On Teaching Discrete Mathematics to Freshman Computer Science Students

Discrete Mathematics is an inevitable part of any undergraduate computer science degree programme. However, today's computer science student typically finds this to be at best a necessary evil with which they struggle to engage. Twenty years ago, we started to address this issue seriously in our university, and we have instituted a number of innovations throughout the years which have had a positive effect on engagement and, thus, attainment. In this paper, we describe and motivate the innovations which we introduced, and provide a detailed analysis of how and why engagement and attainment levels varied over two decades as a direct result of these innovation

Markov model and markers of small cell lung cancer: assessing the influence of reversible serum NSE, CYFRA 21-1 and TPS levels on prognosis

High serum NSE and advanced tumour stage are well-known negative prognostic determinants of small cell lung cancer (SCLC) when observed at presentation. However, such variables are reversible disease indicators as they can change during the course of therapy. The relationship between risk of death and marker level and disease state during treatment of SCLC chemotherapy is not known. A total of 52 patients with SCLC were followed during cisplatin-based chemotherapy (the median number of tumour status and marker level assessments was 4). The time-homogeneous Markov model was used in order to analyse separately the prognostic significance of change in the state of the serum marker level (NSE, CYFRA 21-1, TPS) or the change in tumour status. In this model, transition rate intensities were analysed according to three different states: alive with low marker level (state 0), alive with high marker level (state 1) and dead (absorbing state). The model analysing NSE levels showed that the mean time to move out of state ‘high marker level’ was short (123 days). There was a 44% probability of the opposite reversible state ‘low marker level’ being reached, which demonstrated the reversible property of the state ‘high marker level’. The relative risk of death from this state ‘high marker level’ was about 2.24 times greater in comparison with that of state 0 ‘low marker level’ (Wald's test; P < 0.01). For patients in state ‘high marker level’ at time of sampling, the probability of death increased dramatically, a transition explaining the rapid decrease in the probability of remaining stationary at this state. However, a non-nil probability to change from state 1 ‘high marker level’ to the opposite transient level, state 0 ‘low marker level’, was observed suggesting that, however infrequently, patients in state 1 ‘high marker level’ might still return to state 0 ‘low marker level’. Almost similar conclusions can be drawn regarding the three-state model constructed using the tumour response status. For the two cytokeratin markers, the Markov model suggests the lack of a true reversible property of these variables as there was only a very weak probability of a patient returning to state ‘low marker level’ once having entered state ‘high marker level’. In conclusion, The Markov model suggests that the observation of an increase in serum NSE level or a lack of response of the disease at any time during follow-up (according to the homogeneous assumption) was strongly associated with a worse prognosis but that the reversion to a low mortality risk state remains possible. © 1999 Cancer Research Campaig

An antibody that prevents serpin polymerisation acts by inducing a novel allosteric behaviour.

Serpins are important regulators of proteolytic pathways with an anti-protease activity that involves a conformational transition from a metastable to a hyperstable state. Certain mutations permit the transition to occur in the absence of a protease; when associated with an inter-molecular interaction, this yields linear polymers of hyperstable serpin molecules, which accumulate at the site of synthesis. This is the basis of a number of pathologies termed the serpinopathies. We have previously identified a monoclonal antibody (mAb4B12) that, in single-chain form, blocks α1-antitrypsin (α1-AT) polymerisation in cells. Here we describe the structural basis for this activity. The mAb4B12 epitope was found to encompass residues Glu32, Glu39, and His43 on helix A and Leu306 on helix I. This is not a region typically associated with the serpin mechanism of conformational change, and correspondingly the epitope was present in all tested structural forms of the protein. Antibody binding rendered β-sheet A - on the opposite face of the molecule - more liable to adopt an 'open' state, mediated by changes distal to the breach region and proximal to helix F. The allosteric propagation of induced changes through the molecule was evidenced by an increased rate of peptide incorporation and destabilisation of pre-formed serpin-enzyme complex following mAb4B12 binding. These data suggest that prematurely shifting the β-sheet A equilibrium towards the 'open' state out of sequence with other changes suppresses polymer formation. This work identifies a region potentially exploitable for rational design of ligands that is able to dynamically influence α1-AT polymerisation

