagation environment. Simulations for the proposed adaptive equalizer are conducted using a training sequence method to determine optimal performance through a comparative analysis. Results show an improvement of 0.15 in BER (at a SNR of 16 dB) when using Adaptive Equalization and RLS algorithm compared to the case in which no equalization is employed. In general, adaptive equalization using LMS and RLS algorithms showed to be significantly beneficial for MU-MIMO-OFDM systems.

Does 'habitus' count in Chinese Australians' mathematics achievement?

Large-scale international comparative studies and cross-ethnic studies have revealed that Chinese students, whether living in China or overseas, consistently outperform their counterparts in mathematics achievement. These studies tended to explain this result from psychological, educational, or cultural perspectives. However, there is scant sociological investigation addressing Chinese students’ better mathematics achievement. Drawing on Bourdieu’s sociological theory, this study conceptualises Chinese Australians’ “Chineseness” by the notion of ‘habitus’ and considers this “Chineseness” generating but not determinating mechanism that underpins Chinese Australians’ mathematics learning. Two hundred and thirty complete responses from Chinese Australian participants were collected by an online questionnaire. Simple regression model statistically significantly well predicted mathematics achievement by “Chineseness” (F = 141.90, R = .62, t = 11.91, p < .001). Taking account of “Chineseness” as a sociological mechanism for Chinese Australians’ mathematics learning, this study complements psychological and educational impacts on better mathematics achievement of Chinese students revealed by previous studies. This study also challenges the cultural superiority discourse that attributes better mathematics achievement of Chinese students to cultural factors.

A sociological quantitative study about Chineseness and Chinese heritage language for young Chinese Australian adults in urban Australia

The relationship between Heritage Language and ethnic identity has gained significant research ground in North America. However, there is a dearth of similar research conducted in other regions of the world. There seems to be little if any work investigating the link between Chinese Australians’ ethnic identity and their Chinese Heritage Language. This sociological quantitative study interpreted Chinese Australians’ “Chineseness” as their ethnic identity, linked this “Chineseness” to their Chinese Heritage Language, and did so by virtue of Bourdieu’s key concept ‘habitus’. 227 cases were analyzed by Structural Equation Modelling. The result demonstrated a statistically significant strong positive relationship between Chinese Australian urban young adults’ “Chineseness” and their self-perceptions of their Chinese Heritage Language proficiency (r=.73). This paper explained the findings in light of Bourdieu’s (1991) contention that people make choices about languages according to the habitus they have.