A Purely Functional Computer Algebra System Embedded in Haskell

We demonstrate how methods in Functional Programming can be used to implement a computer algebra system. As a proof-of-concept, we present the computational-algebra package. It is a computer algebra system implemented as an embedded domain-specific language in Haskell, a purely functional programming language. Utilising methods in functional programming and prominent features of Haskell, this library achieves safety, composability, and correctness at the same time. To demonstrate the advantages of our approach, we have implemented advanced Gr\"{o}bner basis algorithms, such as Faug\`{e}re's $F_4$ and $F_5$, in a composable way.Comment: 16 pages, Accepted to CASC 201

Demonstration of the Zero-Crossing Phasemeter with a LISA Test-bed Interferometer

The Laser Interferometer Space Antenna (LISA) is being designed to detect and study in detail gravitational waves from sources throughout the Universe such as massive black hole binaries. The conceptual formulation of the LISA space-borne gravitational wave detector is now well developed. The interferometric measurements between the sciencecraft remain one of the most important technological and scientific design areas for the mission. Our work has concentrated on developing the interferometric technologies to create a LISA-like optical signal and to measure the phase of that signal using commercially available instruments. One of the most important goals of this research is to demonstrate the LISA phase timing and phase reconstruction for a LISA-like fringe signal, in the case of a high fringe rate and a low signal level. We present current results of a test-bed interferometer designed to produce an optical LISA-like fringe signal previously discussed in the literature.Comment: find minor corrections in the CQG versio

Bottom sediments of Lake Rotoma

Lake Rotoma is a deep (70-80 m), oligotrophic, warm monomictic lake of volcanic origin with insignificant stream inflow and no clearly defined outflow. For at least 60 years up to 1972 the lake level fluctuated markedly about an overall rising trend of some 6-10 m. Nearshore profiles are related to the prevailing wave climate superimposed upon the overall rising lake level, shelves being wider, less steep, and deeper about the more exposed eastern and southern shorelines. The outer portions of shelves extending well below modern storm wave base into waters as deep as 15-25 m are relict features from lower lake level stands. Sediments fine from sand-gravel mixtures nearshore to silts in basinal areas. Their composition reflects a composite provenance involving the lavas and tephras about the lake, as well as intralake diatom frustules and organic matter. The distribution pattern of surficial bottom sediments is an interplay between grains of both biological and terrigenous origin, supplied presently and in the past by a variety of processes, that have been dispersed either by the modern hydrodynamic regime or by former ones associated with lower lake levels. These interrelationships are structured by erecting 5 process-age sediment classes in the lake, namely neoteric, amphoteric, proteric, palimpsest, and relict sediments, analogous to categories postulated for sediments on oceanic continental shelves. Short-core stratigraphy includes the Kaharoa (A.D. -1020) and Tarawera (A.D. 1886) tephras. The rates of sedimentation of diatomaceous silts in basinal areas have more than doubled since the Tarawera eruption, indicating an overall increase in the fertility level of lake waters associated, perhaps, with recent farm development in the catchment

Genetic testing of children for adult-onset conditions: opinions of the British adult population and implications for clinical practice

This study set out to explore the attitudes of a representative sample of the British public towards genetic testing in children to predict disease in the future. We sought opinions about genetic testing for adult-onset conditions for which no prevention/treatment is available during childhood, and about genetic 'carrier' status to assess future reproductive risks. The study also examined participants' level of agreement with the reasons professional organisations give in favour of deferring such testing. Participants (n=2998) completed a specially designed questionnaire, distributed by email. Nearly half of the sample (47%) agreed that parents should be able to test their child for adult-onset conditions, even if there is no treatment or prevention at time of testing. This runs contrary to professional guidance about genetic testing in children. Testing for carrier status was supported by a larger proportion (60%). A child's future ability to decide for her/himself if and when to be tested was the least supported argument in favour of deferring testing.European Journal of Human Genetics advance online publication, 5 November 2014; doi:10.1038/ejhg.2014.221

Pseudomonas Aeruginosa-Induced Bleb-Niche Formation in Epithelial Cells Is Independent of Actinomyosin Contraction and Enhanced by Loss of Cystic Fibrosis Transmembrane-Conductance Regulator Osmoregulatory Function

