The basic framework and - conceptual understanding of the metallurgy of Ti alloys is strong and this has enabled the use of titanium and its alloys in safety-critical structures such as those in ...aircraft and aircraft engines. Nevertheless, a focus on cost-effectiveness and the compression of product development time by effectively integrating design with manufacturing in these applications, as well as those emerging in bioengineering, has driven research in recent decades towards a greater predictive capability through the use of computational materials engineering tools. Therefore this paper focuses on the complexity and variety of fundamental phenomena in this material system with a focus on phase transformations and mechanical behaviour in order to delineate the challenges that lie ahead in achieving these goals.
There has been an explosion of interest in mindfulness-based programs (MBPs) such as Mindfulness-Based Stress Reduction (MBSR) and Mindfulness-Based Cognitive Therapy. This is demonstrated in ...increased research, implementation of MBPs in healthcare, educational, criminal justice and workplace settings, and in mainstream interest. For the sustainable development of the field there is a need to articulate a definition of what an MBP is and what it is not. This paper provides a framework to define the essential characteristics of the family of MBPs originating from the parent program MBSR, and the processes which inform adaptations of MBPs for different populations or contexts. The framework addresses the essential characteristics of the program and of teacher. MBPs: are informed by theories and practices that draw from a confluence of contemplative traditions, science, and the major disciplines of medicine, psychology and education; underpinned by a model of human experience which addresses the causes of human distress and the pathways to relieving it; develop a new relationship with experience characterized by present moment focus, decentering and an approach orientation; catalyze the development of qualities such as joy, compassion, wisdom, equanimity and greater attentional, emotional and behavioral self-regulation, and engage participants in a sustained intensive training in mindfulness meditation practice, in an experiential inquiry-based learning process and in exercises to develop understanding. The paper's aim is to support clarity, which will in turn support the systematic development of MBP research, and the integrity of the field during the process of implementation in the mainstream.
•∼250 billion radiance measurements of the Moon compiled into a global dataset.•Maps reveal the complex and extreme nature of the lunar surface thermal environment.•Global view of how the regolith ...stores and exchanges thermal energy with space.•Daytime maximum temperatures are sensitive to the radiative properties of the surface.•Nighttime temperatures are sensitive to the thermophysical properties of the regolith.
The Diviner Lunar Radiometer Experiment onboard the Lunar Reconnaissance Orbiter (LRO) has been acquiring solar reflectance and mid-infrared radiance measurements nearly continuously since July of 2009. Diviner is providing the most comprehensive view of how regoliths on airless bodies store and exchange thermal energy with the space environment. Approximately a quarter trillion calibrated radiance measurements of the Moon, acquired over 5.5 years by Diviner, have been compiled into a 0.5° resolution global dataset with a 0.25h local time resolution. Maps generated with this dataset provide a global perspective of the surface energy balance of the Moon and reveal the complex and extreme nature of the lunar surface thermal environment. Our achievable map resolution, both spatially and temporally, will continue to improve with further data acquisition.
Daytime maximum temperatures are sensitive to the albedo of the surface and are ∼387–397K at the equator, dropping to ∼95K just before sunrise, though anomalously warm areas characterized by high rock abundances can be > 50K warmer than the zonal average nighttime temperatures. An asymmetry is observed between the morning and afternoon temperatures due to the thermal inertia of the lunar regolith with the dusk terminator ∼30K warmer than the dawn terminator at the equator. An increase in albedo with incidence angle is required to explain the observed decrease in temperatures with latitude. At incidence angles exceeding ∼40°, topography and surface roughness influence temperatures resulting in increasing scatter in temperatures and anisothermality between Diviner channels.
Nighttime temperatures are sensitive to the thermophysical properties of the regolith. High thermal inertia (TI) materials such as large rocks, remain warmer during the long lunar night and result in anomalously warm nighttime temperatures and anisothermality in the Diviner channels. Anomalous maximum and minimum temperatures are highlighted by subtracting the zonal mean temperatures from maps. Terrains can be characterized as low or high reflectance and low or high TI. Low maximum temperatures result from high reflectance surfaces while low minimum temperatures from low-TI material. Conversely, high maximum temperatures result from dark surface, and high minimum temperatures from high-TI materials.
