Replication enhancer elements within the open reading frame of tick-borne encephalitis virus and their evolution within the Flavivirus genus

We provide experimental evidence of a replication enhancer element (REE) within the capsid gene of tick-borne encephalitis virus (TBEV, genus Flavivirus). Thermodynamic and phylogenetic analyses predicted that the REE folds as a long stable stem–loop (designated SL6), conserved among all tick-borne flaviviruses (TBFV). Homologous sequences and potential base pairing were found in the corresponding regions of mosquito-borne flaviviruses, but not in more genetically distant flaviviruses. To investigate the role of SL6, nucleotide substitutions were introduced which changed a conserved hexanucleotide motif, the conformation of the terminal loop and the base-paired dsRNA stacking. Substitutions were made within a TBEV reverse genetic system and recovered mutants were compared for plaque morphology, single-step replication kinetics and cytopathic effect. The greatest phenotypic changes were observed in mutants with a destabilized stem. Point mutations in the conserved hexanucleotide motif of the terminal loop caused moderate virus attenuation. However, all mutants eventually reached the titre of wild-type virus late post-infection. Thus, although not essential for growth in tissue culture, the SL6 REE acts to up-regulate virus replication. We hypothesize that this modulatory role may be important for TBEV survival in nature, where the virus circulates by non-viraemic transmission between infected and non-infected ticks, during co-feeding on local rodents.

Investigating familiar interfaces to help older adults learn computer applications more easily

Many older adults wish to gain competence in using a computer, but many application interfaces are perceived as complex and difficult to use, deterring potential users from investing the time to learn them. Hence, this study looks at the potential of ‘familiar’ interface design which builds upon users’ knowledge of real world interactions, and applies existing skills to a new domain. Tools are provided in the form of familiar visual objects, and manipulated like real-world counterparts, rather than with buttons, icons and menus found in classic WIMP interfaces. This paper describes the formative evaluation of computer interactions that are based upon familiar real world tasks, which supports multitouch interaction, involves few buttons and icons, no menus, no right-clicks or double-clicks and no dialogs. Using an example of an email client to test the principles of using “familiarity”, the initial feedback was very encouraging, with 3 of the 4 participants being able to undertake some of the basic email tasks with no prior training and little or no help. The feedback has informed a number of refinements of the design principles, such as providing clearer affordance for visual objects. A full study is currently underway.

CUP Intermediate Greek-English Lexicon

Document design and typeface design: A typographic specification for a new Intermediate Greek-English Lexicon by CUP, accompanied by typefaces modified for the specific typographic requirements of the text. The Lexicon is a substantial (over 1400 pages) publication for HE students and academics intended to complement Liddell-Scott (the standard reference for classical Greek since the 1850s), and has been in preparation for over a decade. The typographic appearance of such works has changed very little since the original editions, largely to the lack of suitable typefaces: early digital proofs of the Lexicon utilised directly digitised versions of historical typefaces, making the entries difficult to navigate, and the document uneven in typographic texture. Close collaboration with the editors of the Lexicon, and discussion of the historical precedents for such documents informed the design at all typographic levels to achieve a highly reader-friendly results that propose a model for this kind of typography. Uniquely for a work of this kind, typeface design decisions were integrated into the wider document design specification. A rethinking of the complex typography for Greek and English based on historical editions as well as equivalent bilingual reference works at this level (from OUP, CUP, Brill, Mondadori, and other publishers) led a redefinition of multi-script typeface pairing for the specific context, taking into account recent developments in typeface design. Specifically, the relevant weighting of elements within each entry were redefined, as well as the typographic texture of type styles across the two scripts. In details, Greek typefaces were modified to emphasise clarity and readability, particularly of diacritics, at very small sizes. The relative weights of typefaces typeset side-by-side were fine-tuned so that the visual hierarchy of the entires was unambiguous despite the dense typesetting.

Integrated palaeoecology and archaeology: a powerful approach for understanding pre-Columbian Amazonia

The old paradigm that Amazonia's tropical ecosystems prevented cultural development beyond small-scale shifting agricultural economies, that had little environmental impact, no longer holds true for much of Amazonia. A diversity of archaeological evidence, including terra preta soils, raised fields, causeways, large habitation mounds, geometric earthworks, and megalithic monuments, all point to considerable cultural complexity and environmental impacts. However, uncertainty remains over the chronology of these cultures, their diet and economy, and the scale of environmental impact and land use associated with them. Here, we argue that a cross-disciplinary approach, closely coupling palaeoecology and archaeology, can potentially resolve these uncertainties. We show how, with careful site selection (pairing small and large lakes, close proximity to archaeological sites, transects of soil pits) and choice of techniques (e.g., pollen, phytoliths, starch grains, charcoal, stable isotopes), these two disciplines can be successfully integrated to provide a powerful tool for investigating the relationship between pre-Columbian cultures and their environment.

A critical revision of the estimation of the latent heat flux from two-wavelength scintillometry

Simultaneous scintillometer measurements at multiple wavelengths (pairing visible or infrared with millimetre or radio waves) have the potential to provide estimates of path-averaged surface fluxes of sensible and latent heat. Traditionally, the equations to deduce fluxes from measurements of the refractive index structure parameter at the two wavelengths have been formulated in terms of absolute humidity. Here, it is shown that formulation in terms of specific humidity has several advantages. Specific humidity satisfies the requirement for a conserved variable in similarity theory and inherently accounts for density effects misapportioned through the use of absolute humidity. The validity and interpretation of both formulations are assessed and the analogy with open-path infrared gas analyser density corrections is discussed. Original derivations using absolute humidity to represent the influence of water vapour are shown to misrepresent the latent heat flux. The errors in the flux, which depend on the Bowen ratio (larger for drier conditions), may be of the order of 10%. The sensible heat flux is shown to remain unchanged. It is also verified that use of a single scintillometer at optical wavelengths is essentially unaffected by these new formulations. Where it may not be possible to reprocess two-wavelength results, a density correction to the latent heat flux is proposed for scintillometry, which can be applied retrospectively to reduce the error.

