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This work demonstrates the application of a 3D culture system - Cells-in-Gels-in-Paper (CiGiP) - in evaluating the metabolic response of lung cancer cells to ionizing radiation. The 3D tissue-like construct - prepared by stacking multiple sheets of paper containing cell-embedded hydrogels - generates a gradient of oxygen and nutrients that decreases monotonically in the stack. Separating the layers of the stack after exposure enabled analysis of the cellular response to radiation as a function of oxygen and nutrient availability; this availability is dictated by the distance between the cells and the source of oxygenated medium. As the distance between the cells and source of oxygenated media increased, cells show increased levels of hypoxia-inducible factor 1-alpha, decreased proliferation, and reduced sensitivity to ionizing radiation. Each of these cellular responses are characteristic of cancer cells observed in solid tumors. With this setup we were able to differentiate three isogenic variants of A549 cells based on their metabolic radiosensitivity; these three variants have known differences in their metastatic behavior in vivo. This system can, therefore, capture some aspects of radiosensitivity of populations of cancer cells related to mass-transport phenomenon, carry out systematic studies of radiation response in vitro that decouple effects from migration and proliferation of cells, and regulate the exposure of oxygen to subpopulations of cells in a tissue-like construct either before or after irradiation., Chemistry and Chemical Biology

This work describes a 3D, paper-based assay that can isolate subpopulations of cells based on their invasiveness (i.e., distance migrated in a hydrogel) in a gradient of concentration of oxygen (O2). Layers of paper impregnated with a cell-compatible hydrogel are stacked and placed in a plastic holder to form the invasion assay. Stacking the layers of paper assembles them into 3D tissue-like constructs of defined thickness and composition. The plastic holder ensures the layers of paper are in conformal contact; this geometry allows the cells to migrate between adjacent layers through the embedded hydrogel. In most assays, the stack comprises a single layer of paper containing mammalian cells suspended in a hydrogel, sandwiched between multiple layers of paper containing only hydrogel (into which the cells migrate). Cells in the stack consume and produce small molecules; these molecules diffuse throughout the stack to generate gradients both in the stack, and between the stack and the bulk culture medium. Placing the cell-containing layer in different positions of the stack, or modifying the permeability of the holder to oxygen or proteins, alters the profile of the gradients within the stack. Physically separating the layers after culture isolates subpopulations of cells that migrated different distances, and enables their subsequent analysis or culture. Using this system, three independent cell lines derived from A549 cancer cells are shown to produce distinguishable migration behavior in a gradient of oxygen. This result is the first experimental demonstration that oxygen acts as a chemoattractant for cancer cells., Chemistry and Chemical Biology

Indicator species (IS) are used to monitor environmental changes, assess the efficacy of management, and provide warning signals for impending ecological shifts. Though widely adopted in recent years by ecologists, conservation biologists, and environmental practitioners, the use of IS has been criticized for several reasons, notably the lack of justification behind the choice of any given indicator. In this review, we assess how ecologists have selected, used, and evaluated the performance of the indicator species. We reviewed all articles published in Ecological Indicators (EI) between January 2001 and December 2014, focusing on the number of indicators used (one or more); common taxa employed; terminology, application, and rationale behind selection criteria; and performance assessment methods. Over the last 14 years, 1914 scientific papers were published in EI, describing studies conducted in 53 countries on six continents; of these, 817 (43%) used biological organisms as indicators. Terms used to describe organisms in IS research included “ecological index”, “environmental index”, “indicator species”, “bioindicator”, and “biomonitor,” but these and other terms often were not clearly defined. Twenty percent of IS publications used only a single species as an indicator; the remainder used groups of species as indicators. Nearly 50% of the taxa used as indicators were animals, 70% of which were invertebrates. The most common applications behind the use of IS were to: monitor ecosystem or environmental health and integrity (42%); assess habitat restoration (18%); and assess effects of pollution and contamination (18%). Indicators were chosen most frequently based on previously cited research (40%), local abundance (5%), ecological significance and/or conservation status (13%), or a combination of two or more of these reasons (25%). Surprisingly, 17% of the reviewed papers cited no clear justification for their choice of indicator. The vast majority (99%) of publications used statistical methods to assess the performance of the selected indicators. This review not only improves our understanding of the current uses and applications of IS, but will also inform practitioners about how to better select and evaluate ecological indicators when conducting future IS research., Organismic and Evolutionary Biology

The development of reproducible folding in the gyrencephalic cerebral cortex is a topic of great interest to neuroscientists. In a recent paper in Cell, del Toro et al. (2017) show that changing the adhesive properties of neurons in the normally lissencephalic mouse cortex leads to the formation of stereotyped folding., Stem Cell and Regenerative Biology

