Engineering of vascularized adipose constructs

Adipose tissue engineering offers a promising alternative to the current surgical techniques for the treatment of soft tissue defects. It is a challenge to find the appropriate scaffold that not only represents a suitable environment for cells but also allows fabrication of customized tissue constructs, particularly in breast surgery. We investigated two different scaffolds for their potential use in adipose tissue regeneration. Sponge-like polyurethane scaffolds were prepared by mold casting with methylal as foaming agent, whereas polycaprolactone scaffolds with highly regular stacked-fiber architecture were fabricated with fused deposition modeling. Both scaffold types were seeded with human adipose tissuederived precursor cells, cultured and implanted in nude mice using a femoral arteriovenous flow-through vessel loop for angiogenesis. In vitro, cells attached to both scaffolds and differentiated into adipocytes. In vivo, angiogenesis and adipose tissue formation were observed throughout both constructs after 2 and 4 weeks, with angiogenesis being comparable in seeded and unseeded constructs. Fibrous tissue formation and adipogenesis were more pronounced on polyurethane foam scaffolds than on polycaprolactone prototyped scaffolds. In conclusion, both scaffold designs can be effectively used for adipose tissue engineering.

Human activity-induced vibration in slender structural systems

Human activity-induced vibrations in slender structural sys tems become apparent in many different excitation modes and consequent action effects that cause discomfort to occupants, crowd panic and damage to public infrastructure. Resulting loss of public confidence in safety of structures, economic losses, cost of retrofit and repairs can be significant. Advanced computational and visualisation techniques enable engineers and architects to evolve bold and innovative structural forms, very often without precedence. New composite and hybrid materials that are making their presence in structural systems lack historical evidence of satisfactory performance over anticipated design life. These structural systems are susceptible to multi-modal and coupled excitation that are very complex and have inadequate design guidance in the present codes and good practice guides. Many incidents of amplified resonant response have been reported in buildings, footbridges, stadia a nd other crowded structures with adverse consequences. As a result, attenuation of human-induced vibration of innovative and slender structural systems very ofte n requires special studies during the design process. Dynamic activities possess variable characteristics and thereby induce complex responses in structures that are sensitive to parametric variations. Rigorous analytical techniques are available for investigation of such complex actions and responses to produce acceptable performance in structural systems. This paper presents an overview and a critique of existing code provisions for human-induced vibration followed by studies on the performance of three contrasting structural systems that exhibit complex vibration. The dynamic responses of these systems under human-induced vibrations have been carried out using experimentally validated computer simulation techniques. The outcomes of these studies will have engineering applications for safe and sustainable structures and a basis for developing design guidance.

Inhibition of guinea-pig renal [Na + K]-ATPase by normotensive human plasma : effects of a high sodium diet

The effect of plasma taken from normotensive humans, while on a low and high sodium diet, on [Na + K]-ATPase and 3H-ouabain binding was measured in tubules from guinea-pig kidneys. Plasma from the high sodium, compared to the low sodium, diet period: (a) inhibited [Na + K]-ATPase activity; (b) decreased 3H-ouabain affinity for binding sites; (c) increased the number of available 3H-ouabain binding sites; (d) decreased [Na + K]-ATPase turnover (activity/3H-ouabain binding sites). The inhibition of [Na + K]-ATPase suggests an increase in a (possible) natriuretic factor. The decreased affinity of 3H-ouabain binding suggests an endogenous ouabainoid, which may be the natriuretic factor.

ATF5, a possible regulator of osteogenic differentiation in human adipose-derived stem cells

The regulatory pathways involved in maintaining the pluripotency of embryonic stem cells are partially known, whereas the regulatory pathways governing adult stem cells and their "stem-ness" are characterized to an even lesser extent. We, therefore, screened the transcriptome profiles of 20 osteogenically induced adult human adipose-derived stem cell (ADSC) populations and investigated for putative transcription factors that could regulate the osteogenic differentiation of these ADSC. We studied a subgroup of donors' samples that had a disparate osteogenic response transcriptome from that of induced human fetal osteoblasts and the rest of the induced human ADSC samples. From our statistical analysis, we found activating transcription factor 5 (ATF5) to be significantly and consistently down-regulated in a randomized time-course study of osteogenically differentiated adipose-derived stem cells from human donor samples. Knockdown of ATF5 with siRNA showed an increased sensitivity to osteogenic induction. This evidence suggests a role for ATF5 in the regulation of osteogenic differentiation in adipose-derived stem cells. To our knowledge, this is the first report that indicates a novel role of transcription factors in regulating osteogenic differentiation in adult or tissue specific stem cells. © 2012 Wiley Periodicals, Inc.

