From Robot Arm to Intentional Agent: the Articulated Head

Robot arms have come a long way from the humble beginnings of the first Unimate robot at a General Motors plant installed to unload parts from a die-casting machine to the flexible and versatile tool ubiquitous and indispensable in many fields of industrial production nowadays. The other chapters of this book attest to the progress in the field and the plenitude of applications of robot arms. It is still fair, however, to say that currently industrial robot arms are primarily applied in continuously repeated manufacturing task for which they are pre-programmed. They are known for their precision and reliability but in general use only limited sensory input and the changes in the execution of their task due to varying environmental factors are minimal. If one was to compare a robot arm with an animal, even a very simple one, this property of robot arm applications would immediately stand out as one of the most striking differences. Living organisms must sense changes in the environment that are crucial to their survival and must have some flexibility to adjust their behaviour. In most robot arm contexts, such a comparison is currently at best of academic interest, though it might gain relevance very quickly in the future if robot arms are to be used to assist humans to a larger extend than at present. If robot arms will work in close proximity with and directly supporting humans in accomplishing a task, it becomes inevitable for the control system of the robot to have far reaching situational awareness and the capability to adjust its ‘behaviour’ according to the acquired situational information. In addition, robot perception and action have to conform a large degree to the expectations of the human co-worker

SDE-driven modeling of phenotypically heterogeneous tumors: The influence of cancer cell stemness

We deduce cell population models describing the evolution of a tumor (possibly interacting with its environment of healthy cells) with the aid of differential equations. Thereby, different subpopulations of cancer cells allow accounting for the tumor heterogeneity. In our settings these include cancer stem cells known to be less sensitive to treatment and differentiated cancer cells having a higher sensitivity towards chemo- and radiotherapy. Our approach relies on stochastic differential equations in order to account for randomness in the system, arising e.g., due to the therapy-induced decreasing number of clonogens, which renders a pure deterministic model arguable. The equations are deduced relying on transition probabilities characterizing innovations of the two cancer cell subpopulations, and similarly extended to also account for the evolution of normal tissue. Several therapy approaches are introduced and compared by way of tumor control probability (TCP) and uncomplicated tumor control probability (UTCP). A PDE approach allows to assess the evolution of tumor and normal tissue with respect to time and to cell population densities which can vary continuously in a given set of states. Analytical approximations of solutions to the obtained PDE system are provided as well.RTI2018- 093416-B-I0

Isolation of the Two Monoferric Human Transferrins by Preparative Isoelectric Focussing

Peer Reviewe

Generalisation in environmental sound classification : the ‘making sense of sounds’ data set and challenge

Humans are able to identify a large number of environmental sounds and categorise them according to high-level semantic categories, e.g. urban sounds or music. They are also capable of generalising from past experience to new sounds when applying these categories. In this paper we report on the creation of a data set that is structured according to the top-level of a taxonomy derived from human judgements and the design of an associated machine learning challenge, in which strong generalisation abilities are required to be successful. We introduce a baseline classification system, a deep convolutional network, which showed strong performance with an average accuracy on the evaluation data of 80.8%. The result is discussed in the light of two alternative explanations: An unlikely accidental category bias in the sound recordings or a more plausible true acoustic grounding of the high-level categories

Mice Lacking the Circadian Modulators SHARP1 and SHARP2 Display Altered Sleep and Mixed State Endophenotypes of Psychiatric Disorders

Increasing evidence suggests that clock genes may be implicated in a spectrum of psychiatric diseases, including sleep and mood related disorders as well as schizophrenia. The bHLH transcription factors SHARP1/DEC2/BHLHE41 and SHARP2/DEC1/ BHLHE40 are modulators of the circadian system and SHARP1/DEC2/BHLHE40 has been shown to regulate homeostatic sleep drive in humans. In this study, we characterized Sharp1 and Sharp2 double mutant mice (S1/2(-/-)) using online EEG recordings in living animals, behavioral assays and global gene expression profiling. EEG recordings revealed attenuated sleep/wake amplitudes and alterations of theta oscillations. Increased sleep in the dark phase is paralleled by reduced voluntary activity and cortical gene expression signatures reveal associations with psychiatric diseases. S1/2(-/-) mice display alterations in novelty induced activity, anxiety and curiosity. Moreover, mutant mice exhibit impaired working memory and deficits in prepulse inhibition resembling symptoms of psychiatric diseases. Network modeling indicates a connection between neural plasticity and clock genes, particularly for SHARP1 and PER1. Our findings support the hypothesis that abnormal sleep and certain (endo) phenotypes of psychiatric diseases may be caused by common mechanisms involving components of the molecular clock including SHARP1 and SHARP2