The molecular linkage between neocortical projection neuron subtype and area development, which enables the establishment of functional areas by projection neuron populations appropriate for specific sensory and motor functions, is poorly understood. Here, we report that Ctip1 controls precision of neocortical development by regulating subtype identity in deep-layer projection neurons. Ctip1 is expressed by postmitotic callosal and corticothalamic projection neurons, but is excluded over embryonic development from corticospinal motor neurons, which instead express its close relative, Ctip2. Loss of Ctip1 function results in a striking bias in favor of subcerebral projection neuron development in sensory cortex at the expense of corticothalamic and deep-layer callosal development, while misexpression of Ctip1 in vivo represses subcerebral gene expression and projections. As we report in a paired paper, Ctip1 also controls acquisition of sensory area identity. Therefore, Ctip1 couples subtype and area specification, enabling specific functional areas to organize precise ratios of appropriate output projections., Stem Cell and Regenerative Biology

Research consistently shows that college choice in an important predictor of college completion and labor market outcomes. These longer term implications of college choice, combined with suboptimal choices made by many low-income but high-achieving students, has sparked several large-scale initiatives to improve college choice. Strategically targeting those students most susceptible to making questionable decisions in the college-choice process remains challenging, as variation in college choice is largely unexplained by easily measurable socio-demographic characteristics. This paper explores the potential to improve upon existing models and, more generally, to better understand college choice by documenting the similarities in college enrollment patterns between younger and older siblings. To do so, we identify siblings in the millions of SAT test-takers between the 2004 and 2011 high school graduation cohorts. We find that younger siblings enroll in the same college as their older sibling 21.2 percent of the time. Also, conditional on their own SAT scores, we find that younger siblings whose older siblings enrolled in four-year colleges and the most selective colleges are 17.4 and 21.3 percentage points, respectively, more likely to themselves enroll in four-year and the most selective colleges. Overall, adding characteristics and enrollment decisions of older siblings to standard college choice models improves model fit and consequently, are valuable pieces of information for explanatory and predictive power., Economics

Silicon is a promising anode material for lithium-ion batteries due to its enormous theoretical energy density. Fracture during electrochemical cycling has limited the practical viability of silicon electrodes, but recent studies indicate that fracture can be prevented by taking advantage of lithiation-induced plasticity. In this paper, we provide experimental insight into the nature of plasticity in amorphous LixSi thin films. To do so, we vary the rate of lithiation of amorphous silicon thin films and simultaneously measure stresses. An increase in the rate of lithiation results in a corresponding increase in the flow stress. These observations indicate that rate-sensitive plasticity occurs in a-LixSi electrodes at room temperature and at charging rates typically used in lithium-ion batteries. Using a simple mechanical model, we extract material parameters from our experiments, finding a good fit to a power law relationship between the plastic strain rate and the stress. These observations provide insight into the unusual ability of a-LixSi to flow plastically, but fracture in a brittle manner. Moreover, the results have direct ramifications concerning the rate-capabilities of silicon electrodes: faster charging rates (i.e., strain rates) result in larger stresses and hence larger driving forces for fracture., Engineering and Applied Sciences

Few research papers in economics have examined the extent, causes or consequences of physical stature decline in aging populations. Using repeated observations on objectively measured data from the English Longitudinal Study of Aging (ELSA), we document that reduction in height is an important phenomenon among respondents aged 50 and over. On average, physical stature decline occurs at an annual rate of between 0.08% and 0.10% for males, and 0.12% and 0.14% for females—which approximately translates into a 2–4 cm reduction in height over the life course. Since height is commonly used as a measure of long-run health, our results demonstrate that failing to take age-related height loss into account substantially overstates the health advantage of older birth cohorts relative to their younger counterparts. We also show that there is an absence of consistent predictors of physical stature decline at the individual level. However, we demonstrate how deteriorating health and reductions in height occur simultaneously. We document that declines in muscle mass and bone density are likely to be the mechanism through which these effects are operating. If this physical stature decline is determined by deteriorating health in adulthood, the coefficient on measured height when used as an input in a typical empirical health production function will be affected by reverse causality. While our analysis details the inherent difficulties associated with measuring height in older populations, we do not find that significant bias arises in typical empirical health production functions from the use of height which has not been adjusted for physical stature decline. Therefore, our results validate the use of height among the population aged over 50.

