55 resultados para 3 d]pyrimidine


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Inhibition of insulin-regulated aminopeptidase (IRAP) has been demonstrated to facilitate memory in rodents, making IRAP a potential target for the development of cognitive enhancing therapies. In this study, we generated a 3-D model of the catalytic domain of IRAP based on the crystal structure of leukotriene A4 hydrolase (LTA4H). This model identified two key residues at the ‘entrance’ of the catalytic cleft of IRAP, Ala427 and Leu483, which present a more open arrangement of the S1 subsite compared with LTA4H. These residues may define the size and 3-D structure of the catalytic pocket, thereby conferring substrate and inhibitor specificity. Alteration of the S1 subsite by the mutation A427Y in IRAP markedly increased the rate of substrate cleavage V of the enzyme for a synthetic substrate, although a corresponding increase in the rate of cleavage of peptide substrates Leu-enkephalin and vasopressin was was not apparent. In contrast, [L483F]IRAP demonstrated a 30-fold decrease in activity due to changes in both substrate affinity and rate of substrate cleavage. [L483F]IRAP, although capable of efficiently cleaving the N-terminal cysteine from vasopressin, was unable to cleave the tyrosine residue from either Leu-enkephalin or Cyt6-desCys1-vasopressin (2–9), both substrates of IRAP. An 11-fold reduction in the affinity of the peptide inhibitor norleucine1-angiotensin IV was observed, whereas the affinity of angiotensin IV remained unaltered. In additionm we predict that the peptide inhibitors bind to the catalytic site, with the NH2-terminal P1 residue occupying the catalytic cleft (S1 subsite) in a manner similar to that proposed for peptide substrates.

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Opening keynote address.

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Virtual Werribee is collaborative research in applying 3-D modelling and visualisation as a planning support tool in comparison to 2-D plans and drawings. It was a joint initiative involving Deakin University and the Wyndham City Council to demonstrate the use of 3-D visualisation for planning process in the actual context of a planning authority in Australia. The objective of this project was to assist the council in preparing for the revised Local Structure Plan. By reconstructing the council’s data into easily understood information, 3-D model and visualisation served as a verification and discussion tool for decision making. The integration of wider site context also provided a better understanding of the surrounding development areas. This could equip other stakeholders as well as the community to participate in council’s planning agenda activities, such as increasing the urban density and building heights limit.

Virtual Werribee included the development planning agenda, categorised as new, re-development and hypothetical. The modelling process progressed with sufficient data from the council. Some changes to the initial plan were made, including the use of CAD modelling software instead of GIS software, and production of a block model with selected detail buildings, instead of a full draped 3-D model. The council decided that the block model would be sufficient for their planning purposes. This was determined while taking into consideration the available facilities at the council.

The potentials of the model as a planning tool were demonstrated in this paper, and further compared to the council’s existing materials prepared by the project developers. The advantages of the 3-D interactive model and visualisation over the conventional materials have provided the council officer with a tool for better empowerment in the planning process. This was also evident in the increasing engagement level between the officer and the model as the process developed. As a result of this, the project scope has also expanded, finally covering the entire city.

While Virtual Werribee has the potential to better communicate council’s planning agendas to the stakeholders and the community, the key factor, coupled with its visualisation components, was its interactive capability. Property layers with aerial site image that provided a realistic background served as a virtual city platform for different users. Although limited in its analytic capability found in GIS software, this model offered high visualisation content to assist visual impact assessment through its interactive mode along with a series of still images and a simulation movie.

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The mechanical behaviours of metal foams greatly depend on their cell topology, including cell shape, cell size etc. as well as relative density and material properties of the cell wall. However, the cell shape effect on the mechanical behaviours of such materials appears to be ignored in previous research. In this paper, both analytic and finite element models are developed and employed to investigate the effect of cell shape on the mechanical behaviour of open-cell magnesium alloy (AZ91) foams under compression, including deformation modes and failure modes. For numerical modelling, both two-dimensional (2-D) and three-dimensional (3-D) finite element models are developed to predict the compressive behaviours of typical open-cell metal foams and capture the deformation modes and failure mechanisms. Two typical cell shapes i.e. cubic and diamond are taken into consideration. To validate these models, the analytic and numerical results are compared to the experimental data. Both the numerical and experimental data indicate that the cell shape significantly affects the compression behaviour of open-cell metal foams. In general, numerical results from the three-dimensional solid-element model show better agreement with the experimental results than those from other finite element models.

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Wide area surveillance requires high-resolution images of the object of interest derived possibly from only low-resolution video of the whole scene. We propose a combined tracking and resolution enhancement approach that increases the resolution of the object of interest during tracking. The key idea is the use of an object-specific 3D mesh model with which we are able to track non-planar objects across a large number of frames. This model is subdivided such that every triangle is smaller than a pixel when projected into the image to facilitate super-resolution on the model rather than on the image. We apply our approach to faces and show that it outperforms interpolation methods by achieving resolution enhancement, while being less blurred.

