Quantification of mesoscale variability and geometrical reconstruction of a textile

Automated image analysis of textile surfaces allowed determination and quantification of intrinsic yarn path variabilities in a 2/2 twill weave during the lay-up process. The yarn paths were described in terms of waves and it was found that the frequencies are similar in warp and weft directions and hardly affected by introduced yarn path deformations. The most significant source of fabric variability was introduced during handling before cutting. These resulting systematic deformations will need to be considered when designing or analysing a composite component. An automated method for three dimensional reconstruction of the analysed lay-up was implemented in TexGen which will allow virtual testing of components in the future

Blood borne transit of CJD from brain to gut at early stages of infection

BACKGROUND: In Creutzfeldt-Jakob disease (CJD) and other related transmissible spongiform encephalopathies it is critical to understand the various pathways by which the infectious agent spreads to different organs. METHODS: We injected a CJD agent into mice, either intracerebrally (ic) or intraperitoneally (ip) and monitored the progressive appearance of abnormal PrP in peripheral tissues over time. RESULTS: Abnormal PrP was detected in lymphoreticular tissues of the gastrointestinal tract as early as 28 to 32 days after infection by both routes. This change persisted until the terminal stages of disease. In contrast, abnormal PrP was not detected in brain or spinal cord until 80 to 120 days after ic inoculation, or until 170 days after ip inoculation. CONCLUSIONS: Brain lacks significant lymphatic drainage, and has little infectivity before 40 days, even after ic inoculation. Thus the infectious inoculum must spread to the gut by a vascular route, a direction opposite to that generally assumed. This interpretation is consistent with previous studies demonstrating white blood cell infectivity as well as perivascular PrP accumulations in CJD. Notably, enteric infection at early as well as later stages of disease, and regardless of the route of agent entry, implicates potential environmental spread by fecal matter

Fast Multiplane Functional Imaging Combining Acousto-optic Switching and Remote Focusing

Networks of neurons are inherently three-dimensional in nature, whereas conventional imaging methods, such as laser scanning two-photon microscopy, usually provide only fast two-dimensional imaging. Rapid volumetric imaging would however be preferable for imaging neurons. To get a more complete picture of the dynamics of the neuron-to-neuron interactions, we have developed a pseudo-parallelised multi-plane two-photon excitation imaging system through the incorporation of an acousto-optic switching and a remote focusing technique into a resonant scanning microscope. This permits the recording of millisecond scale fluorescence transients of calcium indicators from large populations of neurons upon neural firing events at multiple chosen axial planes in very short time frame. While the remote focusing system offers aberration-free axial scanning over a few hundreds of micrometres of depth, the acousto-optic deflector provides high speed optical switching between different laser beam paths in sub-microsecond timescale which in turn, controls the axial focal plane to be targeted. Here, we report on the development of the high temporal resolution multi-plane targeted microscope and its potential application

Solving Quantum Ground-State Problems with Nuclear Magnetic Resonance

Quantum ground-state problems are computationally hard problems; for general many-body Hamiltonians, there is no classical or quantum algorithm known to be able to solve them efficiently. Nevertheless, if a trial wavefunction approximating the ground state is available, as often happens for many problems in physics and chemistry, a quantum computer could employ this trial wavefunction to project the ground state by means of the phase estimation algorithm (PEA). We performed an experimental realization of this idea by implementing a variational-wavefunction approach to solve the ground-state problem of the Heisenberg spin model with an NMR quantum simulator. Our iterative phase estimation procedure yields a high accuracy for the eigenenergies (to the 10^-5 decimal digit). The ground-state fidelity was distilled to be more than 80%, and the singlet-to-triplet switching near the critical field is reliably captured. This result shows that quantum simulators can better leverage classical trial wavefunctions than classical computers.Comment: 11 pages, 13 figure

