891 resultados para Concavifiability of preferences
Resumo:
Technology is increasingly infiltrating all aspects of our lives and the rapid uptake of devices that live near, on or in our bodies are facilitating radical new ways of working, relating and socialising. This distribution of technology into the very fabric of our everyday life creates new possibilities, but also raises questions regarding our future relationship with data and the quantified self. By embedding technology into the fabric of our clothes and accessories, it becomes ‘wearable’. Such ‘wearables’ enable the acquisition of and the connection to vast amounts of data about people and environments in order to provide life-augmenting levels of interactivity. Wearable sensors for example, offer the potential for significant benefits in the future management of our wellbeing. Fitness trackers such as ‘Fitbit’ and ‘Garmen’ provide wearers with the ability to monitor their personal fitness indicators while other wearables provide healthcare professionals with information that improves diagnosis. While the rapid uptake of wearables may offer unique and innovative opportunities, there are also concerns surrounding the high levels of data sharing that come as a consequence of these technologies. As more ‘smart’ devices connect to the Internet, and as technology becomes increasingly available (e.g. via Wi-Fi, Bluetooth), more products, artefacts and things are becoming interconnected. This digital connection of devices is called The ‘Internet of Things’ (IoT). IoT is spreading rapidly, with many traditionally non-online devices becoming increasingly connected; products such as mobile phones, fridges, pedometers, coffee machines, video cameras, cars and clothing. The IoT is growing at a rapid rate with estimates indicating that by 2020 there will be over 25 billion connected things globally. As the number of devices connected to the Internet increases, so too does the amount of data collected and type of information that is stored and potentially shared. The ability to collect massive amounts of data - known as ‘big data’ - can be used to better understand and predict behaviours across all areas of research from societal and economic to environmental and biological. With this kind of information at our disposal, we have a more powerful lens with which to perceive the world, and the resulting insights can be used to design more appropriate products, services and systems. It can however, also be used as a method of surveillance, suppression and coercion by governments or large organisations. This is becoming particularly apparent in advertising that targets audiences based on the individual preferences revealed by the data collected from social media and online devices such as GPS systems or pedometers. This type of technology also provides fertile ground for public debates around future fashion, identity and broader social issues such as culture, politics and the environment. The potential implications of these type of technological interactions via wearables, through and with the IoT, have never been more real or more accessible. But, as highlighted, this interconnectedness also brings with it complex technical, ethical and moral challenges. Data security and the protection of privacy and personal information will become ever more present in current and future ethical and moral debates of the 21st century. This type of technology is also a stepping-stone to a future that includes implantable technology, biotechnologies, interspecies communication and augmented humans (cyborgs). Technologies that live symbiotically and perpetually in our bodies, the built environment and the natural environment are no longer the stuff of science fiction; it is in fact a reality. So, where next?... The works exhibited in Wear Next_ provide a snapshot into the broad spectrum of wearables in design and in development internationally. This exhibition has been curated to serve as a platform for enhanced broader debate around future technology, our mediated future-selves and the evolution of human interactions. As you explore the exhibition, may we ask that you pause and think to yourself, what might we... Wear Next_? WEARNEXT ONLINE LISTINGS AND MEDIA COVERAGE: http://indulgemagazine.net/wear-next/ http://www.weekendnotes.com/wear-next-exhibition-gallery-artisan/ http://concreteplayground.com/brisbane/event/wear-next_/ http://www.nationalcraftinitiative.com.au/news_and_events/event/48/wear-next http://bneart.com/whats-on/wear-next_/ http://creativelysould.tumblr.com/post/124899079611/creative-weekend-art-edition http://www.abc.net.au/radionational/programs/breakfast/smartly-dressed-the-future-of-wearable-technology/6744374 http://couriermail.newspaperdirect.com/epaper/viewer.aspx RADIO COVERAGE http://www.abc.net.au/radionational/programs/breakfast/wear-next-exhibition-whats-next-for-wearable-technology/6745986 TELEVISION COVERAGE http://www.abc.net.au/radionational/programs/breakfast/wear-next-exhibition-whats-next-for-wearable-technology/6745986 https://au.news.yahoo.com/video/watch/29439742/how-you-could-soon-be-wearing-smart-clothes/#page1
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Standard mechanism inhibitors are attractive design templates for engineering reversible serine protease inhibitors. When optimizing interactions between the inhibitor and target protease, many studies focus on the nonprimed segment of the inhibitor's binding loop (encompassing the contact β-strand). However, there are currently few methods for screening residues on the primed segment. Here, we designed a synthetic inhibitor library (based on sunflower trypsin inhibitor-1) for characterizing the P2′ specificity of various serine proteases. Screening the library against 13 different proteases revealed unique P2′ preferences for trypsin, chymotrypsin, matriptase, plasmin, thrombin, four kallikrein-related peptidases, and several clotting factors. Using this information to modify existing engineered inhibitors yielded new variants that showed considerably improved selectivity, reaching up to 7000-fold selectivity over certain off-target proteases. Our study demonstrates the importance of the P2′ residue in standard mechanism inhibition and unveils a new approach for screening P2′ substitutions that will benefit future inhibitor engineering studies.
