Proteogenomics of selective susceptibility to endotoxin using circulating acute phase biomarkers and bioassay development in sheep: a review

Scientists have injected endotoxin into animals to investigate and understand various pathologies and novel therapies for several decades. Recent observations have shown that there is selective susceptibility to Escherichia coli lipopolysaccharide (LPS) endotoxin in sheep, despite having similar breed characteristics. The reason behind this difference is unknown, and has prompted studies aiming to explain the variation by proteogenomic characterisation of circulating acute phase biomarkers. It is hypothesised that genetic trait, biochemical, immunological and inflammation marker patterns contribute in defining and predicting mammalian response to LPS. This review discusses the effects of endotoxin and host responses, genetic basis of innate defences, activation of the acute phase response (APR) following experimental LPS challenge, and the current approaches employed in detecting novel biomarkers including acute phase proteins (APP) and micro-ribonucleic acids (miRNAs) in serum or plasma. miRNAs are novel targets for elucidating molecular mechanisms of disease because of their differential expression during pathological, and in healthy states. Changes in miRNA profiles during a disease challenge may be reflected in plasma. Studies show that gel-based two-dimensional electrophoresis (2-DE) coupled with either matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) or liquid chromatography-mass spectrometry (LC-MS/MS) are currently the most used methods for proteome characterisation. Further evidence suggests that proteomic investigations are preferentially shifting from 2-DE to non-gel based LC-MS/MS coupled with data extraction by sequential window acquisition of all theoretical fragment-ion spectra (SWATH) approaches that are able to identify a wider range of proteins. Enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), and most recently proteomic methods have been used to quantify low abundance proteins such as cytokines. qRT-PCR and next generation sequencing (NGS) are used for the characterisation of miRNA. Proteogenomic approaches for detecting APP and novel miRNA profiling are essential in understanding the selective resistance to endotoxin in sheep. The results of these methods could help in understanding similar pathology in humans. It might also be helpful in the development of physiological and diagnostic screening assays for determining experimental inclusion and endpoints, and in clinical trials in future

A CCG virtual system for big data application communication costs analysis

Network topology and routing are two important factors in determining the communication costs of big data applications at large scale. As for a given Cluster, Cloud, or Grid system, the network topology is fixed and static or dynamic routing protocols are preinstalled to direct the network traffic. Users cannot change them once the system is deployed. Hence, it is hard for application developers to identify the optimal network topology and routing algorithm for their applications with distinct communication patterns. In this study, we design a CCG virtual system (CCGVS), which first uses container-based virtualization to allow users to create a farm of lightweight virtual machines on a single host. Then, it uses software-defined networking (SDN) technique to control the network traffic among these virtual machines. Users can change the network topology and control the network traffic programmingly, thereby enabling application developers to evaluate their applications on the same system with different network topologies and routing algorithms. The preliminary experimental results through both synthetic big data programs and NPB benchmarks have shown that CCGVS can represent application performance variations caused by network topology and routing algorithm.

Click functionalization of methacrylate-based hydrogels and their cellular response

Methacrylate-based hydrogels, such as homo- and copolymers of 2-hydroxyethyl methacrylate (HEMA), have demonstrated significant potential for use in biomedical applications. However, many of these hydrogels tend to resist cell attachment and growth at their surfaces, which can be detrimental for certain applications. In this article, glycidyl methacrylate (GMA) was copolymerized with HEMA to generate gels functionalized with epoxide groups. The epoxides were then functionalized by two sequential click reactions, namely, nucleophilic ring opening of epoxides with sodium azide and then coupling of small molecules and peptides via Huisgen's copper catalyzed 1,3-dipolar cycloaddition of azides with alkynes. Using this strategy it was possible to control the degree of functionalization by controlling the feed ratio of monomers during polymerization. In vitro cell culture of human retinal pigment epithelial cell line (ARPE-19) with the hydrogels showed improved cell adhesion, growth and proliferation for hydrogels that were functionalized with a peptide containing the RGD sequence. In addition, the cell attachment progressively decreased with increasing densities of the RGD containing peptide. In summary, a facile methodology has been presented that gives rise to hydrogels with controlled degrees of functionality, such that the cell response is directly related to the levels and nature of that functionality.