Acute scrotum as a complication of Thiersch operation for rectal prolapse in a child

BACKGROUND: We report a case of acute scrotal condition that presented in a four year old male child one year after being treated for an idiopathic rectal prolapse utilizing Thiersch wire. CASE PRESENTATION: The acute scrotum had resulted from spreading perianal infection due to erosion of the circlage wire. The condition was treated with antibiotics and removal of the wire. The child made an uneventful recovery. CONCLUSION: This case highlights that patients with Thiersch wire should be followed until the wire is removed. Awareness of anal lesions as a cause of acute scrotal conditions, and history and physical examination are emphasized

The evolution of postpollination reproductive isolation in Costus

Reproductive isolation is critical to the diversification of species. Postpollination barriers may be important in limiting gene flow between closely related species, but they are relatively cryptic and their evolution is poorly understood. Here, we review the role of postpollination reproductive isolation in plants, including the various stages at which it operates and the hypotheses for how it may evolve. We then review empirical studies in the plant genus Costus, evaluating documented postpollination barriers in light of these hypotheses. We summarize isolation due to parental style length differences and present evidence supporting the hypothesis that the differences are in part a by-product of selection on floral morphology. Additionally, we show that reduced pollen adhesion, germination, and tube growth contribute to reproductive isolation between two closely related sympatric species of Costus. Geographic variation in the strength of these crossing barriers supports the hypothesis that they evolved under reinforcement, or direct natural selection to strengthen isolation

Recommendations for exercise adherence measures in musculoskeletal settings : a systematic review and consensus meeting (protocol)

Background: Exercise programmes are frequently advocated for the management of musculoskeletal disorders; however, adherence is an important pre-requisite for their success. The assessment of exercise adherence requires the use of relevant and appropriate measures, but guidance for appropriate assessment does not exist. This research will identify and evaluate the quality and acceptability of all measures used to assess exercise adherence within a musculoskeletal setting, seeking to reach consensus for the most relevant and appropriate measures for application in research and/or clinical practice settings. Methods/design: There are two key stages to the proposed research. First, a systematic review of the quality and acceptability of measures used to assess exercise adherence in musculoskeletal disorders; second, a consensus meeting. The systematic review will be conducted in two phases and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to ensure a robust methodology. Phase one will identify all measures that have been used to assess exercise adherence in a musculoskeletal setting. Phase two will seek to identify published and unpublished evidence of the measurement and practical properties of identified measures. Study quality will be assessed against the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) guidelines. A shortlist of best quality measures will be produced for consideration during stage two: a meeting of relevant stakeholders in the United Kingdom during which consensus on the most relevant and appropriate measures of exercise adherence for application in research and/or clinical practice settings will be sought. Discussion: This study will benefit clinicians who seek to evaluate patients’ levels of exercise adherence and those intending to undertake research, service evaluation, or audit relating to exercise adherence in the musculoskeletal field. The findings will impact upon new research studies which aim to understand the factors that predict adherence with exercise and which test different adherence-enhancing interventions. PROSPERO reference: CRD4201300621

Complete Primate Skeleton from the Middle Eocene of Messel in Germany: Morphology and Paleobiology

The best European locality for complete Eocene mammal skeletons is Grube Messel, near Darmstadt, Germany. Although the site was surrounded by a para-tropical rain forest in the Eocene, primates are remarkably rare there, and only eight fragmentary specimens were known until now. Messel has now yielded a full primate skeleton. The specimen has an unusual history: it was privately collected and sold in two parts, with only the lesser part previously known. The second part, which has just come to light, shows the skeleton to be the most complete primate known in the fossil record.We describe the morphology and investigate the paleobiology of the skeleton. The specimen is described as Darwinius masillae n.gen. n.sp. belonging to the Cercamoniinae. Because the skeleton is lightly crushed and bones cannot be handled individually, imaging studies are of particular importance. Skull radiography shows a host of teeth developing within the juvenile face. Investigation of growth and proportion suggest that the individual was a weaned and independent-feeding female that died in her first year of life, and might have attained a body weight of 650-900 g had she lived to adulthood. She was an agile, nail-bearing, generalized arboreal quadruped living above the floor of the Messel rain forest.Darwinius masillae represents the most complete fossil primate ever found, including both skeleton, soft body outline and contents of the digestive tract. Study of all these features allows a fairly complete reconstruction of life history, locomotion, and diet. Any future study of Eocene-Oligocene primates should benefit from information preserved in the Darwinius holotype. Of particular importance to phylogenetic studies, the absence of a toilet claw and a toothcomb demonstrates that Darwinius masillae is not simply a fossil lemur, but part of a larger group of primates, Adapoidea, representative of the early haplorhine diversification