A unified description language for human to automated services

Through the rise of cloud computing, on-demand applications, and business networks, services are increasingly being exposed and delivered on the Internet and through mobile communications. So far, services have mainly been described through technical interface descriptions. The description of business details, such as pricing, service-level, or licensing, has been neglected and is therefore hard to automatically process by service consumers. Also, third-party intermediaries, such as brokers, cloud providers, or channel partners, are interested in the business details in order to extend services and their delivery and, thus, further monetize services. In this paper, the constructivist design of the UnifiedServiceDescriptionLanguage (USDL), aimed at describing services across the human-to-automation continuum, is presented. The proposal of USDL follows well-defined requirements which are expressed against a common service discourse and synthesized from currently available servicedescription efforts. USDL's concepts and modules are evaluated for their support of the different requirements and use cases.

Dynamic compression improves biosynthesis of human zonal chondrocytes from osteoarthritis patients

Objective: We hypothesize that chondrocytes from distinct zones of articular cartilage respond differently to compressive loading, and that zonal chondrocytes from osteoarthritis (OA) patients can benefit from optimized compressive stimulation. Therefore, we aimed to determine the transcriptional response of superficial (S) and middle/deep (MD) zone chondrocytes to varying dynamic compressive strain and loading duration. To confirm effects of compressive stimulation on overall matrix production, we subjected zonal chondrocytes to compression for 2 weeks. Design: Human S and MD chondrocytes from osteoarthritic joints were encapsulated in 2% alginate, pre-cultured, and subjected to compression with varying dynamic strain (5, 15, 50% at 1 Hz) and loading duration (1, 3, 12 h). Temporal changes in cartilage-specific, zonal, and dedifferentiation genes following compression were evaluated using quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR). The benefits of long-term compression (50% strain, 3 h/day, for 2 weeks) were assessed by measuring construct glycosaminoglycan (GAG) content and compressive moduli, as well as immunostaining. Results: Compressive stimulation significantly induced aggrecan (ACAN), COL2A1, COL1A1, proteoglycan 4 (PRG4), and COL10A1 gene expression after 2 h of unloading, in a zone-dependent manner (P < 0.05). ACAN and PRG4 mRNA levels depended on strain and load duration, with 50% and 3 h loading resulting in highest levels (P < 0.05). Long-term compression increased collagen type II and ACAN immunostaining and total GAG (P < 0.05), but only S constructs showed more PRG4 stain, retained more GAG (P < 0.01), and developed higher compressive moduli than non-loaded controls. Conclusions: The biosynthetic activity of zonal chondrocytes from osteoarthritis joints can be enhanced with selected compression regimes, indicating the potential for cartilage tissue engineering applications. © 2012 Osteoarthritis Research Society International.

Inhibitors of human immunodeficiency virus type 1 reverse transcriptase target distinct phases of early reverse transcription

Early HIV-1 reverse transcription can be separated into initiation and elongation phases. Here we show, using PCR analysis of negative-strand strong-stop DNA [(−)ssDNA] synthesis in intact virus, that different reverse transcriptase (RT) inhibitors affect distinct phases of early natural endogenous reverse transcription (NERT). The effects of nevirapine on NERT were consistent with a mechanism of action including both specific and nonspecific binding events. The nonspecific component of this inhibition targeted the elongation reaction, whereas the specific effect seemed principally to be directed at very early events (initiation or the initiation-elongation switch). In contrast, foscarnet and the nucleoside analog ddATP inhibited both early and late (−)ssDNA synthesis in a similar manner. We also examined compounds that targeted other viral proteins and found that Ro24-7429 (a Tat antagonist) and rosmarinic acid (an integrase inhibitor) also directly inhibited RT. Our results indicate that NERT can be used to identify and evaluate compounds that directly target the reverse transcription complex.

A tissue engineering solution for segmental defect regeneration in load-bearing long bones

The reconstruction of large defects (>10 mm) in humans usually relies on bone graft transplantation. Limiting factors include availability of graft material, comorbidity, and insufficient integration into the damaged bone. We compare the gold standard autograft with biodegradable composite scaffolds consisting of medical-grade polycaprolactone and tricalcium phosphate combined with autologous bone marrow-derived mesenchymal stem cells (MSCs) or recombinant human bone morphogenetic protein 7 (rhBMP-7). Critical-sized defects in sheep - a model closely resembling human bone formation and structure - were treated with autograft, rhBMP-7, or MSCs. Bridging was observed within 3 months for both the autograft and the rhBMP-7 treatment. After 12 months, biomechanical analysis and microcomputed tomography imaging showed significantly greater bone formation and superior strength for the biomaterial scaffolds loaded with rhBMP-7 compared to the autograft. Axial bone distribution was greater at the interfaces. With rhBMP-7, at 3 months, the radial bone distribution within the scaffolds was homogeneous. At 12 months, however, significantly more bone was found in the scaffold architecture, indicating bone remodeling. Scaffolds alone or with MSC inclusion did not induce levels of bone formation comparable to those of the autograft and rhBMP-7 groups. Applied clinically, this approach using rhBMP-7 could overcome autograft-associated limitations.

