The failure of exoskeletons and endoskeletons

A theoretical analysis is made of the mechanical advantages of exoskeletons and endoskeletons. More complicated and realistic loading systems are considered than have been by previous authors. For all cases involving static loading, an exoskeleton would seem to be advantageous, but sometimes the advantage is quite small. If impact is considered, the advantage of exoskeletons becomes very much reduced, even on theoretical calculations; and it is likely that in life the advantage may be converted to a disadvantage, particularly in large active animals such as vertebrates.     

The simulation approach in synthetic biology

Synthetic biology and systems biology are often highlighted as antagonistic strategies for dealing with the overwhelming complexity of biology (engineering versus understanding; tinkering in the lab versus modelling in the computer). However, a closer view of contemporary engineering methods (inextricably interwoven with mathematical modelling and simulation) and of the situation in biology (inextricably confronted with the intrinsic complexity of biomolecular environments) demonstrates that tinkering in the lab is increasingly supported by rational design methods. In other words: Synthetic biology and systems biology are merged by the use of computational techniques. These computational techniques are needed because the intrinsic complexity of biomolecular environments (stochasticity, non-linearities, system-level organization, evolution, independence, etc.) require advanced concepts of bio bricks and devices. A philosophical investigation of the history and nature of bio parts and devices reveals that these objects are imitating generic objects of engineering (switches, gates, oscillators, sensors, etc.), but the well-known design principles of generic objects are not sufficient for complex environments like cells. Therefore, the rational design methods have to be used to create more advanced generic objects, which are not only generic in their use, but also adaptive in their behavior. Case studies will show how simulation-based rational design methods are used to identify adequate parameters for synthesized designs (stability analyses), to improve lab experiments by ‘looking through noise’ (estimation of hidden variables and parameters), and to replace laborious and time-consuming post hoc tweaking in the lab by in-silico guidance (in-silico variation of bio brick properties). The overall aim of these developments, as will be argued in the discussion, is to achieve adaptive-generic instrumentality for bio parts and devices and thus increasingly merging systems and synthetic biology.     

Non-plasma bonding of PDMS for inexpensive fabrication of microfluidic devices

In this video, we demonstrate how to use the neuron microfluidic device without plasma bonding. In some cases it may be desirable to reversibly bond devices to the Corning No. 1 cover glass. This could be due, perhaps, to a plasma cleaner not being available. In other instances, it may be desirable to remove the device from the glass after the culturing of neurons for certain types of microscopy or for immunostaining, though it is not necessary to remove the device for immunostaining since the neurons can be stained in the device. Some researchers, however, still prefer to remove the device. In this case, reversible bonding of the device to the cover glass makes that possible. There are some disadvantages to non-plasma bonding of the devices in that not as tight of a seal is formed. In some cases axons may grow under the grooves rather than through them. Also, because the glass and PDMS are hydrophobic, liquids do not readily enter the device making it necessary at times to force media and other reagents into the device. Liquids will enter the device via capillary action, but it takes significantly longer as compared to devices that have been plasma bonded. The plasma cleaner creates temporary hydrophilic charges on the glass and device that facilitate the flow of liquids through the device after bonding within seconds. For non-plasma bound devices, liquid flow through the devices takes several minutes. It is also important to note that the devices to be used with non-plasma bonding need to be sterilized first, whereas plasma treated devices do not need to be sterilized prior to use because the plasma cleaner will sterilize them.     

Exotendons for assistance of human locomotion

Background  

Powered robotic exoskeletons for assistance of human locomotion are currently under development for military and medical applications. The energy requirements for such devices are excessive, and this has become a major obstacle for practical applications. Legged locomotion in many animals, however, is very energy efficient. We propose that poly-articular elastic mechanisms are a major contributor to the economy of locomotion in such specialized animals. Consequently, it should be possible to design unpowered assistive devices that make effective use of similar mechanisms.     

