Predicting residue-wise contact orders in proteins by support vector regression

Background: The residue-wise contact order (RWCO) describes the sequence separations between the residues of interest and its contacting residues in a protein sequence. It is a new kind of one-dimensional protein structure that represents the extent of long-range contacts and is considered as a generalization of contact order. Together with secondary structure, accessible surface area, the B factor, and contact number, RWCO provides comprehensive and indispensable important information to reconstructing the protein three-dimensional structure from a set of one-dimensional structural properties. Accurately predicting RWCO values could have many important applications in protein three-dimensional structure prediction and protein folding rate prediction, and give deep insights into protein sequence-structure relationships. Results: We developed a novel approach to predict residue-wise contact order values in proteins based on support vector regression (SVR), starting from primary amino acid sequences. We explored seven different sequence encoding schemes to examine their effects on the prediction performance, including local sequence in the form of PSI-BLAST profiles, local sequence plus amino acid composition, local sequence plus molecular weight, local sequence plus secondary structure predicted by PSIPRED, local sequence plus molecular weight and amino acid composition, local sequence plus molecular weight and predicted secondary structure, and local sequence plus molecular weight, amino acid composition and predicted secondary structure. When using local sequences with multiple sequence alignments in the form of PSI-BLAST profiles, we could predict the RWCO distribution with a Pearson correlation coefficient (CC) between the predicted and observed RWCO values of 0.55, and root mean square error (RMSE) of 0.82, based on a well-defined dataset with 680 protein sequences. Moreover, by incorporating global features such as molecular weight and amino acid composition we could further improve the prediction performance with the CC to 0.57 and an RMSE of 0.79. In addition, combining the predicted secondary structure by PSIPRED was found to significantly improve the prediction performance and could yield the best prediction accuracy with a CC of 0.60 and RMSE of 0.78, which provided at least comparable performance compared with the other existing methods. Conclusion: The SVR method shows a prediction performance competitive with or at least comparable to the previously developed linear regression-based methods for predicting RWCO values. In contrast to support vector classification (SVC), SVR is very good at estimating the raw value profiles of the samples. The successful application of the SVR approach in this study reinforces the fact that support vector regression is a powerful tool in extracting the protein sequence-structure relationship and in estimating the protein structural profiles from amino acid sequences.

A novel, dynamic, in vivo, non-contact method of measuring oxygen depletion rate of the anterior eye

Despite the importance of oxygen measurements, techniques have been limited by their invasive nature and small corneal area of assessment. The aim of this study was to assess a non-contact way of measuring oxygen uptake of the whole anterior eye.

Contact lenses and sport

Contact lenses seem to be the ideal method of vision correction for ametropic people who participate in sporting activities. This thesis sets out to evaluate the viewpoint of the optometric professional and that of the patient on the use of contact lenses in sport and to establish if education is needed within this area. It also aims to provide some scientific evidence on the effect of exercise on the physiology of the cornea with and without contact lenses. Silicone hydrogel contact lenses have previously been suggested to impede heat dissipation from the cornea compared to mid water hydrogels. This was further demonstrated with exercise. The physiological integrity of the cornea is dependant on the amount of oxygen available to its surfaces. Contact lenses can disrupt the diffusion of oxygen to the cornea. Previous methods of measuring the oxygen consumption of the cornea have been limited by their invasive nature and assessment of only a small surface area of the cornea. They are not suitable to measure corneal oxygen consumption during exercise with and without contact lenses. A new method needed to be established. This was achieved by designing a novel method by the use of an oxygen sensor inside an airtight goggle using dynamic quenching of luminescence method. This established a non-contact way of measuring the effect oxygen uptake with and without contact lenses in vivo, allowing the contact lens to be undisturbed in their natural environment. The new method differentiated between the closed-eye and the open-eye condition with a good within-visit repeatability. It also illustrated that the cornea utilises oxygen at a faster rate during controlled aerobic exercise at moderate intensity. New contact lenses are available specifically for sport, these claim to reduce glare and increase contrast for daylight outdoor sports. However, visual benefits of these types of contact lenses cannot be measured easily in an indoor clinical environment, such as the optometric practice. To demonstrate any potential benefits of these lenses emulation of them should be conducted outdoors.