Vastu Purusha Mandala : A human ecological framework for designing living environments

This paper aims to present ‘vastu purusha mandala’(VPM), a symbolic diagram used in the indigenous system of Indian architecture as a human ecologic frame work for designing living environments. The article begins with an attempt to provide a working definition for the ‘living environment’ based on the theories developed by Rapoport (2005) and Lawrence (2001). It then discusses the symbolism and the human ecologic significance of VPM. This is substantiated through the works of Kramrisch (1976), Moore (1989), Shukla (1996) and Chakrabarthi (1998). Some recent papers on Vastu Shastra are also examined. Furthermore, VPM is compared with the livability guidelines developed for high-rise living by the Centre for Subtropical Design, Queensland University of Technology, Brisbane, Australia. A meaningful interpretation of vastushastra which is free from mysticism and symbolism is proffered through this paper.

Embedding human expert cognition and real-time trajectory planning in autonomous UAS

This thesis presents a new approach to compute and optimize feasible three dimensional (3D) flight trajectories using aspects of Human Decision Making (HDM) strategies, for fixed wing Unmanned Aircraft (UA) operating in low altitude environments in the presence of real time planning deadlines. The underlying trajectory generation strategy involves the application of Manoeuvre Automaton (MA) theory to create sets of candidate flight manoeuvres which implicitly incorporate platform dynamic constraints. Feasible trajectories are formed through the concatenation of predefined flight manoeuvres in an optimized manner. During typical UAS operations, multiple objectives may exist, therefore the use of multi-objective optimization can potentially allow for convergence to a solution which better reflects overall mission requirements and HDM preferences. A GUI interface was developed to allow for knowledge capture from a human expert during simulated mission scenarios. The expert decision data captured is converted into value functions and corresponding criteria weightings using UTilite Additive (UTA) theory. The inclusion of preferences elicited from HDM decision data within an Automated Decision System (ADS) allows for the generation of trajectories which more closely represent the candidate HDM’s decision strategies. A novel Computationally Adaptive Trajectory Decision optimization System (CATDS) has been developed and implemented in simulation to dynamically manage, calculate and schedule system execution parameters to ensure that the trajectory solution search can generate a feasible solution, if one exists, within a given length of time. The inclusion of the CATDS potentially increases overall mission efficiency and may allow for the implementation of the system on different UAS platforms with varying onboard computational capabilities. These approaches have been demonstrated in simulation using a fixed wing UAS operating in low altitude environments with obstacles present.

Polycaprolactone-based scaffold plus recombinant human bone morphogenetic protein (rhBMP-2) in an ovine model of anterior spinal fusion

Synthetic scaffolds combined with growth factors have the potential to replace allograft or autograft as a graft material for spinal interbody fusion. Such tissue engineering approaches may be useful in Adolescent Idiopathic Scoliosis (AIS) surgery, however there are no studies to date examining the use of such biodegradable implants in combination with biologics in a thoracic spine model. This in vivo study examines the use of biodegradable polycaprolactone (PCL) based scaffolds with rhBMP-2 as a bone graft substitute in a sheep thoracic fusion model, where an anterior approach is used to simulate minimally invasive surgical deformity correction in the setting of AIS.

A human-simulated immune evolutionary computation approach

Premature convergence to local optimal solutions is one of the main difficulties when using evolutionary algorithms in real-world optimization problems. To prevent premature convergence and degeneration phenomenon, this paper proposes a new optimization computation approach, human-simulated immune evolutionary algorithm (HSIEA). Considering that the premature convergence problem is due to the lack of diversity in the population, the HSIEA employs the clonal selection principle of artificial immune system theory to preserve the diversity of solutions for the search process. Mathematical descriptions and procedures of the HSIEA are given, and four new evolutionary operators are formulated which are clone, variation, recombination, and selection. Two benchmark optimization functions are investigated to demonstrate the effectiveness of the proposed HSIEA.

Preface to special issue on digital human modelling for vehicle design and manufacturing

The automotive industry has been the focus of digital human modeling (DHM) research and application for many years. In the highly competitive marketplace for personal transportation, the desire to improve the customer’s experience has driven extensive research in both the physical and cognitive interaction between the vehicle and its occupants. Human models provide vehicle designers with tools to view and analyze product interactions before the first prototypes are built, potentially improving the design while reducing cost and development time. The focus of DHM research and applications began with prediction and representation of static postures for purposes of driver workstation layout, including assessments of seat adjustment ranges and exterior vision. Now DHMs are used for seat design and assessment of driver reach and ingress/egress. DHMs and related simulation tools are expanding into the cognitive domain, with computational models of perception and motion, and into the dynamic domain with models of physical responses to ride and vibration. Moreover, DHMs are now widely used to analyze the ergonomics of vehicle assembly tasks. In this case, the analysis aims to determine whether workers can be expected to complete the tasks safely and with good quality. This preface provides a review of the literature to provide context for the nine new papers presented in this special issue.