Innate Immunity In Degenerative Diseases Of The Retina And Brain

Innate immunity plays a critical role in degenerative diseases of the central nervous system (CNS). However, many of the molecular pathways by which innate inflammation contributes to individual diseases remain unknown. Herein, we use a combination of primary cell culture, in vivo animal studies and human data to explore two distinct pathways of neuroinflammation. The first, focuses on the role of reactive astrocytes as mediators of innate inflammation and neurodegeneration in glaucoma. The second, highlights the role of nutritional immunity, a division of the innate immune system, in iron dysregulation observed across multiple CNS diseases including age-related macular degeneration and Parkinson’s disease. Together these data highlight the multiple mechanisms by which maladaptive activation of innate immunity can contribute to CNS dysfunction and identify new targets for therapeutic intervention

Postsecondary Attainment: Identifying Areas to Improve Retention for North Carolina Community Colleges

This paper details ways that North Carolina Community Colleges can improve retention by investigating curriculum completion and success in students’ first year of college. A complete repository of data from community colleges in North Carolina was built for this analysis featuring 1950 variables related to the colleges and their surrounding communities from five main publicly available data sources. Leading factors were identified to help explain why one-third of students in North Carolina community colleges do not return for their second year of college. Our research revealed that racial demographics along with success from educationally at risk, English as a Second Language (ESL) individuals receiving Adult Education and Family Literacy Act (AEFLA) services are leading factors to predicting retention. Our research uses elastic net regularized regression techniques to determine the feature importance of variables connected to students’ success in their first year of college

EV’s Leading in China, Ford is a Few Cars Behind

As the world is looking at sustainable energy sources, electric vehicles are likely to be a big part of the perceived future. China has 18.47% of the world’s population, is one of the highest emitters of carbon dioxide, and is the world’s largest market for electric vehicles (Country Meters). China’s GDP was USD 13.608 trillion in 2018 and is expected to increase substantially in coming years (Wang, 2019). With 25 million vehicles sold in 2019, China’s automobile market is the biggest in the world. With that, China accounts for 27.52% of the world’s CO2 emissions (Statista). To decrease that number, China stated in 2019 their goal was to have 60% of all automobiles sold in 2035 to run on electric motors (Tian, 2019). With car sales in China declining rapidly over the past 3 years, automobile companies are looking for a way to develop a sustainable competitive advantage. Ford Motor Company, a $156 billion global leader, has been struggling to compete in China and is now looking to the electric vehicle market as a way to expand. However, China’s EV market is hypercompetitive with over 400 domestic EV manufacturers, including some multinationals like General Motors. To differentiate themselves from the competition, Ford announced plans of building facilities that will specialize in creating technology for their EV’s. SYNC+ is a popular technological option available to enhance the consumers experience (Media Ford, 2019). However, investment in technology could raise the prices of their vehicles. With annual income in China at about 82,413 yuan ($11,727 USD), raising prices may not be an option for Ford (Statista). This case study discusses the many challenges that Ford faces in China and how it needs to change its marketing mix in order to succeed there. Keywords: Ford, China, Electric Vehicles, Pollution, Environment, Automobiles, Case Study, Emerging Markets, International marketin

Relationships between cardiorespiratory fitness, hippocampal volume, and episodic memory in a population at risk for Alzheimer’s disease

Introduction: Cardiorespiratory fitness (CRF) has been shown to be related to brain health in older adults. In individuals at risk for developing Alzheimer\u27s disease (AD), CRF may be a modifiable risk factor that could attenuate anticipated declines in brain volume and episodic memory. The objective of this study was to determine the association between CRF and both hippocampal volume and episodic memory in a cohort of cognitively healthy older adults with familial and/or genetic risk for Alzheimer\u27s disease (AD). Methods: Eighty‐six enrollees from the Wisconsin Registry for Alzheimer\u27s Prevention participated in this study. Participants performed a graded maximal exercise test, underwent a T‐1 anatomical magnetic resonance imaging scan, and completed the Rey Auditory Verbal Learning Test (RAVLT). Results: There were no significant relationships between CRF and HV or RAVLT memory scores for the entire sample. When the sample was explored on the basis of gender, CRF was significantly associated with hippocampal volume for women. For men, significant positive associations were observed between CRF and RAVLT memory scores. Summary: These results suggest that CRF may be protective against both hippocampal volume and episodic memory decline in older adults at risk for AD, but that the relationships may be gender specific

