755 research outputs found
Computational modelling and experimental characterisation of heterogeneous materials
Heterogeneous materials can exhibit behaviour under load that cannot be described by classical continuum elasticity. Beams in bending can show a relative stiffening as the beam depth tends to zero, a size effect. Size effects are recognised in higher order continuum elastic theories such as micropolar elasticity. The drawback of higher order theories is the requirement of addition constitutive relations and associated properties that are often difficult to establish experimentally. Furthermore the finite element method, of great benefit in classical elasticity, has shown limitations when applied to micropolar elasticity. The determination of additional constitutive properties and the computational modelling of micropolar elasticity will be discussed in the context of a model heterogeneous material loaded in simple 3 point bending. The model material was created by drilling holes in aluminium bar in a regular pattern, with the hole axis normal to the plane of bending. The bending tests show that a size effect is present. These results are compared against modelling the detailed beam geometries in the finite element package ANSYS, which again shows the size effect. These two bending test are used to extract the additional micropolar elastic material properties. A comparison is then made against analytical solutions,numerical solutions using a micropolar beam finite element and a micropolar plane stress control volume method.It will be shown that the need for extensive experimental testing to determine the additional constitutive properties may not be necessary with the appropriate use of numerical methods
Seasonal forecasting of groundwater levels in principal aquifers of the United Kingdom
To date, the majority of hydrological forecasting studies have focussed on using medium-range (3ā15 days) weather forecasts to drive hydrological models and make predictions of future river flows. With recent developments in seasonal (1ā3 months) weather forecast skill, such as those from the latest version of the UK Met Office global seasonal forecast system (GloSea5), there is now an opportunity to use similar methodologies to forecast groundwater levels in more slowly responding aquifers on seasonal timescales. This study uses seasonal rainfall forecasts and a lumped groundwater model to simulate groundwater levels at 21 locations in the United Kingdom up to three months into the future. The results indicate that the forecasts have skill; outperforming a persistence forecast and demonstrating reliability, resolution and discrimination. However, there is currently little to gain from using seasonal rainfall forecasts over using site climatology for this type of application. Furthermore, the forecasts are not able to capture extreme groundwater levels, primarily because of inadequacies in the driving rainfall forecasts. The findings also show that the origin of forecast skill, be it from the meteorological input, groundwater model or initial condition, is site specific and related to the groundwater response characteristics to rainfall and antecedent hydro-meteorological conditions
Electromagnetic heating for industrial kilning of malt: a feasibility study
Industrial malting operations use ~800kWh/t of energy to produce the heat required to kiln malt. Electromagnetic heating technologies are suggested as a way to potentially improve the energy efficiency of the kilning processing. In this work, the potential for using electromagnetic heating to dry malt to commercially acceptable moisture levels, whilst preserving the activity of enzymes critical for downstream brewing processes is investigated. The 2450 MHz bulk dielectric properties of malt at moisture contents consistent with those occurring at different points in the kilning process are evaluated; 12% is shown to be a critical moisture level below which drying becomes more energy intensive. Calculated penetration depths of electromagnetic energy in malt at radio frequency are 100 fold higher than at microwave frequencies, showing a significant advantage for commercial scale batch processing. The moisture contents and alpha and beta amylase activity of malt subjected to RF heating at different temperatures, treatment times and RF energy inputs in the intermediate and bound water drying regions were determined. It is shown for the first time that whilst significantly reduced process times are attainable, significant energy efficiency improvements compared to conventional kilning can only be achieved at higher product temperatures and thus at the expense of enzyme survival. It is suggested that RF heating may be feasible where higher bulk temperatures are not critical for downstream use of the material or when used in hybrid systems
Quantitative Swept-Source Optical Coherence Tomography of Early Enamel Erosion in vivo
Swept-source optical coherence tomography (SS-OCT) has potential for in vivo quantitative evaluation of micro-structural enamel surface phenomena occurring during early erosive demineralisation. This randomized controlled single-blind crossover clinical study aimed to evaluate the use of SS-OCT for detection of optical changes in the enamel of 30 healthy volunteers subjected to orange juice rinsing (erosive challenge) in comparison to mineral water rinsing (control), according to wiped and non-wiped enamel surface states. Participants were randomly allocated to 60 minutes orange juice rinsing (pH 3.8) followed by 60 minutes water rinsing (pH 6.7) and vice versa, with a two-week wash-out period. In addition, the labial surfaces of the right or left maxillary incisors were wiped prior to SS-OCT imaging. An automated ImageJ algorithm was designed to analyse the backscattered OCT signal intensity (D) after orange juice rinsing compared to after water rinsing. D was quantified as the OCT signal scattering from the ~33 Āµm subsurface enamel, normalised by the total OCT signal intensity entering the enamel. The backscattered OCT signal intensity increased 3.1% (95% CI 1.1% to 5.1%) in the wiped incisors and 3.5% (95% CI 1.5% to 5.5%) in the unwiped incisors (P<0.0001). Wiping reduced the backscattered OCT signal intensity by 1.7% (95% CI -3.2 % to -0.3%) (p=0.02), in comparison to the unwiped enamel surfaces, for both rinsing solutions (P=0.2). Swept-source Optical Coherence Tomography detected OCT signal changes in the superficial subsurface enamel of maxillary central incisor teeth of healthy volunteers after orange juice rinsing
