511 research outputs found

    Seasonal performance of air conditioners - an analysis of the DOE test procedures: the thermostat and measurement errors. Report No. 2

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    Two aspects of the DOE test procedures are analyzed. First, the role of the thermostat in controlling the cycling of conditioning equipment is investigated. The test procedures call for a cycling scheme of 6 minutes on, 24 minutes off for Test D. To justify this cycling scheme as being representative of cycling in the field, it is assumed that the thermostat is the major factor in controlling the cycle rate. This assumption is examined by studying a closed-loop feedback model consisting of a thermostat, a heating/cooling plant and a conditioned space. Important parameters of this model are individually studied to determine their influence on the system. It is found that the switch differential and the anticipator gain are the major parameters in controlling the cycle rate. This confirms the thermostat's dominant role in the cycling of a system. The second aspect of the test procedures concerns transient errors or differences in the measurement of cyclic capacity. In particular, errors due to thermocouple response, thermocouple grid placement, dampers and nonuniform velocity and temperature distributions are considered. Problems in these four areas are mathematically modeled and the basic assumptions are stated. Results from these models help to clarify the problem areas and give an indication of the magnitude of the errors involved. It is found that major disagreement in measured capacity can arise in these four areas and can be mainly attributed to test set-up differences even though such differences are allowable in the test procedures. An understanding of such differences will aid in minimizing many problems in the measurement of cyclic capacity

    Clinical management and research priorities for high-risk prostate cancer in the UK:meeting report of a multidisciplinary panel in conjunction with the NCRI Prostate Cancer Clinical Studies Localised Subgroup

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    The management of high-risk prostate cancer has become increasingly sophisticated, with refinements in radical therapy and the inclusion of adjuvant local and systemic therapies. Despite this, high-risk prostate cancer continues to have significant treatment failure rates, with progression to metastasis, castrate resistance and ultimately disease-specific death. In an effort to discuss the challenges in this field, the UK National Clinical Research Institute’s Prostate Cancer Clinical Studies localised subgroup convened a multidisciplinary national meeting in the autumn of 2014. The remit of the meeting was to debate and reach a consensus on the key clinical and research challenges in high-risk prostate cancer and to identify themes that the UK would be best placed to pursue to help improve outcomes. This report presents the outcome of those discussions and the key recommendations for future research in this highly heterogeneous disease entity

    Engineering the Controlled Assembly of Filamentous Injectisomes in E. coli K-12 for Protein Translocation into Mammalian Cells.

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    Bacterial pathogens containing type III protein secretion systems (T3SS) assemble large needle-like protein complexes in the bacterial envelope, called injectisomes, for translocation of protein effectors into host cells. The application of these molecular syringes for the injection of proteins into mammalian cells is hindered by their structural and genomic complexity, requiring multiple polypeptides encoded along with effectors in various transcriptional units (TUs) with intricate regulation. In this work, we have rationally designed the controlled expression of the filamentous injectisomes found in enteropathogenic Escherichia coli (EPEC) in the nonpathogenic strain E. coli K-12. All structural components of EPEC injectisomes, encoded in a genomic island called the locus of enterocyte effacement (LEE), were engineered in five TUs (eLEEs) excluding effectors, promoters and transcriptional regulators. These eLEEs were placed under the control of the IPTG-inducible promoter Ptac and integrated into specific chromosomal sites of E. coli K-12 using a marker-less strategy. The resulting strain, named synthetic injector E. coli (SIEC), assembles filamentous injectisomes similar to those in EPEC. SIEC injectisomes form pores in the host plasma membrane and are able to translocate T3-substrate proteins (e.g., translocated intimin receptor, Tir) into the cytoplasm of HeLa cells reproducing the phenotypes of intimate attachment and polymerization of actin-pedestals elicited by EPEC bacteria. Hence, SIEC strain allows the controlled expression of functional filamentous injectisomes for efficient translocation of proteins with T3S-signals into mammalian cells

    Measurement and Modeling of Particle Radiation in Coal Flames

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    This work aims at developing a methodology that can provide information of in-flame particle radiation in industrial-scale flames. The method is based on a combination of experimental and modeling work. The experiments have been performed in the high-temperature zone of a 77 kWth swirling lignite flame. Spectral radiation, total radiative intensity, gas temperature, and gas composition were measured, and the radiative intensity in the furnace was modeled with an axisymmetric cylindrical radiation model using Mie theory for the particle properties and a statistical narrow-band model for the gas properties. The in-flame particle radiation was measured with a Fourier transform infrared (FTIR) spectrometer connected to a water-cooled probe via fiber optics. In the cross-section of the flame investigated, the particles were found to be the dominating source of radiation. Apart from giving information about particle radiation and temperature, the methodology can also provide estimates of the amount of soot radiation and the maximum contribution from soot radiation compared to the total particle radiation. In the center position in the flame, the maximum contribution from soot radiation was estimated to be less than 40% of the particle radiation. As a validation of the methodology, the modeled total radiative intensity was compared to the total intensity measured with a narrow angle radiometer and the agreement in the results was good, supporting the validity of the used approach