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In this paper, 3D textile structures, their types and applications have been discussed. Woven structures especially multi-layer woven structures are discussed in detail. A simple and quick method to produce 3D textile woven preforms on conventional looms is also given at the end of this paper. 3D textile fabrics give composite structures weight reduction with improved mechanical properties in comparison to traditionally used materials.

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Isotopic discrimination and turn-over are fundamental to the application of stable isotope ecology in animals. However, detailed information for specific tissues and species are widely lacking, notably for herbivorous species. We provide details on tissue-specific carbon and nitrogen discrimination and turn-over times from food to blood, feathers, claws, egg tissues and offspring down feathers in four species of herbivorous waterbirds. Source-to-tissue discrimination factors for carbon (δ13C) and nitrogen stable isotope ratios (δ15N) showed little variation across species but varied between tissues. Apparent discrimination factors ranged between −0.5 to 2.5‰ for δ13C and 2.8 to 5.2‰ for δ15N, and were more similar between blood components than between keratinous tissues or egg tissue. Comparing these results with published data from other species we found no effect of foraging guild on discrimination factors for carbon but a significant foraging-guild effect for nitrogen discrimination factors.

Turn-over of δ13C in tissues was most rapid in blood plasma, with a half-life of 4.3 d, whereas δ13C in blood cells had a half-life of approximately 32 d. Turn-over times for albumen and yolk in laying females were similar to those of blood plasma, at 3.2 and 6.0 d respectively. Within yolk, we found decreasing half-life times of δ13C from inner yolk (13.3 d) to outer yolk (3.1 d), related to the temporal pattern of tissue formation.

We found similarities in tissue-specific turn-over times across all avian species studied to date. Yet, while generalities regarding discrimination factors and tissue turn-over times can be made, a large amount of variation remains unexplained.

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The fabrication of tissue engineering scaffolds is a well-established field that has gained recent prominence for the in vivo repair of a variety of tissue types. Recently, increasing levels of sophistication have been engineered into adjuvant scaffolds facilitating the concomitant presentation of a variety of stimuli (both physical and biochemical) to create a range of favourable cellular microenvironments. It is here that self-assembling peptide scaffolds have shown considerable promise as functional biomaterials, as they are not only formed from peptides that are physiologically relevant, but through molecular recognition can offer synergy between the presentation of biochemical and physio-chemical cues. This is achieved through the utilisation of a unique, highly ordered, nano- to microscale 3-D morphology to deliver mechanical and topographical properties to improve, augment or replace physiological function. Here, we will review the structures and forces underpinning the formation of self-assembling scaffolds, and their application in vivo for a variety of tissue types.

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Males often produce elaborate displays that increase their attractiveness to females, and some species extend their displays to include structures or objects that are not part of their body. Such "extended phenotypes" may communicate information that cannot be transmitted by bodily signals or may provide a more reliable signal than bodily signals. However, it is unclear whether these signals are individually distinct and whether they are consistent over long periods of time. Male bowerbirds construct and decorate bowers that function in mate choice. Bower display courts constructed by male great bowerbirds (Ptilonorhynchus nuchalis) induce a visual illusion known as forced perspective for the female viewing the male's display over the court, and the quality of illusion is associated with mating success. We improved the quality of the forced perspective to determine whether males maintained it at the new higher level, decreased the perspective quality back to its original value, or allowed it to decay at random over time. We found that the original perspective quality was actively recovered to individual original values within 3 d.We measured forced perspective over the course of one breeding season and compared the forced perspective of individual males between two successive breeding seasons. We found that differences in the quality of visual illusion among males were consistent within and between two breeding seasons. This suggests that forced perspective is actively and strongly maintained at a different level by each individual male.

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Objective : To investigate the effect of front-of-pack labels on taste perception and use of table salt for currently available and sodium-reduced soups.

Design : Within-subject design.

Setting :
Sensory laboratory.

Subjects :
Participants (n 50, mean age 34·8 (sd 13·6) years) were randomly served nine soups (250 ml each) across 3 d. Servings differed in: (i) health label (i.e. no health label, reduced-salt label or Heart Foundation Tick); and (ii) sodium reduction (no reduction – benchmark, 15 % less sodium or 30 % less sodium). Before tasting, participants rated their expected salt intensity and liking. After tasting, participants rated their perceived salt intensity and liking, after which they could add salt to the soup to make it more palatable.

Results :
Reduced-salt labels generated a negative taste expectation and actual taste experience in terms of liking (P < 0·05) and perceived saltiness (P < 0·05). Perceived saltiness of sodium-reduced soups decreased more (P < 0·05), and consumers added more salt (P < 0·05), when soups carried the reduced-salt label. The tick logo and soups without health labels had no such influence on taste perception.

Conclusions :
Emphasizing salt reduction by means of a front-of-pack label can have a negative effect on taste perception and salt use, especially when consumers are able to taste differences between their regular soup and the sodium-reduced soup. Overall health logos which do not emphasize the reduction in salt are less likely to affect perceived salt intensity and therefore are viable solutions to indicate the healthiness of sodium-reduced products.