Impact craters are found to modify regolith properties over large distances. The thermal signature of Tycho is asymmetric, consistent with an oblique impact coming from the west. Some prominent crater rays are visible in the thermal data and require material with a higher thermal inertial than nominal regolith. The influence of the formation of the Orientale basin on the regolith properties is observable over a substantial portion of the western hemisphere despite its age (∼3.8Gyr), and may have contributed to mixing of highland and mare material on the southwest margin of Oceanus Procellarum where the gradient in radiative properties at the mare-highland contact is broad (∼200km).
Although widely accepted as a measure of the comparative lifetime costs of electricity generation alternatives, levelised cost of energy (LCOE) lacks a theoretical foundation in the academic ...literature and encompasses a number of areas where caution is important. Therefore, this paper seeks to provide a theoretical foundation by comparing the metric with alternative cost of energy metrics and by undertaking a brief literature review to describe its strengths and weaknesses. In comparison with other potential measures of unit cost of energy, LCOE is found to be the preferred choice, in large part because of its widespread adoption. The weaknesses of the LCOE are found to centre on discount rate, inflation effects and the sensitivity of results to uncertainty in future commodity costs. These weaknesses are explored in the context of comparing combined cycle gas fired generation and offshore wind in the UK, based on publicly available cost measures. It is found that with variability of future fuel gas prices, and a Monte Carlo approach to modelling LCOE, the range of LCOE for CCGT is much broader in comparison to the LCOE of offshore wind. It is urged that explicit account be taken of the areas of weakness in future use of LCOE.
•The Levelised Cost of Energy (LCOE) metric is given a theoretical footing.•The strengths and weaknesses of LCOE are compared to other measures.•The sensitivity of LCOE to key variables is assessed.•Monte Carlo analysis shows how variable fuel costs impact the LCOE of CCGT vs wind.
Electronic circular dichroism and circularly polarized luminescence acid/base switching activity has been demonstrated in helicene‐bipyridine proligand 1 a and in its “rollover” cycloplatinated ...derivative 2 a. Whereas proligand 1 a displays a strong bathochromic shift (>160 nm) of the nonpolarized and circularly polarized luminescence upon protonation, complex 2 a displays slightly stronger emission. This strikingly different behavior between singlet emission in the organic helicene and triplet emission in the organometallic derivative has been rationalized by using quantum‐chemical calculations. The very large bathochromic shift of the emission observed upon protonation of azahelicene‐bipyridine 1 a has been attributed to the decrease in aromaticity (promoting a charge‐transfer‐type transition rather than a π–π* transition) as well as an increase in the HOMO–LUMO character of the transition and stabilization of the LUMO level upon protonation.
Rollover platination: A 6helicene‐bipyridine derivative has been used as a proligand for “rollover” cycloplatination and for the conception of acid/base chiroptical switches. Protonation triggers a change in the nature of the HOMO–LUMO transition, from a π–π* to a charge‐transfer transition, and significantly modifies the circularly polarized luminescence and electronic circular dichroism spectra of the organic and organometallic helicenes (see figure).
Although T lymphocytes have long been appreciated for their role in the immunosurveillance of cancer, it has been the realization that cancer cells may ultimately escape a response from ...tumor-reactive T cells that has ignited efforts to enhance the efficacy of anti-tumor immune responses. Recent advances in our understanding of T cell immunobiology have been particularly instrumental in informing therapeutic strategies to overcome mechanisms of tumor immune escape, and immune checkpoint blockade has emerged as one of the most promising therapeutic options for patients in the history of cancer treatment. Designed to interfere with inhibitory pathways that naturally constrain T cell reactivity, immune checkpoint blockade releases inherent limits on the activation and maintenance of T cell effector function. In the context of cancer, where negative T cell regulatory pathways are often overactive, immune checkpoint blockade has proven to be an effective strategy for enhancing the effector activity and clinical impact of anti-tumor T cells. Checkpoint inhibitors targeting CTLA-4, PD-1, and PD-L1 have yielded unprecedented and durable responses in a significant percentage of cancer patients in recent years, leading to U.S. FDA approval of six checkpoint inhibitors for numerous cancer indications since 2011. In this review, we highlight the clinical success of these FDA-approved immune checkpoint inhibitors and discuss current challenges and future strategies that must be considered going forward to maximize the efficacy of immune checkpoint blockade therapy for cancer.