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The test drive is a well-known step in car buying. In the emerging plug-in electric vehicle (PEV) market, however, the influence of a pre-purchase test drive on a consumer's inclination to purchase is unknown. Policy makers and industry participants both are eager to understand what factors motivate vehicle consumers at the point-of-sale. A number of researchers have used choice models to shed light on consumer perceptions of PEVs, and others have investigated consumer change in disposition toward a PEV over the course of a trial, wherein test driving a PEV may take place over a number of consecutive days, weeks or months. However, there is little written on the impact of a short-term test drive - a typical experience at dealerships or public "ride-and-drive" events. The impact of a typical test drive, often measured in minutes of driving, is not well understood. This paper first presents a synthesis of the literature on the effect of PEV test drives as they relate to consumer disposition toward PEVs. An analysis of data obtained from an Australian case study whereby attitudinal and stated preference data were collected pre- and post- test drive at public "ride-and-drive" event held Brisbane, Queensland in March 2014 using a custom-designed iPad application. Motorists' perceptions and choice preferences around PEVs were captured, revealing the relative importance of their experience behind the wheel. Using the Australian context as a case-study, this paper presents an exploratory study of consumers' stated preferences toward PEVs both before and after a short test drive.
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We examine the moving and housing preferences of middle-aged and older in Finland, a country where population composition and movement through the life course are changing. A logistic regression reveals that middle-aged, moderate income residents, renters, those who have lived in their houses only a short time, and residents who are generally dissatisfied are most likely to consider moving. Downsizing appeals to residents with lower incomes who live alone, and who have been in their current houses longer. All potential movers agree on the importance of transportation access and a neighborhood grocery store; however, those preferring to downsize are also interested in house and neighborhood design as well as services that will allow aging in place. Income limitations may create affordability problems for some potential movers.
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Understanding the key factors that influence the interaction preferences of amino acids in the folding of proteins have remained a challenge. Here we present a knowledge-based approach for determining the effective interactions between amino acids based on amino acid type, their secondary structure, and the contact based environment that they find themselves in the native state structure as measured by their number of neighbors. We find that the optimal information is approximately encoded in a 60 x 60 matrix describing the 20 types of amino acids in three distinct secondary structures (helix, beta strand, and loop). We carry out a clustering scheme to understand the similarity between these interactions and to elucidate a nonredundant set. We demonstrate that the inferred energy parameters can be used for assessing the fit of a given sequence into a putative native state structure.
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Background Interest in the use of healing gardens in healthcare settings to provide therapeutic benefits is increasing, however insight is needed to determine whether patients, patient families and friends, and staff who spend time in these gardens use these in the manner for which they were designed, and experience the benefits suggested by broader research in this field. Objective(s) Visitors to four of the LCCH gardens have left comments in ‘bench diaries’ (visitors books). Analysis of these comments yields valuable insights into the use of the gardens, enabling reflection on the design intent and outcomes and guidance regarding how the gardens might be better utilised, as well as a basis for further investigation into the use and value of the gardens. Method(s) Comments have been coded and analysed using a thematic analysis approach to identify patterns relating to the reasons for which people appear to come to the healing gardens; benefits they appear to receive from spending time there; and features and aspects of the gardens that they appear to appreciate in particular. Only comments related to the gardens have been used in this analysis, with all comments being deidentified. Outcome/Conclusion Comments left in the Adventure Garden and Secret Garden bench diaries were used for the analysis, as Staff Garden and Babies Garden bench diary comments did not relate to the garden. There were no negative comments relating to the gardens, other than one comment requesting additional benches. The vast majority of comments expressed gratitude for the space. The four most frequently observed themes from the comments left in the Secret Garden Bench Diary indicated that they were seeking ‘time out’ from their experiences of being at the hospital, a desire for a ‘dose of nature’ (greenery, beautiful garden, etc), and fresh air, and that the garden space provided a restorative experience to them in some manner. Comments in the Adventure Garden Bench Diary related predominately to the view. Analysis of the comments emphasises the importance of gardens providing multi-sensory experiences that significantly differentiate the space from the hospital ward and provide visitors with a sense of being away, of peacefulness, and of familiarity with the outside world. Positioning gardens with prospect, and solar aspect, appears important in these regards, as does the presence of visible greenery. Adequate seating in locations that provide pleasing views appears particularly important for staff and adult visitors. Whilst comments in the Bench Diaries did not indicate direct awareness of the stress and anxiety-reducing effects that research elsewhere has found from viewing plants and nature, however these effects may underpin many of these experiences that visitors did share.
