Controlled systemic release of interleukin-12 after gene electrotransfer to muscle for cancer gene therapy alone or in combination with ionizing radiation in murine sarcomas

Background: The present study aimed to evaluate the antitumor effectiveness of systemic interleukin (IL)-12 gene therapy in murine sarcoma models, and to evaluate its interaction with the irradiation of tumors and metastases. To avoid toxic side-effects of IL-12 gene therapy, the objective was to achieve the controlled release of IL-12 after intramuscular gene electrotransfer. Methods: Gene electrotransfer of the plasmid pORF-mIL12 was performed into the tibialis cranialis in A/J and C57BL/6 mice. Systemic release of the IL-12 was monitored in the serum of mice after carrying out two sets of intramuscular IL-12 gene electrotransfer of two different doses of plasmid DNA. The antitumor effectiveness of IL-12 gene electrotransfer alone or in combination with local tumor or lung irradiation with X-rays, was evaluated on subcutaneous SA-1 and LPB tumors, as well as on lung metastases. Results: A synergistic antitumor effect of intramuscular gene electrotransfer combined with local tumor irradiation was observed as a result of the systemic distribution of IL-12. The gene electrotransfer resulted in up to 28% of complete responses of tumors. In combination with local tumor irradiation, the curability was increased by up to 100%. The same effect was observed for lung metastases, where a potentiating factor of 1.3-fold was determined. The amount of circulating IL-12 was controlled by the number of repeats of gene electrotransfer and by the amount of the injected plasmid. Conclusions: The present study demonstrates the feasibility of treatment by IL-12 gene electrotransfer combined with local tumor or lung metastases irradiation on sarcoma tumors for translation into the clinical setting. Copyright © 2009 John Wiley & Sons, Ltd.

Analysis of photoluminescence background of Raman spectra of carbon nanotips grown by plasma-enhanced chemical vapor deposition

Carbon nanotips with different structures were synthesized by plasma-enhanced hot filament chemical vapor deposition and plasma-enhanced chemical vapor deposition using different deposition conditions, and they were investigated by scanning electron microscopy and Raman spectroscopy. The results indicate that the photoluminescence background of the Raman spectra is different for different carbon nanotips. Additionally, the Raman spectra of the carbon nanotips synthesized using nitrogen-containing gas precursors show a peak located at about 2120 cm-1 besides the common D and G peaks. The observed difference in the photoluminescence background is related to the growth mechanisms, structural properties, and surface morphology of a-C:H and a-C:H:N nanotips, in particular, the sizes of the emissive tips.

The sideways hourglass : establishing the lemniscate as a narrative structure for writing and reading non-linear stories

This thesis is a study in narratology that examines the pre-theoretical ideas that underlie the study of narrative and time. The thesis explores how the lemniscate can be transported from geometry to narrative in order to structure a non-linear story that breaks the rules of causality and chronology by coupling physical movement through space with the backward pull of memory. The findings offer new possibilities for understanding the nexus between shape and story and for recording non-linear narratives that are marked by simultaneity, counterpoint, and reversal.

Reading words into statutes : when Homer nods

The grammatical meaning of a statutory provision may not always gel with the purpose of the statute. The court may strive to give the provision an interpretation at odds with its ordinary and natural meaning to meet the purpose of the legislation. On occasion, this may involve notionally adding words to, or substituting words in, a statutory provision. This process of “reading in” words demands that close attention be paid to the boundary between statutory construction and judicial legislation, particularly where a court is invited to carve out an exception from grammatically clear words. In Jones v Wrotham Park Settled Estates [1980] AC 74, Lord Diplock identified three pre-conditions to reading words into a statute. This article analyses the utility of those conditions within the context of the modern purposive approach to statutory interpretation and evaluates whether they remain sufficient guideposts for identifying the boundary between interpretation and legislation.

The implications of educational and methodological background for the career success of Nobel Laureates : an investigation of major awards

Nobel laureates have achieved the highest recognition in academia, reaching the boundaries of human knowledge and understanding. Owing to past research, we have a good understanding of the career patterns behind their performance. Yet, we have only limited understanding of the factors driving their recognition with respect to major institutionalized scientific honours. We therefore look at the award life cycle achievements of the 1901–2000 Nobel laureates in physics, chemistry, and physiology or medicine. The results show that Nobelists with a theoretical orientation achieved more awards than laureates with an empirical orientation. Moreover, it seems their educational background shapes their future recognition. Researchers educated in Great Britain and the US tend to attract more awards than other Nobelists, although there are career pattern differences. Among those, laureates educated at Cambridge or Harvard are more successful in Chemistry, those from Columbia and Cambridge excel in Physics, while Columbia educated laureates dominate in Physiology or Medicine.