Oligonucleotide compound and method for treating nidovirus infections

A method and oligonucleotide compound for inhibiting replication of a nidovirus in virus-infected animal cells are disclosed. The compound (i) has a nuclease-resistant backbone, (ii) is capable of uptake by the infected cells, (iii) contains between 8-25 nucleotide bases, and (iv) has a sequence capable of disrupting base pairing between the transcriptional regulatory sequences in the 5′ leader region of the positive-strand viral genome and negative-strand 3′ subgenomic region. In practicing the method, infected cells are exposed to the compound in an amount effective to inhibit viral replication.

Analysis of the bacterial communities present in lungs of patients with cystic fibrosis from American and British centers

The aim of this study was to determine whether geographical differences impact the composition of bacterial communities present in the airways of cystic fibrosis (CF) patients attending CF centers in the United States or United Kingdom. Thirty-eight patients were matched on the basis of clinical parameters into 19 pairs comprised of one U.S. and one United Kingdom patient. Analysis was performed to determine what, if any, bacterial correlates could be identified. Two culture-independent strategies were used: terminal restriction fragment length polymorphism (T-RFLP) profiling and 16S rRNA clone sequencing. Overall, 73 different terminal restriction fragment lengths were detected, ranging from 2 to 10 for U.S. and 2 to 15 for United Kingdom patients. The statistical analysis of T-RFLP data indicated that patient pairing was successful and revealed substantial transatlantic similarities in the bacterial communities. A small number of bands was present in the vast majority of patients in both locations, indicating that these are species common to the CF lung. Clone sequence analysis also revealed that a number of species not traditionally associated with the CF lung were present in both sample groups. The species number per sample was similar, but differences in species presence were observed between sample groups. Cluster analysis revealed geographical differences in bacterial presence and relative species abundance. Overall, the U.S. samples showed tighter clustering with each other compared to that of United Kingdom samples, which may reflect the lower diversity detected in the U.S. sample group. The impact of cross-infection and biogeography is considered, and the implications for treating CF lung infections also are discussed.

Infrared and millimetre-wave scintillometry in the suburban environment – Part 1: Structure parameters

Scintillometry, a form of ground-based remote sensing, provides the capability to estimate surface heat fluxes over scales of a few hundred metres to kilometres. Measurements are spatial averages, making this technique particularly valuable over areas with moderate heterogeneity such as mixed agricultural or urban environments. In this study, we present the structure parameters of temperature and humidity, which can be related to the sensible and latent heat fluxes through similarity theory, for a suburban area in the UK. The fluxes are provided in the second paper of this two-part series. A millimetre-wave scintillometer was combined with an infrared scintillometer along a 5.5 km path over northern Swindon. The pairing of these two wavelengths offers sensitivity to both temperature and humidity fluctuations, and the correlation between wavelengths is also used to retrieve the path-averaged temperature–humidity correlation. Comparison is made with structure parameters calculated from an eddy covariance station located close to the centre of the scintillometer path. The performance of the measurement techniques under different conditions is discussed. Similar behaviour is seen between the two data sets at sub-daily timescales. For the two summer-to-winter periods presented here, similar evolution is displayed across the seasons. A higher vegetation fraction within the scintillometer source area is consistent with the lower Bowen ratio observed (midday Bowen ratio < 1) compared with more built-up areas around the eddy covariance station. The energy partitioning is further explored in the companion paper.

English-Spanish bilingual learners of Portuguese as a third language: non-redundant acquisition and its typological nature

This chapter has two goals: (a) to discuss the Spanish-Portuguese interface in current formal language acquisition research and (b) to highlight the contributions of this language pairing in the emerging field of formal third language acquisition. The authors discuss two L3 acquisition studies (Montrul, Dias, & Santos, 2011; Giancaspro, Halloran, & Iverson, in press) examining Differential Object Marking, a morphological case marker present in Spanish but not in Portuguese, arguing that the results show how data from Spanish-English bilinguals learning Brazilian Portuguese as an L3 illuminate the deterministic role of structural and typological similarity in linguistic transfer. The data provide supportive evidence for only one of three existing L3 transfer models: the Typological Proximity Model (Rothman, 2010, 2011, 2013).

Towards expressive rule induction on IP network event streams

In order to gain insights into events and issues that may cause errors and outages in parts of IP networks, intelligent methods that capture and express causal relationships online (in real-time) are needed. Whereas generalised rule induction has been explored for non-streaming data applications, its application and adaptation on streaming data is mostly undeveloped or based on periodic and ad-hoc training with batch algorithms. Some association rule mining approaches for streaming data do exist, however, they can only express binary causal relationships. This paper presents the ongoing work on Online Generalised Rule Induction (OGRI) in order to create expressive and adaptive rule sets real-time that can be applied to a broad range of applications, including network telemetry data streams.

Shadow lines in the arithmetic of elliptic curves

Let E/Q be an elliptic curve and p a rational prime of good ordinary reduction. For every imaginary quadratic field K/Q satisfying the Heegner hypothesis for E we have a corresponding line in E(K)\otimes Q_p, known as a shadow line. When E/Q has analytic rank 2 and E/K has analytic rank 3, shadow lines are expected to lie in E(Q)\otimes Qp. If, in addition, p splits in K/Q, then shadow lines can be determined using the anticyclotomic p-adic height pairing. We develop an algorithm to compute anticyclotomic p-adic heights which we then use to provide an algorithm to compute shadow lines. We conclude by illustrating these algorithms in a collection of examples.