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Protein conformations and dynamics can be studied by nuclear magnetic resonance spectroscopy using dilute liquid crystalline samples. This work clarifies the interpretation of residual dipolar coupling data yielded by the experiments. It was discovered that unfolded proteins without any additional structure beyond that of a mere polypeptide chain exhibit residual dipolar couplings. Also, it was found that molecular dynamics induce fluctuations in the molecular alignment and doing so affect residual dipolar couplings. The finding clarified the origins of low order parameter values observed earlier. The work required the development of new analytical and computational methods for the prediction of intrinsic residual dipolar coupling profiles for unfolded proteins. The presented characteristic chain model is able to reproduce the general trend of experimental residual dipolar couplings for denatured proteins. The details of experimental residual dipolar coupling profiles are beyond the analytical model, but improvements are proposed to achieve greater accuracy. A computational method for rapid prediction of unfolded protein residual dipolar couplings was also developed. Protein dynamics were shown to modulate the effective molecular alignment in a dilute liquid crystalline medium. The effects were investigated from experimental and molecular dynamics generated conformational ensembles of folded proteins. It was noted that dynamics induced alignment is significant especially for the interpretation of molecular dynamics in small, globular proteins. A method of correction was presented. Residual dipolar couplings offer an attractive possibility for the direct observation of protein conformational preferences and dynamics. The presented models and methods of analysis provide significant advances in the interpretation of residual dipolar coupling data from proteins.
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This study views each protein structure as a network of noncovalent connections between amino acid side chains. Each amino acid in a protein structure is a node, and the strength of the noncovalent interactions between two amino acids is evaluated for edge determination. The protein structure graphs (PSGs) for 232 proteins have been constructed as a function of the cutoff of the amino acid interaction strength at a few carefully chosen values. Analysis of such PSGs constructed on the basis of edge weights has shown the following: 1), The PSGs exhibit a complex topological network behavior, which is dependent on the interaction cutoff chosen for PSG construction. 2), A transition is observed at a critical interaction cutoff, in all the proteins, as monitored by the size of the largest cluster (giant component) in the graph. Amazingly, this transition occurs within a narrow range of interaction cutoff for all the proteins, irrespective of the size or the fold topology. And 3), the amino acid preferences to be highly connected (hub frequency) have been evaluated as a function of the interaction cutoff. We observe that the aromatic residues along with arginine, histidine, and methionine act as strong hubs at high interaction cutoffs, whereas the hydrophobic leucine and isoleucine residues get added to these hubs at low interaction cutoffs, forming weak hubs. The hubs identified are found to play a role in bringing together different secondary structural elements in the tertiary structure of the proteins. They are also found to contribute to the additional stability of the thermophilic proteins when compared to their mesophilic counterparts and hence could be crucial for the folding and stability of the unique three-dimensional structure of proteins. Based on these results, we also predict a few residues in the thermophilic and mesophilic proteins that can be mutated to alter their thermal stability.
