Self-assembly of sensory neurons into ganglia-like microtissues

Unraveling intra- and inter-cellular signaling networks managing cell-fate control, coordinating complex differentiation regulatory circuits and shaping tissues and organs in living systems remain major challenges in the post-genomic era. Resting on the laurels of past-century monolayer culture technologies, the cell culture community has only recently begun to appreciate the potential of three-dimensional mammalian cell culture systems to reveal the full scope of mechanisms orchestrating the tissue-like cell quorum in space and time. Capitalizing on gravity-enforced self-assembly of monodispersed primary embryonic mouse cells in hanging drops, we designed and characterized a three-dimensional cell culture model for ganglion-like structures. Within 24h, a mixture of mouse embryonic fibroblasts (MEF) and cells, derived from the dorsal root ganglion (DRG) (sensory neurons and Schwann cells) grown in hanging drops, assembled to coherent spherical microtissues characterized by a MEF feeder core and a peripheral layer of DRG-derived cells. In a time-dependent manner, sensory neurons formed a polar ganglion-like cap structure, which coordinated guided axonal outgrowth and innervation of the distal pole of the MEF feeder spheroid. Schwann cells, present in embryonic DRG isolates, tended to align along axonal structures and myelinate them in an in vivo-like manner. Whenever cultivation exceeded 10 days, DRG:MEF-based microtissues disintegrated due to an as yet unknown mechanism. Using a transgenic MEF feeder spheroid, engineered for gaseous acetaldehyde-inducible interferon-beta (ifn-beta) production by cotransduction of retro-/ lenti-viral particles, a short 6-h ifn-beta induction was sufficient to rescue the integrity of DRG:MEF spheroids and enable long-term cultivation of these microtissues. In hanging drops, such microtissues fused to higher-order macrotissue-like structures, which may pave the way for sophisticated bottom-up tissue engineering strategies. DRG:MEF-based artificial micro- and macrotissue design demonstrated accurate key morphological aspects of ganglions and exemplified the potential of self-assembled scaffold-free multicellular micro-/macrotissues to provide new insight into organogenesis.

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.

(Table 1) Reproductive performance of brown skua pairs with and without feeding territories at Potter Peninsula/King George Island from 1998/1999 to 2000/2001

In the maritime Antarctic, brown skuas (Catharacta antarctica lonnbergi) show two foraging strategies: some pairs occupy feeding territories in penguin colonies, while others can only feed in unoccupied areas of a penguin colony without defending a feeding territory. One-third of the studied breeding skua population in the South Shetlands occupied territories of varying size (48 to >3,000 penguin nests) and monopolised 93% of all penguin nests in sub-colonies. Skuas without feeding territories foraged in only 7% of penguin sub-colonies and in part of the main colony. Females owning feeding territories were larger in body size than females without feeding territories; no differences in size were found in males. Territory holders permanently controlled their resources but defence power diminished towards the end of the reproductive season. Territory ownership guaranteed sufficient food supply and led to a 5.5 days earlier egg-laying and chick-hatching. Short distances between nest and foraging site allowed territorial pairs a higher nest-attendance rate such that their chicks survived better (71%) than chicks from skua pairs without feeding territories (45%). Due to lower hatching success in territorial pairs, no difference in breeding success of pairs with and without feeding territories was found in 3 years. We conclude that skuas owning feeding territories in penguin colonies benefit from the predictable and stable food resource by an earlier termination of the annual breeding cycle and higher offspring survivorship.

Development of mathematical models to elaborate strategies, select alternatives and development of plans for adaptation of communities to climate change in different geographical areas including costs to implement it.

