111 resultados para INSTRUMENTED SHARP INDENTATION
Resumo:
We consider four-dimensional variational data assimilation (4DVar) and show that it can be interpreted as Tikhonov or L2-regularisation, a widely used method for solving ill-posed inverse problems. It is known from image restoration and geophysical problems that an alternative regularisation, namely L1-norm regularisation, recovers sharp edges better than L2-norm regularisation. We apply this idea to 4DVar for problems where shocks and model error are present and give two examples which show that L1-norm regularisation performs much better than the standard L2-norm regularisation in 4DVar.
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The development of architecture and the settlement is central to discussions concerning the Neolithic transformation asthe very visible evidence for the changes in society that run parallel to the domestication of plants and animals. Architecture hasbeen used as an important aspect of models of how the transformation occurred, and as evidence for the sharp difference betweenhunter-gatherer and farming societies. We suggest that the emerging evidence for considerable architectural complexity from theearly Neolithic indicates that some of our interpretations depend too much on a very basic understanding of structures which arenormally seen as being primarily for residential purposes and containing households, which become the organising principle for thenew communities which are often seen as fully sedentary and described as villages. Recent work in southern Jordan suggests that inthis region at least there is little evidence for a standard house, and that structures are constructed for a range of diverse primary purposes other than simple domestic shelters.
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Salmonella is the second most commonly reported human foodborne pathogen in England and Wales, and antimicrobial-resistant strains of Salmonella are an increasing problem in both human and veterinary medicine. In this work we used a generalized linear spatial model to estimate the spatial and temporal patterns of antimicrobial resistance in Salmonella Typhimurium in England and Wales. Of the antimicrobials considered we found a common peak in the probability that an S. Typhimurium incident will show resistance to a given antimicrobial in late spring and in mid to late autumn; however, for one of the antimicrobials (streptomycin) there was a sharp drop, over the last 18 months of the period of investigation, in the probability of resistance. We also found a higher probability of resistance in North Wales which is consistent across the antimicrobials considered. This information contributes to our understanding of the epidemiology of antimicrobial resistance in Salmonella.
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This paper explores the changing survival patterns of cereal crop variety innovations in the UK since the introduction of plant breeders’ rights in the mid-1960s. Using non-parametric, semi-parametric and parametric approaches, we examine the determinants of the survival of wheat variety innovations, focusing on the impacts of changes to Plant Variety Protection (PVP) regime over the last four decades. We find that the period since the introduction of the PVP regime has been characterised by the accelerated development of new varieties and increased private sector participation in the breeding of cereal crop varieties. However, the increased flow of varieties has been accompanied by a sharp decline in the longevity of innovations. These trends may have contributed to a reduction in the returns appropriated by plant breeders from protected variety innovations and may explain the decline of conventional plant breeding in the UK. It may also explain the persistent demand from the seed industry for stronger protection. The strengthening of the PVP regime in conformity with the UPOV Convention of 1991, the introduction of EU-wide protection through the Community Plant Variety Office and the introduction of royalties on farm-saved seed have had a positive effect on the longevity of protected variety innovations, but have not been adequate to offset the long term decline in survival durations.
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In order to fabricate a biomimetic skin for an octopus inspired robot, a new process was developed based on mechanical properties measured from real octopus skin. Various knitted nylon textiles were tested and the one of 10-denier nylon was chosen as reinforcement. A combination of Ecoflex 0030 and 0010 silicone rubbers was used as matrix of the composite to obtain the right stiffness for the skin-analogue system. The open mould fabrication process developed allows air bubble to escape easily and the artificial skin produced was thin and waterproof. Material properties of the biomimetic skin were characterised using static tensile and instrumented scissors cutting tests. The Young’s moduli of the artificial skin are 0.08 MPa and 0.13 MPa in the longitudinal and transverse directions, which are much lower than those of the octopus skin. The strength and fracture toughness of the artificial skin, on the other hand are higher than those of real octopus skins. Conically-shaped skin prototypes to be used to cover the robotic arm unit were manufactured and tested. The biomimetic skin prototype was stiff enough to maintain it conical shape when filled with water. The driving force for elongation was reduced significantly compared with previous prototypes.