Respite & Recoery at Al Wakra

International Design Competition for Qatar Psychiatric Hospital. The scheme for the Al Wakra Respite and Recovery Centre delivers on an all-in attitude toward evidence-based design. It sets new benchmarks in so many ways: the way it allows excellent separation between patient cohorts without unnecessary or visible restrictions; the way it allows sharing of most of the clinical kit and spaces; the way services reticulation and facilities management takes place without compromising security and safety; the ways It abandons the institutional axioms that are still so ubiquitous elsewhere, so it can appear as the friendly, welcoming and wholesome; the way it allows incredible flexibility to allow changes or flexion on the fly; the way it has such ‘good bones’ for more structural changes as the future unfolds. But most importantly, the scheme will be exemplary in the way the building itself plays a role in promoting the recovery and mental well-being of its residents. Like no other, the Centre will rise to the challenges of supporting and inspiring an exemplary mental health service and promote the well-being of the patients. The 160 bed scheme allows for 43,000m2 of landscape, packed with wholesome things to do and experience. The Aspire zone even has stables and a falconry, both to celebrate the love that Qatari people have for horses and birds.

How talk and interaction unfold in a digitally enabled preschool classroom

The use of mobile digital devices, such as laptops and tablets, has implications for how teachers interact with young students within the institutional context of educational settings. This article examines language and participation in a digitally enabled preschool classroom as students engage with teachers and peers. Ethnomethodology, conversation analysis and membership categorization analysis are used to explicate video-recorded episodes of students (aged 3-5 years) interacting while using a laptop and a tablet. Attending to the sequential organization (when, how) and the context relevance (where) of talk and interaction, analysis shows how the intersection of interactions involving the teacher, students and digital devices, shape the ways that talk and interactions unfold. Analysis found that the teacher-student interactions were jointly arranged around a participation framework that included: 1) the teacher’s embodied action that mobilizes an accompanying action by a student, 2) allocation of turn-taking and participation while using a digital device and, 3) the affordances of the digital device in relation to the participants’ social organization. In this way, it is possible to understand not just what a digital device is or does, but the affordances of what it makes possible in constituting teachers’ and students’ social and learning relationships.

Studies of water and electrolyte movement from oral rehydration solutions (rice- and glucose-based) across a normal and secreting gut using a dual isotope tracer technique in a rat perfusion model

Aims: To establish a model to measure bidirectional flow of water from a glucose oral rehydration solution (G-ORS) and a newly developed rice-based oral rehydration solution (R-ORS) using a dual isotope tracer technique in a rat perfusion model. To measure net water, sodium and potassium absorption from the ORS. Methods: In viva steady-state perfusion studies were carried out in normal and secreting (induced by cholera toxin) rat small intestine (n = 11 in each group). To determine bidirectional flow of water from the ORS the animals were initially labelled with tritium, and deuterium was added to the perfusion solution. Sequential perfusate and blood samples were collected after attainment of steady-state conditions and analysed for water and electrolyte content. Results: There was a significant increase in net water absorption from the R-ORS compared to the G-ORS in both the normal (P < 0.02) and secreting intestine (P < 0.05). Water efflux was significantly reduced in the R-ORS group compared to the G-ORS group in both the normal (P < 0.01) and the secreting intestine (P < 0.01). There was an increase in sodium absorption in the R-ORS group compared to the G-ORS. The G-ORS produced a significantly greater blood glucose level at 75 min compared to the R-ORS (P < 0.03) in the secreting intestine. Conclusions: This study demonstrates the improved water absorption from a rice-based ORS in both the normal and secreting intestine. Evidence that the absorption of water may be influenced by the osmolality of the ORS was also demonstrated.

The high temperature mechanical characteristics of superplastic 3 mol% yttria stabilized zirconia

A detailed study was undertaken to characterize the deformation behavior of a superplastic 3 mol% yttria-stabilized tetragonal zirconia (3YTZ) over a wide range of strain rates, temperatures and grain sizes. The experimental data were analyzed in terms of the following equation for high temperature deformation: Image Full-size image ∞ σn d−pexp(−Q/RT), where Image Full-size image is the strain rate, σ is the flow stress, d is the grain size, Q is the activation energy, R is the gas constant, T is the absolute temperature, and n and p are constants termed the stress exponent and the inverse grain size exponent, respectively. The experimental data over a wide range of stresses revealed a transition in stress exponent. Deformation in the low and high stress regions was associated with n not, vert, similar 3 and p not, vert, similar 1, and n not, vert, similar 2 and p not, vert, similar 3, respectively. The transition stress between the two regions decreased with increasing grain size. The activation energy was similar for both regions with a value of not, vert, similar 550 kJ mol−1. Microstructural measurements revealed that grains remained essentially equiaxed after the accumulation of large strains, and very limited concurrent grain growths occurred in most experiments. Assessment of possible rate controlling creep mechanisms and comparison with previous studied indicate that in the n not, vert, similar 2 region, deformation occurs by a grain boundary sliding process whose rate is independent of impurity content. Deformation in the n not, vert, similar 3 region is controlled by an interface reaction that is highly sensitive to impurity content. It is concluded that an increase in impurity content increases yttrium segregation to grain boundaries, which enhances the rate of the interface reaction, thereby decreasing the apparent transition stress between the n not, vert, similar 2 and n not, vert, similar 3 regions. This unified approach incorporating two sequential mechanisms can rationalize many of the apparently dissimilar results that have been reported previously for deformation of 3YTZ.