Future of contact lens usage

I was recently part of a small committee looking at higher qualifications in contact lens practice and the discussion turned to future technologies. There was mention of different materials and different applications of contact lenses. Drug delivery with contact lenses was discussed as this has been talked about in the literature for a while. The first paper I could find that talked about using contact lenses for drug delivery dates back over 40 years. There was a review paper in CLAE in 2008 that looked specifically at this too [1]. However, where are these products? Why are we not seeing them in the market place? Maybe the technology is not quite there yet, or maybe patents are prohibiting usage or maybe the market is not big enough to develop such products? We do have lenses on the market with slow release of lubricating agents but not therapeutic agents used for ocular or systemic conditions. Contact lenses with pathogen detectors may be part of our contact lens armoury of the future and again we can already see papers in the literature that have trialled this technology for glucose monitoring in diabetics or lactate concentration in the tear film. Future contact lenses may incorporate better optics based on aberration control and we see this starting to emerge with aspheric designs designed to minimise spherical aberration. Irregular corneas can be fitted with topography based designs and again this technology exists and is being used by some manufacturers in their designs already. Moreover, the topography based fitting of irregular corneas is certainly something we see a lot of today and CLAE has seen many articles related to this over the last decade or so. What about further into the future? Well one interesting area must the 3-dimensional contact lenses, or contact lenses with electronic devices built in that simulate a display screen. A little like the virtual display spectacles that are already sold by electronics companies. It does not take much of a stretch of the imagination to see a large electronic company taking this technology on and making it viable. Will we see people on the train watching movies on these electronic virtual reality contact lenses? I think we will, but when is harder to know.

Neurophysiological evaluation of convergent afferents innervating the human esophagus and area of referred pain on the anterior chest wall

Noxious stimuli in the esophagus cause pain that is referred to the anterior chest wall because of convergence of visceral and somatic afferents within the spinal cord. We sought to characterize the neurophysiological responses of these convergent spinal pain pathways in humans by studying 12 healthy subjects over three visits (V1, V2, and V3). Esophageal pain thresholds (Eso-PT) were assessed by electrical stimulation and anterior chest wall pain thresholds (ACW-PT) by use of a contact heat thermode. Esophageal evoked potentials (EEP) were recorded from the vertex following 200 electrical stimuli, and anterior chest wall evoked potentials (ACWEP) were recorded following 40 heat pulses. The fear of pain questionnaire (FPQ) was administered on V1. Statistical data are shown as point estimates of difference +/- 95% confidence interval. Pain thresholds increased between V1 and V3 [Eso-PT: V1-V3 = -17.9 mA (-27.9, -7.9) P < 0.001; ACW-PT: V1-V3 = -3.38 degrees C (-5.33, -1.42) P = 0.001]. The morphology of cortical responses from both sites was consistent and equivalent [P1, N1, P2, N2 complex, where P1 and P2 are is the first and second positive (downward) components of the CEP waveform, respectively, and N1 and N2 are the first and second negative (upward) components, respectively], indicating activation of similar cortical networks. For EEP, N1 and P2 latencies decreased between V1 and V3 [N1: V1-V3 = 13.7 (1.8, 25.4) P = 0.02; P2: V1-V3 = 32.5 (11.7, 53.2) P = 0.003], whereas amplitudes did not differ. For ACWEP, P2 latency increased between V1 and V3 [-35.9 (-60, -11.8) P = 0.005] and amplitudes decreased [P1-N1: V1-V3 = 5.4 (2.4, 8.4) P = 0.01; P2-N2: 6.8 (3.4, 10.3) P < 0.001]. The mean P1 latency of EEP over three visits was 126.6 ms and that of ACWEP was 101.6 ms, reflecting afferent transmission via Adelta fibers. There was a significant negative correlation between FPQ scores and Eso-PT on V1 (r = -0.57, P = 0.05). These data provide the first neurophysiological evidence of convergent esophageal and somatic pain pathways in humans.

Determining which factors influence the optimum multifocal contact lens correction for presbyopia