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The administration of antisense oligonucleotides (AOs) to skip one or more exons in mutated forms of the DMD gene and so restore the reading frame of the transcript is one of the most promising approaches to treat Duchenne muscular dystrophy (DMD). At present, preclinical studies demonstrating the efficacy and safety of long-term AO administration have not been conducted. Furthermore, it is essential to determine the minimal effective dose and frequency of administration. In this study, two different low doses (LDs) of phosphorodiamidate morpholino oligomer (PMO) designed to skip the mutated exon 23 in the mdx dystrophic mouse were administered for up to 12 months. Mice treated for 50 weeks showed a substantial dose-related amelioration of the pathology, particularly in the diaphragm. Moreover, the generalized physical activity was profoundly enhanced compared to untreated mdx mice showing that widespread, albeit partial, dystrophin expression restores the normal activity in mdx mice. Our results show for the first time that a chronic long-term administration of LDs of unmodified PMO, equivalent to doses in use in DMD boys, is safe, significantly ameliorates the muscular dystrophic phenotype and improves the activity of dystrophin-deficient mice, thus encouraging the further clinical translation of this approach in humans.
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The epoxide ring in 5,6-dihydro-5,6-epoxy-1,10-phenanthroline (L) opens up in its reaction with 4-methylaniline and 4-methoxyaniline in water in equimolar proportion at room temperature without any Lewis acid catalyst to give a monohydrate of 6-(4-methyl-phenylamino)-5,6-dihydro-1,10-phenanthrolin-5-ol (L′·H2O) and 6-(4-methoxyphenyl-amino)-5,6-dihydro-1,10-phenanthrolin-5-ol (L″) respectively. Reaction time decreases from 72 to 14 h in boiling water. But the yields become less. Reaction of L with Zn(ClO4)2·6H2O in methanol in 3:1 molar ratio at room temperature affords white [ZnL3](ClO4)2·H2O. The X-ray crystal structure of the acetonitrile solvate [ZnL3](ClO4)2·MeCN has been determined which shows that the metal has a distorted octahedral N6 coordination sphere. [ZnL3](ClO4)2·2H2O reacts with 4-methylaniline and 4-methoxyaniline in boiling water in 1:3 molar proportion in the absence of any Lewis acid catalyst to produce [ZnL′3](ClO4)2·4H2O and [ZnL″3](ClO4)2·H2O, respectively in 1–4 h time in somewhat low yield. In the 1H NMR spectra of [ZnL′3](ClO4)2·4H2O and [ZnL″3](ClO4)2·H2O, only one sharp methyl signal is observed implicating that only one diastereomer out of the 23 possibilities is formed. The same diastereomers are obtained when L′·H2O and L″ are reacted directly with Zn(ClO4)2·6H2O in tetrahydrofuran at room temperature in very good yields. Reactions of L′·H2O and L″ with Ru(phen)2Cl2·2H2O (phen = 1,10-phenanthroline) in equimolar proportion in methanol–water mixture under refluxing condition lead to the isolation of two diastereomers of [Ru(phen)2L′](ClO4)2·2H2O and [Ru(phen)2L″](ClO4)2·2H2O.
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Upper Cenomanian pelagic sediments from the northern Alpine Helvetic fold-and-thrust belt (northern Tethyan margin) coeval with Oceanic Anoxic Event (OAE) 2 are characterized by the temporal persistence of micrite sedimentation and lack of organic carbon-rich layers. We studied an expanded section in the Chrummflueschlucht (east of Euthal, Switzerland), which encompasses the OAE 2 time interval. In order to identify the paleoceanographic and paleoenvironmental conditions during OAE 2 in this part of the northern Tethyan margin, and more specifically to trace eventual changes in nutrient levels and oxic conditions, we investigated the biostratigraphy (planktonic foraminifera), the bulk-rock mineralogy, and measured stable carbon- and oxygen-isotopes, total phosphorus (P) and redox-sensitive trace-element (RSTE) contents. We were able to determine – with some remaining uncertainties – the different planktonic foraminiferal biozones characteristic of the Cenomanian–Turonian boundary interval (Rotalipora cushmani, Whiteinella archaeocretacea and Helvetoglobotruncana helvetica zones). In the lower part of the section (R. cushmani total range zone), the bulk-rock δ13C record shows a long-term increase. Within sediments attributed to the W. archaeocretacea partial range zone, δ13C values reach a maximum of 3.3‰ (peak “a”). In the following the values decrease and increase again to arrive at a plateau with high δ13C values of around 3.1‰, which ends with a peak of 3.3‰ (peak “c”). At the top of the section, in sediments belonging to the H. helvetica total range zone, δ13C values decrease to post-OAE values of around 2.2‰. The last occurrence of R. cushmani is observed just above the positive δ13C shift characterizing OAE 2. P contents display small variations along the section with a long-term decreasing trend towards the top. Before the OAE 2 interval, P values show higher values and relatively good covariation with detrital input, indicating higher nutrient input before OAE 2. In sediments corresponding to the onset of the δ13C positive excursion, P content is marked by a sharp peak probably linked to a slowdown in sedimentation rates and/or the presence of a small hiatus, as is shown by the presence of glauconite and phosphatic grains. In the interval corresponding to OAE 2, P values remain low and increase slightly at the end of the positive shift in the δ13C record (in the H. helvetica total range zone). The average contents of RSTE (U, V, As, Co, Mo and Mn) remain low throughout the section and appreciable RSTE enrichments have not been observed for the sedimentary interval corresponding to OAE 2. No correlation is observed with stratigraphic trends in RSTE contents in organic-rich deeper-water sections. The presence of double-keeled planktonic foraminifera species during most of the Cenomanian/Turonian boundary event is another evidence of relatively well-oxygenated conditions in this part of the northern Tethyan outer shelf. Our results show that the Chrummflueschlucht section corresponds to one of the most complete section for the Cenomanian–Turonian boundary interval known from the Helvetic realm even if a small hiatus may be present at the onset of the δ13C record (peak “a”). The evolution of P contents suggests an increase in input of this nutritive element at the onset of OAE2. However, the trends in RSTE contents and the planktonic foraminifera assemblages show that the Helvetic realm has not been affected by strongly depleted oxygen conditions during OAE 2.
