A novel 2D-based approach to the discovery of candidate substrates for the metalloendopeptidase meprin

In the past, protease-substrate finding proved to be rather haphazard and was executed by in vitro cleavage assays using singly selected targets. In the present study, we report the first protease proteomic approach applied to meprin, an astacin-like metalloendopeptidase, to determine physiological substrates in a cell-based system of Madin-Darby canine kidney epithelial cells. A simple 2D IEF/SDS/PAGE-based image analysis procedure was designed to find candidate substrates in conditioned media of Madin-Darby canine kidney cells expressing meprin in zymogen or in active form. The method enabled the discovery of hitherto unknown meprin substrates with shortened (non-trypsin-generated) N- and C-terminally truncated cleavage products in peptide fragments upon LC-MS/MS analysis. Of 22 (17 nonredundant) candidate substrates identified, the proteolytic processing of vinculin, lysyl oxidase, collagen type V and annexin A1 was analysed by means of immunoblotting validation experiments. The classification of substrates into functional groups may propose new functions for meprins in the regulation of cell homeostasis and the extracellular environment, and in innate immunity, respectively.

RAPID SPACE TRAJECTORY GENERATION USING A FOURIER SERIES SHAPE-BASED APPROACH

With the insatiable curiosity of human beings to explore the universe and our solar system, it is essential to benefit from larger propulsion capabilities to execute efficient transfers and carry more scientific equipment. In the field of space trajectory optimization the fundamental advances in using low-thrust propulsion and exploiting the multi-body dynamics has played pivotal role in designing efficient space mission trajectories. The former provides larger cumulative momentum change in comparison with the conventional chemical propulsion whereas the latter results in almost ballistic trajectories with negligible amount of propellant. However, the problem of space trajectory design translates into an optimal control problem which is, in general, time-consuming and very difficult to solve. Therefore, the goal of the thesis is to address the above problem by developing a methodology to simplify and facilitate the process of finding initial low-thrust trajectories in both two-body and multi-body environments. This initial solution will not only provide mission designers with a better understanding of the problem and solution but also serves as a good initial guess for high-fidelity optimal control solvers and increases their convergence rate. Almost all of the high-fidelity solvers enjoy the existence of an initial guess that already satisfies the equations of motion and some of the most important constraints. Despite the nonlinear nature of the problem, it is sought to find a robust technique for a wide range of typical low-thrust transfers with reduced computational intensity. Another important aspect of our developed methodology is the representation of low-thrust trajectories by Fourier series with which the number of design variables reduces significantly. Emphasis is given on simplifying the equations of motion to the possible extent and avoid approximating the controls. These facts contribute to speeding up the solution finding procedure. Several example applications of two and three-dimensional two-body low-thrust transfers are considered. In addition, in the multi-body dynamic, and in particular the restricted-three-body dynamic, several Earth-to-Moon low-thrust transfers are investigated.

Performance Availability and Anticipatory Change Planning of Intralogistics Systems: A Simulation-Based Approach

In recent years, the ability to respond to real time changes in operations and reconfigurability in equipment are likely to become essential characteristics for next generation intralogistics systems as well as the level of automation, cost effectiveness and maximum throughput. In order to cope with turbulences and the increasing level of dynamic conditions, future intralogistics systems have to feature short reaction times, high flexibility in processes and the ability to adapt to frequent changes. The increasing autonomy and complexity in processes of today’s intralogistics systems requires new and innovative management approaches, which allow a fast response to (un)anticipated events and adaptation to changing environment in order to reduce the negative consequences of these events. The ability of a system to respond effectively a disruption depends more on the decisions taken before the event than those taken during or after. In this context, anticipatory change planning can be a usable approach for managers to make contingency plans for intralogistics systems to deal with the rapidly changing marketplace. This paper proposes a simulation-based decision making framework for the anticipatory change planning of intralogistics systems. This approach includes the quantitative assessments based on the simulation in defined scenarios as well as the analysis of performance availability that combines the flexibility corridors of different performance dimensions. The implementation of the approach is illustrated on a new intralogistics technology called the Cellular Transport System.

Potential Economic Returns from Selling Beef in a Specified Value-Based Market

Three groups of steers--one theoretical group and two experimental groups—were evaluated for marketing cattle live, as boxed beef, and grade and yield when the live price was $71 to $73/cwt, grade and yield price $125/cwt for Choice yield grade 3 carcasses with $20/cwt discount for Select carcasses, and in a commodity-trim or close-trim boxed beef market. The results show that the value of highyielding steers can be significantly increased if sold in a close-trim boxed beef market. The close-trim premiums ranged from $5.06 per head for Select close-trim yield grade 4 carcasses to $87.18 per head for close-trim Choice yield grade 1 carcasses. A group of experimental steers averaging 82% Choice and 60% yield grades 1 and 2 returned an additional $104 in the close-trim boxed market compared with selling live for $73/cwt. Another group of experimental steers averaging 21% Choice, 18% Standard, and 93% yield grades 1 and 2 had $29 per head greater return than if the steers had been sold live for $71/cwt. These comparisons emphasize the importance of knowing how cattle will potentially grade before selecting an alternative marketing strategy. This prior knowledge is most important when the spread in price between Choice and Select is high. Producers need to learn more about their cattle to predict how the cattle may grade for a specified value-based market.