Presbyopia is a consequence of ageing and is therefore increasing inprevalence due to an increase in the ageing population. Of the many methods available to manage presbyopia, the use of contact lenses is indeed a tried and tested reversible option for those wishing to be spectacle free. Contact lens options to correct presbyopia include multifocal contact lenses and monovision.Several options have been available for many years with available guides to help choose multifocal contact lenses. However there is no comprehensive way to help the practitioner selecting the best option for an individual. An examination of the simplest way of predicting the most suitable multifocal lens for a patient will only enhance and add to the current evidence available. The purpose of the study was to determine the current use of presbyopic correction modalities in an optometric practice population in the UK and to evaluate and compare the optical performance of four silicone hydrogel soft multifocal contact lenses and to compare multifocal performance with contact lens monovision. The presbyopic practice cohort principal forms of refractive correction were distance spectacles (with near and intermediate vision providedby a variety of other forms of correction), varifocal spectacles and unaided distance with reading spectacles, with few patients wearing contact lenses as their primary correction modality. The results of the multifocal contact lens randomised controlled trial showed that there were only minor differences in corneal physiology between the lens options. Visual acuity differences were observed for distance targets, but only for low contrast letters and under mesopic lighting conditions. At closer distances between 20cm and 67cm, the defocus curves demonstrated that there were significant differences in acuity between lens designs (p < 0.001) and there was an interaction between the lens design and the level of defocus (p < 0.001). None of the lenses showed a clear near addition, perhaps due to their more aspheric rather than zoned design. As expected, stereoacuity was reduced with monovision compared with the multifocal contact lens designs, although there were some differences between the multifocal lens designs (p < 0.05). Reading speed did not differ between lens designs (F = 1.082, p = 0.368), whereas there was a significant difference in critical print size (F = 7.543, p < 0.001). Glare was quantified with a novel halometer and halo size was found to significantly differ between lenses(F = 4.101, p = 0.004). The rating of iPhone image clarity was significantly different between presbyopic corrections (p = 0.002) as was the Near Acuity Visual Questionnaire (NAVQ) rating of near performance (F = 3.730, p = 0.007).The pupil size did not alter with contact lens design (F = 1.614, p = 0.175), but was larger in the dominant eye (F = 5.489, p = 0.025). Pupil decentration relative to the optical axis did not alter with contact lens design (F = 0.777, p =0.542), but was also greater in the dominant eye (F = 9.917, p = 0.003). It was interesting to note that there was no difference in spherical aberrations induced between the contact lens designs (p > 0.05), with eye dominance (p > 0.05) oroptical component (ocular, corneal or internal: p > 0.05). In terms of subjective patient lens preference, 10 patients preferred monovision,12 Biofinity multifocal lens, 7 Purevision 2 for Presbyopia, 4 AirOptix multifocal and 2 Oasys multifocal contact lenses. However, there were no differences in demographic factors relating to lifestyle or personality, or physiological characteristics such as pupil size or ocular aberrations as measured at baseline,which would allow a practitioner to identify which lens modality the patient would prefer. In terms of the performance of patients with their preferred lens, it emerged that Biofinity multifocal lens preferring patients had a better high contrast acuity under photopic conditions, maintained their reading speed at smaller print sizes and subjectively rated iPhone clarity as better with this lens compared with the other lens designs trialled. Patients who preferred monovision had a lower acuity across a range of distances and a larger area of glare than those patients preferring other lens designs that was unexplained by the clinical metrics measured. However, it seemed that a complex interaction of aberrations may drive lens preference. New clinical tests or more diverse lens designs which may allow practitioners to prescribe patients the presbyopic contact lens option that will work best for them first time remains a hope for the future.

Ocular biotribology and the contact lens:Surface interactions and ocular response

Biotribology is essentially the study of friction, lubrication and wear in biological systems. The area has been widely studied in relation to the behaviour of synovial joints and the design and behaviour of hip joint prostheses, but only in the last decade have serious studies been extended to the eye. In the ocular environment - as distinct from articular joints - wear is not a major factor. Both lubrication and friction are extremely important, however; this is particularly the case in the presence of the contact lens, which is a medical device important not only in vision correction but also as a therapeutic bandage for the compromised cornea. This chapter describes the difficulty in replicating experimental conditions that accurately reflect the complex nature of the ocular environment together with the factors such as load and rate of travel of the eyelid, which is the principal moving surface in the eye. Results obtained across a range of laboratories are compared.

By our tongues united? Irish and Scots language contact in rural Ulster

This article suggests that the impact of long-term language contact between the languages of Irish, Scots and English in the province of Ulster led to a hybridisation of accent which challenges traditional ethnolinguistic differentiations - namely, the myth that Catholics and Protestants can be differentiated by their accent. The digitisation of archive recordings from the Tape Recorded Survey of Hiberno-English (TRSHE) permitted a detailed phonetic analysis of two speakers from Atticall, a rural townland in the Mourne Mountains with a unique geographical and linguistic setting, due to the close proximity of Ulster Scots and Irish speakers in the area. Phonological features associated with Irish, Northern English and Lowland Scots were garnered from previous dialectological research in Irish, English and Scots phonologies, which aided with the interpretation of the data. Other contemporaneous recordings from the TRSHE allowed further comparison of phonological features with areas of Ulster in which linguistic interaction between Scots and Irish was expected to be less prevalent, such as Arranmore, Donegal (primarily Irish) and Glarryford, Antrim (primarily Scots). Accommodation theory and substrate/superstrate interaction illuminate patterns of phonological transfer in Mourne, Arranmore and Glarryford English, supporting the conclusion that accent in contemporary Northern Ireland is built upon a linguistic heritage of contact and exchange, rather than political or ethnolinguistic division

