Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
24,646
result(s) for
"CLARK, ANDREW"
Sort by:
The Cambridge Introduction to Literature and the Environment
\"Environmental criticism is a relatively new discipline that brings the global problem of environmental crisis to the forefront of literary and cultural studies. This introduction defines what ecocriticism is and provides a set of conceptual tools to encourage students to look at the texts they're reading in a new way\"-- Provided by publisher.
Book
Recent Explosive Human Population Growth Has Resulted in an Excess of Rare Genetic Variants
Human populations have experienced recent explosive growth, expanding by at least three orders of magnitude over the past 400 generations. This departure from equilibrium skews patterns of genetic variation and distorts basic principles of population genetics. We characterized the empirical signatures of explosive growth on the site frequency spectrum and found that the discrepancy in rare variant abundance across demographic modeling studies is mostly due to differences in sample size. Rapid recent growth increases the load of rare variants and is likely to play a role in the individual genetic burden of complex disease risk. Hence, the extreme recent human population growth needs to be taken into consideration in studying the genetics of complex diseases and traits.
Journal Article
Increased brain uptake of targeted nanoparticles by adding an acid-cleavable linkage between transferrin and the nanoparticle core
Most therapeutic agents are excluded from entering the central nervous system by the blood–brain barrier (BBB). Receptor mediated transcytosis (RMT) is a common mechanism used by proteins, including transferrin (Tf), to traverse the BBB. Here, we prepared Tf-containing, 80-nm gold nanoparticles with an acid-cleavable linkage between the Tf and the nanoparticle core to facilitate nanoparticle RMT across the BBB. These nanoparticles are designed to bind to Tf receptors (TfRs) with high avidity on the blood side of the BBB, but separate from their multidentate Tf–TfR interactions upon acidification during the transcytosis process to allow release of the nanoparticle into the brain. These targeted nanoparticles show increased ability to cross an in vitro model of the BBB and, most important, enter the brain parenchyma of mice in greater amounts in vivo after systemic administration compared with similar high-avidity nanoparticles containing noncleavable Tf. In addition, we investigated this design with nanoparticles containing high-affinity antibodies (Abs) to TfR. With the Abs, the addition of the acid-cleavable linkage provided no improvement to in vivo brain uptake for Ab-containing nanoparticles, and overall brain uptake was decreased for all Ab-containing nanoparticles compared with Tf-containing ones. These results are consistent with recent reports of high-affinity anti-TfR Abs trafficking to the lysosome within BBB endothelium. In contrast, high-avidity, Tf-containing nanoparticles with the acid-cleavable linkage avoid major endothelium retention by shedding surface Tf during their transcytosis.
Journal Article
The origins of happiness : the science of well-being over the life course
\"What makes people happy? Why should governments care about people's well-being? How would policy change if well-being was the main objective? The Origins of Happiness seeks to revolutionize how we think about human priorities and to promote public policy changes that are based on what really matters to people. Drawing on a uniquely comprehensive range of evidence from longitudinal data on over one hundred thousand individuals in Britain, the United States, Australia, and Germany, the authors consider the key factors that affect human well-being. The authors explore factors such as income, education, employment, family conflict, health, childcare, and crime -- and their findings are not what we might expect. Contrary to received wisdom, income inequality accounts for only two percent or less of the variance in happiness across the population; the critical factors affecting a person's happiness are their relationships and their mental and physical health. More people are in misery due to mental illness than to poverty, unemployment, or physical illness. Examining how childhood influences happiness in adulthood, the authors show that academic performance is a less important predictor than emotional health and behavior, which is shaped tremendously by schools, individual teachers, and parents. For policymakers, the authors propose new forms of cost-effectiveness analysis that places well-being at center stage. Groundbreaking in its scope and results, The Origins of Happiness offers all of us a new vision for how we might become more healthy, happy, and whole\"-- Provided by publisher.
Book
RepeatModeler2 for automated genomic discovery of transposable element families
SignificanceGenome sequences are being produced for more and more eukaryotic species. The bulk of these genomes are composed of parasitic, self-mobilizing transposable elements (TEs) that play important roles in organismal evolution. Thus there is a pressing need for developing software that can accurately identify the diverse set of TEs dispersed in genome sequences. Here we introduce RepeatModeler2, an easy-to-use package for the production of reference TE libraries which can be applied to any eukaryotic species. Through several major improvements over the previous version, RepeatModeler2 is able to produce libraries that recapitulate the known composition of three model species with some of the most complex TE landscapes. Thus RepeatModeler2 will greatly enhance the discovery and annotation of TEs in genome sequences.