Risk of classic Kaposi sarcoma with exposures to plants and soils in Sicily

<p>Abstract</p> <p>Background</p> <p>Ecologic and in vitro studies suggest that exposures to plants or soil may influence risk of Kaposi sarcoma (KS).</p> <p>Methods</p> <p>In a population-based study of Sicily, we analyzed data on contact with 20 plants and residential exposure to 17 soils reported by 122 classic KS cases and 840 sex- and age-matched controls. With 88 KS-associated herpesvirus (KSHV) seropositive controls as the referent group, novel correlates of KS risk were sought, along with factors distinguishing seronegatives, in multinomial logistic regression models that included matching variables and known KS cofactors - smoking, cortisone use, and diabetes history. All plants were summed for cumulative exposure. Factor and cluster analyses were used to obtain scores and groups, respectively. Individual plants and soils in three levels of exposure with <it>P</it>_trend≤ 0.15 were retained in a backward elimination regression model.</p> <p>Results</p> <p>Adjusted for known cofactors, KS was not related to cumulative exposures to 20 plants [per quartile adjusted odds ratio (OR_adj) 0.96, 95% confidence interval (CI) 0.73 - 1.25, <it>P</it>_trend= 0.87], nor was it related to any factor scores or cluster of plants (<it>P </it>= 0.11 to 0.81). In the elimination regression model, KS risk was associated with five plants (<it>P</it>_trend= 0.02 to 0.10) and with residential exposure to six soils (<it>P</it>_trend= 0.01 to 0.13), including three soils (eutric regosol, chromic/pellic vertisol) used to cultivate durum wheat. None of the KS-associated plants and only one soil was also associated with KSHV serostatus. Diabetes was associated with KSHV seronegativity (OR_adj4.69, 95% CI 1.97 - 11.17), but the plant and soil associations had little effect on previous findings that KS risk was elevated for diabetics (OR_adj7.47, 95% CI 3.04 - 18.35) and lower for current and former smokers (OR_adj0.26 and 0.47, respectively, <it>P</it>_trend= 0.05).</p> <p>Conclusions</p> <p>KS risk was associated with exposure to a few plants and soils, but these may merely be due to chance. Study of the effects of durum wheat, which was previously associated with cKS, may be warranted.</p

Combined inhibition of DNA methylation and histone acetylation enhances gene re-expression and drug sensitivity in vivo

Histone deacetylation and DNA methylation have a central role in the control of gene expression in tumours, including transcriptional repression of tumour suppressor genes and genes involved in sensitivity to chemotherapy. Treatment of cisplatin-resistant cell lines with an inhibitor of DNA methyltransferases, 2-deoxy-5′azacytidine (decitabine), results in partial reversal of DNA methylation, re-expression of epigenetically silenced genes including hMLH1 and sensitisation to cisplatin both in vitro and in vivo. We have investigated whether the combination of decitabine and a clinically relevant inhibitor of histone deacetylase activity (belinostat, PXD101) can further increase the re-expression of genes epigenetically silenced by DNA methylation and enhance chemo-sensitisation in vivo at well-tolerated doses. The cisplatin-resistant human ovarian cell line A2780/cp70 has the hMLH1 gene methylated and is resistant to cisplatin both in vitro and when grown as a xenograft in mice. Treatment of A2780/cp70 with decitabine and belinostat results in a marked increase in expression of epigenetically silenced MLH1 and MAGE-A1 both in vitro and in vivo when compared with decitabine alone. The combination greatly enhanced the effects of decitabine alone on the cisplatin sensitivity of xenografts. As the dose of decitabine that can be given to patients and hence the maximum pharmacodynamic effect as a demethylating agent is limited by toxicity and eventual re-methylation of genes, we suggest that the combination of decitabine and belinostat could have a role in the efficacy of chemotherapy in tumours that have acquired drug resistance due to DNA methylation and gene silencing

Bottom mixed layer oxygen dynamics in the Celtic Sea

The seasonally stratified continental shelf seas are highly productive, economically important environments which are under considerable pressure from human activity. Global dissolved oxygen concentrations have shown rapid reductions in response to anthropogenic forcing since at least the middle of the twentieth century. Oxygen consumption is at the same time linked to the cycling of atmospheric carbon, with oxygen being a proxy for carbon remineralisation and the release of CO2. In the seasonally stratified seas the bottom mixed layer (BML) is partially isolated from the atmosphere and is thus controlled by interplay between oxygen consumption processes, vertical and horizontal advection. Oxygen consumption rates can be both spatially and temporally dynamic, but these dynamics are often missed with incubation based techniques. Here we adopt a Bayesian approach to determining total BML oxygen consumption rates from a high resolution oxygen time-series. This incorporates both our knowledge and our uncertainty of the various processes which control the oxygen inventory. Total BML rates integrate both processes in the water column and at the sediment interface. These observations span the stratified period of the Celtic Sea and across both sandy and muddy sediment types. We show how horizontal advection, tidal forcing and vertical mixing together control the bottom mixed layer oxygen concentrations at various times over the stratified period. Our muddy-sand site shows cyclic spring-neap mediated changes in oxygen consumption driven by the frequent resuspension or ventilation of the seabed. We see evidence for prolonged periods of increased vertical mixing which provide the ventilation necessary to support the high rates of consumption observed

