Clamp loaders are pentameric AAA+ assemblies that use ATP to open and close circular DNA sliding clamps around DNA. Clamp loaders show homology in all organisms, from bacteria to human. The eukaryotic PCNA clamp is loaded onto 3′ primed DNA by the replication factor C (RFC) hetero‐pentameric clamp loader. Eukaryotes also have three alternative RFC‐like clamp loaders (RLCs) in which the Rfc1 subunit is substituted by another protein. One of these is the yeast Rad24‐RFC (...) (Rad17‐RFC in human) that loads a 9‐1‐1 heterotrimer clamp onto a recessed 5′ end of DNA. Recent structural studies of Rad24‐RFC have discovered an unexpected 5′ DNA binding site on the outside of the clamp loader and reveal how a 5′ end can be utilized for loading the 9‐1‐1 clamp onto DNA. In light of these results, new studies reveal that RFC also contains a 5′ DNA binding site, which functions in gap repair. These studies also reveal many new features of clamp loaders. As reviewed herein, these recent studies together have transformed our view of the clamp loader mechanism. (shrink)

Ojectives Low energy hip fractures are one of the greatest causes of morbidity and mortality in orthopaedics. This study aims to evaluate written consent forms with respect to basic standards as set out in the Good Practice in Consent Initiative. In particular the stated risks and benefits of each procedure were assessed. Methods 100 consecutive consent forms were reviewed prospectively. The stated procedure, side and complications were recorded. Appropriate signature and legibility was assessed. 13 consultant orthopaedic surgeons were surveyed to (...) identify what risks and benefits they thought should be stated. Results Of 100 consent forms, 31 were for patients who are unable to consent. All 100 consent forms were correctly filled in with patient details and signed. 98% were legible. All stated the side of the operation. The number of complications listed per form ranged from 4 to 11. Infection, bleeding and thromboembolic complications were stated in the majority of consent forms. In total, 30 different complications were recorded; some were only stated once. Discussion and Conclusions This work suggests consent forms are completed well with respect to patient identifiers, legibility and procedure. The variability of complications stated is vast. We suggest standard pre-printed consent forms containing risks and benefits should be used as this may improve standards of informed consent. This has also been recently supported by the British Orthopaedic Association. (shrink)

Arthur M. Glenberg omits discussion of motivation and this leads him to an underestimation of the part played by pleasure and pain and desire and fear in both the clamping and the updating of percepts. This commentary aims at rectifying this omission, showing that mutual correction plays an important role.

In particular, one of Gould's important contributions as a paleontologist was to convince us that there are long periods in evolution where species don't change very much, that Darwinian gradualism doesn't guarantee a steady course of improvements. And that there are periods -- not at all inconsistent with Darwinian gradualism -- when things progress considerably faster. I tuned right into what Steve was saying since both of my main interests in evolution, the evolution of the big brain in only several (...) million years, and the use of the Darwinian process in the brain to improve the quality of the next sentence you speak in a matter of seconds, involve the search for speedy ways of evolving things. (shrink)

Canada and California each introduced legislation to permit medical assistance in dying in June, 2016. Each jurisdiction publishes annual reports on the number of deaths that occurred under their respective legislations in the previous years. The numbers are disturbingly different. In 2021, 486 individuals died under California’s End of Life Option. In the same year 10,064 Canadians died under that country’s Medical Assistance in Dying (MAiD) legislation. California has a slightly larger population than Canada, and while medically assisted deaths as (...) a percentage of total deaths remained virtually unchanged in California from 2020-2021, Canada saw a 30% increase from 2020 to 2021. This essay examines some of the factors propelling Canada down the slippery slope of medically assisted suicide, as well as those that may be keeping California and other US jurisdictions from taking the slide. At a time of increasing pressure in many jurisdictions (both nationally and internationally) to liberalize access to medical assistance in dying, some lessons from this comparative analysis are offered. (shrink)

In October 2017, after an 11-year-old battle, the Global Association of International Sports Federation classified pole dancing as a professional sport. In this essay, I argue that pole dan...