What is missing in autonomous discovery: Open challenges for the community

Self-driving labs (SDLs) leverage combinations of artificial intelligence, automation, and advanced computing to accelerate scientific discovery. The promise of this field has given rise to a rich community of passionate scientists, engineers, and social scientists, as evidenced by the development of the Acceleration Consortium and recent Accelerate Conference. Despite its strengths, this rapidly developing field presents numerous opportunities for growth, challenges to overcome, and potential risks of which to remain aware. This community perspective builds on a discourse instantiated during the first Accelerate Conference, and looks to the future of self-driving labs with a tempered optimism. Incorporating input from academia, government, and industry, we briefly describe the current status of self-driving labs, then turn our attention to barriers, opportunities, and a vision for what is possible. Our field is delivering solutions in technology and infrastructure, artificial intelligence and knowledge generation, and education and workforce development. In the spirit of community, we intend for this work to foster discussion and drive best practices as our field grows

Intracellular Trafficking and Synaptic Function of APL-1 in Caenorhabditis elegans

Background: Alzheimer’s disease (AD) is a neurodegenerative disorder primarily characterized by the deposition of b-amyloid plaques in the brain. Plaques are composed of the amyloid-b peptide derived from cleavage of the amyloid precursor protein (APP). Mutations in APP lead to the development of Familial Alzheimer’s Disease (FAD), however, the normal function of this protein has proven elusive. The organism Caenorhabditis elegans is an attractive model as the amyloid precursor-like protein (APL-1) is the single ortholog of APP, and loss of apl-1 leads to a severe molting defect and early larval lethality. Methodology/Principal Findings: We report here that lethality and molting can be rescued by full length APL-1, C-terminal mutations as well as a C-terminal truncation, suggesting that the extracellular region of the protein is essential for viability. RNAi knock-down of apl-1 followed by drug testing on the acetylcholinesterase inhibitor aldicarb showed that loss of apl-1 leads to aldicarb hypersensitivity, indicating a defect in synaptic function. The aldicarb hypersensitivity can be rescued by full length APL-1 in a dose dependent fashion. At the cellular level, kinesins UNC-104/KIF-1A and UNC-116/kinesin-1 are positive regulators of APL-1 expression in the neurons. Knock-down of the small GTPase rab-5 also leads to a dramatic decrease in the amount of apl-1 expression in neurons, suggesting that trafficking from the plasma membrane to the early endosome is important for apl-1 function. Loss of function of a different small GTPase, UNC-108, on the contrary, leads t

The DOE E3SM Coupled Model Version 1: Overview and Evaluation at Standard Resolution