This paper argues that the 2009 pledge of $100 billion in 2020 by rich countries for mitigation and adaptation should not be used for mitigation by commercial firms in developing countries, since that would artificially create competitive advantage for such firms and provoke protectionist reactions in the rich countries where firms must bear the costs of mitigation, thereby undermining the world trading system. The costs of heating the earth's surface should be borne by all emitters, just as the price of copper and other scarce resources is paid by all users, rich or poor. That will still leave scope for rich country help in adaptation to climate change and in bringing to fruition new technologies to reduce emissions., Economics

The majority of the population of the planet (6.6 billion) now live in urban areas, which have distinct impacts upon climate at scales from the local to the global. This urban effect is due to the physical form of the city (its three-dimensional geometry and material composition) and its functions (the day-to-day activity patterns that generate emissions of waste heat and materials into the overlying air). While a substantial body of knowledge on the science of urban climates has been developed over the past fifty years, there is little evidence that this knowledge is incorporated into urban planning and design practice. This paper focuses on this gap by examining the nature of urban climate expertise and the needs of those that make decisions about urban areas. In conclusion it makes recommendations to maintain and enhance urban observations and data; to improve understanding of local, regional and global climate linkages; to develop tools for practical planning; and to disseminate urban climate knowledge and its relevance to urban planning to both practicing meteorologists and urban decision makers.

This paper investigates the effects of the education level, product market rigidities and employment protection legislation on growth. It exploits macro-panel data for OECD countries. For countries close to the technological frontier, education and rigidities are significantly related to TFP growth. The contribution of the interaction between product market regulation and labour market rigidity seems particularly substantial., Economics

SWAN (Semantic Web Application in Neuromedicine) is a project to construct a semantically-organized, community-curated, distributed knowledge base of Theory, Evidence, and Discussion in biomedicine. Unlike Wikipedia and similar approaches, SWAN’s ontology is designed to represent and foreground both harmonizing and contradictory assertions within the total community discourse. Releases of the software, content and ontology will be initially by and for the Alzheimer Disease (AD) research community, with the obvious potential for extension into other disease research areas. The Alzheimer Research Forum, a 4,000-member web community for AD researchers, will host SWAN’s initial public release, currently scheduled for late 2007. This paper presents the current version of SWAN’s ontology of scientific discourse and presents our current thinking about its evolution including extensions and alignment with related communities, projects and ontologies.

To study the potential impacts of climate change on air quality and public health over the eastern United States, a coupled global/regional-scale modeling system consisting of the NASA-Goddard Institute for Space Studies Atmosphere–Ocean model, the MM5 mesoscale meteorological model and the Community Multiscale Air Quality (CMAQ) model for air quality has been developed. Evaluation results of the modeling system used to simulate climate and ozone air quality over the eastern United States during the five summers of 1993–1997 are presented in this paper. The results indicate that MM5 and CMAQ capture interannual and synoptic-scale variability present in surface temperature and ozone observations in the current climate, while the magnitude of fluctuations on shorter time scales is underestimated. A comparison of observed and predicted spatial patterns of daily maximum ozone concentrations shows best performance in predicting patterns for average and above-average ozone concentrations. The frequency distributions of the duration of extreme heat and ozone events show similar features for both model predictions and observations. Finally, application of a synoptic map-typing procedure reveals that the MM5/CMAQ system succeeded in simulating the average ozone concentrations associated with several frequent pressure patterns, indicating that the effects of synoptic-scale meteorology on ozone concentrations are captured by the modeling system. It is concluded that the GCM/MM5/CMAQ system is a suitable tool for the simulation of summertime surface temperature and ozone air quality conditions over the eastern United States in the present climate.

This paper develops a model of an unregulated banking system based around a private clearing house arrangement. Whilst such a system may dominate one with a public safety net in reducing moral hazard in lending and therefore the scope for individual bank insolvency, it also increases the likelihood of contagious bank failures following a systemic shock or an aggregate liquidity shortage., Economics

Of all the changes in the history of women's market work, few have been more impressive than the rapid emergence and feminization of the clerical sector and the related decline in manufacturing employment for women. Although a century ago few women were clerical workers, as early as 1920 22% of all employed non-farm women were, and about 50% of all clerical workers were women. Employment for women in the clerical sector expanded at five times the annual rate in manufacturing from 1890 to 1930, and during the same period of time wages for female clerical workers fell relative to those in manufacturing. This paper explores the underlying causes of these dramatic sectoral shifts by estimating the relationship between earnings and experience for manufacturing and clerical workers from 1888 to 1940. It is seen that earnings profiles for employment in manufacturing rose steeply with experience and peaked early, while those in the clerical sector were much flatter and did not peak within the relevant range. Returns to off-job training and depreciation with age and with time away from the labor force also differed between these occupations. A model of sectoral shift is developed in which workers choose occupations and therefore the time path of training on the basis of their life-cycle labor force participation and their consumption value of education. The coefficients from the earnings function estimations are used to demonstrate that the decline in the relative wage of clerical to manufacturing work from 1890 to 1930 can be explained by such a model, Finally, it is shown that a sizable percentage of the difference in the growth of female employment in the manufacturing and clerical sectors can be explained by various labor supply factors., Economics