The influence of trace impurities on the mechanical characteristics of a superplastic 2 mol% yttria stabilized zirconia

In contrast to metallic alloys, the mechanical characteristics of superplastic ceramics are very sensitive to minor changes in levels of trace impurities. In the present study, the mechanical behavior of a 2 mol% yttria stabilized tetragonal zirconia was studied in tension and compression in two batches of material, with small variations in levels of trace impurities, to examine the influence of stress axis and impurity content on the deformation behavior. The mechanical properties of the material were characterized in terms of the expression: (epsilon)over dot proportional to sigma(n) where (epsilon)over dot is the strain rate, sigma is the stress and n is termed the stress exponent. The mechanical behavior of the ceramic was identical in tension and compression, for a material with a given level of impurity. The high purity specimens exhibited a transition from a stress exponent of similar to 3 to similar to 2 with an increase in stress, whereas the low purity material displayed only n similar to 2 behavior over the entire stress range studied. Detailed high resolution and analytical electron microscopy studies revealed that there was no amorphous phase at interfaces in both batches of material; however, segregation of Al at interfaces was detected only in the low purity material. The observed transition in stress exponents can be rationalized in terms of two sequential mechanisms: grain boundary sliding with n similar to 2 and interface reaction controlled grain boundary sliding with n similar to 3. The transition from n similar to 3 to similar to 2 occurred at lower stresses with an increase in the grain size and a decrease in the purity level.

Finite Element Solution Of Surface-Tension Driven Flows In Laser Surface-Melting

Lasers are very efficient in heating localized regions and hence they find a wide application in surface treatment processes. The surface of a material can be selectively modified to give superior wear and corrosion resistance. In laser surface-melting and welding problems, the high temperature gradient prevailing in the free surface induces a surface-tension gradient which is the dominant driving force for convection (known as thermo-capillary or Marangoni convection). It has been reported that the surface-tension driven convection plays a dominant role in determining the melt pool shape. In most of the earlier works on laser-melting and related problems, the finite difference method (FDM) has been used to solve the Navier Stokes equations [1]. Since the Reynolds number is quite high in these cases, upwinding has been used. Though upwinding gives physically realistic solutions even on a coarse grid, the results are inaccurate. McLay and Carey have solved the thermo-capillary flow in welding problems by an implicit finite element method [2]. They used the conventional Galerkin finite element method (FEM) which requires that the pressure be interpolated by one order lower than velocity (mixed interpolation). This restricts the choice of elements to certain higher order elements which need numerical integration for evaluation of element matrices. The implicit algorithm yields a system of nonlinear, unsymmetric equations which are not positive definite. Computations would be possible only with large mainframe computers.Sluzalec [3] has modeled the pulsed laser-melting problem by an explicit method (FEM). He has used the six-node triangular element with mixed interpolation. Since he has considered the buoyancy induced flow only, the velocity values are small. In the present work, an equal order explicit FEM is used to compute the thermo-capillary flow in the laser surface-melting problem. As this method permits equal order interpolation, there is no restriction in the choice of elements. Even linear elements such as the three-node triangular elements can be used. As the governing equations are solved in a sequential manner, the computer memory requirement is less. The finite element formulation is discussed in this paper along with typical numerical results.

ACE research briefing paper 009: Global Entrepreneurship Monitor: GEM Australia - 2014 National Report

Most policymakers and academics agree that entrepreneurship is critical to the development and wellbeing of society. Entrepreneurs create jobs. They drive and shape innovation, thereby speeding up structural changes in the economy. By introducing new competition they contribute indirectly to increased productivity and overall economic activity. Entrepreneurship is thus a catalyst for economic growth and national competitiveness. In 2014, the Global Entrepreneurship Monitor (GEM)conducted its 15th annual survey of the rate and profile of entrepreneurial activity around the globe. GEM interviewed over 206,000 adults aged 18–64 in 70 economies, spanning diverse geographies and a range of development levels. The Australian Centre for Entrepreneurship Research (ACE) participated as the Australian GEM partner, surveying 2,177 Australian adults. This report provides a summary of entrepreneurship in Australia as measured by GEM, and benchmarks this against other countries. We compare the level of entrepreneurship in the population across different phases of the entrepreneurial process, and provide a profile of some key characteristics of entrepreneurs and the businesses they are starting. We also report on some of the institutional and framework conditions that support entrepreneurship.