A varied air volume air-conditioning system comprises diverse input and/or output disturbances, which are commonly nonlinear, with large lag and uncertainty. Based on the traditional control methods, testing the controlling parameters of a VAV air-conditioning system is challenging. Sliding mode control could improve the robustness of the system due to the adaptive capacity of disturbance rejection. Moreover, the fuzzy algorithm could be employed to determine the stability of a sliding control system by adjusting the parameters in the approach (...) rate, reducing the switching frequency, and weakening chatter. Fuzzy sliding mode control is investigated in this paper to improve the performance of a VAV air-conditioning system. Simulation results verify that the sliding mode control is suitable for a VAV air-conditioning system to achieve good adaptability and robustness considering the influence of multiple external variable disturbances. In addition, the chattering of the system is improved after the introduction of fuzzy control. (shrink)

The ability of Glenberg's model to explain the development of complex symbolic abilities is questioned. Specifically, it is proposed that the concepts of clamping and suppression fall short of providing an explanation for higher symbolic processes such as autobiographical memory and language comprehension. A related concept, “holding in mind” (Olson 1993), is proposed as an alternative.

Since at least the advent of Jack Kevorkian’s “suicide machine” the major argument against adopting physician-assisted suicide laws has been that they will lead us down a slippery slope to state-sa...

In this paper, an adaptive sliding mode control method based on neural networks is presented for a class of manipulator systems. The main characteristic of the discussed system is that the output variable is required to keep within a constraint set. In order to ensure that the system output meets the time-varying constraint condition, the asymmetric barrier Lyapunov function is selected in the design process. According to Lyapunov stability theory, the stability of the closed-loop system is analyzed. It is (...) demonstrated that all signals in the resulted system are bounded, the tracking error converges to a small compact set, and the system output limits in its constrained set. Finally, the simulation example is used to show the effectiveness of the presented control strategy. (shrink)

Historically, the practice of medicine has been a physically intimate endeavor. Physicians have used their hands to palpate and reveal the secrets hidden within the body. Smelling the breath for the ketosis of diabetes or tasting the skin for the saltiness of cystic fibrosis were among the physician's essential practices. Today, perhaps the most defining characteristic of a brilliant clinician is the ability to synthesize many images—from electrocardiograms, ultrasounds, CT scans, and so forth—into a coherent picture that can guide our (...) diagnosis and treatment. Yet this is rapidly becoming a Sisyphean task. Just as we are about to drown in a deluge of data, AI is throwing us a life preserver, to save not only our patients but ourselves. But where will AI take us? (shrink)

In this issue of The Journal of Clinical Ethics, Emily Bell and Eric Racine are guest editors of a special section focusing on the use of deep brain stimulation (DBS) to treat Parkinson’s disease. In “Deep Brain Stimulation, Ethics, and Society,” Bell and Racine report that DBS already has been used to treat more than 50,000 patients. The ethical issues raised in this special section are important not only in regard to Parkinson’s disease and DBS, but in many areas of (...) medicine.The articles discuss sound, state-of-the-art ethical approaches. This introduction to the issue presents approaches that are adjunctive and intended to increase careproviders’ options, that should increase careproviders’ ability to individualize the care that they provide to their patients. (shrink)

Various theories of liberation and release in Indian philosophies have often been understood as proclaiming a fixed threshold of ultimate freedom，to be attained by some yoga-technique. The author argues that there is no such thing either within Buddhism or within Brahmanism：the goal to be reached for is perpetually shifting, even beyond the unspeakable of the mystic. She compares the teaching about "kośa" to Foucault's understanding (especially in Deleuze's interpretation) of the relationship within-without，inside-outside：the relative subjectivation is but an "inner" pocket of (...) the externality; it is called "karma" in the Indian tradition. (shrink)

