Optimal control-based methodology for active vibration control of pedestrian structures

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.Civil structures such as floor systems with open-plan layouts or lightweight footbridges can be susceptible to excessive levels of vibrations caused by human activities. Active vibration control (AVC) via inertial-mass actuators has been shown to be a viable technique to mitigate vibrations, allowing structures to satisfy vibration serviceability limits. It is generally considered that the determination of the optimal placement of sensors and actuators together with the output feedback gains leads to a tradeoff between the regulation performance and the control effort. However, the "optimal" settings may not have the desired effect when implemented because simplifications assumed in the control scheme components may not be valid and/or the actuator/sensor limitations are not considered. This work proposes a design methodology for multi-input multi-output vibration control of pedestrian structures to simultaneously obtain the sensor/actuator placement and the control law. This novel methodology consists of minimising a performance index that includes all the significant practical issues involved when inertial-mass actuators and accelerometers are used to implement a direct velocity feedback in practice. Experimental results obtained on an in-service indoor walkway confirm the viability of the proposed methodology.The authors acknowledge the financial support provided by the Fundación Caja Madrid through the grant “II Convocatoria de Becas de Movilidad para profesores de las universidades públicas de Madrid durante el curso académico 2012/2013” and also the UK Engineering and Physical Sciences Research Council (EPSRC) though grant EP/J004081/2 entitled “Advanced Technologies for Mitigation of Human-Induced Vibration”

New people, new publisher, and new perspectives

As we begin our sixth year of publishing Pulmonary Circulation, we are excited about several new developments. First, we welcome two new Deputy Editors to the editorial leadership team: Kurt R. Stenmark, MD, and Irene M. Lang, MD

Embryo movement is more frequent in avian brood parasites than birds with parental reproductive strategies.

Funder: Tanzanian Commission for Science and TechnologyFunder: Tanzania Wildlife Research InstituteFunder: NERCFunder: National Science FoundationFunder: Ministry of EducationFunder: German Academic Exchange ServiceFunder: University of Cape TownFunder: Max-Planck-GesellschaftMovement of the embryo is essential for musculoskeletal development in vertebrates, yet little is known about whether, and why, species vary. Avian brood parasites exhibit feats of strength in early life as adaptations to exploit the hosts that rear them. We hypothesized that an increase in embryonic movement could allow brood parasites to develop the required musculature for these demands. We measured embryo movement across incubation for multiple brood-parasitic and non-parasitic bird species. Using a phylogenetically controlled analysis, we found that brood parasites exhibited significantly increased muscular movement during incubation compared to non-parasites. This suggests that increased embryo movement may facilitate the development of the stronger musculoskeletal system required for the demanding tasks undertaken by young brood parasites

HIV Prevention in Care and Treatment Settings: Baseline Risk Behaviors among HIV Patients in Kenya, Namibia, and Tanzania.

HIV care and treatment settings provide an opportunity to reach people living with HIV/AIDS (PLHIV) with prevention messages and services. Population-based surveys in sub-Saharan Africa have identified HIV risk behaviors among PLHIV, yet data are limited regarding HIV risk behaviors of PLHIV in clinical care. This paper describes the baseline sociodemographic, HIV transmission risk behaviors, and clinical data of a study evaluating an HIV prevention intervention package for HIV care and treatment clinics in Africa. The study was a longitudinal group-randomized trial in 9 intervention clinics and 9 comparison clinics in Kenya, Namibia, and Tanzania (N = 3538). Baseline participants were mostly female, married, had less than a primary education, and were relatively recently diagnosed with HIV. Fifty-two percent of participants had a partner of negative or unknown status, 24% were not using condoms consistently, and 11% reported STI symptoms in the last 6 months. There were differences in demographic and HIV transmission risk variables by country, indicating the need to consider local context in designing studies and using caution when generalizing findings across African countries. Baseline data from this study indicate that participants were often engaging in HIV transmission risk behaviors, which supports the need for prevention with PLHIV (PwP). TRIAL REGISTRATION: ClinicalTrials.gov NCT01256463

A transient homotypic interaction model for the influenza A virus NS1 protein effector domain