Mobile Phones and Contact Arrangements for Children Living in Care

This article reports the findings from the first UK study to examine the use of mobile phones by looked after children. Contact with family and friends is important, but it has sometimes to be carefully managed to avoid unintended consequences such as placement instability. The study examined the ways in which mobile phone technology impacts on contact, drawing on the experiences of children and young people in foster-care and residential care, and of policy makers, social workers, foster parents and residential care staff. No guidance was available that addressed the issue of mobile phone contact arrangements for looked after children and young people. Three years on from the start of the study, this remains the case in the area where the study was conducted, resulting in variation in the way mobile phone use for contact is managed; the issue appears only to be specifically addressed when identified as a problem. The position of mobile phone facilitated contact as a recognised form of contact requires review. The evidence suggests it should routinely form part of children’s care plans, and that residential staff and foster parents need to be adequately prepared and supported for the dynamics of mobile phone facilitated contact.

Discussion about the validity of virtual practices in subjects in the radioccomunication area. Results of the educational experience

[EN]Nowadays we are living a virtual learning boom. Mainly, it is due to two facts: first, easy spreading of the knowledge and second, virtual learning is cheaper than classic instrumentation laboratories. This cost is even bigger in radiocommunication and high frequency area. In fact, time and time again there are more universities that give up offering the realization of laboratory practice. In the present report we propose a discussion about the increase of virtual practices when contact with instrumentation and circuits is basic. The experience of seven lecturers of the Communications Engineering Group (GIC) will be exposed.

Quichua-Spanish language contact in Salcedo, Ecuador: revisiting media lengua syncretic language practices