The suspension system is referred to as the set of springs, shock absorbers, and linkages that connect the car to the wheel system. The main purpose of the suspension system is to provide comfort for the passengers, which is created by reducing the effects of road bumpiness. It is worth noting that reducing the effects of such vibrations also diminishes the noise and undesirable sound as well as the effects of fatigue on mechanical parts of the vehicle. Due to the (...) importance of the abovementioned issues, the objective of this article is to reduce such vibrations on the car by implementing an active control method on the suspension system. For this purpose, a conventional first-order sliding mode controller has been designed for stochastic control of the quarter-car model. It is noteworthy that this controller has a significant ability to overcome the stochastic effects, uncertainty, and deal with nonlinear factors. To design a controller, the governing dynamical equation of the quarter-car system has been presented by considering the nonlinear terms in the springs and shock absorber, as well as taking into account the uncertainty factors in the system and the actuator. The design process of the sliding mode controller has been presented and its stability has been investigated in terms of the Lyapunov stability. In the current research, road surface variations are considered as Gaussian white noise. The dynamical system behavior for controlled and uncontrolled situations has been simulated and the extracted results have been presented. Besides, the effects of existing uncertainty in the suspension system and actuator have been evaluated and controller robustness has been checked. Also, the obtained quantitative and qualitative compressions have been presented. Moreover, the effect of controller parameters on the basin of attraction set and its extensiveness has been assessed. The achieved results have indicated the good performance and significant robustness of the designed controller to stabilize the suspension system and mitigate the effects of road bumpiness in the presence of uncertainty and noise factors. (shrink)

This paper focuses on the problem of load frequency control and sensor fault-tolerant control in the multiarea power grid. To solve these problems, a sliding mode control strategy based on an interval observer is designed. First, an interval observer is designed to obtain the boundary estimation information of the system state online, which is used to reconstruct the load disturbance online. Based on the reconstructed values, an integral sliding mode controller is designed to keep the system frequency stable (...) when the load is disturbed. Then, sensor fault is diagnosed by interval residual. An augmented observer is designed to estimate sensor fault online by equivalent transformation, and the sensor fault is compensated by the fault estimation to reduce the influence of fault on system performance and ensure the reliable and stable operation of the power system. The simulation results show the superiority of the proposed control strategy. (shrink)

Gender Identity Disorder (GID) is regarded as a mental illness and included in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). It will also appear in the DSM-V, due to be published in 2013. The classification of GID as a mental illness is contentious. But what would happen to sufferers if it were removed from the diagnostic manuals? Would people lose their entitlement to funded medical care, or to reimbursement under insurance schemes? On what basis should medical treatment for (...) GID be provided? What are the moral arguments for and against funded or reimbursed medical care for GID? This paper starts out with a fiction: GID is removed from the diagnostic manuals. Then the paper splits in two, as in happened in the Howitt’s 1998 film Sliding Doors . The two scenarios run parallel. In one, it is argued that GID is on a par with other body modifications, such as cosmetic and racial surgery, and that, for ethical reasons, treatment for GID should be privately negotiated by applicants and professionals and privately paid for. In the other scenario, it is argued that the comparison between GID and other body modifications is misleading. Whether or not medical treatment should be funded or reimbursed is independent of whether GID is on a par with other forms of body dissatisfaction. (shrink)

This paper presents an adaptive fuzzy sliding-mode controller for multiple Euler–Lagrange systems communicated with directed topology. Based on the graph theory and Lyapunov–Krasovskii functions, a delay-dependent sufficient condition for the existence of sliding surfaces is given in terms of linear matrix inequalities. The asymptotic stability is analyzed by using the Lyapunov method in the presence of unknown parametric dynamics, actuator faults, and time-varying delays. The usage of adaptive techniques is to adapt the unknown parameters so that the objective (...) of globally asymptotic stability is achieved. Finally, simulation results are provided to illustrate the effectiveness of the proposed control scheme. (shrink)

The human tumour suppressor protein p53 is critical for regulation of the cell cycle on genotoxic insult. When DNA is damaged by radiation, chemicals or viral infection, cells respond rapidly by arresting the cell cycle. A G1 arrest requires the activity of wild‐type p53, as it is not observed in cells lacking functionally wild‐type protein, and at least some component of S phase and G2/M arrests is also thought to be p53‐dependent. p53 functions as a transcription factor which binds specific (...) DNA sequences, and recently major downstream targets have been identified, including p21Cip1 an inhibitor of the cell cycle kinases that also blocks the replicative but not the repair function of DNA polymerase δ auxiliary factor, PCNA. Current interest focuses on developing novel cancer therapies based on our knowledge of the activity of p53 and p21Cip1 in the cell cycle. (shrink)

