Integer programming for minimal perturbation problems in university course timetabling

In this paper we present a general integer programming-based approach for the minimal perturbation problem in university course timetabling. This problem arises when an existing timetable contains hard constraint violations, or infeasibilities, which need to be resolved. The objective is to resolve these infeasibilities while minimising the disruption or perturbation to the remainder of the timetable. This situation commonly occurs in practical timetabling, for example when there are unexpected changes to course enrolments or available rooms. Our method attempts to resolve each infeasibility in the smallest neighbourhood possible, by utilising the exactness of integer programming. Operating within a neighbourhood of minimal size keeps the computations fast, and does not permit large movements of course events, which cause widespread disruption to timetable structure. We demonstrate the application of this method using examples based on real data from the University of Auckland

Plans for a 10-m Submillimeter-wave Telescope at the South Pole

A 10 meter diameter submillimeter-wave telescope has been proposed for the NSF Amundsen-Scott South Pole Station. Current evidence indicates that the South Pole is the best submillimeter-wave telescope site among all existing or proposed ground-based observatories. Proposed scientific programs place stringent requirements on the optical quality of the telescope design. In particular, reduction of the thermal background and offsets requires an off-axis, unblocked aperture, and the large field of view needed for survey observations requires shaped optics. This mix of design elements is well-suited for large scale (square degree) mapping of line and continuum radiation from submillimeter-wave sources at moderate spatial resolutions (4 to 60 arcsecond beam size) and high sensitivity (milliJansky flux density levels). the telescope will make arcminute angular scale, high frequency Cosmic Microwave Background measurements from the best possible ground-based site, using an aperture which is larger than is currently possible on orbital or airborne platforms. Effective use of this telescope will require development of large (1000 element) arrays of submillimeter detectors which are background-limited when illuminated by antenna temperatures near 50 K.Comment: 12 pages, 3 figure

The Early Optical Afterglow of GRB 030418 and Progenitor Mass Loss

The ROTSE-IIIa telescope and the SSO 40 inch (1.0 m) telescope, both located at Siding Spring Observatory, imaged the early-time afterglow of GRB 030418. In this report, we present observations of the early afterglow, first detected by the ROTSE-IIIa telescope 211 s after the start of the burst and only 76 s after the end of the gamma-ray activity. We detect optical emission that rises for ∼600 s, slowly varies around R = 17.3 mag for ∼1400 s, and then fades as a power law of index α = -1.36. Additionally, the ROTSE-IIIb telescope, located at McDonald Observatory, imaged the early-time afterglow of GRB 030723. The behavior of this light curve was qualitatively similar to that of GRB 030418, but 2 mag dimmer. These two afterglows are dissimilar to other afterglows such as GRB 990123 and GRB 021211. We investigate whether or not the early afterglow can be attributed to a synchrotron break in a cooling synchrotron spectrum as it passes through the optical band, but we find that this model is unable to accurately describe the early light curve. We present a simple model for gamma-ray burst emission emerging from a wind medium surrounding a massive progenitor star. This model provides an effective description of the data and suggests that the rise of the afterglow can be ascribed to extinction in the local circumburst environment. In this interpretation, these events provide further evidence of the connection between gamma-ray bursts and the collapse of massive stars.This work has been supported by NASA grants NAG5- 5281 and F006794, NSF grants AST 01-19685 and 01-05221, the Australian Research Council, the University of New South Wales, and the University of Michigan. Work performed at LANL is supported by NASA SR&T through Department of Energy (DOE) contract W-7405-ENG-36 and through internal LDRD funding

