Conformational Dynamics of the Human Propeller Telomeric DNA Quadruplex on a Microsecond Time Scale

The human telomeric DNA sequence with four repeats can fold into a parallel-stranded propeller-type topology. NMR structures solved under molecular crowding experiments correlate with the crystal structures found with crystal-packing interactions that are effectively equivalent to molecular crowding. This topology has been used for rationalization of ligand design and occurs experimentally in a number of complexes with a diversity of ligands, at least in the crystalline state. While G-quartet stems have been well characterised, the interactions of the TTA loop with the G-quartets are much less defined. To better understand the conformational variability and structural dynamics of the propeller-type topology, we performed molecular dynamics simulations in explicit solvent up to 1.5 µs. The analysis provides a detailed atomistic account of the dynamic nature of the TTA loops highlighting their interactions with the G-quartets including formation of an A:A base pair, triad, pentad and hexad. The results present a threshold in quadruplex simulations, with regards to understanding the flexible nature of the sugar-phosphate backbone in formation of unusual architecture within the topology. Furthermore, this study stresses the importance of simulation time in sampling conformational space for this topology.

Lateralisation of language function in young adults born very preterm

Objective: To explore, using functional magnetic resonance imaging (MRI), the functional organisation of phonological processing in young adults born very preterm.

Subjects: Six right handed male subjects with radiological evidence of thinning of the corpus callosum were selected from a cohort of very preterm subjects. Six normal right handed male volunteers acted as controls.

Method: Blood oxygenation level dependent contrast echoplanar images were acquired over five minutes at 1.5 T while subjects performed the tasks. During the ON condition, subjects were visually presented with pairs of non-words and asked to press a key when a pair of words rhymed (phonological processing). This task alternated with the OFF condition, which required subjects to make letter case judgments of visually presented pairs of consonant letter strings (orthographic processing). Generic brain activation maps were constructed from individual images by sinusoidal regression and non-parametric testing. Between group differences in the mean power of experimental response were identified on a voxel wise basis by analysis of variance.

Results: Compared with controls, the subjects with thinning of the corpus callosum showed significantly reduced power of response in the left hemisphere, including the peristriate cortex and the cerebellum, as well as in the right parietal association area. Significantly increased power of response was observed in the right precentral gyrus and the right supplementary motor area.

Conclusions: The data show evidence of increased frontal and decreased occipital activation in male subjects with neurodevelopmental thinning of the corpus callosum, which may be due to the operation of developmental compensatory mechanisms.

Fast recognition of musical sounds based on timbre

Human listeners seem to have an impressive ability to recognize a wide variety of natural sounds. However, there is surprisingly little quantitative evidence to characterize this fundamental ability. Here the speed and accuracy of musical-sound recognition were measured psychophysically with a rich but acoustically balanced stimulus set. The set comprised recordings of notes from musical instruments and sung vowels. In a first experiment, reaction times were collected for three target categories: voice, percussion, and strings. In a go/no-go task, listeners reacted as quickly as possible to members of a target category while withholding responses to distractors (a diverse set of musical instruments). Results showed near-perfect accuracy and fast reaction times, particularly for voices. In a second experiment, voices were recognized among strings and vice-versa. Again, reaction times to voices were faster. In a third experiment, auditory chimeras were created to retain only spectral or temporal features of the voice. Chimeras were recognized accurately, but not as quickly as natural voices. Altogether, the data suggest rapid and accurate neural mechanisms for musical-sound recognition based on selectivity to complex spectro-temporal signatures of sound sources.

Patterns of synchrony in natterjack toad breeding activity and reproductive success at local and regional scales