Thinking head: Towards human centred robotics

Thinking Head project is a multidisciplinary approach to building intelligent agents for human machine interaction. The Thinking Head Framework evolved out of the Thinking Head Project and it facilitates loose coupling between various components and forms the central nerve system in a multimodal perception-action system. The paper presents the overall architecture, components and the attention system. The paper then concludes with a preliminary behavioral experiment that studies the intelligibility of the audiovisual speech output produced by the Embodied Conversational Agent (ECA) that is part of the system. These results provide the baseline for future evaluations of the system as the project progresses through multiple evaluate and refine cycles

High Sustained Antibody Titers in Patients with Classic Infantile Pompe Disease Following Immunomodulation at Start of Enzyme Replacement Therapy

Objective: To evaluate whether immunomodulation at start of enzyme replacement therapy induces immune tolerance to recombinant human acid alpha-glucosidase (rhGAA) in patients with classic infantile Pompe disease. Study design: Three patients (1 cross reactive immunologic material negative, 2 cross reactive immunologic material positive) were treated with 4 weekly doses of rituximab, weekly methotrexate, and monthly intravenous immunoglobulin and enzyme replacement therapy at 40 mg/kg/week. Antibody titers were measured using enzyme-linked immunosorbent assay. Neutralizing effects on rhGAA activity and cellular uptake were determined and combined with pharmacokinetic analysis. Clinical efficacy was evaluated by (ventilator-free) survival, reduction in left ventricular mass index, and improvement of motor function. Results: Immunomodulation induced B cell depletion that was accompanied by absence of antibody formation in all 3 patients. Upon cessation of rituximab treatment, all 3 patients showed B cell recovery, which was accompanied by formation of very high sustained antibody titers in 2 patients. Neutralizing effects on infused rhGAA were low to mild/moderate. All patients were alive at study end, learned to walk, and showed (near) normalization of left ventricular mass index. Conclusions: Immunomodulation as recommended in the literature prevented formation of rhGAA antibodies only during B cell depletion but failed to induce immune tolerance in 2 out of 3 patients

Coupling of protein localization and cell movements by a dynamically localized response regulator in Myxococcus xanthus

Myxococcus xanthus cells harbor two motility machineries, type IV pili (Tfp) and the A-engine. During reversals, the two machineries switch polarity synchronously. We present a mechanism that synchronizes this polarity switching. We identify the required for motility response regulator (RomR) as essential for A-motility. RomR localizes in a bipolar, asymmetric pattern with a large cluster at the lagging cell pole. The large RomR cluster relocates to the new lagging pole in parallel with cell reversals. Dynamic RomR localization is essential for cell reversals, suggesting that RomR relocalization induces the polarity switching of the A-engine. The analysis of RomR mutants shows that the output domain targets RomR to the poles and the receiver domain is essential for dynamic localization. The small GTPase MglA establishes correct RomR polarity, and the Frz two-component system regulates dynamic RomR localization. FrzS localizes with Tfp at the leading pole and relocates in an Frz-dependent manner to the opposite pole during reversals; FrzS and RomR localize and oscillate independently. The Frz system synchronizes these oscillations and thus the synchronous polarity switching of the motility machineries

Enzyme therapy and immune response in relation to CRIM status: the Dutch experience in classic infantile Pompe disease

BACKGROUND: Enzyme-replacement therapy (ERT) in Pompe disease—an inherited metabolic disorder caused by acid α-glucosidase deficiency and characterized in infants by generalized muscle weakness and cardiomyopathy—can be complicated by immune responses. Infants that do not produce any endogenous acid α-glucosidase, so-called CRIM-negative patients, reportedly develop a strong response. We report the clinical outcome of our Dutch infants in relation to their CRIM status and immune response. METHODS: Eleven patients were genotyped and their CRIM status was determined. Antibody formation and clinical outcome were assessed for a minimum of 4 years. RESULTS: ERT was commenced between 0.1 and 8.3 months of age, and patients were treated from 0.3 to 13.7 years. All patients developed antibodies. Those with a high antibody titer (above 1:31,250) had a poor response. The antibody titers varied substantially between patients and did not strictly correlate with the patients’ CRIM status. Patients who started ERT beyond 2 months of age tended to develop higher titers than those who started earlier. All three CRIM-negative patients in our study succumbed by the age of 4 years seemingly unrelated to the height of their antibody titer. CONCLUSION: Antibody formation is a common response to ERT in classic infantile Pompe disease and counteracts the effect of treatment. The counteracting effect seems determined by the antibody:enzyme molecular stoichiometry. The immune response may be minimized by early start of ERT and by immune modulation, as proposed by colleagues. The CRIM-negative status itself seems associated with poor outcome. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10545-014-9707-6) contains supplementary material, which is available to authorized users