There is evidence that the climate changes and that now, the change is influenced and accelerated by the CO2 augmentation in atmosphere due to combustion by humans. Such ?Climate change? is on the policy agenda at the global level, with the aim of understanding and reducing its causes and to mitigate its consequences. In most countries and international organisms UNO (e.g. Rio de Janeiro 1992), OECD, EC, etc . . . the efforts and debates have been directed to know the possible causes, to predict the future evolution of some variable conditioners, and trying to make studies to fight against the effects or to delay the negative evolution of such. The Protocol of Kyoto 1997 set international efforts about CO2 emissions, but it was partial and not followed e.g. by USA and China . . . , and in Durban 2011 the ineffectiveness of humanity on such global real challenges was set as evident. Among all that, the elaboration of a global model was not boarded that can help to choose the best alternative between the feasible ones, to elaborate the strategies and to evaluate the costs, and the authors propose to enter in that frame for study. As in all natural, technological and social changes, the best-prepared countries will have the best bear and the more rapid recover. In all the geographic areas the alternative will not be the same one, but the model must help us to make the appropriated decision. It is essential to know those areas that are more sensitive to the negative effects of climate change, the parameters to take into account for its evaluation, and comprehensive plans to deal with it. The objective of this paper is to elaborate a mathematical model support of decisions, which will allow to develop and to evaluate alternatives of adaptation to the climatic change of different communities in Europe and Latin-America, mainly in especially vulnerable areas to the climatic change, considering in them all the intervening factors. The models will consider criteria of physical type (meteorological, edaphic, water resources), of use of the ground (agriculturist, forest, mining, industrial, urban, tourist, cattle dealer), economic (income, costs, benefits, infrastructures), social (population), politician (implementation, legislation), educative (Educational programs, diffusion) and environmental, at the present moment and the future. The intention is to obtain tools for aiding to get a realistic position for these challenges, which are an important part of the future problems of humanity in next decades.

MILP for the inventory and routing problem for replenishment the car assembly line.

The inbound logistic for feeding the workstation inside the factory represents a critical issue in the car manufacturing industry. Nowadays, this issue is even more critical than in the past since more types of car are being produced in the assembly lines. Consequently, as workstations have to install many types of components, they also need to have an inventory of different types of the component in a compact space. The replenishment is a critical issue since a lack of inventory could cause line stoppage or reworking. On the other hand, an excess of inventory could increase the holding cost or even block the replenishment paths. The decision of the replenishment routes cannot be made without taking into consideration the inventory needed by each station during the production time which will depend on the production sequence. This problem deals with medium-sized instances and it is solved using online solvers. The contribution of this paper is a MILP for the replenishment and inventory of the components in a car assembly line.

Spatial memory and orientation strategies in the elasmobranch Potamotrygon motoro

We investigated whether juvenile freshwater stingrays (Potamotrygon motoro) can solve spatial tasks by constructing a cognitive map of their environment. Two experimental conditions were run: allocentric and ego-allocentric. Rays were trained to locate food within a four-arm maze placed in a room with visual spatial cues. The feeding location (goal) within the maze (room) remained constant while the starting position varied for the allocentrically but not for the ego-allocentrically trained group. After training, all rays solved the experimental tasks; however, different orientation strategies were used within and between groups. Allocentrically trained rays reached the goal via novel routes starting from unfamiliar locations, while ego-allocentrically trained rays primarily solved the task on the basis of an egocentric turn response. Our data suggest that P. motoro orients by constructing a visual cognitive map of its environment, but also uses egocentric and/or other orientation strategies alone or in combination for spatial orientation, a choice which may be governed by the complexity of the problem. We conclude that spatial memory functions are a general feature of the vertebrate brain.

Evaluating design implementation strategies using enterprise simulation

Concurrent engineering and design for manufacture and assembly strategies have become pervasive in use in a wide array of industrial settings. These strategies have generally focused on product and process design issues based on capability concerns. The strategies have been historically justified using cost savings calculations focusing on easily quantifiable costs such as raw material savings or manufacturing or assembly operations no longer required. It is argued herein that neither the focus of the strategies nor the means of justification are adequate. Product and process design strategies should include both capability and capacity concerns and justification procedures should include the financial effects that the product and process changes would have on the entire company. The authors of this paper take this more holistic view of the problem and examine an innovative new design strategy using a comprehensive enterprise simulation tool. The results indicate that both the design strategy and the simulator show promise for further industrial use. © 2001 Elsevier Science B.V. All rights reserved.

Block copolymer strategies for solar cell technology

A simple overview of the methods used and the expected benefits of block copolymers in organic photovoltaic devices is given in this review. The description of the photovoltaic process makes it clear how the detailed self-assembly properties of block copolymers can be exploited. Organic photovoltaic technology, an inexpensive, clean and renewable energy source, is an extremely promising option for replacing fossil fuels. It is expected to deliver printable devices processed on flexible substrates using high-volume techniques. Such devices, however, currently lack the long-term stability and efficiency to allow organic photovoltaics to surpass current technologies. Block copolymers are envisaged to help overcome these obstacles because of their long term structural stability and their solid-state morphology being of the appropriate dimensions to efficiently perform charge collection and transfer to electrodes.