Empirical studies of the spatiotemporal dynamics of populations are required to better understand natural fluctuations in abundance and reproductive success, and to better target conservation and monitoring programmes. In particular, spatial synchrony in amphibian populations remains little studied. We used data from a comprehensive three year study of natterjack toad Bufo calamita populations breeding at 36 ponds to assess whether there was spatial synchrony in the toad breeding activity (start and length of breeding season, total number of egg strings) and reproductive success (premetamorphic survival and production of metamorphs). We defined a novel approach to assess the importance of short-term synchrony at both local and regional scales. The approach employs similarity indices and quantifies the interaction between the temporal and spatial components of populations using mixed effects models. There was no synchrony in the toad breeding activity and reproductive success at the local scale, suggesting that populations function as individual clusters independent of each other. Regional synchrony was apparent in the commencement and duration of the breeding season and in the number of egg strings laid (indicative of female population size). Regional synchrony in both rainfall and temperature are likely to explain the patterns observed (e.g. Moran effect). There was no evidence supporting regional synchrony in reproductive success, most likely due to spatial variability in the environmental conditions at the breeding ponds, and to differences in local population fitness (e.g. fecundity). The small scale asynchronous dynamics and regional synchronous dynamics in the number of breeding females indicate that it is best to monitor several populations within a subset of regions. Importantly, variations in the toad breeding activity and reproductive success are not synchronous, and it is thus important to consider them both when assessing the conservation status of pond-breeding amphibians. © 2012 The Authors. Ecography © 2012 Nordic Society Oikos.

Dynamical symmetry breaking with optimal control: Reducing the number of pieces

We analyze the production of defects during the dynamical crossing of a mean-field phase transition with a real order parameter. When the parameter that brings the system across the critical point changes in time according to a power-law schedule, we recover the predictions dictated by the well-known Kibble-Zurek theory. For a fixed duration of the evolution, we show that the average number of defects can be drastically reduced for a very large but finite system, by optimizing the time dependence of the driving using optimal control techniques. Furthermore, the optimized protocol is robust against small fluctuations.

The influence of providing perches and string on activity levels, fearfulness and leg health in commercial broiler chickens

The aim of this study was to assess the effect of providing environmental enrichment in the form of perches and string on the behaviour and welfare of commercial broiler chickens. Houses containing ~23 000 broiler chickens were assigned to one of four treatments in a 2×2 factorial design. Treatments involved two levels of access to perches (P) (present (24/house) ‘+P’ or absent ‘−P’) and two levels of access to string (S) (present (24/house) ‘+S’ or absent ‘−S’). All houses contained windows, and 30 straw bales were provided from day 10 of the rearing cycle. Treatments were applied in one of four houses on a single farm, and were replicated over four production cycles. Behaviour and leg health were observed in weeks 3 to 5 of the rearing cycle. Production performance and environmental parameters were also measured. There was an interaction between perches and age in the percentage of birds observed lying, with higher percentages of birds observed lying in the +P treatment than in the −P treatment during weeks 4 and 5. There was also a significant interaction between string and age in the percentage of birds observed in locomotion, with higher percentages observed in locomotion in the −S treatment than in the +S treatment during weeks 4 and 5. There was also an interaction between string and age in average gait scores, with lower gait scores in the +S treatment than in the −S treatment during weeks 3 and 5 but not within week 4. Daytime observations showed that perches and strings were used frequently, with one bout of perching occurring approximately every 80 s/perch, and one bout of pecking at string occurring every 78 s/string on average. There was a significant effect of age on use of perches (P<0.001) and string (P<0.001), with perching peaking during week 5 and string pecking peaking during week 3. We conclude that commercial broilers in windowed houses with access to straw bales display an interest in additional enrichment stimuli in the form of perches and string, and therefore that these stimuli have the potential to improve welfare. In addition, provision of string as a pecking device appeared to positively influence walking ability. However, this effect was numerically small, was only shown in certain weeks and was not reflected in the other leg health measure (latency to lie). The results also showed an apparent negative effect of string and perches on the activity levels of birds (recorded away from the immediate vicinity of these enrichments) towards the end of the production cycle. These results emphasise the need for further research into optimum design and layout of enrichment stimuli for modern broilers in windowed houses to ensure that their provision leads to clear welfare benefits.

Energy conserving schemes for the simulation of musical instrument contact dynamics

Collisions are an innate part of the function of many musical instruments. Due to the nonlinear nature of contact forces, special care has to be taken in the construction of numerical schemes for simulation and sound synthesis. Finite difference schemes and other time-stepping algorithms used for musical instrument modelling purposes are normally arrived at by discretising a Newtonian description of the system. However because impact forces are non-analytic functions of the phase space variables, algorithm stability can rarely be established this way. This paper presents a systematic approach to deriving energy conserving schemes for frictionless impact modelling. The proposed numerical formulations follow from discretising Hamilton׳s equations of motion, generally leading to an implicit system of nonlinear equations that can be solved with Newton׳s method. The approach is first outlined for point mass collisions and then extended to distributed settings, such as vibrating strings and beams colliding with rigid obstacles. Stability and other relevant properties of the proposed approach are discussed and further demonstrated with simulation examples. The methodology is exemplified through a case study on tanpura string vibration, with the results confirming the main findings of previous studies on the role of the bridge in sound generation with this type of string instrument.