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Interobserver reliability for the classification of proximal humeral fractures is limited. The aim of this study was to test the null hypothesis that interobserver reliability of the AO classification of proximal humeral fractures, the preferred treatment, and fracture characteristics is the same for two-dimensional (2-D) and three-dimensional (3-D) computed tomography (CT). Members of the Science of Variation Group--fully trained practicing orthopaedic and trauma surgeons from around the world--were randomized to evaluate radiographs and either 2-D CT or 3-D CT images of fifteen proximal humeral fractures via a web-based survey and respond to the following four questions: (1) Is the greater tuberosity displaced? (2) Is the humeral head split? (3) Is the arterial supply compromised? (4) Is the glenohumeral joint dislocated? They also classified the fracture according to the AO system and indicated their preferred treatment of the fracture (operative or nonoperative). Agreement among observers was assessed with use of the multirater kappa (κ) measure. Interobserver reliability of the AO classification, fracture characteristics, and preferred treatment generally ranged from "slight" to "fair." A few small but statistically significant differences were found. Observers randomized to the 2-D CT group had slightly but significantly better agreement on displacement of the greater tuberosity (κ = 0.35 compared with 0.30, p < 0.001) and on the AO classification (κ = 0.18 compared with 0.17, p = 0.018). A subgroup analysis of the AO classification results revealed that shoulder and elbow surgeons, orthopaedic trauma surgeons, and surgeons in the United States had slightly greater reliability on 2-D CT, whereas surgeons in practice for ten years or less and surgeons from other subspecialties had slightly greater reliability on 3-D CT. Proximal humeral fracture classifications may be helpful conceptually, but they have poor interobserver reliability even when 3-D rather than 2-D CT is utilized. This may contribute to the similarly poor interobserver reliability that was observed for selection of the treatment for proximal humeral fractures. The lack of a reliable classification confounds efforts to compare the outcomes of treatment methods among different clinical trials and reports.

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Across an individual's life, foraging decisions will be affected by multiple intrinsic and extrinsic drivers that act at differing timescales. This study aimed to assess how female Australian fur seals allocated foraging effort and the behavioural changes used to achieve this at three temporal scales: within a day, across a foraging trip and across the final six months of the lactation period. Foraging effort peaked during daylight hours (57% of time diving) with lulls in activity just prior to and after daylight. Dive duration reduced across the day (196 s to 168 s) but this was compensated for by an increase in the vertical travel rate (1500–1600 m•h−1) and a reduction in postdive duration (111–90 s). This suggests physiological constraints (digestive costs) or prey availability may be limiting mean dive durations as a day progresses. During short trips (<2.9 d), effort remained steady at 55% of time diving, whereas, on long trips (>2.9 d) effort increased up to 2–3 d and then decreased. Dive duration decreased at the same rate in short and long trips, respectively, before stabilising (long trips) between 4–5 d. Suggesting that the same processes (digestive costs or prey availability) working at the daily scale may also be present across a trip. Across the lactation period, foraging effort, dive duration and vertical travel rate increased until August, before beginning to decrease. This suggests that as the nutritional demands of the suckling pup and developing foetus increase, female effort increases to accommodate this, providing insight into the potential constraints of maternal investment in this species

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Effect of weighted vest suit worn during daily activities on running speed, jumping power, and agility in young men. J Strength Cond Res 26(11): 3030-3035, 2012-Previous weighted vest interventions using exercise in addition to hypergravity have been successful in improving postural balance and power production capacity. The purpose of this study was to investigate if hypergravity alone in daily activities excluding sporting activities is effective in improving neuromuscular performance in young adults. Eight male subjects (age = 32 [SD: 6] years, height = 178 [5] cm, and body mass = 81 [8] kg) wore weighted vests 3 d.wk-1 for 3 weeks during waking hours, excluding sporting activities. Control group comprised 9 male subjects (age = 32 [6] years, height = 179 [5] cm, and body mass = 83 [9] kg). Performance was assessed with countermovement jump (body mass normalized peak power), figure-of-8 running test (running time), and running velocity test at baseline and at the end of the intervention. At baseline, the groups did not differ from each other (multivariate analysis of variance [MANOVA] p = 0.828). A significant group × time interaction (MANOVA F = 5.1, p = 0.015) was observed for performance variables. Analysis of covariance indicated that the intervention improved the figureof- 8 running time (p = 0.016) (22.2 vs. 0.5%), whereas normalized peak power (0.0 vs. 1.6%) and running velocity (1.3 vs. 0.1%) were unaffected (p ≥ 0.095). Wearing weighted vests was effective in slightly improving agility-related performance in young men. Because the effect was small, applying hypergravity only during exercise probably suffices. It appears that a proper volume and intensity of hypergravity could be in the order of 5-10% body weight vest worn during up to 50% of the training sessions for a period of 3-4 weeks.