Investigating the effects of particle shape on normal compression and overconsolidation using DEM

Discrete element modelling of normal compression has been simulated on a sample of breakable two-ball clumps and compared to that of spheres. In both cases the size effect on strength is assumed to be that of real silica sand. The slopes of the normal compression lines are compared and found to be consistent with the proposed equation of the normal compression line. The values of the coefficient of earth pressure at rest K0,nc are also compared and related to the critical state fiction angles for the two materials. The breakable samples have then been unloaded to establish the stress ratios on unloading. At low overconsolidation ratios the values of K0 follow a well-established empirical relationship and realistic Poisson ratios are observed. On progressive unloading both samples head towards passive failure, and the values of the critical state lines in extension in q–p' space are found to be consistent with the critical state angles deduced from the values of K0 during normal compression. The paper highlights the important role of particle shape in governing the stress ratio during both normal compression and subsequent overconsolidation

Notes on Ipomoea L. (Convolvulaceae) in Cuba and neighbouring islands with a checklist of species found in Cuba

An updated checklist of species of Ipomoea L. found in Cuba is presented with analysis of the different elements represented. I. alterniflora Griseb. is defined broadly to include I. obtusata Griseb. and I. excisa Urb. and its differences from the little-known I. cubensis (House) Urb. are discussed. I. calophylla C. Wright ex Griseb. is reinstated as the correct name for the species generally known as I. lacteola House. I. praecox C. Wright is recognised as a distinct species from I. argentifolia A. Rich. and images are provided to help distinguish the two species. I. flavopurpurea Urb. and I. dajabonensis Alain are shown to be conspecific with I. longeramosa Choisy, whose disjunct distribution is mapped and discussed. The little-known I. montecristina Hadač is described and illustrated and the cited collections show it to be locally common in the Guantánamo region. I. microdonta J. R. I. Wood and Scotland is described as new from Camagüey in central Cuba. Eight species endemic to Cuba collected by Ekman and described by Urban in 1924 – 25 are evaluated but only two, I. balioclada Urb. and I. erosa Urb., are deemed to warrant recognition as distinct endemic species. The origin and typification of I. horsfalliae Hook. are discussed and an epitype designated. Cultivated plants named I. horsfalliae occur in many tropical countries including Cuba but their extreme variation suggests hybrid origin. Four species from Jamaica, I. rubella House, I. lineolata Urb., I. carmesina Proctor and the Jamaican plant called I. horsfalliae are treated as synonyms of a variable I. lineolata, which is endemic to the island. I. saxicola Proctor is treated as var. saxicola J. R. I. Wood and Scotland of I. ternata Jacq. I. cyanantha Griseb. is treated as a synonym of I. lindenii M. Martens and Galeotti. Lectotypes are designated for I. cyanantha, I. lindenii, I. praecox, I. punctata C. Wright, I. geranioides Meisn. and I. grisebachii Urb

Three-dimensional simulation for fast forward flight of a calliope hummingbird

We present a computational study of flapping-wing aerodynamics of a calliope hummingbird (Selasphorus calliope) during fast forward flight. Three-dimensional wing kinematics were incorporated into the model by extracting time-dependent wing position from high-speed videos of the bird flying in a wind tunnel at 8.3 m s−1. The advance ratio, i.e. the ratio between flight speed and average wingtip speed, is around one. An immersed-boundary method was used to simulate flow around the wings and bird body. The result shows that both downstroke and upstroke in a wingbeat cycle produce significant thrust for the bird to overcome drag on the body, and such thrust production comes at price of negative lift induced during upstroke. This feature might be shared with bats, while being distinct from insects and other birds, including closely related swifts

Search algorithms as a framework for the optimization of drug combinations

Combination therapies are often needed for effective clinical outcomes in the management of complex diseases, but presently they are generally based on empirical clinical experience. Here we suggest a novel application of search algorithms, originally developed for digital communication, modified to optimize combinations of therapeutic interventions. In biological experiments measuring the restoration of the decline with age in heart function and exercise capacity in Drosophila melanogaster, we found that search algorithms correctly identified optimal combinations of four drugs with only one third of the tests performed in a fully factorial search. In experiments identifying combinations of three doses of up to six drugs for selective killing of human cancer cells, search algorithms resulted in a highly significant enrichment of selective combinations compared with random searches. In simulations using a network model of cell death, we found that the search algorithms identified the optimal combinations of 6-9 interventions in 80-90% of tests, compared with 15-30% for an equivalent random search. These findings suggest that modified search algorithms from information theory have the potential to enhance the discovery of novel therapeutic drug combinations. This report also helps to frame a biomedical problem that will benefit from an interdisciplinary effort and suggests a general strategy for its solution.Comment: 36 pages, 10 figures, revised versio

Learning to mark: a qualitative study of the experiences and concerns of medical markers