Instrumental Parasites: Interfacing the Fragile and the Robust

The parasitical relationship between the grand piano and the myriad objects used in its preparation as pioneered by John Cage in the late 1940’s is here discussed from a perspective of free improvisation practice. Preparations can be defined as the use of a “non-instrument” object (screws, bolts, rubbers etc…) to alter or modify the behaviour of an instrument or part of an instrument. Although also present in instrumental practices based on the electric guitar or the drum kit, the piano provides a privileged space of exploration given its large‐scale resonant body. It also highlights the transgressive aspect of preparation (the piano to be prepared often belongs to a venue rather than to the pianist herself, hence highlighting relationships of trust, care and respect). Since 2007 I have used a guitar-object (a small wooden board with strings and pick ups) connected to a small amplifier to prepare the grand piano in my free improvisation practice. This paper addresses the different relationships afforded by this type preparation which is characterised by the fact that the object for preparation is in itself an instrument (albeit a simplified one), and the preparation is ephemeral and intrinsic to the performance. The paper also reflects on the process of designing an interface from and for a particular practice and in collaboration with a guitar luthier.

Malware detection: program run length against detection rate

N-gram analysis is an approach that investigates the structure of a program using bytes, characters or text strings. This research uses dynamic analysis to investigate malware detection using a classification approach based on N-gram analysis. A key issue with dynamic analysis is the length of time a program has to be run to ensure a correct classification. The motivation for this research is to find the optimum subset of operational codes (opcodes) that make the best indicators of malware and to determine how long a program has to be monitored to ensure an accurate support vector machine (SVM) classification of benign and malicious software. The experiments within this study represent programs as opcode density histograms gained through dynamic analysis for different program run periods. A SVM is used as the program classifier to determine the ability of different program run lengths to correctly determine the presence of malicious software. The findings show that malware can be detected with different program run lengths using a small number of opcodes

N-gram density based malware detection

N-gram analysis is an approach that investigates the structure of a program using bytes, characters or text strings. This research uses dynamic analysis to investigate malware detection using a classification approach based on N-gram analysis. The motivation for this research is to find a subset of Ngram features that makes a robust indicator of malware. The experiments within this paper represent programs as N-gram density histograms, gained through dynamic analysis. A Support Vector Machine (SVM) is used as the program classifier to determine the ability of N-grams to correctly determine the presence of malicious software. The preliminary findings show that an N-gram size N=3 and N=4 present the best avenues for further analysis.

Characteristics of Corticospinal Projections to the Intrinsic Hand Muscles in Skilled Harpists.

The process of learning to play a musical instrument necessarily alters the functional organisation of the cortical motor areas that are involved in generating the required movements. In the case of the harp, the demands placed on the motor system are quite specific. During performance, all digits with the sole exception of the little finger are used to pluck the strings. With a view to elucidating the impact of having acquired this highly specialized musical skill on the characteristics of corticospinal projections to the intrinsic hand muscles, focal transcranial magnetic stimulation (TMS) was used to elicit motor evoked potentials (MEPs) in three muscles (of the left hand): abductor pollicis brevis (APB); first dorsal interosseous (FDI); and abductor digiti minimi (ADM) in seven harpists. Seven non-musicians served as controls. With respect to the FDI muscle–which moves the index finger, the harpists exhibited reliably larger MEP amplitudes than those in the control group. In contrast, MEPs evoked in the ADM muscle–which activates the little finger, were smaller in the harpists than in the non-musicians. The locations on the scalp over which magnetic stimulation elicited discriminable responses in ADM also differed between the harpists and the non-musicians. This specific pattern of variation in the excitability of corticospinal projections to these intrinsic hand muscles exhibited by harpists is in accordance with the idiosyncratic functional demands that are imposed in playing this instrument.