Market-driven strategies and the design of flexible production systems: evidence from the electronics industry

Links the concept of market-driven business strategies with the design of production systems. It draws upon the case of a firm which, during the last decade, changed its strategy from being “technology led” to “market driven”. The research, based on interdisciplinary fieldwork involving long-term participant observation, investigated the factors which contribute to the successful design and implementation of flexible production systems in electronics assembly. These investigations were conducted in collaboration with a major computer manufacturer, with other electronics firms being studied for comparison. The research identified a number of strategies and actions seen as crucial to the development of efficient flexible production systems, namely: effective integration of subsystems, development of appropriate controls and performance measures, compatibility between production system design and organization structure, and the development of a climate conducive to organizational change. Overall, the analysis suggests that in the electronics industry there exists an extremely high degree of environmental complexity and turbulence. This serves to shape the strategic, technical and social structures that are developed to match this complexity, examples of which are niche marketing, flexible manufacturing and employee harmonization.

Finding qualitative research: an evaluation of search strategies

Background Qualitative research makes an important contribution to our understanding of health and healthcare. However, qualitative evidence can be difficult to search for and identify, and the effectiveness of different types of search strategies is unknown. Methods Three search strategies for qualitative research in the example area of support for breast-feeding were evaluated using six electronic bibliographic databases. The strategies were based on using thesaurus terms, free-text terms and broad-based terms. These strategies were combined with recognised search terms for support for breast-feeding previously used in a Cochrane review. For each strategy, we evaluated the recall (potentially relevant records found) and precision (actually relevant records found). Results A total yield of 7420 potentially relevant records was retrieved by the three strategies combined. Of these, 262 were judged relevant. Using one strategy alone would miss relevant records. The broad-based strategy had the highest recall and the thesaurus strategy the highest precision. Precision was generally poor: 96% of records initially identified as potentially relevant were deemed irrelevant. Searching for qualitative research involves trade-offs between recall and precision. Conclusions These findings confirm that strategies that attempt to maximise the number of potentially relevant records found are likely to result in a large number of false positives. The findings also suggest that a range of search terms is required to optimise searching for qualitative evidence. This underlines the problems of current methods for indexing qualitative research in bibliographic databases and indicates where improvements need to be made.

Breast-feeding, maternal feeding practices and mealtime negativity at one year

This paper explores whether breast-feeding, mediated by lower maternal use of controlling strategies, predicts more positive mealtime interactions between mothers and their 1 year old infants. Eighty-seven women completed questionnaires regarding breast-feeding, assessing their control over child feeding and mealtime negativity at 1 year of infant age. Seventy-four of these women were also observed feeding their infants solid food at 1 year. Mediation analyses demonstrated that the experience of breast-feeding, mediated by lower reported maternal control over child feeding, predicted maternal reports of less negative mealtime interactions. The experience of breast-feeding also predicted observations of less conflict at mealtimes, mediated by observations of maternal sensitivity during feeding interactions. The implications of these findings are discussed.

Metrology enhanced tooling for aerospace (META):strategies for improved accuracy of jig built structures

The accuracy of many aerospace structures is limited by the accuracy of assembly tooling which is in turn limited by the accuracy of the measurements used to set the tooling. Further loss of accuracy results from different rates of thermal expansion for the components and tooling. This paper describes improved tooling designs and setting processes which have the potential to significantly improve the accuracy of aerospace structures. The most advanced solution described is environmentally isolated interferometer networks embedded within tooling combined with active compensation of component pick-ups. This would eliminate environmental effects on measurements while also allowing compensation for thermal expansion. A more immediately realizable solution is the adjustment of component pick-ups using micrometer jacking screws allowing multilateration to be employed during the final stages of the setting process to generate the required offsets. Copyright © 2011 SAE International.

Testing of Interposer-Based 2.5D Integrated Circuits

The unprecedented and relentless growth in the electronics industry is feeding the demand for integrated circuits (ICs) with increasing functionality and performance at minimum cost and power consumption. As predicted by Moore's law, ICs are being aggressively scaled to meet this demand. While the continuous scaling of process technology is reducing gate delays, the performance of ICs is being increasingly dominated by interconnect delays. In an effort to improve submicrometer interconnect performance, to increase packing density, and to reduce chip area and power consumption, the semiconductor industry is focusing on three-dimensional (3D) integration. However, volume production and commercial exploitation of 3D integration are not feasible yet due to significant technical hurdles.