Impact of Space Weather on Climate and Habitability of Terrestrial Type Exoplanets

The current progress in the detection of terrestrial type exoplanets has opened a new avenue in the characterization of exoplanetary atmospheres and in the search for biosignatures of life with the upcoming ground-based and space missions. To specify the conditions favorable for the origin, development and sustainment of life as we know it in other worlds, we need to understand the nature of astrospheric, atmospheric and surface environments of exoplanets in habitable zones around G-K-M dwarfs including our young Sun. Global environment is formed by propagated disturbances from the planet-hosting stars in the form of stellar flares, coronal mass ejections, energetic particles, and winds collectively known as astrospheric space weather. Its characterization will help in understanding how an exoplanetary ecosystem interacts with its host star, as well as in the specification of the physical, chemical and biochemical conditions that can create favorable and/or detrimental conditions for planetary climate and habitability along with evolution of planetary internal dynamics over geological timescales. A key linkage of (astro) physical, chemical, and geological processes can only be understood in the framework of interdisciplinary studies with the incorporation of progress in heliophysics, astrophysics, planetary and Earth sciences. The assessment of the impacts of host stars on the climate and habitability of terrestrial (exo)planets will significantly expand the current definition of the habitable zone to the biogenic zone and provide new observational strategies for searching for signatures of life. The major goal of this paper is to describe and discuss the current status and recent progress in this interdisciplinary field and to provide a new roadmap for the future development of the emerging field of exoplanetary science and astrobiology.Comment: 206 pages, 24 figures, 1 table; Review paper. International Journal of Astrobiology (2019

Effects of Thyroxine Exposure on Osteogenesis in Mouse Calvarial Pre-Osteoblasts

The incidence of craniosynostosis is one in every 1,800-2500 births. The gene-environment model proposes that if a genetic predisposition is coupled with environmental exposures, the effects can be multiplicative resulting in severely abnormal phenotypes. At present, very little is known about the role of gene-environment interactions in modulating craniosynostosis phenotypes, but prior evidence suggests a role for endocrine factors. Here we provide a report of the effects of thyroid hormone exposure on murine calvaria cells. Murine derived calvaria cells were exposed to critical doses of pharmaceutical thyroxine and analyzed after 3 and 7 days of treatment. Endpoint assays were designed to determine the effects of the hormone exposure on markers of osteogenesis and included, proliferation assay, quantitative ALP activity assay, targeted qPCR for mRNA expression of Runx2, Alp, Ocn, and Twist1, genechip array for 28,853 targets, and targeted osteogenic microarray with qPCR confirmations. Exposure to thyroxine stimulated the cells to express ALP in a dose dependent manner. There were no patterns of difference observed for proliferation. Targeted RNA expression data confirmed expression increases for Alp and Ocn at 7 days in culture. The genechip array suggests substantive expression differences for 46 gene targets and the targeted osteogenesis microarray indicated 23 targets with substantive differences. 11 gene targets were chosen for qPCR confirmation because of their known association with bone or craniosynostosis (Col2a1, Dmp1, Fgf1, 2, Igf1, Mmp9, Phex, Tnf, Htra1, Por, and Dcn). We confirmed substantive increases in mRNA for Phex, FGF1, 2, Tnf, Dmp1, Htra1, Por, Igf1 and Mmp9, and substantive decreases for Dcn. It appears thyroid hormone may exert its effects through increasing osteogenesis. Targets isolated suggest a possible interaction for those gene products associated with calvarial suture growth and homeostasis as well as craniosynostosis. © 2013 Cray et al