"No Encores" The Royal Dublin Society Concert Archive Recitals in Retrospect: 1925-50

A large archive of sources for the RDS classical music recitals is extant in the Society’s Library, Ballsbridge, Dublin. The recitals were established in 1886 for the promotion of chamber music and in order to expose Dublin audiences to the works of the great composers. Extant in the collection are minute books; autographed programmes; newspaper cuttings which include previews, reviews and advertisements; correspondences with artists and agents; promotional material; selections of photographs; records of attendance, artists fees and takings; and volumes of printed music.
This paper will document the organisation, management and occurrence of the RDS classical music recitals for the period 1925 to 1950 and will encompass the opening of the current concert hall (The Members’ Hall, 1925), the Society’s bi-centenary celebrations (1931) and the continuance of the recitals within the context of the Second World War (1939- 45). The paper will examine and analyse the following: networks, repertoire and reception.
The RDS music committee established significant links with many performers and UK-based classical music agents. Recitalists include musicians of international renown; Myra Hess, Isolde Menges, Lili Kraus, Joseph Szigeti, Leon Goossens, Sir Hamilton Harty and The Hallé Orchestra, The Catterall Quartet and many local, Dublin-based musicians; Raidió Éireann Orchestra, Dublin String Orchestra, Dublin Philharmonic Orchestra and Culwick Choral Society. The compromises and collaborations in evidence between the music committee, agents and performers resulted in the presentation of varied and well-balanced programmes featuring sonatas, quartets, trios, concerti, overtures, symphonies and songs by composers including Beethoven, Mozart, Haydn and Brahms. Works by contemporary composers including Bax, Dohnanyi, Szymanowski and Suk were also regularly performed, as were works with an Irish influence or flavour. Audiences mainly consisted of members of the Society, music students were encouraged to attend at a reduced rate and reviews were regularly published in the Irish Times, Irish Independent and Irish Press.

Fast response to human voices in autism

Individuals with autism spectrum disorders (ASD) are reported to allocate less spontaneous attention to voices. Here, we investigated how vocal sounds are processed in ASD adults, when those sounds are attended. Participants were asked to react as fast as possible to target stimuli (either voices or strings) while ignoring distracting stimuli. Response times (RTs) were measured. Results showed that, similar to neurotypical (NT) adults, ASD adults were faster to recognize voices compared to strings. Surprisingly, ASD adults had even shorter RTs for voices than the NT adults, suggesting a faster voice recognition process. To investigate the acoustic underpinnings of this effect, we created auditory chimeras that retained only the temporal or the spectral features of voices. For the NT group, no RT advantage was found for the chimeras compared to strings: both sets of features had to be present to observe an RT advantage. However, for the ASD group, shorter RTs were observed for both chimeras. These observations indicate that the previously observed attentional deficit to voices in ASD individuals could be due to a failure to combine acoustic features, even though such features may be well represented at a sensory level.

Is Our Students Learning - QuestionMark: Extending E-Assessment Systems for Adapative Marking and Feedback

Our key contribution is a flexible, automated marking system that adds desirable functionality to existing E-Assessment systems. In our approach, any given E-Assessment system is relegated to a data-collection mechanism, whereas marking and the generation and distribution of personalised per-student feedback is handled separately by our own system. This allows content-rich Microsoft Word feedback documents to be generated and distributed to every student simultaneously according to a per-assessment schedule.

The feedback is adaptive in that it corresponds to the answers given by the student and provides guidance on where they may have gone wrong. It is not limited to simple multiple choice which are the most prescriptive question type offered by most E-Assessment Systems and as such most straightforward to mark consistently and provide individual per-alternative feedback strings. It is also better equipped to handle the use of mathematical symbols and images within the feedback documents which is more flexible than existing E-Assessment systems, which can only handle simple text strings.

As well as MCQs the system reliably and robustly handles Multiple Response, Text Matching and Numeric style questions in a more flexible manner than Questionmark: Perception and other E-Assessment Systems. It can also reliably handle multi-part questions where the response to an earlier question influences the answer to a later one and can adjust both scoring and feedback appropriately.

New question formats can be added at any time provided a corresponding marking method conforming to certain templates can also be programmed. Indeed, any question type for which a programmatic method of marking can be devised may be supported by our system. Furthermore, since the student’s response to each is question is marked programmatically, our system can be set to allow for minor deviations from the correct answer, and if appropriate award partial marks.