The purpose of the current thesis is to develop a better understanding of the interaction between Spanish and Quichua in the Salcedo region and provide more information for the processes that might have given rise to Media Lengua, a ‘mixed’ language comprised of a Quichua grammar and Spanish lexicon. Muysken attributes the formation of Media Lengua to relexification, ruling out any influence from other bilingual phenomena. I argue that the only characteristic that distinguishes Media Lengua from other language contact varieties in central Ecuador is the quantity of the overall Spanish borrowings and not the type of processes that might have been employed by Quichua speakers during the genesis of Media Lengua. The results from the Salcedo data that I have collected show how processes such as adlexification, code-mixing, and structural convergence produce Media Lengua-type sentences, evidence that supports an alternative analysis to Muysken’s relexification hypothesis. Overall, this dissertation is developed around four main objectives: (1) to describe the variation of Spanish loanwords within a bilingual community in Salcedo; (2) to analyze some of the prominent and recent structural changes in Quichua and Spanish; (3) to determine whether Spanish loanword use can be explained by the relationship consultants have with particular social categories; and (4) to analyze the consultants’ language ideologies toward syncretic uses of Spanish and Quichua. Overall, 58% of the content words, 39% of the basic vocabulary, and 50% of the subject pronouns in the Salcedo corpus were derived from Spanish. When compared to Muysken’s description of highlander Quichua in the 1970’s, Spanish loanwords have more than doubled in each category. The overall level of Spanish loanwords in Salcedo Quichua has grown to a level between highlander Quichua in the 1970’s and Media Lengua. Similar to Spanish’s lexical influence in Media Lengua, the increase of Spanish borrowings in today’s rural Quichua can be seen in non-basic and basic vocabularies as well as the subject pronoun system. Significantly, most of the growth has occurred through forms of adlexification i.e., doublets, well-established borrowings, and cultural borrowings, suggesting that ‘ordinary’ lexical borrowing is also capable of producing Media Lengua-type sentences. I approach the second objective by investigating two separate phenomena related to structural convergence. The first examines the complex verbal constructions that have developed in Quichua through Spanish loan translations while the second describes the type of Quichua particles that are attached to Spanish lexemes while speaking Spanish. The calquing of the complex verbal constructions from Spanish were employed when speaking standard Quichua. Since this standard form is typically used by language purists, I argue that their use of calques is a strategy of exploiting the full range of expression from Spanish without incorporating any of the Spanish lexemes which would give the appearance of ‘contamination’. The use of Quichua particles in local varieties of Spanish is a defining characteristic of Quichuacized Spanish, spoken most frequently by women and young children in the community. Although the use of Quichua particles was probably not the main catalyst engendering Media Lengua, I argue that its contribution as a source language to other ‘mixed’ varieties, such as Media Lengua, needs to be accounted for in descriptions of BML genesis. Contrary to Muysken’s representation of relatively ‘unmixed’ Spanish and Quichua as the two source languages of Media Lengua, I propose that local varieties of Spanish might have already been ‘mixed’ to a large degree before Media Lengua was created. The third objective attempts to draw a relationship between particular social variables and the use of Spanish loanwords. Whisker Boxplots and ANOVAs were used to determine which social group, if any, have been introducing new Spanish borrowings into the bilingual communities in Salcedo. Specifically, I controlled for age, education, native language, urban migration, and gender. The results indicate that none of the groups in each of the five social variables indicate higher or lower loanword use. The implication of these results are twofold: (a) when lexical borrowing occurs, it is immediately adopted as the community-wide norm and spoken by members from different backgrounds and generations, or (b) this level of Spanish borrowing (58%) is not a recent phenomenon. The fourth and final objective draws on my ethnographic research that addresses the attitudes of syncretic language use. I observed that Quichuacized Spanish and Hispanicized Quichua are highly stigmatized varieties spoken by the country’s most marginalized populations and families, yet within the community, syncretic ways of speaking are in fact the norm. It was shown that there exists a range of different linguistic definitions for ‘Chaupi Lengua’ and other syncretic language practices as well as many contrasting connotations, most of which were negative. One theme that emerged from the interviews was that speaking syncretic varieties of Quichua weakened the consultant’s claim to an indigenous identity. The linguistic and social data presented in this dissertation supports an alternative view to Muysken’s relexification hypothesis, one that has the advantage of operating with well-precedented linguistic processes and which is actually observable in the present-day Salcedo area. The results from the study on lexical borrowing are significant because they demonstrate how a dynamic bilingual speech community has gradually diversified their Quichua lexicon under intense pressure to shift toward Spanish. They also show that Hispanicized Quichua (Quichua with heavy lexical borrowing) clearly arose from adlexification and prolonged lexical borrowing, and is one of at least six identifiable speech styles found in Salcedo. These results challenge particular interpretations of language contact outcomes, such as, ones that depict sources languages as discrete and ‘unmixed.’ The bilingual continuum presented in this thesis shows on the one hand, the range of speech styles that are accessible to different speakers, and on the other hand, the overlapping, syncretic features that are shared among the different registers and language varieties. It was observed that syncretic speech styles in Salcedo are employed by different consultants in varied interactional contexts, and in turn, produce different evaluations by other fellow community members. In the current dissertation, I challenge the claim that relexification and Media Lengua-type sentences develop in isolation and without the influence of other bilingual phenomena. Based on Muysken's Media Lengua example sentences and the speech styles from the Salcedo corpus, I argue that Media Lengua may have arisen as an institutionalized variant of the highly mixed "middle ground" within the range of the Salcedo bilingual continuum discussed above. Such syncretic forms of Spanish and Quichua strongly resemble Media Lengua sentences in Muysken’s research, and therefore demonstrate how its development could have occurred through several different language contact processes and not only through relexification.

Motivação e desempenho de tarefas num trabalho de Contact Center

Mestrado em Ciências Empresariais

An investigation of contact transmission of methicillin-resistant staphylococcus aureus

Hand hygiene is critical in the healthcare setting and it is believed that methicillin-resistant Staphylococcus aureus (MRSA), for example, is transmitted from patient to patient largely via the hands of health professionals. A study has been carried out at a large teaching hospital to estimate how often the gloves of a healthcare worker are contaminated with MRSA after contact with a colonized patient. The effectiveness of handwashing procedures to decontaminate the health professionals' hands was also investigated, together with how well different healthcare professional groups complied with handwashing procedures. The study showed that about 17% (9–25%) of contacts between a healthcare worker and a MRSA-colonized patient results in transmission of MRSA from a patient to the gloves of a healthcare worker. Different health professional groups have different rates of compliance with infection control procedures. Non-contact staff (cleaners, food services) had the shortest handwashing times. In this study, glove use compliance rates were 75% or above in all healthcare worker groups except doctors whose compliance was only 27%.