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Carbon based prosthetic devices
This is the final report of a one-year, Laboratory Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The project objective was to evaluate the use of carbon/carbon-fiber-reinforced composites for use in endoprosthetic devices. The application of these materials for the metacarpophalangeal (MP) joints of the hand was investigated. Issues concerning mechanical properties, bone fixation, biocompatibility, and wear are discussed. A system consisting of fiber reinforced materials with a pyrolytic carbon matrix and diamond-like, carbon-coated wear surfaces was developed. Processes were developed for the chemical vapor infiltration (CVI) of pyrolytic carbon into porous fiber preforms with the ability to tailor the outer porosity of the device to provide a surface for bone in-growth. A method for coating diamond-like carbon (DLC) on the articulating surface by plasma-assisted chemical vapor deposition (CVD) was developed. Preliminary results on mechanical properties of the composite system are discussed and initial biocompatibility studies were performed
Long-term perturbations due to a disturbing body in elliptic inclined orbit
In the current study, a double-averaged analytical model including the action
of the perturbing body's inclination is developed to study third-body
perturbations. The disturbing function is expanded in the form of Legendre
polynomials truncated up to the second-order term, and then is averaged over
the periods of the spacecraft and the perturbing body. The efficiency of the
double-averaged algorithm is verified with the full elliptic restricted
three-body model. Comparisons with the previous study for a lunar satellite
perturbed by Earth are presented to measure the effect of the perturbing body's
inclination, and illustrate that the lunar obliquity with the value 6.68\degree
is important for the mean motion of a lunar satellite. The application to the
Mars-Sun system is shown to prove the validity of the double-averaged model. It
can be seen that the algorithm is effective to predict the long-term behavior
of a high-altitude Martian spacecraft perturbed by Sun. The double-averaged
model presented in this paper is also applicable to other celestial systems.Comment: 28 pages, 6 figure
Stress corrosion cracking in Al-Zn-Mg-Cu aluminum alloys in saline environments
Copyright 2013 ASM International. This paper was published in Metallurgical and Materials Transactions A, 44A(3), 1230 - 1253, and is made
available as an electronic reprint with the permission of ASM International. One print or electronic copy may
be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via
electronic or other means, duplications of any material in this paper for a fee or for commercial purposes, or
modification of the content of this paper are prohibited.Stress corrosion cracking of Al-Zn-Mg-Cu (AA7xxx) aluminum alloys exposed to saline environments at temperatures ranging from 293 K to 353 K (20 Ā°C to 80 Ā°C) has been reviewed with particular attention to the influences of alloy composition and temper, and bulk and local environmental conditions. Stress corrosion crack (SCC) growth rates at room temperature for peak- and over-aged tempers in saline environments are minimized for Al-Zn-Mg-Cu alloys containing less than ~8 wt pct Zn when Zn/Mg ratios are ranging from 2 to 3, excess magnesium levels are less than 1 wt pct, and copper content is either less than ~0.2 wt pct or ranging from 1.3 to 2 wt pct. A minimum chloride ion concentration of ~0.01 M is required for crack growth rates to exceed those in distilled water, which insures that the local solution pH in crack-tip regions can be maintained at less than 4. Crack growth rates in saline solution without other additions gradually increase with bulk chloride ion concentrations up to around 0.6 M NaCl, whereas in solutions with sufficiently low dichromate (or chromate), inhibitor additions are insensitive to the bulk chloride concentration and are typically at least double those observed without the additions. DCB specimens, fatigue pre-cracked in air before immersion in a saline environment, show an initial period with no detectible crack growth, followed by crack growth at the distilled water rate, and then transition to a higher crack growth rate typical of region 2 crack growth in the saline environment. Time spent in each stage depends on the type of pre-crack (āpop-inā vs fatigue), applied stress intensity factor, alloy chemistry, bulk environment, and, if applied, the external polarization. Apparent activation energies (E a) for SCC growth in Al-Zn-Mg-Cu alloys exposed to 0.6 M NaCl over the temperatures ranging from 293 K to 353 K (20 Ā°C to 80 Ā°C) for under-, peak-, and over-aged low-copper-containing alloys (~0.8 wt pct), they are typically ranging from 20 to 40 kJ/mol for under- and peak-aged alloys, and based on limited data, around 85 kJ/mol for over-aged tempers. This means that crack propagation in saline environments is most likely to occur by a hydrogen-related process for low-copper-containing Al-Zn-Mg-Cu alloys in under-, peak- and over-aged tempers, and for high-copper alloys in under- and peak-aged tempers. For over-aged high-copper-containing alloys, cracking is most probably under anodic dissolution control. Future stress corrosion studies should focus on understanding the factors that control crack initiation, and insuring that the next generation of higher performance Al-Zn-Mg-Cu alloys has similar longer crack initiation times and crack propagation rates to those of the incumbent alloys in an over-aged condition where crack rates are less than 1 mm/month at a high stress intensity factor
RAS/MAPK activation is associated with reduced Tumor-infiltrating lymphocytes in Triple-Negative Breast Cancer: Therapeutic Cooperation Between MEK and PD-1/PD-L1 Immune Checkpoint Inhibitors
PURPOSE:
Tumor-infiltrating lymphocytes (TIL) in the residual disease (RD) of triple-negative breast cancers (TNBC) after neoadjuvant chemotherapy (NAC) are associated with improved survival, but insight into tumor cell-autonomous molecular pathways affecting these features are lacking.