Iron Incorporation and Post-Malaria Anaemia

BACKGROUND: Iron supplementation is employed to treat post-malarial anaemia in environments where iron deficiency is common. Malaria induces an intense inflammatory reaction that stalls reticulo-endothelial macrophagal iron recycling from haemolysed red blood cells and inhibits oral iron absorption, but the magnitude and duration of these effects are unclear. METHODOLOGY/PRINCIPAL FINDINGS: We examined the red blood cell incorporation of oral administered stable isotopes of iron and compared incorporation between age matched 18 to 36 months old children with either anaemia post-malaria (n = 37) or presumed iron deficiency anaemia alone (n = 36). All children were supplemented for 30 days with 2 mg/kg elemental iron as liquid iron sulphate and administered (57)Fe and (58)Fe on days 1 and 15 of supplementation respectively. (57)Fe and(58)Fe incorporation were significantly reduced (8% vs. 28%: p<0.001 and 14% vs. 26%: p = 0.045) in the malaria vs. non-malaria groups. There was a significantly greater haemoglobin response in the malaria group at both day 15 (p = 0.001) and 30 (p<0.000) with a regression analysis estimated greater change in haemoglobin of 7.2 g/l (s.e. 2.0) and 10.1 g/l (s.e. 2.5) respectively. CONCLUSION/SIGNIFICANCE: Post-malaria anaemia is associated with a better haemoglobin recovery despite a significant depressant effect on oral iron incorporation which may indicate that early erythropoetic iron need is met by iron recycling rather than oral iron. Supplemental iron administration is of questionable utility within 2 weeks of clinical malaria in children with mild or moderate anaemia

Georges Perec’s experimental fieldwork; Perecquian fieldwork

© 2016 Informa UK Limited, trading as Taylor & Francis GroupThis paper traces key themes in contemporary experimental fieldwork – explorations of ordinary places by artists, writers, activists, enthusiasts, students and researchers – to the works of Georges Perec. Preoccupations of this work – including playfulness, attention to the ordinary, and writing as a fieldwork practice – are all anticipated and elaborated in Perec’s oeuvre, where they converge around an ‘essayistic’ approach. Exhibiting these traits, some contemporary fieldwork is more convincingly Perecquian than psychogeographical or Situationist, despite the tendency to identify it with the latter. Through Perec, it is therefore possible to bring contemporary experimental fieldwork into focus, identifying a coherence and sense of project within it, while speaking to the question of what it means and could mean to conduct fieldwork experimentally. Particular attention is paid in this paper to Perec’s most accomplished and sustained field texts, both of which have been translated into English: An Attempt at Exhausting a Place in Paris (2010, from 1975 original in French) and Species of Spaces (1999/1974)

The Rapid ASKAP Continuum Survey I: Design and First Results

The Rapid ASKAP Continuum Survey (RACS) is the first large-area survey to be conducted with the full 36-antenna Australian Square Kilometre Array Pathfinder (ASKAP) telescope. RACS will provide a shallow model of the ASKAP sky that will aid the calibration of future deep ASKAP surveys. RACS will cover the whole sky visible from the ASKAP site in Western Australia, and will cover the full ASKAP band of $700-1800$ MHz. The RACS images are generally deeper than the existing NRAO VLA Sky Survey (NVSS) and Sydney University Molonglo Sky Survey (SUMSS) radio surveys and have better spatial resolution. All RACS survey products will be public, including radio images (with $\sim 15$ arcsecond resolution) and catalogues of about three million source components with spectral index and polarisation information. In this paper, we present a description of the RACS survey and the first data release of 903 images covering the sky south of declination $+41^\circ$ made over a 288 MHz band centred at 887.5 MHz.Comment: 24 pages, 17 figures, 4 tables. For associated data see https://data.csiro.au/collections/domain/casdaObservation/results/PRAS110%20-%20The%20Rapid%20ASKAP%20Continuu

Is bisexuality invisible? A review of sexualities scholarship 1970–2015

This article provides a review of sexualities scholarship within the social sciences between 1970 and 2015. It takes an innovative approach by focusing on the way in which bisexuality is addressed in this body of literature. The article reveals the marginalisation, under-representation and invisibility of bisexuality within and across the social sciences in relation to both bisexual experience and identity. Reasons for this varied across the different eras, including the heterosexist nature of the literature, the impact of gay and lesbian-focused identity politics, and queer deconstructionism. In addition, patterns of bisexual erasure and invisibility were uneven, with some scholarship taking inclusive approaches or criticising prejudice against bisexuality. The initial findings of the review were enriched by critical commentary from key relevant sociologists and political scientists. The article concludes that future sexualities scholarship could be enhanced by greater consideration of bisexuality

Nonsense Mediated Decay Resistant Mutations Are a Source of Expressed Mutant Proteins in Colon Cancer Cell Lines with Microsatellite Instability