Influenza A virus NS1 protein is a multifunctional virulence factor consisting of an RNA binding domain (RBD), a short linker, an effector domain (ED), and a C-terminal 'tail'. Although poorly understood, NS1 multimerization may autoregulate its actions. While RBD dimerization seems functionally conserved, two possible apo ED dimers have been proposed (helix-helix and strand-strand). Here, we analyze all available RBD, ED, and full-length NS1 structures, including four novel crystal structures obtained using EDs from divergent human and avian viruses, as well as two forms of a monomeric ED mutant. The data reveal the helix-helix interface as the only strictly conserved ED homodimeric contact. Furthermore, a mutant NS1 unable to form the helix-helix dimer is compromised in its ability to bind dsRNA efficiently, implying that ED multimerization influences RBD activity. Our bioinformatical work also suggests that the helix-helix interface is variable and transient, thereby allowing two ED monomers to twist relative to one another and possibly separate. In this regard, we found a mAb that recognizes NS1 via a residue completely buried within the ED helix-helix interface, and which may help highlight potential different conformational populations of NS1 (putatively termed 'helix-closed' and 'helix-open') in virus-infected cells. 'Helix-closed' conformations appear to enhance dsRNA binding, and 'helix-open' conformations allow otherwise inaccessible interactions with host factors. Our data support a new model of NS1 regulation in which the RBD remains dimeric throughout infection, while the ED switches between several quaternary states in order to expand its functional space. Such a concept may be applicable to other small multifunctional proteins

X-ray Absorption and Reflection in Active Galactic Nuclei

X-ray spectroscopy offers an opportunity to study the complex mixture of emitting and absorbing components in the circumnuclear regions of active galactic nuclei, and to learn about the accretion process that fuels AGN and the feedback of material to their host galaxies. We describe the spectral signatures that may be studied and review the X-ray spectra and spectral variability of active galaxies, concentrating on progress from recent Chandra, XMM-Newton and Suzaku data for local type 1 AGN. We describe the evidence for absorption covering a wide range of column densities, ionization and dynamics, and discuss the growing evidence for partial-covering absorption from data at energies > 10 keV. Such absorption can also explain the observed X-ray spectral curvature and variability in AGN at lower energies and is likely an important factor in shaping the observed properties of this class of source. Consideration of self-consistent models for local AGN indicates that X-ray spectra likely comprise a combination of absorption and reflection effects from material originating within a few light days of the black hole as well as on larger scales. It is likely that AGN X-ray spectra may be strongly affected by the presence of disk-wind outflows that are expected in systems with high accretion rates, and we describe models that attempt to predict the effects of radiative transfer through such winds, and discuss the prospects for new data to test and address these ideas.Comment: Accepted for publication in the Astronomy and Astrophysics Review. 58 pages, 9 figures. V2 has fixed an error in footnote

Loss of heterozygosity at 7p in Wilms' tumour development

Chromosome 7p alterations have been implicated in the development of Wilms' tumour (WT) by previous studies of tumour cytogenetics, and by our analysis of a constitutional translocation (t(1;7)(q42;p15)) in a child with WT and radial aplasia. We therefore used polymorphic microsatellite markers on 7p for a loss of heterozygosity (LOH) study, and found LOH in seven out of 77 informative WTs (9%). The common region of LOH was 7p15–7p22, which contains the region disrupted by the t(1;7) breakpoint. Four WTs with 7p LOH had other genetic changes; a germline WT1 mutation with 11p LOH, LOH at 11p, LOH at 16q, and loss of imprinting of IGF2. Analysis of three tumour-associated lesions from 7p LOH cases revealed a cystic nephroma-like area also having 7p LOH. However, a nephrogenic rest and a contralateral WT from the two other cases showed no 7p LOH. No particular clinical phenotype was associated with the WTs which showed 7p LOH. The frequency and pattern of 7p LOH demonstrated in our studies indicate the presence of a tumour suppressor gene at 7p involved in the development of Wilms' tumour. © 2000 Cancer Research Campaig