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Potential vorticity (PV) succinctly describes the evolution of large-scale atmospheric flow because of its material conservation and invertibility properties. However, diabatic processes in extratropical cyclones can modify PV and influence both mesoscale weather and the evolution of the synoptic-scale wave pattern. In this investigation, modification of PV by diabatic processes is diagnosed in a Met Office Unified Model (MetUM) simulation of a North Atlantic cyclone using a set of PV tracers. The structure of diabatic PV within the extratropical cyclone is investigated and linked to the processes responsible for it. On the mesoscale, a tripole of diabatic PV is generated across the tropopause fold extending down to the cold front. The structure results from a dipole in heating across the frontal interface due to condensation in the warm conveyor belt flanking the upper side of the fold and evaporation of precipitation in the dry intrusion and below. On isentropic surfaces intersecting the tropopause, positive diabatic PV is generated on the stratospheric side, while negative diabatic PV is generated on the tropospheric side. The stratospheric diabatic PV is generated primarily by long-wave cooling which peaks at the tropopause itself due to the sharp gradient in humidity there. The tropospheric diabatic PV originates locally from the long-wave radiation and non-locally by advection out of the top of heating associated with the large-scale cloud, convection and boundary layer schemes. In most locations there is no diabatic modification of PV at the tropopause itself but diabatic PV anomalies would influence the tropopause indirectly through the winds they induce and subsequent advection. The consequences of this diabatic PV dipole for the evolution of synoptic-scale wave patterns are discussed.
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Anglo-Saxon monastic archaeology has been constrained by the limited scale of past investigations and their overriding emphasis on core buildings. This paper draws upon the results of an ongoing campaign of archaeological research that is redressing the balance through an ambitious programme of open-area excavation at Lyminge, Kent, the site of a royal double monastery founded in the seventh century ad. The results of five completed fieldwork seasons are assessed and contextualised in a narrative sequence emphasising the dynamic character of Lyminge as an Anglo-Saxon monastic settlement. In so doing, the study brings into sharp focus how early medieval monasteries were emplaced in the landscape, with specific reference to Anglo-Saxon Kent, a regional context offering key insights into how the process of monastic foundation redefined antecedent central places of long-standing politico-religious significance and social action.
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Aleks Sierz in his important survey of mid 1990s drama has identified the plays of Sarah Kane as exemplars of what he terms ‘In-Yer Face’ theatre. Sierz argues that Kane and her contemporaries such as Mark Ravenhill and Judy Upton represent a break with the ideological concerns of the previous generation of playwrights such as Doug Lucie and Stephen Lowe, whose work was shaped through recognizable political concerns, often in direct opposition to Thatcherism. In contrast Sarah Kane and her generation have frequently been seen as literary embodiments of ‘Thatcher’s Children’, whereby following the fall of the Berlin Wall and the inertia of the Major years, their drama eschews a recognizable political position, and seems more preoccupied with the plight of individuals cut adrift from society. In the case of Sarah Kane her frequently quoted statement, ‘I have no responsibility as a woman writer because I don’t believe there’s such a thing’, has compounded this perception. Moreover, its dogmatism also echoes the infamous comments attributed to Mrs Thatcher regarding the role of the individual to society. However, this article seeks to reassess Kane’s position as a woman writer and will argue that her drama is positioned somewhere between the female playwrights who emerged after 1979 such as Sarah Daniels, Timberlake Wertenbaker and Clare McIntyre, whose drama was distinguished by overtly feminist concerns, and its subsequent breakdown, best exemplified by the brief cultural moment associated with the newly elected Blair government known as ‘Cool Britannia’. Drawing on a variety of sources, including Kane’s unpublished monologues, written while she was a student just after Mrs Thatcher left office, this paper will argue that far from being an exponent of post-feminism, Kane’s drama frequently revisits and is influenced by the generation of dramatists whose work was forged out the sharp ideological positions that characterized the 1980s and a direct consequence of Thatcherism.