This paper proposes a novel adaptive fuzzy super-twisting sliding mode control scheme for microgyroscopes with unknown model uncertainties and external disturbances. Firstly, an adaptive algorithm is used to estimate the unknown parameters and angular velocity of microgyroscopes. Secondly, in order to improve the performance of the system and the superiority of the super-twisting algorithm, this paper utilizes the universal approximation characteristic of the fuzzy system to approach the gain of the super-twisting sliding mode controller and identify the gain (...) of the controller online, realizing the adaptive adjustment of the controller parameters. Simulation results verify the superiority and the effectiveness of the proposed approach, compared with adaptive super-twisting sliding mode control without fuzzy approximation; the proposed method is more effective. (shrink)

This study addresses the challenge of attitude tracking control for a rigid-flexible spacecraft with high-inertia rotating appendages. The Lagrange method was used to establish the kinematic and dynamic models of the spacecraft. The translation and rotation of the spacecraft, vibrations of solar panels, and imbalance caused by the rotating appendages, which cause a complex control problem, were considered. To address the complex control problem, a novel, fast nonsingular integral sliding mode control method is proposed to perform the attitude tracking (...) function of spacecraft. A sliding mode control law was established for the high-inertia appendages to maintain an appropriate angular velocity during rotation. Finally, the effectiveness of the proposed attitude control law was verified by numerical simulations for a spacecraft with high-inertia rotating appendages and symmetrical flexible solar panels. (shrink)

Films, compared with emotional static pictures, represent true-to-life dynamic stimuli that are both ecological and effective in inducing an emotional response given the involvement of multimodal stimulation (i.e., visual and auditory systems). We hypothesized that a direct comparison between the two methods would have shown greater efficacy of movies, compared to standardized slides, in eliciting emotions at both subjective and neurophysiological levels. To this end, we compared these two methods of emotional stimulation in a group of 40 young adults (20 (...) females). Electroencephalographic (EEG) Alpha rhythm (8–12 Hz) was recorded from 64 scalp sites while participants watched (in counterbalanced order across participants) two separate blocks of 45 slides and 45 clips. Each block included three groups of 15 validated stimuli classified as Erotic, Neutral and Fear content. Greater self-perceived arousal was found after the presentation of Fear and Erotic video clips compared with the same slide categories. sLORETA analysis showed a different lateralization pattern: slides induced decreased Alpha power (greater activation) in the left secondary visual area (Brodmann Area, BA, 18) to Erotic and Fear compared with the Neutral stimuli. Instead, video clips elicited reduced Alpha in the homologous right secondary visual area (BA 18) again to both Erotic and Fear contents compared with Neutral ones. Comparison of emotional stimuli showed smaller Alpha power to Erotic than to Fear stimuli in the left precuneus/posterior cingulate cortex (BA 7/31) for the slide condition, and in the left superior parietal lobule (BA 7) for the clip condition. This result matched the parallel analysis of the overlapped Mu rhythm (corresponding to the upper Alpha band) and can be interpreted as Mu/Alpha EEG suppression elicited by greater motor action tendency to Erotic (approach motivation) compared to Fear (withdrawal motivation) stimuli. Correlation analysis found lower Alpha in the left middle temporal gyrus (BA 21) associated with greater pleasantness to Erotic slides (r38= –0.62,p= 0.009), whereas lower Alpha in the right supramarginal/angular gyrus (BA 40/39) was associated with greater pleasantness to Neutral clips (r38= –0.69,p= 0.012). Results point to stronger emotion elicitation of movies vs. slides, but also to a specific involvement of the two hemispheres during emotional processing of slides vs. video clips, with a shift from the left to the right associative visual areas. (shrink)

Nowadays, the power systems are getting more and more complicated because of the delays introduced by the communication networks. The existence of the delays usually leads to the degradation and/or instability of power system performance. On account of this point, the traditional load frequency control approach for power system sketches a destabilizing impact and an unacceptable system performance. Therefore, this paper proposes a new LFC based on adaptive integral second-order sliding mode control approach for the large-scale power system with (...) communication delays. First, a new linear matrix inequality is derived to ensure the stability of whole power systems using Lyapunov stability theory. Second, an AISOSMC law is designed to ensure the finite time reachability of the system states. To the best of our knowledge, this is the first time the AISOSMC is designed for LFC of the LSPSwCD. In addition, the report of testing results presents that the suggested LFC based on AISOSMC can not only decrease effectively the frequency variation but also make successfully less in mount of power oscillation/fluctuation in tie-line exchange. (shrink)