Integrated Assessment of Large-Scale Biofuel Production

This paper proposes a different framework for discussing the possibility of replacing a significant fraction of fossil energy consumption of modern economies with biofuels. The proposed analysis is not based on the two classic feasibility checks—land availability and output/input energy ratio—debated in the majority of the literature in this field. Rather, the focus is on the desirability of an energy sector powered by biomass energy. Discussing of desirability requires introducing a multicriteria approach, that in turn requires a definition of a set of criteria of performance for such an energy sector. The concepts of societal metabolism and ecosystem metabolism are introduced to define five criteria of performance for an energy sector powered by alternative sources.

This paper does not tell the society whether or not biofuels should be used to replace fossil energy. Rather, it proposes a method of characterization of pros and cons for the option biofuel which can be used to make more informed choices. An analysis of three systems of production—corn-ethanol, sunflower-biodiesel, and SRWC-methanol—is provided to indicate the existence of systemic characteristics associated with an energy sector powered by biofuels. These characteristics are likely to persist even when different technical coefficients will be achieved. The conclusion is that, at the moment, it is not possible to replace the actual performance of an energy sector based on fossil energy with an energy sector running on biofuel. Biomass energy can and will have to play an important role in the sustainability of humankind, but this will require a better understanding of (i) the role that an energy sector plays within a given structure of societal metabolism; and (ii) the impact generated on ecosystem metabolism by societal metabolism, plus a lot of wisdom.     

Synchronous moulting of krill,<Emphasis Type="Italic"> Euphausia superba</Emphasis>, in the Bransfield Strait (Antarctica)

A large mass of cast exoskeletons of the Antarctic krill Euphausia superba was fished in February 2001 at one station in the Bransfield Strait between 411 and 153 m. We assume that the mass of cast exoskeletons originated from a synchronous moult of thousands of individuals. Depending on the size of the krill moulted, the amount of exoskeletons corresponded to a krill abundance of 1,480–48,000 individuals per 1,000 m³.     

The role of apoptosis-induced proliferation for regeneration and cancer

Genes dedicated to killing cells must have evolved because of their positive effects on organismal survival. Positive functions of apoptotic genes have been well established in a large number of biological contexts, including their role in eliminating damaged and potentially cancerous cells. More recently, evidence has suggested that proapoptotic proteins-mostly caspases-can induce proliferation of neighboring surviving cells to replace dying cells. This process, that we will refer to as "apoptosis-induced proliferation," may be critical for stem cell activity and tissue regeneration. Depending on the caspases involved, at least two distinct types of apoptosis-induced proliferation can be distinguished. One of these types have been studied using a model in which cells have initiated cell death, but are prevented from executing it because of effector caspase inhibition, thereby generating "undead" cells that emit persistent mitogen signaling and overgrowth. Such conditions are likely to contribute to certain forms of cancer. In this review, we summarize the current knowledge of apoptosis-induced proliferation and discuss its relevance for tissue regeneration and cancer.     

Production and applications of carbohydrate-derived sugar acids as generic biobased chemicals

This review considers the chemical and biotechnological synthesis of acids that are obtained by direct oxidation of mono- or oligosaccharide, referred to as sugar acids. It focuses on sugar acids which can be readily derived from plant biomass sources and their current and future applications. The three main classes of sugar acids are aldonic, aldaric and uronic acids. Interest in organic acids derived from sugars has recently increased, as part of the interest to develop biorefineries which produce not only biofuels, but also chemicals to replace those currently derived from petroleum. More than half of the most desirable biologically produced platform chemicals are organic acids. Currently, the only sugar acid with high commercial production is d-gluconic acid. However, other sugar acids such as d-glucaric and meso-galactaric acids are being produced at a lower scale. The sugar acids have application as sequestering agents and binders, corrosion inhibitors, biodegradable chelators for pharmaceuticals and pH regulators. There is also considerable interest in the use of these molecules in the production of synthetic polymers, including polyamides, polyesters and hydrogels. Further development of these sugar acids will lead to higher volume production of the appropriate sugar acids and will help support the next generation of biorefineries.     