Measuring the impact and costs of a universal group based parenting programme : protocol and implementation of a trial

Background Sub-optimal parenting is a common risk factor for a wide range of negative health, social and educational outcomes. Most parenting programmes have been developed in the USA in the context of delinquency prevention for targeted or indicated groups and the main theoretical underpinning for these programmes is behaviour management. The Family Links Nurturing Programme (FLNP) focuses on family relationships as well as behaviour management and is offered on a universal basis. As a result it may be better placed to improve health and educational outcomes. Developed in the UK voluntary sector, FLNP is popular with practitioners, has impressed policy makers throughout the UK, has been found to be effective in before/after and qualitative studies, but lacks a randomised controlled trial (RCT) evidence base. Methods/Design A multi-centre, investigator blind, randomised controlled trial of the FLNP with a target sample of 288 south Wales families who have a child aged 2-4 yrs living in or near to Flying Start/Sure Start areas. Changes in parenting, parent child relations and parent and child wellbeing are assessed with validated measures immediately and at 6 months post intervention. Economic components include cost consequences and cost utility analyses based on parental ranking of states of quality of life. Attendance and completion rates and fidelity to the FLNP course delivery are assessed. A nested qualitative study will assess reasons for participation and non-participation and the perceived value of the programme to families. By the end of May 2010, 287 families have been recruited into the trial across four areas of south Wales. Recruitment has not met the planned timescales with barriers including professional anxiety about families entering the control arm of the trial, family concern about video and audio recording, programme facilitator concern about the recording of FLNP sessions for fidelity purposes and delays due to the new UK research governance procedures. Discussion Whilst there are strong theoretical arguments to support universal provision of parenting programmes, few universal programmes have been subjected to randomised controlled trials. In this paper we describe a RCT protocol with quantitative and qualitative outcome measures and an economic evaluation designed to provide clear evidence with regard to effectiveness and costs. We describe challenges implementing the protocol and how we are addressing these

Quantum Simulation of Tunneling in Small Systems

A number of quantum algorithms have been performed on small quantum computers; these include Shor's prime factorization algorithm, error correction, Grover's search algorithm and a number of analog and digital quantum simulations. Because of the number of gates and qubits necessary, however, digital quantum particle simulations remain untested. A contributing factor to the system size required is the number of ancillary qubits needed to implement matrix exponentials of the potential operator. Here, we show that a set of tunneling problems may be investigated with no ancillary qubits and a cost of one single-qubit operator per time step for the potential evolution. We show that physically interesting simulations of tunneling using 2 qubits (i.e. on 4 lattice point grids) may be performed with 40 single and two-qubit gates. Approximately 70 to 140 gates are needed to see interesting tunneling dynamics in three-qubit (8 lattice point) simulations.Comment: 4 pages, 2 figure

Output from VIP cells of the mammalian central clock regulates daily physiological rhythms

The suprachiasmatic nucleus (SCN) circadian clock is critical for optimising daily cycles in mammalian physiology and behaviour. The roles of the various SCN cell types in communicating timing information to downstream physiological systems remain incompletely understood, however. In particular, while vasoactive intestinal polypeptide (VIP) signalling is essential for SCN function and whole animal circadian rhythmicity, the specific contributions of VIP cell output to physiological control remains uncertain. Here we reveal a key role for SCN VIP cells in central clock output. Using multielectrode recording and optogenetic manipulations, we show that VIP neurons provide coordinated daily waves of GABAergic input to target cells across the paraventricular hypothalamus and ventral thalamus, supressing their activity during the mid to late day. Using chemogenetic manipulation, we further demonstrate specific roles for this circuitry in the daily control of heart rate and corticosterone secretion, collectively establishing SCN VIP cells as influential regulators of physiological timing