In an editorial to a recent issue of Neurology, Richard Dees expresses the same criticism in an even more rigorous epistemic tone: Veikko Launis, Ph.D., is Professor of Medical Ethics and Adjunct Professor of Ethics and Social Philosophy at the University of Turku, Finland.FootnotesThis article is part of the Neuroethics of Brainreading research project, directed by myself and funded by the Academy of Finland. I am grateful to Olli Koistinen, Pekka Louhiala, Helena Siipi, and an anonymous referee for helpful comments, (...) criticism, and suggestions. (shrink)

This paper investigates the vehicle platoon control problems with both velocity constraints and input saturation. Firstly, radial basis function neural networks are employed to approximate the unknown driving resistance of a vehicle’s dynamic model. Then, a bidirectional topology, where vehicles can only communicate with their direct preceding and following neighbors, is used to depict the relationship among the vehicles in the platoon. On this basis, a neural adaptive sliding-mode control algorithm with an anti-windup compensation technique is proposed to maintain (...) the vehicle platoon with desired distance. Moreover, the string stability and the strong string stability of the whole vehicle platoon are proven through the stability theorem. Finally, numerical simulations verify the feasibility and effectiveness of the proposed control method. (shrink)

What does it mean to be a modern American today? These slides summarize the discussion from five lectures delivered in winter 2019 at the University of Oregon's Osher Lifelong Learning Institute. The lectures themselves are available on YouTube -/- Just how different is American from other cultural identities? We have thought of ourselves as the specially modern nation, spreading the revolutionary gospel of freedom from traditional restrictions. Some condemn this American exceptionalism, while others celebrate it. Don't take sides too quickly, (...) there are deep issues here. -/- -- The first lecture poses the question whether American identity is a rigid given set of traditional substantive values, or a free floating modern identity with at most a set of formal procedural values. -/- -- The second and third lectures dismantle these options, arguing that any substantive identity must include areas of inner freedom and mobility, and any formal procedural identity needs substantive style and content in order to exist at all. Personal and social identities are two leveled, with given values and projects plus inner self-reflection and space for revision. -/- -- The fourth lecture argues that what makes American identity special is neither its substantive values nor its modern formalism, which are shared with other modern nations, but rather the particular slant of its second level attitudes and practices towards first level substance. -/- -- The fifth lecture asks what America can learn and teach in an increasingly multicultural world. (shrink)

Microbial fuel cell is a renewable clean energy. Microorganisms are used as catalysts to convert the chemical energy of organic matter in the sewage into electrical energy to realize sewage treatment and recover energy at the same time. It has good development prospects. However, the output power of MFC is affected by many factors, and it is difficult to achieve a stable voltage output. For the control-oriented single-chamber MFC, a fuzzy integral sliding mode control is designed. The continuous adjustment (...) of the sliding surface ensures that the system only moves on the sliding surface, which eliminates the arrival stage and improves robustness. For chattering existing in the system, the control scheme is further optimized to obtain fuzzy integral sliding mode control, and the fuzzy module adaptively adjusts the control parameters according to the system state, which effectively reduces the system chattering. Experiments prove that the control scheme reduces chattering while ensuring the stable output of the system. (shrink)

This paper addresses the sliding mode control problem for a class of networked control systems with long time delay and consecutive packet dropout. A new modeling method is proposed, through which time delay and packet dropout are modeled in a unified model described by one Markov chain. To avoid the chattering problem of classic reaching law, a new chattering-free reaching law is proposed. Then with a focus on the problem that controller-actuator channel network condition cannot be foreseen by the (...) controller, a new compensation strategy is proposed, which can effectively compensate for the effect of time delay and packet dropout in controller-actuator channel. Finally, a simulation example is presented to demonstrate the effectiveness of the proposed approach. (shrink)