Simulated hyperopic anisometropia and reading, visual information processing, and reading-related eye movement performance in children

Purpose: This study investigated the impact of simulated hyperopic anisometropia and sustained near work on performance of academic-related measures in children. Methods: Participants included 16 children (mean age: 11.1 ± 0.8 years) with minimal refractive error. Academic-related outcome measures included a reading test (Neale Analysis of Reading Ability), visual information processing tests (Coding and Symbol Search subtests from the Wechsler Intelligence Scale for Children) and a reading-related eye movement test (Developmental Eye Movement test). Performance was assessed with and without 0.75 D of imposed monocular hyperopic defocus (administered in a randomised order), before and after 20 minutes of sustained near work. Unilateral hyperopic defocus was systematically assigned to either the dominant or non-dominant sighting eye to evaluate the impact of ocular dominance on any performance decrements. Results: Simulated hyperopic anisometropia and sustained near work both independently reduced performance on all of the outcome measures (p<0.001). A significant interaction was also observed between simulated anisometropia and near work (p<0.05), with the greatest decrement in performance observed during simulated anisometropia in combination with sustained near work. Laterality of the refractive error simulation (ocular dominance) did not significantly influence the outcome measures (p>0.05). A reduction of up to 12% in performance was observed across the range of academic-related measures following sustained near work undertaken during the anisometropic simulation. Conclusion: Simulated hyperopic anisometropia significantly impaired academic–related performance, particularly in combination with sustained near work. The impact of uncorrected habitual anisometropia on academic-related performance in children requires further investigation.

Socially inclusive learning in a community setting

People with mental health problems, learning difficulties and poor literacy and numeracy are at risk of social exclusion including homelessness. They are often disconnected from the Vocational Education and Training (VET) system, with few opportunities for education and employment. Academic research has demonstrated a link between literacy and numeracy and social inclusion, however, the pathways to enact this are not well understood. This report presents insights into how a community based adult literacy program in West End, Brisbane, was first established and has since evolved into a successful model of what we are calling ‘socially inclusive learning’. The research informing the report was conducted as a twelve-month study from April 2013 to April 2014 funded through a partnership involving Anglicare Southern Queensland, A Place to Belong and the School of Public Health and Social Work, Queensland University of Technology. The research was conducted by Greg Marston and Jeffrey Johnson- Abdelmalik. The aim of the study was to clarify the principles, practice and methodology of the Reading and Writing group (hereafter RAW) and identify the characteristics of RAW that support the social inclusion of the individual being provided literacy learning. The questions guiding the research included: • What are the key principles and practices of the RAW model? • How does the acquisition of literacy and numeracy skills contribute to the recovery of people with mental health and other issues? • How can the acquisition of literacy and numeracy skills support people’s social inclusion, including achieving employment and further education outcomes? A related aim of the project was to document how this community based literacy and numeracy program operates so that other organisations with an interest in addressing similar needs can learn from the model, particularly organisations that co-locate support and education and organisations that adopt a recovery approach when working with people with mental health challenges and intellectual and psychiatric disabilities. The report highlights the background to RAW, the learning philosophy of RAW, the profile of the participants in the program and the various roles and responsibilities and structure that supports the work of RAW. The report presents perspectives from the teachers, student participants and tutors on how the group is designed and the principles implemented.

Optimising ketocarotenoid production in potato tubers : effect of genetic background, transgene combinations and environment

Astaxanthin is a high value carotenoid produced by some bacteria, a few green algae, several fungi but only a limited number of plants from the genus Adonis. Astaxanthin has been industrially exploited as a feed supplement in poultry farming and aquaculture. Consumption of ketocarotenoids, most notably astaxanthin, is also increasingly associated with a wide range of health benefits,as demonstrated in numerous clinical studies. Currently astaxanthin is produced commercially by chemical synthesis or from algal production systems. Several studies have used a metabolic engineering approach to produce astaxanthin in transgenic plants. Previous attempts to produce transgenic potato tubers biofortified with astaxanthin have met with limited success. In this study we have investigated approaches to optimising tuber astaxanthin content. It is demonstrated that the selection of appropriate parental genotype for transgenic approaches and stacking carotenoid biosynthetic pathway genes with the cauliflower Or gene result in enhanced astaxanthin content, to give six-fold higher tuber astaxanthin content than has been achieved previously. Additionally we demonstrate the effects of growth environment on tuber carotenoid content in both wild type and astaxanthin-producing transgenic lines and describe the associated transcriptome and metabolome restructuring.

The scholarship of Jonathan Silin: a reading through the lens of sexuality

While Jonathan Silin's ideas have challenged early childhood educators to think seriously about the relationship between developmentalism and revisioning early education, they have done much more than this. They also challenge us to know who we are and how our identities might be enacted in our teacher-selves, whether in the classroom with young children, teacher education students or engaging professionally with teachers. In doing so he shows how to resist injustice and unmasks ways in which institutions function in society to marginalise and exclude.

Lecturing for non-law background students: Assessing the cognitive load of case and legislation-based lecturing approaches

Lecturing is a traditional method for teaching in discipline-based teaching environments and its success in legal discipline depends upon its alignment with learner backgrounds, learning objectives and the lecturing approaches utilised in the classes. In a situation where students do not have any prior knowledge of the given discipline that requires a particular lecturing approach, a mismatch in such an alignment would place learner knowledge acquisition into a challenging situation. From this perspective, this study tests the suitability of two dominant lecturing approaches—the case and the law-based lecturing approaches. It finds that a lecturer should put more emphasis on the case-based approach while lecturing to non-law background business students at the postgraduate level, provided that such an emphasis should be relative to the cognitive ability of the students and their motivation for learning law units.