This work documents the first version of the U.S. Department of Energy (DOE) new Energy Exascale Earth System Model (E3SMv1). We focus on the standard resolution of the fully coupled physical model designed to address DOE mission-relevant water cycle questions. Its components include atmosphere and land (110-km grid spacing), ocean and sea ice (60 km in the midlatitudes and 30 km at the equator and poles), and river transport (55 km) models. This base configuration will also serve as a foundation for additional configurations exploring higher horizontal resolution as well as augmented capabilities in the form of biogeochemistry and cryosphere configurations. The performance of E3SMv1 is evaluated by means of a standard set of Coupled Model Intercomparison Project Phase 6 (CMIP6) Diagnosis, Evaluation, and Characterization of Klima simulations consisting of a long preindustrial control, historical simulations (ensembles of fully coupled and prescribed SSTs) as well as idealized CO2 forcing simulations. The model performs well overall with biases typical of other CMIP-class models, although the simulated Atlantic Meridional Overturning Circulation is weaker than many CMIP-class models. While the E3SMv1 historical ensemble captures the bulk of the observed warming between preindustrial (1850) and present day, the trajectory of the warming diverges from observations in the second half of the twentieth century with a period of delayed warming followed by an excessive warming trend. Using a two-layer energy balance model, we attribute this divergence to the model’s strong aerosol-related effective radiative forcing (ERFari+aci = -1.65 W/m2) and high equilibrium climate sensitivity (ECS = 5.3 K).Plain Language SummaryThe U.S. Department of Energy funded the development of a new state-of-the-art Earth system model for research and applications relevant to its mission. The Energy Exascale Earth System Model version 1 (E3SMv1) consists of five interacting components for the global atmosphere, land surface, ocean, sea ice, and rivers. Three of these components (ocean, sea ice, and river) are new and have not been coupled into an Earth system model previously. The atmosphere and land surface components were created by extending existing components part of the Community Earth System Model, Version 1. E3SMv1’s capabilities are demonstrated by performing a set of standardized simulation experiments described by the Coupled Model Intercomparison Project Phase 6 (CMIP6) Diagnosis, Evaluation, and Characterization of Klima protocol at standard horizontal spatial resolution of approximately 1° latitude and longitude. The model reproduces global and regional climate features well compared to observations. Simulated warming between 1850 and 2015 matches observations, but the model is too cold by about 0.5 °C between 1960 and 1990 and later warms at a rate greater than observed. A thermodynamic analysis of the model’s response to greenhouse gas and aerosol radiative affects may explain the reasons for the discrepancy.Key PointsThis work documents E3SMv1, the first version of the U.S. DOE Energy Exascale Earth System ModelThe performance of E3SMv1 is documented with a set of standard CMIP6 DECK and historical simulations comprising nearly 3,000 yearsE3SMv1 has a high equilibrium climate sensitivity (5.3 K) and strong aerosol-related effective radiative forcing (-1.65 W/m2)Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151288/1/jame20860_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151288/2/jame20860.pd

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

BETRAYAL OF THE AMERICAN DREAM: WHY BLACKS AND LATINOS WERE HIT HARDEST BY THE U.S. HOUSING CRISIS

I contend that the United States housing boom and subsequent crisis were fundamentally structured by the social forces of racial segregation, discrimination, and demographic change in ways that uniquely disadvantaged black and Latino borrowers and communities. Controlling for an array of rival explanations, black-white residential segregation emerges as the strongest predictor of 2006-2008 foreclosure filing rates across the largest 100 metropolitan areas. Using a two-stage least squares estimation, I show that black-white and Hispanic-white disparities in subprime lending link segregation to foreclosure rates in a causal relationship. I explore further the mechanisms that generate for inequality in high cost subprime lending in one of the nation's most segregated cities. I find that blacks and Latinos and borrowers in mostly black and Latino neighborhoods experienced discrimination in broker-originated, high cost, and subprime refinance lending in ways that cannot be explained by credit profile, loan characteristics, borrower income, or other factors. Residence in mostly black and Latino neighborhoods is also strongly significantly related to higher odds of foreclosure, but not default, which is more strongly driven by losses in income and declines in home prices. I return to a national analysis and argue that Latinos were dealt a double-blow by the crisis. First, they experienced discriminatory subprime lending alongside black neighbors in segregated cities. Second, Latinos were twice as likely as blacks to receive new exotic alt-A loans due to their late entry in the housing boom, continued immigration, and greater rates of suburbanization. Among a sample of 200,000 borrowers, I find that Latinos experience the highest foreclosure rate and were twice as likely as blacks to have received alt-A nonprime loans. Using a competing risk framework, I confirm that residence in hard hit states and broker-originated loans with deceptive features account for much of the Latino disparity in foreclosure. I uncover new sources of Latino disadvantage, such as their concentration in states without judicial foreclosure and reduced access to housing counselors and loan modifications. I conclude that, like blacks, Latinos were also victimized by risky subprime and especially alt-A lending, and that unequal lending ultimately betrayed the American Dream of home ownership