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The conformationally restricted CHO-L-Met-Xxx-L-Phe-OY (where Xxx = Aib, Ac3c, Ac5c, Ac6c, and Ac7c; Y = H, Me) tripeptides, analogs of the chemoattractant CHO-L-Met-L-Leu-L-Phe-OH, have been synthesized in solution by classical methods and fully characterized. Compounds were compared to determine the combined effect of backbone conformational preferences and side-chain bulkiness on the relation of three-dimensional structure to biological activity. Each peptide was tested for its ability to induce granule enzyme secretion from rabbit peritoneal polymorphonuclear leukocytes. In parallel, a conformational analysis on the CHO-blocked peptide and their tertbutyloxycarbonylated synthetic precursors was performed in the crystal state and in solution using X-ray diffraction, infrared absorption, and 1H nuclear magnetic resonance. The biological and conformational data are discussed in relation to the proposed model of the chemotactic peptide receptor of rabbit neutrophils.
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Backbone conformations at 1064 asparaginyl residues in 123 non-homologous, high-resolution X-ray structures of proteins were analysed. Asn adopts conformations in left-handed x-helical region and other partially allowed regions in the Ramachandran map more readily than any other non-glycyl residue. Asn conformational clusters in the (phi,psi) regions of left-handed alpha-helix, right-handed alpha-helix and extended (beta) strands were investigated in detail for their occurrence in various secondary structures, especially in beta-turn regions. Preferences were observed for Asn conformations in different positions in various beta-turn types, including the first and fourth positions of the turn. Asparaginyl residues with extended conformations are found to occur frequently in irregular regions, although they are expected to occur predominantly in extended strands or in the third position of type II beta-turns. Asn conformations at the N-cap positions of helices strongly prefer extended conformation than alpha(L), which seems to be characteristic of non-glycyl residues at that position. In the linkers connecting two extended strands and those connecting an alpha-helix and an extended strand, Asn with alpha(L) or alpha(R) conformation is more favoured than Asn with the beta-conformation. Analysis of Asn-Asn doublets and Asn-X-Asn triplets permitted identification of conformational families in such sequences. Results of this investigation provide useful hints in modelling Asn-rich regions in proteins such as malaria parasite coat protein. (C) Munksgaard 1994.
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The peptide Boc-Gly-Dpg-Gly-Gly-Dpg-Gly-NHMe (1) has been synthesized to examine the conformational preferences of Dpg residues in the context of a poor helix promoting sequence. Single crystals of 1 were obtained in the space group P21/c with a = 13.716(2) Å, b = 12.960(2) Å, c = 22.266(4) Å, and β = 98.05(1)°; R = 6.3% for 3660 data with |Fo| > 4σ. The molecular conformation in crystals revealed that the Gly(1)-Dpg(2) segment adopts φ, ψ values distorted from those expected for an ideal type II‘ β-turn (φGly(1) = +72.0°, ψGly(1) = −166.0°; φDpg(2) = −54.0°, ψDpg(2) = −46.0°) with an inserted water molecule between Boc-CO and Gly(3)NH. The Gly(3)-Gly(4) segment adopts φ, ψ values which lie broadly in the right handed helical region (φGly(3) = −78.0°, ψGly(3) = −9.0°; φGly(4) = −80.0°, ψGly(4) = −18.0°). There is a chiral reversal at Dpg(5) which takes up φ, ψ values in the left handed helical region. The Dpg(5)-Gly(6) segment closely resembles an ideal type I‘ β-turn (φDpg(5) = +56.0°, ψDpg(5) = +32.0°; φGly(6) = +85.0°, ψGly(6) = −3.0°). Molecules of both chiral senses are found in the centrosymmetric crystal. The C-terminus forms a hydrated Schellman motif, with water insertion into the potential 6 → 1 hydrogen bond between Gly(1)CO and Gly(6)NH. NMR studies in CDCl3 suggest substantial retention of the multiple turn conformation observed in crystals. In solution the observed NOEs support local helical conformation at the two Dpg residues.