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•CTLA-4, PD-1, and PD-L1 are key negative regulators of anti-tumor T cell reactivity.•Inhibitors of CTLA-4, PD-1, and PD-L1 can enhance anti-tumor T cell reactivity.•Immune checkpoint blockade yields significant clinical benefit in cancer patients.
•PD-L1 has emerged as an important cancer biomarker and target for immunotherapy in UC.•PD-L1 is frequently expressed on tumor cells and tumor-infiltrating immune cells.•Diagnostic assays are ...available, each with different scoring cutoffs to detect PD-L1.•Despite lack of assay standardization, PD-L1 expression can be reproducibly scored.•PD-L1 testing will increasingly guide treatment and should be discussed and offered to patients with UC.
Immune checkpoint inhibitors targeting the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway improve clinical outcomes in patients with locally advanced/metastatic urothelial carcinoma (UC). PD-L1 complementary or companion diagnostic assays are now available for anti–PD-1 and anti–PD-L1 antibodies and these assays enable testing at diagnosis. The role of PD-L1 testing in UC is, however, the subject of much discussion within the medical community, particularly in light of recent restrictions on recruitment of PD-L1–low patients in clinical trials of atezolizumab and pembrolizumab as first-line therapy, and the European Medicines Agency and US Food and Drug Administration limiting use of these agents as first-line therapy in cisplatin-ineligible patients to those with high PD-L1 expression. We explore the evolving evidence for PD-L1 expression testing in UC and the role of PD-L1 expression in both tumor cells and tumor-infiltrating immune cells. We review clinical data on the prognostic and predictive value of PD-L1 expression in response to anti–PD-1/PD-L1 agents as first- and second-line therapy, considering issues such as the differences among complementary diagnostic assays in terms of the type of cells scored, antibodies used, and cutoff values. We consider how PD-L1 testing fits into decision-making and the potential of emerging biomarkers in UC. We conclude that, based on the scientific rationale for its use and evidence from clinical trials, PD-L1 testing provides enriched information on the patients most likely to benefit from immune checkpoint blockade and should be routinely offered to patients with metastatic UC.
Bioelectrical impedance analysis (BIA) and especially its derived parameter phase angle have been widely used in different populations. The variability of BIA measures has often been cited as a major ...limitation for its clinical use in evaluating nutritional status and overall health of patients. Cancer patients often present with malnourishment and cachexia, which complicate the course of treatment and affect outcomes. PubMed, CINAHL, EBSCO and Cochrane Library have been searched for relevant publications in English for BIA in cancer patients. Out of 197 total results, 27 original research articles related to BIA measures in cancer patients were included in this review. Studies indicate that the use of BIA and phase angle measures can benefit in the clinical management of cancer patients in multiple ways: in the prevention; diagnosis; prognosis; and outcomes related to treatments that affect nutritional and overall health status. Phase angle and fat-free mass measures were most commonly evaluated and correlated with nutritional status and survival rate. One limitation of BIA measures is the high interpatient variability which requires careful interpretation of results in the context of the individual patient rather than comparison with population data. The BIA and phase angle provide practitioners for the evaluation of nutritional and overall health status in cancer patients with a convenient and non-invasive technique and should be encouraged.
Ecosystem services are typically valued for their immediate material or cultural benefits to human wellbeing, supported by regulating and supporting services. Under climate change, with more frequent ...stresses and novel shocks, 'climate adaptation services', are defined as the benefits to people from increased social ability to respond to change, provided by the capability of ecosystems to moderate and adapt to climate change and variability. They broaden the ecosystem services framework to assist decision makers in planning for an uncertain future with new choices and options. We present a generic framework for operationalising the adaptation services concept. Four steps guide the identification of intrinsic ecological mechanisms that facilitate the maintenance and emergence of ecosystem services during periods of change, and so materialise as adaptation services. We applied this framework for four contrasted Australian ecosystems. Comparative analyses enabled by the operational framework suggest that adaptation services that emerge during trajectories of ecological change are supported by common mechanisms: vegetation structural diversity, the role of keystone species or functional groups, response diversity and landscape connectivity, which underpin the persistence of function and the reassembly of ecological communities under severe climate change and variability. Such understanding should guide ecosystem management towards adaptation planning.
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