Block-control methods for low-order automotive control

Robust linear and nonlinear control is a continuing requirement for automotive powertrain controls. Newton iteration techniques have been proposed for both nonparametric linear and recently nonlinear control. Such nonparametric methods may eventually allow benefits of both low-order controllers and more rapid calibration time. This paper evaluates the feasibility of such Newton iteration techniques by an experimental comparison of a standard Riccati method a Riccati J-spectral factorisation and a novel l2 algebraic J-spectral factorisation using Newton iteration techniques in a SI engine idle controller. The methods are each applied in a 2- block H∞formulation. The results of experimentally implementing robust idle speed controllers show broadly similar outcomes for all the methods compared and thus indicate the potential of the Newton iteration methods for further development in more advanced nonparametric, low-order and nonlinear control

Mitochondrial Mislocalization Underlies Aβ42-Induced Neuronal Dysfunction in a Drosophila Model of Alzheimer's Disease

The amyloid-β 42 (Aβ42) is thought to play a central role in the pathogenesis of Alzheimer's disease (AD). However, the molecular mechanisms by which Aβ42 induces neuronal dysfunction and degeneration remain elusive. Mitochondrial dysfunctions are implicated in AD brains. Whether mitochondrial dysfunctions are merely a consequence of AD pathology, or are early seminal events in AD pathogenesis remains to be determined. Here, we show that Aβ42 induces mitochondrial mislocalization, which contributes to Aβ42-induced neuronal dysfunction in a transgenic Drosophila model. In the Aβ42 fly brain, mitochondria were reduced in axons and dendrites, and accumulated in the somata without severe mitochondrial damage or neurodegeneration. In contrast, organization of microtubule or global axonal transport was not significantly altered at this stage. Aβ42-induced behavioral defects were exacerbated by genetic reductions in mitochondrial transport, and were modulated by cAMP levels and PKA activity. Levels of putative PKA substrate phosphoproteins were reduced in the Aβ42 fly brains. Importantly, perturbations in mitochondrial transport in neurons were sufficient to disrupt PKA signaling and induce late-onset behavioral deficits, suggesting a mechanism whereby mitochondrial mislocalization contributes to Aβ42-induced neuronal dysfunction. These results demonstrate that mislocalization of mitochondria underlies the pathogenic effects of Aβ42 in vivo

In pursuit of rigour and accountability in participatory design

The field of Participatory Design (PD) has greatly diversified and we see a broad spectrum of approaches and methodologies emerging. However, to foster its role in designing future interactive technologies, a discussion about accountability and rigour across this spectrum is needed. Rejecting the traditional, positivistic framework, we take inspiration from related fields such as Design Research and Action Research to develop interpretations of these concepts that are rooted in PD׳s own belief system. We argue that unlike in other fields, accountability and rigour are nuanced concepts that are delivered through debate, critique and reflection. A key prerequisite for having such debates is the availability of a language that allows designers, researchers and practitioners to construct solid arguments about the appropriateness of their stances, choices and judgements. To this end, we propose a “tool-to-think-with” that provides such a language by guiding designers, researchers and practitioners through a process of systematic reflection and critical analysis. The tool proposes four lenses to critically reflect on the nature of a PD effort: epistemology, values, stakeholders and outcomes. In a subsequent step, the coherence between the revealed features is analysed and shows whether they pull the project in the same direction or work against each other. Regardless of the flavour of PD, we argue that this coherence of features indicates the level of internal rigour of PD work and that the process of reflection and analysis provides the language to argue for it. We envision our tool to be useful at all stages of PD work: in the planning phase, as part of a reflective practice during the work, and as a means to construct knowledge and advance the field after the fact. We ground our theoretical discussions in a specific PD experience, the ECHOES project, to motivate the tool and to illustrate its workings