A Simple ERP Method for Quantitative Analysis of Cognitive Workload in Myoelectric Prosthesis Control and Human-Machine Interaction

Common goals in the development of human-machine interface (HMI) technology are to reduce cognitive workload and increase function. However, objective and quantitative outcome measures assessing cognitive workload have not been standardized for HMI research. The present study examines the efficacy of a simple event-related potential (ERP) measure of cortical effort during myoelectric control of a virtual limb for use as an outcome tool. Participants trained and tested on two methods of control, direct control (DC) and pattern recognition control (PRC), while electroencephalographic (EEG) activity was recorded. Eighteen healthy participants with intact limbs were tested using DC and PRC under three conditions: passive viewing, easy, and hard. Novel auditory probes were presented at random intervals during testing, and significant task-difficulty effects were observed in the P200, P300, and a late positive potential (LPP), supporting the efficacy of ERPs as a cognitive workload measure in HMI tasks. LPP amplitude distinguished DC from PRC in the hard condition with higher amplitude in PRC, consistent with lower cognitive workload in PRC relative to DC for complex movements. Participants completed trials faster in the easy condition using DC relative to PRC, but completed trials more slowly using DC relative to PRC in the hard condition. The results provide promising support for ERPs as an outcome measure for cognitive workload in HMI research such as prosthetics, exoskeletons, and other assistive devices, and can be used to evaluate and guide new technologies for more intuitive HMI control.     

TRASER--Total Reflection Amplification of Spontaneous Emission of Radiation

Background and Objective

Light and lasers in medical therapy have made dramatic strides since their invention five decades ago. However, the manufacture of lasers can be complex and expensive which often makes treatments limited and costly. Further, no single laser will provide the correct parameters to treat all things. Hence, laser specialists often need multiple devices to practice their specialty. A new concept is described herein that has the potential to replace many lasers and light sources with a single ‘tunable’ device.

Study Design/Material and Methods

This device amplifies spontaneous emission of radiation by capturing and retaining photons through total internal reflection, hence the acronym Total Reflection Amplification of Spontaneous Emission of Radiation, or TRASER.

Results

Specific peaks of light can be produced in a reproducible manner with high peak powers of variable pulse durations, a large spot size, and high repetition rate.

Conclusion

Considering the characteristics and parameters of Traser technology, it is possible that this one device would likely be able to replace the pulsed dye laser and many other light based systems.     

Redesigning healthcare: The 2.4 billion euro question?

Although it has been possible to transfer electrocardiograms via a phone line for more than 100 years, use of internet-based patient monitoring and communication systems in daily care is uncommon. Despite the introduction of numerous health-monitoring devices, and despite most patients having internet access, the implementation of individualised healthcare services is still limited. On the other hand, hospitals have invested heavily in massive information systems offering limited value for money and connectivity. However, the consumer market for personal healthcare devices is developing rapidly and with the current healthcare-related investments by tech companies it can be expected that the way healthcare is provided will change dramatically. Although a variety of initiatives under the banner of ‘e-Health’ are deployed, most are characterised by either industry-driven developments without proven clinical effectiveness or individual initiatives lacking the embedding within the traditional organisations. However, the introduction of numerous smart devices and internet-based technologies facilitates the fundamental redesign of healthcare based on the principle of achieving the best possible care for the individual patient at the lowest possible cost. Conclusion The way healthcare is delivered will change, but to what degree healthcare professionals together with patients will be able to redesign healthcare in a structured manner is still a question.     