BACKGROUND: Frameshift mutations in microsatellite instability high (MSI-High) colorectal cancers are a potential source of targetable neo-antigens. Many nonsense transcripts are subject to rapid degradation due to nonsense-mediated decay (NMD), but nonsense transcripts with a cMS in the last exon or near the last exon-exon junction have intrinsic resistance to nonsense-mediated decay (NMD). NMD-resistant transcripts are therefore a likely source of expressed mutant proteins in MSI-High tumours. METHODS: Using antibodies to the conserved N-termini of predicted mutant proteins, we analysed MSI-High colorectal cancer cell lines for examples of naturally expressed mutant proteins arising from frameshift mutations in coding microsatellites (cMS) by immunoprecipitation and Western Blot experiments. Detected mutant protein bands from NMD-resistant transcripts were further validated by gene-specific short-interfering RNA (siRNA) knockdown. A genome-wide search was performed to identify cMS-containing genes likely to generate NMD-resistant transcripts that could encode for antigenic expressed mutant proteins in MSI-High colon cancers. These genes were screened for cMS mutations in the MSI-High colon cancer cell lines. RESULTS: Mutant protein bands of expected molecular weight were detected in mutated MSI-High cell lines for NMD-resistant transcripts (CREBBP, EP300, TTK), but not NMD-sensitive transcripts (BAX, CASP5, MSH3). Expression of the mutant CREBBP and EP300 proteins was confirmed by siRNA knockdown. Five cMS-bearing genes identified from the genome-wide search and without existing mutation data (SFRS12IP1, MED8, ASXL1, FBXL3 and RGS12) were found to be mutated in at least 5 of 11 (45%) of the MSI-High cell lines tested. CONCLUSION: NMD-resistant transcripts can give rise to expressed mutant proteins in MSI-High colon cancer cells. If commonly expressed in primary MSI-High colon cancers, MSI-derived mutant proteins could be useful as cancer specific immunological targets in a vaccine targeting MSI-High colonic tumours

Virological failure and development of new resistance mutations according to CD4 count at combination antiretroviral therapy initiation

Objectives: No randomized controlled trials have yet reported an individual patient benefit of initiating combination antiretroviral therapy (cART) at CD4 counts > 350 cells/μL. It is hypothesized that earlier initiation of cART in asymptomatic and otherwise healthy individuals may lead to poorer adherence and subsequently higher rates of resistance development. Methods: In a large cohort of HIV-positive individuals, we investigated the emergence of new resistance mutations upon virological treatment failure according to the CD4 count at the initiation of cART. Results: Of 7918 included individuals, 6514 (82.3%), 996 (12.6%) and 408 (5.2%) started cART with a CD4 count ≤ 350, 351-499 and ≥ 500 cells/μL, respectively. Virological rebound occurred while on cART in 488 (7.5%), 46 (4.6%) and 30 (7.4%) with a baseline CD4 count ≤ 350, 351-499 and ≥ 500 cells/μL, respectively. Only four (13.0%) individuals with a baseline CD4 count > 350 cells/μL in receipt of a resistance test at viral load rebound were found to have developed new resistance mutations. This compared to 107 (41.2%) of those with virological failure who had initiated cART with a CD4 count < 350 cells/μL. Conclusions: We found no evidence of increased rates of resistance development when cART was initiated at CD4 counts above 350 cells/μL. HIV Medicin

2D versus 3D human induced pluripotent stem cell-derived cultures for neurodegenerative disease modelling

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS), affect millions of people every year and so far, there are no therapeutic cures available. Even though animal and histological models have been of great aid in understanding disease mechanisms and identifying possible therapeutic strategies, in order to find disease-modifying solutions there is still a critical need for systems that can provide more predictive and physiologically relevant results. One possible avenue is the development of patient-derived models, e.g. by reprogramming patient somatic cells into human induced pluripotent stem cells (hiPSCs), which can then be differentiated into any cell type for modelling. These systems contain key genetic information from the donors, and therefore have enormous potential as tools in the investigation of pathological mechanisms underlying disease phenotype, and progression, as well as in drug testing platforms. hiPSCs have been widely cultured in 2D systems, but in order to mimic human brain complexity, 3D models have been proposed as a more advanced alternative. This review will focus on the use of patient-derived hiPSCs to model AD, PD, HD and ALS. In brief, we will cover the available stem cells, types of 2D and 3D culture systems, existing models for neurodegenerative diseases, obstacles to model these diseases in vitro, and current perspectives in the field