At the present time, interposer-based 2.5D integration is emerging as a precursor to stacked 3D integration. All the dies and the interposer in a 2.5D IC must be adequately tested for product qualification. However, since the structure of 2.5D ICs is different from the traditional 2D ICs, new challenges have emerged: (1) pre-bond interposer testing, (2) lack of test access, (3) limited ability for at-speed testing, (4) high density I/O ports and interconnects, (5) reduced number of test pins, and (6) high power consumption. This research targets the above challenges and effective solutions have been developed to test both dies and the interposer.

The dissertation first introduces the basic concepts of 3D ICs and 2.5D ICs. Prior work on testing of 2.5D ICs is studied. An efficient method is presented to locate defects in a passive interposer before stacking. The proposed test architecture uses e-fuses that can be programmed to connect or disconnect functional paths inside the interposer. The concept of a die footprint is utilized for interconnect testing, and the overall assembly and test flow is described. Moreover, the concept of weighted critical area is defined and utilized to reduce test time. In order to fully determine the location of each e-fuse and the order of functional interconnects in a test path, we also present a test-path design algorithm. The proposed algorithm can generate all test paths for interconnect testing.

In order to test for opens, shorts, and interconnect delay defects in the interposer, a test architecture is proposed that is fully compatible with the IEEE 1149.1 standard and relies on an enhancement of the standard test access port (TAP) controller. To reduce test cost, a test-path design and scheduling technique is also presented that minimizes a composite cost function based on test time and the design-for-test (DfT) overhead in terms of additional through silicon vias (TSVs) and micro-bumps needed for test access. The locations of the dies on the interposer are taken into consideration in order to determine the order of dies in a test path.

To address the scenario of high density of I/O ports and interconnects, an efficient built-in self-test (BIST) technique is presented that targets the dies and the interposer interconnects. The proposed BIST architecture can be enabled by the standard TAP controller in the IEEE 1149.1 standard. The area overhead introduced by this BIST architecture is negligible; it includes two simple BIST controllers, a linear-feedback-shift-register (LFSR), a multiple-input-signature-register (MISR), and some extensions to the boundary-scan cells in the dies on the interposer. With these extensions, all boundary-scan cells can be used for self-configuration and self-diagnosis during interconnect testing. To reduce the overall test cost, a test scheduling and optimization technique under power constraints is described.

In order to accomplish testing with a small number test pins, the dissertation presents two efficient ExTest scheduling strategies that implements interconnect testing between tiles inside an system on chip (SoC) die on the interposer while satisfying the practical constraint that the number of required test pins cannot exceed the number of available pins at the chip level. The tiles in the SoC are divided into groups based on the manner in which they are interconnected. In order to minimize the test time, two optimization solutions are introduced. The first solution minimizes the number of input test pins, and the second solution minimizes the number output test pins. In addition, two subgroup configuration methods are further proposed to generate subgroups inside each test group.

Finally, the dissertation presents a programmable method for shift-clock stagger assignment to reduce power supply noise during SoC die testing in 2.5D ICs. An SoC die in the 2.5D IC is typically composed of several blocks and two neighboring blocks that share the same power rails should not be toggled at the same time during shift. Therefore, the proposed programmable method does not assign the same stagger value to neighboring blocks. The positions of all blocks are first analyzed and the shared boundary length between blocks is then calculated. Based on the position relationships between the blocks, a mathematical model is presented to derive optimal result for small-to-medium sized problems. For larger designs, a heuristic algorithm is proposed and evaluated.

In summary, the dissertation targets important design and optimization problems related to testing of interposer-based 2.5D ICs. The proposed research has led to theoretical insights, experiment results, and a set of test and design-for-test methods to make testing effective and feasible from a cost perspective.

A comparison of individual cow versus group concentrate allocation strategies on dry matter intake, milk production, tissue changes, and fertility of Holstein-Friesian cows offered a grass silage diet