Custom sizing of lower limb exoskeleton actuators using gait dynamic modelling of children with cerebral palsy

The use of exoskeletons as an aid for people with musculoskeletal disorder is the subject to an increasing interest in the research community. These devices are expected to meet the specific needs of users, such as children with cerebral palsy (CP) who are considered a significant population in pediatric rehabilitation. Although these exoskeletons should be designed to ease the movement of people with physical shortcoming, their design is generally based on data obtained from healthy adults, which leads to oversized components that are inadequate to the targeted users. Consequently, the objective of this study is to custom-size the lower limb exoskeleton actuators based on dynamic modeling of the human body for children with CP on the basis of hip, knee, and ankle joint kinematics and dynamics of human body during gait. For this purpose, a multibody modeling of the human body of 3 typically developed children (TD) and 3 children with CP is used. The results show significant differences in gait patterns especially in knee and ankle with respectively 0.39 and ?0.33 (Nm/kg) maximum torque differences between TD children and children with CP. This study provides the recommendations to support the design of actuators to normalize the movement of children with CP.     

Traditional and innovative diagnostic tools: when and why they should be applied

The development of new technological methods surely improves the quality of the Diagnostic Services in Parasitology offered to the National Sanitary Service, however, cost and simplicity have not to be neglected, even when the prime consideration is efficiency. Moreover, the mere fact that something can be done by one of these new approaches does not mean that it should be done that way or that it is most cost-effective to do it that way. A review of diagnostic tools in Parasitology is proposed, to evaluate when and why each of them should be applied. Traditional procedures for the diagnosis of parasitosis are only based on the "direct" recovery and recognition of the parasite, with the microscope as main tool and few other instruments as co-operator. The innovative procedures, recently adjusted on the basis of new scientific knowledge and made possible by the development of the laboratory instrument weapons, can evidence the parasites both directly and indirectly. If it is obvious that the direct identification of a pathogen is more reliable than that indirect, is not so evident what is the most useful direct method, and when it would be better to use indirect diagnostic tools. Advantages and disadvantages of each procedure, cost as well as the purpose of the test (diagnosis, post-treatment, research), and the general condition in which the test have to been applied must be taken into account when we are choosing. In general, we can say that the rationale for their use can be summarised as follows: 1) The macroscopic/microscopic analysis of samples is always recommended (with the exception of samples coming from tissues that need surgery). This "old" procedure allows the identification in 20 minutes of all the parasites present in mixed infections, and the evaluation of the parasite load. It is a cost-effective method which relies ultimately on the skill of the observer to detect and identify parasite stages; 2) Parasite antigen detection is an innovative and expensive immunological diagnostic, which can suffer of sensitivity and specificity. It could be useful to directly diagnose "occult" infections; 3) Parasite DNA/RNA direct detection is an innovative, sensitive and specific procedure, which can also identify sibling species. It is expensive, therefore its use is restricted to reference laboratories; 4) Host antibody detection is an innovative indirect tool to evaluate the presence of a parasite by means the evaluation of the host response to infection. It can suffer of sensitivity and specificity, and the interpretation of the test results may be difficult. It could be applied as first step to evaluate the presence of tissue parasites, whose direct diagnosis would require surgery. Some tests can be performed in well-equipped laboratories; other tests are available through research laboratories. The specimens, appropriately collected and preserved, have always to be processed in security for potential risk of infection hazard, and submitted to tests appropriate to the laboratory's goals, where, therefore, field and research diagnostic tools shouldn't be applied. The test selected for routine use has to be chosen taking into account value and limitations of each method. Reduction in excessive and often unnecessary testing is mandatory, and therefore it is critical for the clinical Parasitology to perform relevant testing while maintaining appropriate quality. To date, the microscopic analysis of samples is the only direct method that allows all identifications in short times, at a reduced cost, independently from geographical origin and peculiar status of the patient. It has to be regarded as the first step in diagnostic procedures for all laboratories. Some molecular techniques have greater sensitivity than traditional methods, but at least at the present time, their costs may well preclude their routine use. It is difficult to know, exactly, where diagnostic Parasitology will be moving in the next few years, although many soothsayers feel very strongly that the area of molecular diagnostics will replace more traditional means. It is also possible that immunological or perhaps cytometric procedures will replace our more standard diagnostic approach; nevertheless they will continue to remain oddities on the outside of the general practice and be confined to a few reference laboratories. As far as semi-automated or automated instruments and robotics-based techniques, they are useful when large numbers of the same test are performed. Supposing that they will enter in our laboratory, that will happen in central facility rather than in each local facility. So, the great interest in using new technological methods to solve old problems probably will have to be seen in the right perspective.     