    Porous hierarchically ordered hydrogels demonstrating structurally dependent mechanical properties

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    While hierarchical ordering is a distinctive feature of natural tissues and is directly responsible for their diverse and unique properties, efforts to synthesize biomaterials have primarily focused on using molecular-based approaches with little emphasis on multiscale structure. Here, we report a bottom-up self-assembly process to produce highly porous hydrogel fibers that resemble extracellular matrices both structurally and mechanically. Physically crosslinked nanostructured micelles form the walls of micrometer-sized water-rich pores with preferred orientation along the fiber direction. Low elastic moduli (<1 kPa), high elasticity (extending by more than 12 times the initial length), non-linear elasticity (e.g., hyperelasticity), and completely reversible extension are derived from unevenly distributed strain between the micrometer-sized pores and the polymer chains, which is reminiscent of cellular solids. Control of the material microstructure and orientation over many orders of magnitude (e.g., nm–μm), while holding the nanostructure constant, reveals how the multiscale structure directly impacts mechanical properties

    Filled pauses in Hungarian: Their phonetic form and function

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    Filled pauses are natural occurrences in spontaneous speech and they may turn up at any level of the speech planning process and in a number of functions. The aim of this paper is to find out whether the diverse functions of filled pauses correlate with diverse articulations resulting in diverse acoustic structures. Spontaneous narratives are used as research material. The duration of the filled pauses and the frequency values of their first two formants are analyzed. The most frequent form, schwa, shows function-dependent realizations as confirmed by the durational values and by the second formant values of these vowel-like sounds

    Extension of DNA in a Nanochannel as a Rod-to-Coil Transition

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    DNA confinement in nanochannels is emerging as an important tool for genomics and an excellent platform for testing the theories of confined wormlike polymers. Using cutting-edge, large scale Monte Carlo simulations of asymptotically long wormlike chains, we show that, in analogy to the rod-to-coil transition for free wormlike polymers, there exists a universal, Gauss–de Gennes regime that connects the classic Odijk and de Gennes regimes of channel-confined chains. For DNA in a nanochannel, this Gauss–de Gennes regime spans practically the entire experimentally relevant range of channel sizes, including the nanochannels used in an incipient genome mapping technology

    Simulation of DNA Extension in Nanochannels

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    We have used a realistic model for double-stranded DNA and Monte Carlo simulations to compute the extension (mean span) of a DNA molecule confined in a nanochannel over the full range of confinement in a high ionic strength buffer. The simulation data for square nanochannels resolve the apparent contradiction between prior simulation studies and the predictions from Flory theory, demonstrating the existence of two transition regimes between weak confinement (the de Gennes regime) and strong confinement (the Odijk regime). The simulation data for rectangular nanochannels support the use of the geometric mean for mapping data obtained in rectangular channels onto models developed for cylinders. The comparison of our results with experimental data illuminates the challenges in applying models for confined, neutral polymers to polyelectrolytes. Using a Flory-type approach, we also provide an improved scaling result for the relaxation time in the transition regime close to that found in experiments

    Modeling the relaxation time of DNA confined in a nanochannel

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    Using a mapping between a Rouse dumbbell model and fine-grained Monte Carlo simulations, we have computed the relaxation time of λ-DNA in a high ionic strength buffer confined in a nanochannel. The relaxation time thus obtained agrees quantitatively with experimental data [Reisner et al., Phys. Rev. Lett. 94, 196101 (2005)] using only a single O(1) fitting parameter to account for the uncertainty in model parameters. In addition to validating our mapping, this agreement supports our previous estimates of the friction coefficient of DNA confined in a nanochannel [Tree et al., Phys. Rev. Lett. 108, 228105 (2012)], which have been difficult to validate due to the lack of direct experimental data. Furthermore, the model calculation shows that as the channel size passes below approximately 100 nm (or roughly the Kuhn length of DNA) there is a dramatic drop in the relaxation time. Inasmuch as the chain friction rises with decreasing channel size, the reduction in the relaxation time can be solely attributed to the sharp decline in the fluctuations of the chain extension. Practically, the low variance in the observed DNA extension in such small channels has important implications for genome mapping

    Mobility of a Semiflexible Chain Confined in a Nanochannel

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    The classic results of de Gennes and Odijk describe the mobility of a semiflexible chain confined in a nanochannel only in the limits of very weak and very strong confinement, respectively. Using Monte Carlo sampling of the Kirkwood diffusivity with full hydrodynamic interactions, we show that the mobility of a semiflexible chain exhibits a broad plateau as a function of extension before transitioning to an Odijk regime, and that the width of the plateau depends on the anisotropy of the monomers. For the particular case of DNA in a high ionic strength buffer, which has highly anisotropic monomers, we predict that this Rouse-like behavior will be observed over most of the measurable chain extensions seen in experiments
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