Expression of chemokine receptors CXCR1 and CXCR2 during cardiopulmonary bypass

AbstractObjective: This study investigated the effects of cardiopulmonary bypass on neutrophil expression of chemokine receptors, CXCR1 and CXCR2, and the β2 integrin CD11b. Methods: Ten patients undergoing coronary artery grafting with cardiopulmonary bypass were studied. Blood samples were collected preoperatively, before bypass, at termination of bypass, and 12 to 18 hours postoperatively. In vitro studies were performed on control subjects to determine changes in the surface expression of CXCR1, CXCR2, and CD11b on stimulation with interleukin 8. Receptor expression was measured by flow cytometry. Plasma levels of interleukin 8 from the patients were determined by enzyme-linked immunoassay. Results: After bypass, CXCR2 expression fell by 66% (P <.0001) and remained low postoperatively (P <.0001). CXCR1 expression persisted at preoperative levels. CD11b expression increased significantly after bypass (P <.0001), returning to prebypass levels postoperatively. In vitro studies showed a dose-related fall of both CXCR1 (P <.0001) and CXCR2 expression (P <.0001) and a significant rise in CD11b expression (P <.0001). Plasma interleukin 8 increased significantly after bypass (P <.0001), remaining elevated 12 to 18 hours postoperatively (P =.02). Correlations between interleukin 8 levels and CXCR2 expression (P <.0001) and CD11b expression (P <.03) were demonstrated. Conclusions: CXCR2 expression is significantly down-regulated after bypass; in contrast, CXCR1 expression remains unchanged. In addition, whereas interleukin 8 is an important determinant of both CXCR1 and CXCR2 expression in vitro, it only correlates with CXCR2 and CD11b expression in vivo. This has implications in the search for antagonists against CXC chemokines and their receptor

Mindcontrol: a web application for brain segmentation quality control

Tissue classification plays a crucial role in the investigation of normal neural development, brain-behavior relationships, and the disease mechanisms of many psychiatric and neurological illnesses. Ensuring the accuracy of tissue classification is important for quality research and, in particular, the translation of imaging biomarkers to clinical practice. Assessment with the human eye is vital to correct various errors inherent to all currently available segmentation algorithms. Manual quality assurance becomes methodologically difficult at a large scale - a problem of increasing importance as the number of data sets is on the rise. To make this process more efficient, we have developed Mindcontrol, an open-source web application for the collaborative quality control of neuroimaging processing outputs. The Mindcontrol platform consists of a dashboard to organize data, descriptive visualizations to explore the data, an imaging viewer, and an in-browser annotation and editing toolbox for data curation and quality control. Mindcontrol is flexible and can be configured for the outputs of any software package in any data organization structure. Example configurations for three large, open-source datasets are presented: the 1000 Functional Connectomes Project (FCP), the Consortium for Reliability and Reproducibility (CoRR), and the Autism Brain Imaging Data Exchange (ABIDE) Collection. These demo applications link descriptive quality control metrics, regional brain volumes, and thickness scalars to a 3D imaging viewer and editing module, resulting in an easy-to-implement quality control protocol that can be scaled for any size and complexity of study

Semantic Dysfunction in Women With Schizotypal Personality Disorder

Objective: This study examined whether early or late processes in semantic networks were abnormal in women with a diagnosis of schizotypal personality disorder. The N400 component of the EEG event-related potentials was used as a probe of semantic processes. Method: Word pairs were presented with short and long stimulus-onset asynchronies to investigate, respectively, early and late semantic processes in 16 women with schizotypal personality disorder and 15 normal female comparison subjects. Event-related potentials were recorded in response to the last words in a pair. Results: With the short stimulus-onset asynchrony, the N400 amplitude was less negative in the schizotypal personality disorder group than in the normal comparison group. No group differences were found with the long stimulus-onset asynchrony. Conclusions: The finding of a less negative than normal N400 amplitude with the short stimulus-onset asynchrony in women with schizotypal personality disorder supports the hypothesis that persons with this disorder evince an overactivation of semantic networks. The absence of group differences with the long stimulus-onset asynchrony, which is primarily sensitive to processes involved in context integration, suggests that in this group of schizotypal personality disorder subjects, additional demands on working memory may be necessary to bring out the semantic dysfunction

Structural diversity in binary nanoparticle superlattices

Assembly of small building blocks such as atoms, molecules and nanoparticles into macroscopic structures - that is, 'bottom up' assembly - is a theme that runs through chemistry, biology and material science. Bacteria(1), macromolecules(2) and nanoparticles(3) can self-assemble, generating ordered structures with a precision that challenges current lithographic techniques. The assembly of nanoparticles of two different materials into a binary nanoparticle superlattice (BNSL)(3-7) can provide a general and inexpensive path to a large variety of materials (metamaterials) with precisely controlled chemical composition and tight placement of the components. Maximization of the nanoparticle packing density has been proposed as the driving force for BNSL formation(3,8,9), and only a few BNSL structures have been predicted to be thermodynamically stable. Recently, colloidal crystals with micrometre-scale lattice spacings have been grown from oppositely charged polymethyl methacrylate spheres(10,11). Here we demonstrate formation of more than 15 different BNSL structures, using combinations of semiconducting, metallic and magnetic nanoparticle building blocks. At least ten of these colloidal crystalline structures have not been reported previously. We demonstrate that electrical charges on sterically stabilized nanoparticles determine BNSL stoichiometry; additional contributions from entropic, van der Waals, steric and dipolar forces stabilize the variety of BNSL structures.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62551/1/nature04414.pd