Working together to respond to the challenges of EU policy to replace animal testing

This paper presents a personal perspective on efforts during the past 15 years to replace animal testing for assessing the safety of chemicals and products. It is based on an invited lecture--the FRAME Annual Lecture--given in October 2005, with the theme of "making progress by working together" (government-industry-academia-NGOs). Where we have achieved some successes, these have clearly been due to effective cooperation and collaboration between the relevant stakeholders. In recent times, there has not been this same level of active commitment and coordination. This needs to change, since, if we are to make good progress in the years to come in responding to the new challenges of the EU policy to replace animal testing, this will undoubtedly require us to work together, hopefully facilitated by effective leadership and coordination from the EU policy-makers themselves.     

A proposed nomenclature for bile acids.

A proposal is made for a system of nomenclature of the more common unconjugated and conjugated bile acids. Acceptable trivial names for bile acids are tabulated, and guidelines are proposed for using these existing trivial names as roots to create acceptable semi-systematic names for other bile acids, as well as for new natural bile acids that will be discovered in the future. The term alpha-hyocholic is recommended to replace hyocholic, and beta-hyocholic to replace omega-muricholic. The term murideoxycholic acid is recommended for 3 alpha,6 beta-dihydroxy-5 beta-cholan-24-oic acid. Proposals are also made for bile acids with epimeric hydroxy groups, for unsaturated bile acids, and for bile acids with oxo- and/or hydroxy-oxo- substituents on the nucleus and/or on the side chain. For conjugated bile acids, the term "aminoacyl amidates" is recommended to replace "amidates" for bile acids conjugated in N-acyl linkage with amino acids. Nomenclature for other types of conjugates (sulfates, glucuronides, glucosides) is included as well as abbreviations. It is recommended that the historic tradition of naming a newly discovered bile acid after the species from which it was isolated be abandoned, and that in the future such a bile acid should be named using the principles contained in this paper.     

Functional tissue engineering: the role of biomechanics

"Tissue engineering" uses implanted cells, scaffolds, DNA, protein, and/or protein fragments to replace or repair injured or diseased tissues and organs. Despite its early success, tissue engineers have faced challenges in repairing or replacing tissues that serve a predominantly biomechanical function. An evolving discipline called "functional tissue engineering" (FTE) seeks to address these challenges. In this paper, the authors present principles of functional tissue engineering that should be addressed when engineering repairs and replacements for load-bearing structures. First, in vivo stress/strain histories need to be measured for a variety of activities. These in vivo data provide mechanical thresholds that tissue repairs/replacements will likely encounter after surgery. Second, the mechanical properties of the native tissues must be established for subfailure and failure conditions. These "baseline data" provide parameters within the expected thresholds for different in vivo activities and beyond these levels if safety factors are to be incorporated. Third, a subset of these mechanical properties must be selected and prioritized. This subset is important, given that the mechanical properties of the designs are not expected to completely duplicate the properties of the native tissues. Fourth, standards must be set when evaluating the repairs/replacements after surgery so as to determine, "how good is good enough?" Some aspects of the repair outcome may be inferior, but other mechanical characteristics of the repairs and replacements might be suitable. New and improved methods must also be developed for assessing the function of engineered tissues. Fifth, the effects of physical factors on cellular activity must be determined in engineered tissues. Knowing these signals may shorten the iterations required to replace a tissue successfully and direct cellular activity and phenotype toward a desired end goal. Finally, to effect a better repair outcome, cell-matrix implants may benefit from being mechanically stimulated using in vitro "bioreactors" prior to implantation. Increasing evidence suggests that mechanical stress, as well as other physical factors, may significantly increase the biosynthetic activity of cells in bioartificial matrices. Incorporating each of these principles of functional tissue engineering should result in safer and more efficacious repairs and replacements for the surgeon and patient.     