Reading Australia Essay: "Romulus, My Father" by Raimond Gaita

This is an introductory essay about the memoir "Romulus, My Father" by Raimond Gaita. The essay was published as part of the Copyright Agency's "Reading Australia" initiative. "In a critical moment of reflection and pause, Romulus, My Father offers the reader a key to its interpretation. The author – philosopher Raimond Gaita – tells us that ‘Plato said that those who love and seek wisdom are clinging in recollection to things they once saw’. This reference to the Greek philosopher’s work Phaedrus occurs when the boy Raimond is about eight years old. He seems already to understand much about his father, in particular his father’s goodness, which he finds expressed in his workmanship, his honesty, and his commitment to friends. And yet, as Plato forewarns us, a search for the ultimate wisdom of such things must come later – several decades on, when Gaita is faced with the task of writing his father’s eulogy. It is then that a sense of his father’s character is joined to his own search for wisdom, a combination of biography and reflection that marks the memoir form at its best, and shapes the ultimate impact of Romulus, My Father...."--publisher website

Shared book reading by parents with young children: Evidence-based practice

There is considerable recognition that shared book reading helps develop young children's early reading and literacy skills. Home is an important context in which children first start to develop their early literacy skills. This paper reviews Australian and international literature of shared book-reading intervention pertaining to the effects of two different strategies (dialogic reading and print referencing) on young children's early literacy skills. Further, a brief summary of findings of a recent Australian study are presented that showed some significant effects of shared reading on children's early literacy skills. This research used a pragmatic RCT (randomised controlled trial) to investigate a combination of these two forms of shared book-reading home intervention with parents and their children enrolled in the Prep year of school in Queensland. The paper concludes with a discussion of the significance of the findings and implications for parents and teachers to use an evidence-based approach to help children develop early literacy skills.

An upstream open reading frame is essential for feedback regulation of ascorbate biosynthesis in arabidopsis

Ascorbate (vitamin C) is an essential antioxidant and enzyme cofactor in both plants and animals. Ascorbate concentration is tightly regulated in plants, partly to respond to stress. Here, we demonstrate that ascorbate concentrations are determined via the posttranscriptional repression of GDP-l-galactose phosphorylase (GGP), a major control enzyme in the ascorbate biosynthesis pathway. This regulation requires a cis-acting upstream open reading frame (uORF) that represses the translation of the downstream GGP open reading frame under high ascorbate concentration. Disruption of this uORF stops the ascorbate feedback regulation of translation and results in increased ascorbate concentrations in leaves. The uORF is predicted to initiate at a noncanonical codon (ACG rather than AUG) and encode a 60- to 65-residue peptide. Analysis of ribosome protection data from Arabidopsis thaliana showed colocation of high levels of ribosomes with both the uORF and the main coding sequence of GGP. Together, our data indicate that the noncanonical uORF is translated and encodes a peptide that functions in the ascorbate inhibition of translation. This posttranslational regulation of ascorbate is likely an ancient mechanism of control as the uORF is conserved in GGP genes from mosses to angiosperms.

Confirmatory factory analysis of the Neck Disability Index in a general problematic neck population indicates a one-factor model

BACKGROUND CONTEXT: The Neck Disability Index frequently is used to measure outcomes of the neck. The statistical rigor of the Neck Disability Index has been assessed with conflicting outcomes. To date, Confirmatory Factor Analysis of the Neck Disability Index has not been reported for a suitably large population study. Because the Neck Disability Index is not a condition-specific measure of neck function, initial Confirmatory Factor Analysis should consider problematic neck patients as a homogenous group. PURPOSE: We sought to analyze the factor structure of the Neck Disability Index through Confirmatory Factor Analysis in a symptomatic, homogeneous, neck population, with respect to pooled populations and gender subgroups. STUDY DESIGN: This was a secondary analysis of pooled data. PATIENT SAMPLE: A total of 1,278 symptomatic neck patients (67.5% female, median age 41 years), 803 nonspecific and 475 with whiplash-associated disorder. OUTCOME MEASURES: The Neck Disability Index was used to measure outcomes. METHODS: We analyzed pooled baseline data from six independent studies of patients with neck problems who completed Neck Disability Index questionnaires at baseline. The Confirmatory Factor Analysis was considered in three scenarios: the full sample and separate sexes. Models were compared empirically for best fit. RESULTS: Two-factor models have good psychometric properties across both the pooled and sex subgroups. However, according to these analyses, the one-factor solution is preferable from both a statistical perspective and parsimony. The two-factor model was close to significant for the male subgroup (p<.07) where questions separated into constructs of mental function (pain, reading headaches and concentration) and physical function (personal care, lifting, work, driving, sleep, and recreation). CONCLUSIONS: The Neck Disability Index demonstrated a one-factor structure when analyzed by Confirmatory Factor Analysis in a pooled, homogenous sample of neck problem patients. However, a two-factor model did approach significance for male subjects where questions separated into constructs of mental and physical function. Further investigations in different conditions, subgroup and sex-specific populations are warranted.