A pattern adaptive thinning algorithm

A simple sequential thinning algorithm for peeling off pixels along contours is described. An adaptive algorithm obtained by incorporating shape adaptivity into this sequential process is also given. The distortions in the skeleton at the right-angle and acute-angle corners are minimized in the adaptive algorithm. The asymmetry of the skeleton, which is a characteristic of sequential algorithm, and is due to the presence of T-corners in some of the even-thickness pattern is eliminated. The performance (in terms of time requirements and shape preservation) is compared with that of a modern thinning algorithm.

An optimal design for screening trials

Yao, Begg, and Livingston (1996, Biometrics 52, 992-1001) considered the optimal group size for testing a series of potentially therapeutic agents to identify a promising one as soon as possible for given error rates. The number of patients to be tested with each agent was fixed as the group size. We consider a sequential design that allows early acceptance and rejection, and we provide an optimal strategy to minimize the sample sizes (patients) required using Markov decision processes. The minimization is under the constraints of the two types (false positive and false negative) of error probabilities, with the Lagrangian multipliers corresponding to the cost parameters for the two types of errors. Numerical studies indicate that there can be a substantial reduction in the number of patients required.

Decision-theoretic designs for dose-finding clinical trials with multiple outcomes

A decision-theoretic framework is proposed for designing sequential dose-finding trials with multiple outcomes. The optimal strategy is solvable theoretically via backward induction. However, for dose-finding studies involving k doses, the computational complexity is the same as the bandit problem with k-dependent arms, which is computationally prohibitive. We therefore provide two computationally compromised strategies, which is of practical interest as the computational complexity is greatly reduced: one is closely related to the continual reassessment method (CRM), and the other improves CRM and approximates to the optimal strategy better. In particular, we present the framework for phase I/II trials with multiple outcomes. Applications to a pediatric HIV trial and a cancer chemotherapy trial are given to illustrate the proposed approach. Simulation results for the two trials show that the computationally compromised strategy can perform well and appear to be ethical for allocating patients. The proposed framework can provide better approximation to the optimal strategy if more extensive computing is available.

An extension of the continual reassessment method using decision theory

The primary goal of a phase I trial is to find the maximally tolerated dose (MTD) of a treatment. The MTD is usually defined in terms of a tolerable probability, q*, of toxicity. Our objective is to find the highest dose with toxicity risk that does not exceed q*, a criterion that is often desired in designing phase I trials. This criterion differs from that of finding the dose with toxicity risk closest to q*, that is used in methods such as the continual reassessment method. We use the theory of decision processes to find optimal sequential designs that maximize the expected number of patients within the trial allocated to the highest dose with toxicity not exceeding q*, among the doses under consideration. The proposed method is very general in the sense that criteria other than the one considered here can be optimized and that optimal dose assignment can be defined in terms of patients within or outside the trial. It includes as an important special case the continual reassessment method. Numerical study indicates the strategy compares favourably with other phase I designs.

Recipient v russkom razgovore : o raspredelenii funkcij mezhdu otvetami da, nu i tak

The study investigates actions by recipients in spontaneous Russian conversations by focusing on DA, NU and TAK, when they are used as responses to the main speaker's larger on-going turn. The database for the study consists of some 7 hours of spontaneous conversations. The participants of the conversations come from different parts of Russia. The use of DA, NU and TAK was analyzed by applying the method of ethnomethodological conversation analysis from the point of view of the type of the context, the sequential placement of the response and its manner of production. The particles were analyzed both in contexts in which they responded to an informing and in affective contexts. The particles NU and TAK were used by the speakers almost exclusively in informing contexts, whereas DA was the central response type in affective contexts. DA was also the most common response to information with affective implications. The information, to which the particle NU provided as response, was often unspesific and projected a spesification or explanation by its speaker as the next action. DA and TAK, by contrast, treated the information as one that could be followed and was sufficient in its local context. As a response to parenthetical information NU responded to information that was only loosely connected with the mainline of talk. The particle DA, by contrast, was used as a response to such parenthetical information, which was more crucial for the larger on-going activity. Only NU was used as a response that invited the main speaker to continue a turn that she or he had offered as possibly complete. NU was also used by the recipient after her or his own contribution as a continuer. In affective contexts, DA expressed, depending on its more spesific context, not only agreement but also other functions, such as giving up arguing or prior knowledge on the topic being discussed. In addition DA responses were used to display empathy and identification with the state of affairs expressed by the co-participant. NU, by contrast, was seldom used as a response to a turn that expressed affect. When it was used in affective contexts, it displayed agreement with the co-participant or just registered an assessment by her or him.