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This study analyses Augustine s concept of concupiscentia, or evil desire (together with two cognate terms, libido and cupiditas) in the context of his entire oeuvre. By the aid of systematic analysis, the concept and its development is explored in four distinct ways. It is claimed that Augustine used the concept of concupiscentia for several theological purposes, and the task of the study is to represent these distinct functions, and their connections to Augustine s general theological and philosophical convictions. The study opens with a survey on terminology. A general overview of the occurrences of the negatively connoted words for desire in Latin literature precedes a corresponding examination of Augustine s own works. In this introductory chapter it is shown that, despite certain preferences in the uses of the words, a sufficient degree of synonymy reigns so as to allow an analysis of the concept without tightly discriminating between the terms. The theological functions of concupiscentia with its distinct contexts are analysed in separate chapters. The function of concupiscentia as a divine punishment is explored first (Ch 3). It is seen how Augustine links together concupiscentia and ideas about divine justice, and finally suggests that in the inordinate, psychologically experienced sexual desire, the original theological disobedience of Adam and Eve can be perceived. Augustine was criticized for this solution already in his own times, and the analysis of the function of concupiscentia as a divine punishment ends in a discussion on the critical response of punitive concupiscentia by Julian of Aeclanum. Augustine also attached to concupiscentia another central theological function by viewing evil desire as an inward originating cause for all external evil actions. In the study, this function is analysed by surveying two formally distinct images of evil desire, i.e. as the root (radix) of all evil, and as a threefold (triplex) matrix of evil actions (Ch 4). Both of these images were based on a single verse of the Bible (1 Jn 2, 16 and 1 Tim 6, 10). This function of concupiscentia was formed both parallel to, and in answer to, Manichaean insights into concupiscentia. Being familiar with the traditional philosophical discussions on the nature and therapy of emotions, Augustine situated concupiscentia also into this context. It is acknowledged that these philosophical traditions had an obvious impact into his way of explaining psychological processes in connection with concupiscentia. Not only did Augustine implicitly receive and exploit these traditions, but he also explicitly moulded and criticized them in connection with concupiscentia. Eventually, Augustine conceives the philosophical traditions of emotions as partly useful but also partly inadequate to deal with concupiscentia (Ch 5). The role of concupiscentia in connection to divine grace and Christian renewal is analysed in the final chapter of the study. Augustine s gradual development in internalizing the effects of concupiscentia also into the life of a baptized Christian are elucidated, as are the strong limitations and mitigations Augustine makes to the concept when attaching it into the life under grace (sub gratia). A crucial part in the development of this function is played by Augustine s changing interpretation of Rom 7, and the way concupiscentia appears in Augustine s readings of this text is therefore also analysed. As a result of the analysis of these four distinct functions and contexts of concupiscentia, it is concluded that Augustine s concept of concupiscentia is fairly tightly and coherently connected to his views of central theological importance. Especially the functions of concupiscentia as a punishment and the function of concupiscentia in Christian renewal were both tightly interwoven into Augustine s view of God s being and God s grace. The study shows the importance of reading Augustine s discussions on evil desire with a constant awareness of their role in their larger context, that is, of their function in each situation. The study warns against too simplistic and unifying readings of Augustine s concupiscentia, emphasizing the need to acknowledge both the necessitating, sinful aspects of concupiscentia, and the domesticated features of concupiscentia during Christian renewal.
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The search engine log files have been used to gather direct user feedback on the relevancy of the documents presented in the results page. Typically the relative position of the clicks gathered from the log files is used a proxy for the direct user feedback. In this paper we identify reasons for the incompleteness of the relative position of clicks for deciphering the user preferences. Hence, we propose the use of time spent by the user in reading through the document as indicative of user preference for a document with respect to a query. Also, we identify the issues involved in using the time measure and propose means to address them.
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Background: MHC/HLA class II molecules are important components of the immune system and play a critical role in processes such as phagocytosis. Understanding peptide recognition properties of the hundreds of MHC class II alleles is essential to appreciate determinants of antigenicity and ultimately to predict epitopes. While there are several methods for epitope prediction, each differing in their success rates, there are no reports so far in the literature to systematically characterize the binding sites at the structural level and infer recognition profiles from them. Results: Here we report a new approach to compare the binding sites of MHC class II molecules using their three dimensional structures. We use a specifically tuned version of our recent algorithm, PocketMatch. We show that our methodology is useful for classification of MHC class II molecules based on similarities or differences among their binding sites. A new module has been used to define binding sites in MHC molecules. Comparison of binding sites of 103 MHC molecules, both at the whole groove and individual sub-pocket levels has been carried out, and their clustering patterns analyzed. While clusters largely agree with serotypic classification, deviations from it and several new insights are obtained from our study. We also present how differences in sub-pockets of molecules associated with a pair of autoimmune diseases, narcolepsy and rheumatoid arthritis, were captured by PocketMatch(13). Conclusion: The systematic framework for understanding structuralvariations in MHC class II molecules enables large scale comparison of binding grooves and sub-pockets, which is likely to have direct implications towards predicting epitopes and understanding peptide binding preferences.