A diverse range of concentrate allocation strategies are adopted on dairy farms. The objectives of this study were to examine the effects on cow performance [dry matter (DM) intake (DMI), milk yield and composition, body tissue changes, and fertility] of adopting 2 contrasting concentrate allocation strategies over the first 140 d of lactation. Seventy-seven Holstein-Friesian dairy cows were allocated to 1 of 2 concentrate allocation strategies at calving, namely group or individual cow. Cows on the group strategy were offered a mixed ration comprising grass silage and concentrates in a 50:50 ratio on a DM basis. Cows on the individual cow strategy were offered a basal mixed ration comprising grass silage and concentrates (the latter included in the mix to achieve a mean intake of 6 kg/cow per day), which was formulated to meet the cow’s energy requirements for maintenance plus 24 kg of milk/cow per day. Additional concentrates were offered via an out-of-parlor feeding system, with the amount offered adjusted weekly based on each individual cow’s milk yield during the previous week. In addition, all cows received a small quantity of straw in the mixed ration part of the diet (approximately 0.3 kg/cow per day), plus 0.5 kg of concentrate twice daily in the milking parlor. Mean concentrate intakes over the study period were similar with each of the 2 allocation strategies (11.5 and 11.7 kg of DM/cow per day for group and individual cow, respectively), although the pattern of intake with each treatment differed over time. Concentrate allocation strategy had no effect on either milk yield (39.3 and 38.0 kg/d for group and individual cow, respectively), milk composition, or milk constituent yield. The milk yield response curves with each treatment were largely aligned with the concentrate DMI curves. Cows on the individual cow treatment had a greater range of concentrate DMI and milk yields than those on the group treatment. With the exception of a tendency for cows on the individual cow treatment to lose more body weight to nadir than cows on the group treatment, concentrate allocation strategy had little effect on either body weight or body condition score over the experimental period. Cows on the individual cow treatment had a higher pregnancy rate to first and second service and tended to have a higher 100-d in calf rate than cows on the group treatment. This study demonstrates that concentrate allocation strategy had little effect on overall production performance.

Computational Foundations for Safe and Efficient Human-Robot Collaboration in Assembly Cells

Human and robots have complementary strengths in performing assembly operations. Humans are very good at perception tasks in unstructured environments. They are able to recognize and locate a part from a box of miscellaneous parts. They are also very good at complex manipulation in tight spaces. The sensory characteristics of the humans, motor abilities, knowledge and skills give the humans the ability to react to unexpected situations and resolve problems quickly. In contrast, robots are very good at pick and place operations and highly repeatable in placement tasks. Robots can perform tasks at high speeds and still maintain precision in their operations. Robots can also operate for long periods of times. Robots are also very good at applying high forces and torques. Typically, robots are used in mass production. Small batch and custom production operations predominantly use manual labor. The high labor cost is making it difficult for small and medium manufacturers to remain cost competitive in high wage markets. These manufactures are mainly involved in small batch and custom production. They need to find a way to reduce the labor cost in assembly operations. Purely robotic cells will not be able to provide them the necessary flexibility. Creating hybrid cells where humans and robots can collaborate in close physical proximities is a potential solution. The underlying idea behind such cells is to decompose assembly operations into tasks such that humans and robots can collaborate by performing sub-tasks that are suitable for them. Realizing hybrid cells that enable effective human and robot collaboration is challenging. This dissertation addresses the following three computational issues involved in developing and utilizing hybrid assembly cells: - We should be able to automatically generate plans to operate hybrid assembly cells to ensure efficient cell operation. This requires generating feasible assembly sequences and instructions for robots and human operators, respectively. Automated planning poses the following two challenges. First, generating operation plans for complex assemblies is challenging. The complexity can come due to the combinatorial explosion caused by the size of the assembly or the complex paths needed to perform the assembly. Second, generating feasible plans requires accounting for robot and human motion constraints. The first objective of the dissertation is to develop the underlying computational foundations for automatically generating plans for the operation of hybrid cells. It addresses both assembly complexity and motion constraints issues. - The collaboration between humans and robots in the assembly cell will only be practical if human safety can be ensured during the assembly tasks that require collaboration between humans and robots. The second objective of the dissertation is to evaluate different options for real-time monitoring of the state of human operator with respect to the robot and develop strategies for taking appropriate measures to ensure human safety when the planned move by the robot may compromise the safety of the human operator. In order to be competitive in the market, the developed solution will have to include considerations about cost without significantly compromising quality. - In the envisioned hybrid cell, we will be relying on human operators to bring the part into the cell. If the human operator makes an error in selecting the part or fails to place it correctly, the robot will be unable to correctly perform the task assigned to it. If the error goes undetected, it can lead to a defective product and inefficiencies in the cell operation. The reason for human error can be either confusion due to poor quality instructions or human operator not paying adequate attention to the instructions. In order to ensure smooth and error-free operation of the cell, we will need to monitor the state of the assembly operations in the cell. The third objective of the dissertation is to identify and track parts in the cell and automatically generate instructions for taking corrective actions if a human operator deviates from the selected plan. Potential corrective actions may involve re-planning if it is possible to continue assembly from the current state. Corrective actions may also involve issuing warning and generating instructions to undo the current task.