Dynamic changes in eIF4F-mRNA interactions revealed by global analyses of environmental stress responses

BACKGROUND: Translation factors eIF4E and eIF4G form eIF4F, which interacts with the messenger RNA (mRNA) 5' cap to promote ribosome recruitment and translation initiation. Variations in the association of eIF4F with individual mRNAs likely contribute to differences in translation initiation frequencies between mRNAs. As translation initiation is globally reprogrammed by environmental stresses, we were interested in determining whether eIF4F interactions with individual mRNAs are reprogrammed and how this may contribute to global environmental stress responses. RESULTS: Using a tagged-factor protein capture and RNA-sequencing (RNA-seq) approach, we have assessed how mRNA associations with eIF4E, eIF4G1 and eIF4G2 change globally in response to three defined stresses that each cause a rapid attenuation of protein synthesis: oxidative stress induced by hydrogen peroxide and nutrient stresses caused by amino acid or glucose withdrawal. We find that acute stress leads to dynamic and unexpected changes in eIF4F-mRNA interactions that are shared among each factor and across the stresses imposed. eIF4F-mRNA interactions stabilised by stress are predominantly associated with translational repression, while more actively initiating mRNAs become relatively depleted for eIF4F. Simultaneously, other mRNAs are insulated from these stress-induced changes in eIF4F association. CONCLUSION: Dynamic eIF4F-mRNA interaction changes are part of a coordinated early translational control response shared across environmental stresses. Our data are compatible with a model where multiple mRNA closed-loop complexes form with differing stability. Hence, unexpectedly, in the absence of other stabilising factors, rapid translation initiation on mRNAs correlates with less stable eIF4F interactions

The Yeast La Related Protein Slf1p Is a Key Activator of Translation during the Oxidative Stress Response

The mechanisms by which RNA-binding proteins control the translation of subsets of mRNAs are not yet clear. Slf1p and Sro9p are atypical-La motif containing proteins which are members of a superfamily of RNA-binding proteins conserved in eukaryotes. RIP-Seq analysis of these two yeast proteins identified overlapping and distinct sets of mRNA targets, including highly translated mRNAs such as those encoding ribosomal proteins. In paralell, transcriptome analysis of slf1Δ and sro9Δ mutant strains indicated altered gene expression in similar functional classes of mRNAs following loss of each factor. The loss of SLF1 had a greater impact on the transcriptome, and in particular, revealed changes in genes involved in the oxidative stress response. slf1Δ cells are more sensitive to oxidants and RIP-Seq analysis of oxidatively stressed cells enriched Slf1p targets encoding antioxidants and other proteins required for oxidant tolerance. To quantify these effects at the protein level, we used label-free mass spectrometry to compare the proteomes of wild-type and slf1Δ strains following oxidative stress. This analysis identified several proteins which are normally induced in response to hydrogen peroxide, but where this increase is attenuated in the slf1Δ mutant. Importantly, a significant number of the mRNAs encoding these targets were also identified as Slf1p-mRNA targets. We show that Slf1p remains associated with the few translating ribosomes following hydrogen peroxide stress and that Slf1p co-immunoprecipitates ribosomes and members of the eIF4E/eIF4G/Pab1p ‘closed loop’ complex suggesting that Slf1p interacts with actively translated mRNAs following stress. Finally, mutational analysis of SLF1 revealed a novel ribosome interacting domain in Slf1p, independent of its RNA binding La-motif. Together, our results indicate that Slf1p mediates a translational response to oxidative stress via mRNA-specific translational control

The ENIGMA sports injury working group - an international collaboration to further our understanding of sport-related brain injury

Sport-related brain injury is very common, and the potential long-term effects include a wide range of neurological and psychiatric symptoms, and potentially neurodegeneration. Around the globe, researchers are conducting neuroimaging studies on primarily homogenous samples of athletes. However, neuroimaging studies are expensive and time consuming, and thus current findings from studies of sport-related brain injury are often limited by small sample sizes. Further, current studies apply a variety of neuroimaging techniques and analysis tools which limit comparability among studies. The ENIGMA Sports Injury working group aims to provide a platform for data sharing and collaborative data analysis thereby leveraging existing data and expertise. By harmonizing data from a large number of studies from around the globe, we will work towards reproducibility of previously published findings and towards addressing important research questions with regard to diagnosis, prognosis, and efficacy of treatment for sport-related brain injury. Moreover, the ENIGMA Sports Injury working group is committed to providing recommendations for future prospective data acquisition to enhance data quality and scientific rigor