BACKGROUND: Although there is published research on the methods markers use in marking various types of assessment, there is relatively little information on the processes markers use in approaching a marking exercise. This qualitative paper describes the preparation and experiences of general practice (GP) teachers who undertake marking a written assessment in an undergraduate medical course. METHODS: Semi-structured interviews were conducted with seven of the 16 GP tutors on an undergraduate course. The purposive sample comprised two new markers, two who had marked for a couple of years and three experienced markers. Each respondent was interviewed twice, once following a formative assessment of a written case study, and again after a summative assessment. All interviews were audio-taped and analysed for emerging themes. A respondent validation exercise was conducted with all 16 GP tutors. RESULTS: Markers had internal concerns about their ability to mark fairly and made considerable efforts to calibrate their marking. They needed guidance and coaching when marking for the first time and adopted a variety of marking styles, reaching a decision through a number of routes. Dealing with pass/fail borderline scripts and the consequences of the mark on the student were particular concerns. Even experienced markers felt the need to calibrate their marks both internally and externally CONCLUSION: Previous experience of marking appears to improve markers' confidence and is a factor in determining the role which markers adopt. Confidence can be improved by giving clear instructions, along with examples of marking. The authors propose that one method of providing this support and coaching could be by a process of peer review of a selection of papers prior to the main marking. New markers in particular would benefit from further guidance, however they are influenced by others early on in their marking career and course organisers should be mindful of this when arranging double marking

Expression and function of proton-sensing G-protein-coupled receptors in inflammatory pain

<p>Abstract</p> <p>Background</p> <p>Chronic inflammatory pain, when not effectively treated, is a costly health problem and has a harmful effect on all aspects of health-related quality of life. Despite the availability of pharmacologic treatments, chronic inflammatory pain remains inadequately treated. Understanding the nociceptive signaling pathways of such pain is therefore important in developing long-acting treatments with limited side effects. High local proton concentrations (tissue acidosis) causing direct excitation or modulation of nociceptive sensory neurons by proton-sensing receptors are responsible for pain in some inflammatory pain conditions. We previously found that all four proton-sensing G-protein-coupled receptors (GPCRs) are expressed in pain-relevant loci (dorsal root ganglia, DRG), which suggests their possible involvement in nociception, but their functions in pain remain unclear.</p> <p>Results</p> <p>In this study, we first demonstrated differential change in expression of proton-sensing GPCRs in peripheral inflammation induced by the inflammatory agents capsaicin, carrageenan, and complete Freund's adjuvant (CFA). In particular, the expression of TDAG8, one proton-sensing GPCR, was increased 24 hours after CFA injection because of increased number of DRG neurons expressing TDAG8. The number of DRG neurons expressing both TDAG8 and transient receptor potential vanilloid 1 (TRPV1) was increased as well. Further studies revealed that TDAG8 activation sensitized the TRPV1 response to capsaicin, suggesting that TDAG8 could be involved in CFA-induced chronic inflammatory pain through regulation of TRPV1 function.</p> <p>Conclusion</p> <p>Each subtype of the OGR1 family was expressed differently, which may reflect differences between models in duration and magnitude of hyperalgesia. Given that TDAG8 and TRPV1 expression increased after CFA-induced inflammation and that TDAG8 activation can lead to TRPV1 sensitization, it suggests that high concentrations of protons after inflammation may not only directly activate proton-sensing ion channels (such as TRPV1) to cause pain but also act on proton-sensing GPCRs to regulate the development of hyperalgesia.</p

Regulation of a rat VL30 element in human breast cancer cells in hypoxia and anoxia: role of HIF-1

Novel approaches to cancer gene therapy currently exploit tumour hypoxia to achieve transcriptional targeting using oxygen-regulated enhancer elements called hypoxia response elements. The activity of such elements in hypoxic cells is directly dependent on upregulation of the hypoxia-inducible transcription factor-1 However tumours also contain areas of anoxia, which may be considered a more tumour-selective transcriptional stimulus than hypoxia for targeting gene therapy to tumours. Another element, from the rat virus-like retrotransposon, VL30 (termed the ‘secondary anoxia response element’) has been reported to be more highly inducible in rat fibroblasts under anoxia than hypoxia. To investigate anoxia as a potential transcriptional target in human tumours, we have examined secondary anoxia response element inducibility in two human breast cancer cell lines, MCF-7 and T47D, under anoxia, hypoxia and normoxia. In both cell types, the trimerised secondary anoxia response element showed greater inducibility in anoxia than hypoxia (1% and 0.5% O2). The anoxic response of the secondary anoxia response element was shown to be dependent on hypoxia-inducible transcription factor-1 and the presence of a hypoxia-inducible transcription binding site consensus (5′-ACGTG-3′). Mutational analysis demonstrated that the base immediately 5′ to this modulates the anoxic/hypoxic induction of the secondary anoxia response element, such that TACGTG>GACGTG>>CACGTG. A similar correlation was found for erythropoietin, phosphoglycerate kinase 1, and aldolase hypoxia response elements, which contain these respective 5′ flanking bases