Strategies for Optimizing Value of Finished Cattle in Value-Based Marketing Grids

Performance and carcass data from 624 steers in three experiments were used to evaluate potential strategies that might be used with incoming feeders to remove animals that produce low value carcasses when cattle are sold in a valuebased grid. Removing 10% of the carcasses with the lowest net value from each group increased the overall average net value of the remaining carcasses $17.50 to $21.09. Carcass weight was found to be the most significant factor determining net value of the carcass. Gain of the steers during the first 3 to 5 weeks of the feeding period was significantly related to average final gain and carcass value, but accounted for a small portion of the overall variation in gain or carcass value. Use of initial gain was successful in identifying ten of the sixty-four carcasses with least net value in a value-based grid. Adding frame score and measurement of initial thickness of backfat along with initial gain did not significantly improve identification of the low-value carcasses. Sorting the steers as feeders based on frame score and initial thickness of backfat resulted in differences in performance and carcass measurements. The low-value carcasses tended to be concentrated in the smaller-framed steers.

Effect of Frame Size and Hormone Implant on Performance and Carcass Characteristics of Finishing Yearling Heifers: Returns to a Value-Based Market

Four groups of yearling heifers representing different frame sizes—small, medium, and large Angus and medium Simmental—were fed high-grain finishing diets to average Low Choice quality grade. Half the heifers were implanted with estrogen and trenbolone acetate. Backfat and ribeye area were measured by ultrasound four times during the study to assess growth of muscle and fat. Increasing frame size resulted in increased feed intake, greater rates of gain, and a trend towards reduced feed conversion. Greater returns would have been realized from each of the four groups had they been sold in a premium market based on yield grade rather than the conventional grade and yield market. Increasing frame size resulted in greater returns to the value-based market. Implants increased rate of gain and improved feed conversion but did not result in significantly greater returns to the value-based market compared with the grade and yield market. Ribeye area and backfat increased with body weight and time on feed. Increase in ribeye area was linear with time, whereas accumulation of backfat was exponential. Rate of increase in area of ribeye tended to increase and backfat tended to decrease as frame size increased. Implants increased rate of increase in ribeye area but had no effect on rate of deposition of subcutaneous fat. Equations describing growth of ribeye area and backfat for each group predicted average growth for the heifers but did not predict growth of individual heifers. Final carcass yield grade was related to initial thickness of backfat but not to initial ribeye area. These results indicate that the type of cattle selected to be fed for a premium market based on yield grade is important to the success of the program. More work is needed to develop growth equations from ultrasound measurements, but ultrasound will likely be a useful tool in selecting feeder cattle for a value-based market.

A social network-based approach to assess de facto independence of regulatory agencies

This article uses a policy network perspective to assess the independence of regulatory agencies (RAs) in liberalized public utility sectors. We focus on the de facto independence of RAs from elected politicians, regulatees and other co-regulators. We go further than previous studies, which only undertook a general analysis of the de jure independence of RAs from political authorities. Specifically, we apply a social network analysis (SNA), which concentrates on the attributes and relational profiles of all actors involved in new regulatory arrangements. The concept of de facto independence is applied to the Swiss telecommunications sector in order to provide initial empirical insights. Results clearly show that SNA indicators are an appropriate tool to identify the de facto independence of RAs and can improve knowledge about the issues arising from the emergence of the ‘regulatory State’.

Re-thinking resuscitation: leaving blood pressure cosmetics behind and moving forward to permissive hypotension and a tissue perfusion-based approach

Definitions of shock and resuscitation endpoints traditionally focus on blood pressures and cardiac output. This carries a high risk of overemphasizing systemic hemodynamics at the cost of tissue perfusion. In line with novel shock definitions and evidence of the lack of a correlation between macro- and microcirculation in shock, we recommend that macrocirculatory resuscitation endpoints, particularly arterial and central venous pressure as well as cardiac output, be reconsidered. In this viewpoint article, we propose a three-step approach of resuscitation endpoints in shock of all origins. This approach targets only a minimum individual and context-sensitive mean arterial blood pressure (for example, 45 to 50 mm Hg) to preserve heart and brain perfusion. Further resuscitation is exclusively guided by endpoints of tissue perfusion irrespectively of the presence of arterial hypotension ('permissive hypotension'). Finally, optimization of individual tissue (for example, renal) perfusion is targeted. Prospective clinical studies are necessary to confirm the postulated benefits of targeting these resuscitation endpoints.

A boundary value problem approach to too-short arc optical track association

Given a short-arc optical observation with estimated angle-rates, the admissible region is a compact region in the range / range-rate space defined such that all likely and relevant orbits are contained within it. An alternative boundary value problem formulation has recently been proposed where range / range hypotheses are generated with two angle measurements from two tracks as input. In this paper, angle-rate information is reintroduced as a means to eliminate hypotheses by bounding their constants of motion before a more computationally costly Lambert solver or differential correction algorithm is run.