The accelerating pace of genome sequencing throughout the tree of life is driving the need for improved unsupervised annotation of genome components such as transposable elements (TEs). Because the types and sequences of TEs are highly variable across species, automated TE discovery and annotation are challenging and time-consuming tasks. A critical first step is the de novo identification and accurate compilation of sequence models representing all of the unique TE families dispersed in the genome. Here we introduce RepeatModeler2, a pipeline that greatly facilitates this process. This program brings substantial improvements over the original version of RepeatModeler, one of the most widely used tools for TE discovery. In particular, this version incorporates a module for structural discovery of complete long terminal repeat (LTR) retroelements, which are widespread in eukaryotic genomes but recalcitrant to automated identification because of their size and sequence complexity. We benchmarked RepeatModeler2 on three model species with diverse TE landscapes and high-quality, manually curated TE libraries: Drosophila melanogaster (fruit fly), Danio rerio (zebrafish), and Oryza sativa (rice). In these three species, RepeatModeler2 identified approximately 3 times more consensus sequences matching with >95% sequence identity and sequence coverage to the manually curated sequences than the original RepeatModeler. As expected, the greatest improvement is for LTR retroelements. Thus, RepeatModeler2 represents a valuable addition to the genome annotation toolkit that will enhance the identification and study of TEs in eukaryotic genome sequences. RepeatModeler2 is available as source code or a containerized package under an open license (https://github.com/Dfam-consortium/RepeatModeler, http://www.repeatmasker.org/RepeatModeler/).
Journal Article
The last exorcism. Part II
At a New Orleans halfway house for girls, Nell Sweetzer attempts to recover from her trauma, but the demon that possessed her returns with an even more horrific plan.
DVD
Mechanical compartmentalization of the intestinal organoid enables crypt folding and collective cell migration
Intestinal organoids capture essential features of the intestinal epithelium such as crypt folding, cellular compartmentalization and collective movements. Each of these processes and their coordination require patterned forces that are at present unknown. Here we map three-dimensional cellular forces in mouse intestinal organoids grown on soft hydrogels. We show that these organoids exhibit a non-monotonic stress distribution that defines mechanical and functional compartments. The stem cell compartment pushes the extracellular matrix and folds through apical constriction, whereas the transit amplifying zone pulls the extracellular matrix and elongates through basal constriction. The size of the stem cell compartment depends on the extracellular-matrix stiffness and endogenous cellular forces. Computational modelling reveals that crypt shape and force distribution rely on cell surface tensions following cortical actomyosin density. Finally, cells are pulled out of the crypt along a gradient of increasing tension. Our study unveils how patterned forces enable compartmentalization, folding and collective migration in the intestinal epithelium.
Pérez-González et al. explore the mechanical properties of intestinal organoids, and report the existence of distinct mechanical domains and that cells are pulled out of the central crypt along a gradient of increasing tension.
Journal Article
The Ability of AI Therapy Bots to Set Limits With Distressed Adolescents: Simulation-Based Comparison Study
Recent developments in generative artificial intelligence (AI) have introduced the general public to powerful, easily accessible tools, such as ChatGPT and Gemini, for a rapidly expanding range of uses. Among those uses are specialized chatbots that serve in the role of a therapist, as well as personally curated digital companions that offer emotional support. However, the ability of AI therapists to provide consistently safe and effective treatment remains largely unproven, and those concerns are especially salient in regard to adolescents seeking mental health support.
This study aimed to determine the willingness of therapy and companion AI chatbots to endorse harmful or ill-advised ideas proposed by fictional teenagers experiencing mental health distress.
A convenience sample of 10 publicly available AI bots offering therapeutic support or companionship were each presented with 3 detailed fictional case vignettes of adolescents with mental health challenges. Each fictional adolescent asked the AI chatbot to endorse 2 harmful or ill-advised proposals, such as dropping out of school, avoiding all human contact for a month, or pursuing a relationship with an older teacher, resulting in a total of 6 proposals presented to each chatbot. The clinical scenarios presented were intended to reflect challenges commonly seen in the practice of therapy with adolescents, and the proposals offered by the fictional teenagers were intended to be clearly dangerous or unwise. The 10 AI bots were selected by the author to represent a range of chatbot types, including generic AI bots, companion bots, and dedicated mental health bots. Chatbot responses were analyzed for explicit endorsement, defined as direct support for the teenagers' proposed behavior.
Across 60 total scenarios, chatbots actively endorsed harmful proposals in 19 out of the 60 (32%) opportunities to do so. Of the 10 chatbots, 4 endorsed half or more of the ideas proposed to them, and none of the bots managed to oppose them all.
A significant proportion of AI chatbots offering mental health or emotional support endorsed harmful proposals from fictional teenagers. These results raise concerns about the ability of some AI-based companion or therapy bots to safely support teenagers with serious mental health issues and heighten concern that AI bots may tend to be overly supportive at the expense of offering useful guidance when appropriate. The results highlight the urgent need for oversight, safety protocols, and ongoing research regarding digital mental health support for adolescents.
Journal Article