The opportunistic pathogen Pseudomonas aeruginosa can infect almost any site in the body but most often targets epithelial cell-lined tissues such as the airways, skin, and the cornea of the eye. A common predisposing factor is cystic fibrosis (CF), caused by defects in the cystic fibrosis transmembrane-conductance regulator (CFTR). Previously, we showed that when P. aeruginosa enters epithelial cells it replicates intracellularly and occupies plasma membrane blebs. This phenotype is dependent on the type 3 secretion system (T3SS) effector ExoS, shown by others to induce host cell apoptosis. Here, we examined mechanisms for P. aeruginosa-induced bleb formation, focusing on its relationship to apoptosis and the CFTR. The data showed that P. aeruginosa-induced blebbing in epithelial cells is independent of actin contraction and is inhibited by hyperosmotic media (400 to 600 mOsM), distinguishing bacterially induced blebs from apoptotic blebs. Cells with defective CFTR displayed enhanced bleb formation upon infection, as demonstrated using bronchial epithelial cells from a patient with cystic fibrosis and a CFTR inhibitor, CFTR(Inh)-172. The defect was found to be correctable either by incubation in hyperosmotic media or by complementation with CFTR (pGFP-CFTR), suggesting that the osmoregulatory function of CFTR counters P. aeruginosa-induced bleb-niche formation. Accordingly, and despite their reduced capacity for bacterial internalization, CFTR-deficient cells showed greater bacterial occupation of blebs and enhanced intracellular replication. Together, these data suggest that P. aeruginosa bleb niches are distinct from apoptotic blebs, are driven by osmotic forces countered by CFTR, and could provide a novel mechanism for bacterial persistence in the host. IMPORTANCE: Pseudomonas aeruginosa is an opportunistic pathogen problematic in hospitalized patients and those with cystic fibrosis (CF). Previously, we showed that P. aeruginosa can enter epithelial cells and replicate within them and traffics to the membrane blebs that it induces. This “bleb-niche” formation requires ExoS, previously shown to cause apoptosis. Here, we show that the driving force for bleb-niche formation is osmotic pressure, differentiating P. aeruginosa-induced blebs from apoptotic blebs. Either CFTR inhibition or CFTR mutation (as seen in people with CF) causes P. aeruginosa to make more bleb niches and provides an osmotic driving force for blebbing. CFTR inhibition also enhances bacterial occupation of blebs and intracellular replication. Since CFTR is targeted for removal from the plasma membrane when P. aeruginosa invades a healthy cell, these findings could relate to pathogenesis in both CF and healthy patient populations

Pioneering the human development revolution: Analysing the trajectory of Mahbub ul Haq

Mahbub ul Haq's work to coordinate, establish and propagate the human development approach offers an example of effective leadership in promoting more ethical socio-economic development. This article reviews Pioneering the Human Development Revolution-An Intellectual Biography of Mahbub ul Haq (edited by Haq and Ponzio), and extends themes from the United Nations Intellectual History Project to examine Haq's contributions in terms of four aspects of leadership: articulating and applying values that combine depth with broad appeal; providing a fruitful and vivid way of seeing, a 'vision', that reflects the values; embodying the values and vision in workable practical proposals; and supporting and communicating the previous aspects through wide and relevant networks. It suggests that the human development approach may need to update its values and vision, including through better integration of human security thinking, if it is to retain the leadership role it acquired thanks to Haq

Rapid cognitive decline, one-year institutional admission and one-year mortality: Analysis of the ability to predict and inter-tool agreement of four validated clinical frailty indexes in the safes cohort

Objectives: To evaluate the predictive ability of four clinical frailty indexes as regards one-year rapid cognitive decline (RCD — defined as the loss of at least 3 points on the MMSE score), and one-year institutional admission (IA) and mortality respectively; and to measure their agreement for identifying groups at risk of these severe outcomes. Design: One-year follow-up and multicentre study of old patients participating in the SAFEs cohort study. Setting: Nine university hospitals in France. Participants: 1,306 patients aged 75 or older (mean age 85±6 years; 65% female) hospitalized in medical divisions through an Emergency department. Measurements: Four frailty indexes (Winograd; Rockwood; Donini; and Schoevaerdts) reflecting the multidimensionality of the frailty concept, using an ordinal scoring system able to discriminate different grades of frailty, and constructed based on the accumulation of identified deficits after comprehensive geriatric assessment conducted during the first week of hospital stay, were used to categorize participants into three different grades of frailty: Gl — not frail; G2 — moderately frail; and G3 — severely frail. Comparisons between groups were performed using Fisher's exact test. Agreement between indexes was evaluated using Cohen's Kappa coefficient. Results: All patients were classified as frail by at least one of the four indexes. The Winograd and Rockwood indexes mainly classified subjects as G2 (85% and 96%), and the Donini and Schoevaerdts indexes mainly as G3 (71% and 67%). Among the SAFEs cohort population, 250, 1047 and 1,306 subjects were eligible for analyses of predictability for RCD, 1-year IA and 1-year mortality respectively. At 1 year, 84 subjects (34%) experienced RCD, 377 (36%) were admitted into an institutional setting, and 445 (34%) had died With the Rockwood index, all subjects who expenenced RCD were classified in G2; and in G2 and G3 when the Donini and Schoevaerdts indexes were used No significant difference was found between frailty grade and RCD, whereas frailty grade was significantly associated with an increased risk of IA and death, whatever the frailty index considered. Agreement between the different indexes of frailty was poor with Kappa coefficients ranging from −0.02 to 0.15. Conclusion: These findings confirm the poor clinimetric properties of these current indexes to measure frailty, underlining the fact that further work is needed to develop a better and more widely-accepted definition of frailty and therefore a better understanding of its pathophysiolog