Re: Principles Of Electrical Engineering Et 115.epub
Sandrine Willert
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Artificially designed molecular systems with programmable behaviors have become a valuable tool in chemistry, biology, material science, and medicine. Although information processing in biological regulatory pathways is remarkably robust to error, it remains a challenge to design molecular systems that are similarly robust. With functionality determined entirely by secondary structure of DNA, strand displacement has emerged as a uniquely versatile building block for cell-free biochemical networks. Here, we experimentally investigate a design principle to reduce undesired triggering in the absence of input (leak), a side reaction that critically reduces sensitivity and disrupts the behavior of strand displacement cascades. Inspired by error correction methods exploiting redundancy in electrical engineering, we ensure a higher-energy penalty to leak via logical redundancy. Our design strategy is, in principle, capable of reducing leak to arbitrarily low levels, and we experimentally test two levels of leak reduction for a core "translator" component that converts a signal of one sequence into that of another. We show that the leak was not measurable in the high-redundancy scheme, even for concentrations that are up to 100 times larger than typical. Beyond a single translator, we constructed a fast and low-leak translator cascade of nine strand displacement steps and a logic OR gate circuit consisting of 10 translators, showing that our design principle can be used to effectively reduce leak in more complex chemical systems.
Rapid advancements in rehabilitation science and the widespread application of engineering techniques are opening the prospect of a new phase of clinical and commercial maturity for Neuroengineering, Assistive and Rehabilitation Technologies (NARTs). As the field enters this new phase, there is an urgent need to address and anticipate the ethical implications associated with novel technological opportunities, clinical solutions, and social applications.
A viable ethical framework for neuroengineering, assistive and rehabilitation technology should be characterized by the convergence of user-centered and value-sensitive approaches to product design through a proactive mode of ethical evaluation. We propose four basic normative requirements for the realization of this framework: minimization of power imbalances, compliance with biomedical ethics, translationality and social awareness. The aims and values of the CYBATHLON competition provide an operative model of this ethical framework and could drive an ethical shift in neuroengineering and rehabilitation.
With rapid advancements in rehabilitation science and the widespread application of engineering techniques for the restoration, compensation, assistance and enhancement of human neural systems, the field of neuroengineering is entering a new phase of clinical and commercial maturity. The first pioneering research prototypes of the 1980s and 90s have evolved into an increasingly mature technological spectrum with direct clinical applications and corroborated efficacy. Over the past two decades, assistive and rehabilitation technologies have increased in number and variety. Concurrently, many invasive and non-invasive neurotechnologies have become available for assistive and rehabilitation aims. This expanded technological domain might be regarded as Neuroengineering, Assistive and Rehabilitation Technology (NART). NARTs have been developed with the main purpose of mitigating several morbidities associated with diseases and traumatic injuries to the human nervous system. Today, this evolving spectrum encompasses five major technological families: devices for robot-assisted training, functional electrical stimulation (FES) techniques, prosthetics, brain-computer interfaces (BCIs) and powered mobility aids, many of which were listed as competing disciplines in the CYBATHLON 2016 [1].
In addition, the clinical implementation of NART raises ethical attention because the end-user population of these technologies is largely composed by vulnerable individuals with neurological conditions and other functional variabilities that, in virtue of their vulnerability, are often entitled to extraordinary ethical protection. For example, clinical BCIs can be used by individuals with advanced neuromuscular disorders, including patients with locked-in syndrome [9], while robot-aided rehabilitation provides effective support during the recovery process of patients following a stroke [10].
First, at the conceptual level, it is often unclear what ethical considerations should be prioritized and at what level of the technology development process (e.g. design, clinical trials, or post-commercialization assessment).
Third, in many assistive domains such as the support and rehabilitation of elderly adults with physical or cognitive disabilities, ethical design remains reportedly sporadic [13] while ethical assessment and compliance with guidelines are often perceived by developers and manufacturers as delay factors in the process of development and commercialization of new products.
In this paper we review possible approaches to the ethics of NART and propose a framework for ethical design and development, which we call the Proactive Ethical Design (PED) framework. We also suggest that the aims and values of the CYBATHLON [1] provide an ostensive and operative model of this ethical framework.
The ethical aspects of NART can be approached either reactively or proactively. Reactive approaches focus on the critical ethical evaluations of novel products and the assessment of their compatibility with existing normative ethical principles. In reactive ethics, ethical conflicts or problems are addressed as they arise, which usually occurs only at the end of the development process when the finished system is being implemented. For example, authors have performed ethical assessment of commercially available consumer-grade BCIs and argued that their security vulnerabilities may conflict with the principle of informational privacy [11, 14].
In contrast, proactive approaches are characterized by the development of strategies and solutions before a new technology becomes a source of potential ethical confrontation or conflict. Instead of merely reacting to an existing ethical problem, proactive approaches anticipate future potential uses, requirements, and unintended consequences of new technologies before they become ethical issues. For example, Bonaci et al. (2015) have anticipated an operative solution to the privacy vulnerability of commercial BCIs and developed a system called BCI Anonymizer that integrates privacy safeguards into the BCI headset [15], hence proactively promoting the ethical principle of respect for privacy.
Reactive and proactive approaches are not necessarily mutually exclusive but can be complementary. As the example above shows, they can be two sequential phases of a continuing technology assessment process: first, in the reactive phase, ethical conflicts are identified and assessed; concurrently, in the proactive phase, further ethical considerations are anticipated and ethically relevant solutions are incorporated into the design of novel products.
First, by putting users at the center of design and development, UC approaches shift the location of power in the research process [28]. Through this approach, users are no longer conceptualized as passive recipients of a new product who are implicitly coerced to change their behavior to accommodate the new technology. In contrast, they are empowered at each stage of the design and development process (requirement analysis, pre-production models, mid-production and post-production). In addition, they are no longer subordinated to designers in the decision-making process regarding a new technology, but actively involved in a cooperative dynamic and on a potentially equal footing.
Third, in determining this shift in the location of power, UC approaches inherently promote ethical principles, especially the respect for autonomy, which is one of the four fundamental principles of biomedical ethics [31]. At least two components of personal autonomy are promoted through UC design: decisional autonomy and executional autonomy [32]. Decisional autonomy is the capability to make decisions without restraint from other actors or pre-imposed designs. This capability is promoted if users are actively involved in the decisional process of product design and enabled to make choices or suggestions based on their wishes and needs. Executional autonomy is the capability to act according to a desired course of action. This capability is promoted if users can successfully use assistive technologies tailored around their needs and wishes, hence become able to perform tasks that they might not be able to perform otherwise.
While we remain agnostic about the specific instantiation of ethical values in the strong sense, in the following, we propose a UC and VSD approach to ethical assistive and rehabilitation technology based on four basic normative requirements. We call this approach the Proactive Ethical Design (PED) framework. Finally, we refer to the experience of the CYBATHLON 2016 competition as an ostensive and operative model of this ethical framework.
There is an increasing consensus that UC and VSD are necessary requirements for ethically sustainable development of assistive and rehabilitation technology [7, 8, 13]. However, little analysis is available on the prerequisites of successful adoption of such approaches. Based on the inherent goals and objectives of UC and VSD described above, we argue that four basic normative requirements are necessary for the successful implementation of ethical NART.
To overcome this problem, there is a need for harmonizing the objectives of all relevant stakeholders involved in the design process through an iterative and dialogic confrontation. This could be achieved by creating cooperative scenarios where all stakeholders are incentivized to pursue a common goal or objective.
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