EXPERIMENTAL DESIGN:
We analyzed TILs in the RD of clinically and molecularly characterized TNBCs after NAC and explored therapeutic strategies targeting combinations of MEK inhibitors with PD-1/PD-L1-targeted immunotherapy in mouse models of breast cancer.
RESULTS:
Presence of TILs in the RD was significantly associated with improved prognosis. Genetic or transcriptomic alterations in Ras-MAPK signaling were significantly correlated with lower TILs. MEK inhibition upregulated cell surface MHC expression and PD-L1 in TNBC cells both in vivo and in vitro. Moreover, combined MEK and PD-L1/PD-1 inhibition enhanced antitumor immune responses in mouse models of breast cancer.
CONCLUSIONS:
These data suggest the possibility that Ras-MAPK pathway activation promotes immune-evasion in TNBC, and support clinical trials combining MEK- and PD-L1-targeted therapies. Furthermore, Ras/MAPK activation and MHC expression may be predictive biomarkers of response to immune checkpoint inhibitors
Barriers for progress in salt reduction in the general population. An international study
Salt reduction is important for reducing hypertension and the risk of cardiovascular events, nevertheless worldwide salt intakes are above recommendations. Consequently strategies to reduce intake are required, however these require an understanding of salt intake behaviours to be effective. As limited information is available on this, an international study was conducted to derive knowledge on salt intake and associated behaviours in the general population. An online cohort was recruited consisting of a representative sample from Germany, Austria, United States of America, Hungary, India, China, South Africa, and Brazil (n=6987; aged 18-65. years; age and gender stratified). Participants completed a comprehensive web-based questionnaire on salt intake and associated behaviours. While salt reduction was seen to be healthy and important, over one third of participants were not interested in salt reduction and the majority were unaware of recommendations. Salt intake was largely underestimated and people were unaware of the main dietary sources of salt. Participants saw themselves as mainly responsible for their salt intake, but also acknowledged the roles of others. Additionally, they wanted to learn more about why salt was bad for health and what the main sources in the diet were. As such, strategies to reduce salt intake must raise interest in engaging in salt reduction through improving understanding of intake levels and dietary sources of salt. Moreover, while some aspects of salt reduction can be globally implemented, local tailoring is required to match level of interest in salt reduction. These findings provide unique insights into issues surrounding salt reduction and should be used to develop effective salt reduction strategies and/or policies. Ā© 2013 The Authors
Functional diversity of chemokines and chemokine receptors in response to viral infection of the central nervous system.
Encounters with neurotropic viruses result in varied outcomes ranging from encephalitis, paralytic poliomyelitis or other serious consequences to relatively benign infection. One of the principal factors that control the outcome of infection is the localized tissue response and subsequent immune response directed against the invading toxic agent. It is the role of the immune system to contain and control the spread of virus infection in the central nervous system (CNS), and paradoxically, this response may also be pathologic. Chemokines are potent proinflammatory molecules whose expression within virally infected tissues is often associated with protection and/or pathology which correlates with migration and accumulation of immune cells. Indeed, studies with a neurotropic murine coronavirus, mouse hepatitis virus (MHV), have provided important insight into the functional roles of chemokines and chemokine receptors in participating in various aspects of host defense as well as disease development within the CNS. This chapter will highlight recent discoveries that have provided insight into the diverse biologic roles of chemokines and their receptors in coordinating immune responses following viral infection of the CNS
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