Chitinases of filamentous fungi: a large group of diverse proteins with multiple physiological functions

Chitin is the second most abundant natural biopolymer and the main structural component of invertebrate exoskeletons and cell walls of filamentous fungi. Fungal chitinases have multiple physiological functions including the degradation of exogenous chitin and cell wall remodelling during hyphal growth, but the regulation of the chitinolytic systems of filamentous fungi is not well understood. Fungi have on average between 10 and 25 different chitinases, but only the increasing number of fungal genome sequencing projects in the last few years has enabled us to assess the whole range and diversity of fungal chitinases. In this review the variety, domain architecture and subgroups of chitinases of filamentous fungi are shown, and how these data integrate with that from molecular biological studies on chitinases are discussed.     

Detection of small lesions of the large bowel; barium enema versus double contrast

Roentgen study with the so-called opaque barium enema with some modifications is superior to double contrast study as the primary means of demonstrating polyps in the colon as well as other lesions. The method described combines fluoroscopy, high kilovoltage radiography, fluoroscopically aimed "spot films" taken with compression, suction and evacuation studies. In this way unsuspected as well as suspected polyps can be demonstrated, particularly if attention is directed to the region where polyps are most likely to be found-namely, the distal third of the large bowel. Double contrast study is quite valuable as a supplement to the modified "single contrast" barium enema, but it has not been sufficiently perfected to replace the modified opaque barium enema as a primary procedure. In many instances a combination of methods will, of course, be required.     

Temporal variation in mycophagy and prevalence of fungi associated with developmental stages of Dendroctonus ponderosae (Coleoptera: Curculionidae)

Mycophagy by bark beetles is widespread. However, little is known regarding which developmental stages of bark beetles actually feed on fungi. To study this question, we sampled fungi associated with Dendroctonus ponderosae Hopkins (Coleoptera: Curculionidae) throughout development in naturally attacked trees. Isolations of fungi were made from phloem adjacent to brood and from brood exoskeletons and guts. Overall, the incidence of fungi with individual brood increased as brood development progressed. Grosmannia clavigera (Robinson-Jeffrey and Davidson) Zipfel, de Beer and Wingf. and Ophiostoma montium (Rumbold) von Arx exhibited generally opposing trends in prevalence. G. clavigera was most likely to be found in phloem adjacent to prewintering third- and postwintering fourth-instar larvae. O. montium was most likely to be found in phloem adjacent to eggs, first-instar larvae, pupae, and teneral adults. In contrast to isolations made from phloem, fungi isolated from brood guts and exoskeletons were not observed to shift in prevalence. First- and third-instar larvae were often observed migrating to older portions of their galleries, indicating that they do not spend all of their time feeding at, and extending, the apex of the gallery. Our results suggest that not only are D. ponderosae brood in contact with and feeding on fungi throughout development, but also, that during development, contact of brood with a particular fungus is likely to change. Such temporal shifts in fungal symbionts may be environmentally driven and have important implications in how these fungi interact with their hosts within and across generations.     

Relationship of claw form and exoskeleton condition to reproductive system size and methyl farnesoate in the male spider crab,Libinia emarginata

Summary

Methyl farnesoate (MF) expression and reproductive system size were compared in five representative groups of male L. emarginata selected from a sample collected in November. The groups differed from each other with respect to carapace size (small, intermediate and large), relative propodus size (small and large claw forms), and condition of the exoskeleton (abraded and unabraded). Large males with large claws and abraded exoskeletons had reproductive system indices which were significantly larger than any other group. The mandibular organs of these crabs also had significantly higher rates of methyl farnesoate synthesis in vitro. Hemolymph titers of methyl farnesoate were also highest in this group, but were not significantly different from the group with small carapaces, small claws and unabraded exoskeletons. Methyl farnesoate titers were significantly lower in all other groups of unabraded animals with small or large claws. These results suggest that methyl farnesoate may play a role in morphogenesis and reproduction in male L. emarginata.