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The internal variability and coupling between the stratosphere and troposphere in CCMVal‐2 chemistry‐climate models are evaluated through analysis of the annular mode patterns of variability. Computation of the annular modes in long data sets with secular trends requires refinement of the standard definition of the annular mode, and a more robust procedure that allows for slowly varying trends is established and verified. The spatial and temporal structure of the models’ annular modes is then compared with that of reanalyses. As a whole, the models capture the key features of observed intraseasonal variability, including the sharp vertical gradients in structure between stratosphere and troposphere, the asymmetries in the seasonal cycle between the Northern and Southern hemispheres, and the coupling between the polar stratospheric vortices and tropospheric midlatitude jets. It is also found that the annular mode variability changes little in time throughout simulations of the 21st century. There are, however, both common biases and significant differences in performance in the models. In the troposphere, the annular mode in models is generally too persistent, particularly in the Southern Hemisphere summer, a bias similar to that found in CMIP3 coupled climate models. In the stratosphere, the periods of peak variance and coupling with the troposphere are delayed by about a month in both hemispheres. The relationship between increased variability of the stratosphere and increased persistence in the troposphere suggests that some tropospheric biases may be related to stratospheric biases and that a well‐simulated stratosphere can improve simulation of tropospheric intraseasonal variability.
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Recent high-resolution radiosonde climatologies have revealed a tropopause inversion layer (TIL) in the extratropics: temperature strongly increases just above a sharp local cold point tropopause. Here, it is asked to what extent a TIL exists in current general circulation models (GCMs) and meteorological analyses. Only a weak hint of a TIL exists in NCEP/NCAR reanalysis data. In contrast, the Canadian Middle Atmosphere Model (CMAM), a comprehensive GCM, exhibits a TIL of realistic strength. However, in data assimilation mode CMAM exhibits a much weaker TIL, especially in the Southern Hemisphere where only coarse satellite data are available. The discrepancy between the analyses and the GCM is thus hypothesized to be mainly due to data assimilation acting to smooth the observed strong curvature in temperature around the tropopause. This is confirmed in the reanalysis where the stratification around the tropopause exhibits a strong discontinuity at the start of the satellite era.
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A programmable data acquisition system to allow novel use of meteorological radiosondes for atmospheric science measurements is described. In its basic form it supports four analogue inputs at 16 bit resolution, and up to two further inputs at lower resolution configurable instead for digital instruments. It also provides multiple instrument power supplies (+8V, +16V, +5V and -8V) from the 9V radiosonde battery. During a balloon flight encountering air temperatures from +17°C to -66°C, the worst case voltage drift in the 5V unipolar digitisation circuitry was 20mV. The system liberates a new range of low cost atmospheric research measurements, by utilising radiosondes routinely launched internationally for weather forecasting purposes. No additional receiving equipment is required. Comparisons between the specially instrumented and standard meteorological radiosondes show negligible effect of the additional instrumentation on the standard meteorological data.
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Duchenne muscular dystrophy is a fatal muscle-wasting disorder. Lack of dystrophin compromises the integrity of the sarcolemma and results in myofibers that are highly prone to contraction-induced injury. Recombinant adenoassociated virus (rAAV)-mediated dystrophin gene transfer strategies to muscle for the treatment of Duchenne muscular dystrophy (DMD) have been limited by the small cloning capacity of rAAV vectors and high titers necessary to achieve efficient systemic gene transfer. In this study, we assess the impact of codon optimization on microdystrophin (ΔAB/R3-R18/ΔCT) expression and function in the mdx mouse and compare the function of two different configurations of codon-optimized microdystrophin genes (ΔAB/R3-R18/ΔCT and ΔR4-R23/ΔCT) under the control of a muscle-restrictive promoter (Spc5-12). Codon optimization of microdystrophin significantly increases levels of microdystrophin mRNA and protein after intramuscular and systemic administration of plasmid DNA or rAAV2/8. Physiological assessment demonstrates that codon optimization of ΔAB/R3-R18/ΔCT results in significant improvement in specific force, but does not improve resistance to eccentric contractions compared with noncodon-optimized ΔAB/ R3-R18/ΔCT. However, codon-optimized microdystrophin ΔR4-R23/ΔCT completely restored specific force generation and provided substantial protection from contraction-induced injury. These results demonstrate that codon optimization of microdystrophin under the control of a muscle-specific promoter can significantly improve expression levels such that reduced titers of rAAV vectors will be required for efficient systemic administration.