Ion access pathway to the transmembrane pore in P2X receptor channels

P2X receptors are trimeric cation channels that open in response to the binding of adenosine triphosphate (ATP) to a large extracellular domain. The x-ray structure of the P2X4 receptor from zebrafish (zfP2X4) receptor reveals that the extracellular vestibule above the gate opens to the outside through lateral fenestrations, providing a potential pathway for ions to enter and exit the pore. The extracellular region also contains a void at the central axis, providing a second potential pathway. To investigate the energetics of each potential ion permeation pathway, we calculated the electrostatic free energy by solving the Poisson-Boltzmann equation along each of these pathways in the zfP2X4 crystal structure and a homology model of rat P2X2 (rP2X2). We found that the lateral fenestrations are energetically favorable for monovalent cations even in the closed-state structure, whereas the central pathway presents strong electrostatic barriers that would require structural rearrangements to allow for ion accessibility. To probe ion accessibility along these pathways in the rP2X2 receptor, we investigated the modification of introduced Cys residues by methanethiosulfonate (MTS) reagents and constrained structural changes by introducing disulfide bridges. Our results show that MTS reagents can permeate the lateral fenestrations, and that these become larger after ATP binding. Although relatively small MTS reagents can access residues in one of the vestibules within the central pathway, no reactive positions were identified in the upper region of this pathway, and disulfide bridges that constrain movements in that region do not prevent ion conduction. Collectively, these results suggest that ions access the pore using the lateral fenestrations, and that these breathe as the channel opens. The accessibility of ions to one of the chambers in the central pathway likely serves a regulatory function

Clinical characteristics associated with the prescribing of SSRI medication in adolescents with major unipolar depression.

Unipolar major depressions (MD) emerge markedly during adolescence. National Institute for Health and Care Excellence (NICE) UK recommends psychological therapies, with accompanying selective serotonin reuptake inhibitors (SSRIs) prescribed in severe cases only. Here, we seek to determine the extent and rationale of SSRI prescribing in adolescent MD before entering a randomised clinical trial. SSRI prescribing, together with their clinical characteristics was determined in 465 adolescent patients with MD prior to receiving a standardised psychological therapy as part of the Improving mood with psychoanalytic and cognitive therapies (IMPACT) clinical trial. Overall, 88 (19 %) had been prescribed antidepressants prior to psychological treatment. The clinical correlates varied by gender: respectively, depression severity in boys and self-harming behaviours in girls. Prescribing also differed between clinical research centres. Medical practitioners consider severity of depression in boys as an indicator for antidepressant prescribing. Self-injury in girls appears to be utilised as a prescribing aid which is inconsistent with past and current revised UK NICE guidelines.RCT Study supported by a grant to IMG (Chief Investigator) from the NIHR-HTA (trial number ISRCTN83033550, grant number 06/05/01).This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Springer

Study of the reaction e^{+}e^{-} -->J/psi\pi^{+}\pi^{-} via initial-state radiation at BaBar

We study the process $e^+e^-\to J/\psi\pi^{+}\pi^{-}$ with initial-state-radiation events produced at the PEP-II asymmetric-energy collider. The data were recorded with the BaBar detector at center-of-mass energies 10.58 and 10.54 GeV, and correspond to an integrated luminosity of 454 $\mathrm{fb^{-1}}$. We investigate the $J/\psi \pi^{+}\pi^{-}$ mass distribution in the region from 3.5 to 5.5 $\mathrm{GeV/c^{2}}$. Below 3.7 $\mathrm{GeV/c^{2}}$ the $\psi(2S)$ signal dominates, and above 4 $\mathrm{GeV/c^{2}}$ there is a significant peak due to the Y(4260). A fit to the data in the range 3.74 -- 5.50 $\mathrm{GeV/c^{2}}$ yields a mass value $4244 \pm 5$ (stat) $\pm 4$ (syst)$\mathrm{MeV/c^{2}}$ and a width value $114 ^{+16}_{-15}$ (stat)$\pm 7$(syst)$\mathrm{MeV}$ for this state. We do not confirm the report from the Belle collaboration of a broad structure at 4.01 $\mathrm{GeV/c^{2}}$. In addition, we investigate the $\pi^{+}\pi^{-}$ system which results from Y(4260) decay