3,664 research outputs found
A study of an electric field measuring instrument
Cesium ion beam electric field measuring instrument
Synthesis of polyethers of hexafluorobenzene and hexafluoropentanediol
Two new polyethers, poly /hexafluoropentamethylene tetrafluoro-p-phenylene ether/ and a completely hydroxyl-terminated polyether, is prepared by reactions of hexafluorobenzene with hexafluoropentanediol. The polyethers can be prepared as low molecular weight oils, as intermediate molecular weight waxes, or as high molecular weight elastomers
Competition and Collaboration in the Nonprofit Sector: Identifying the Potential for Cognitive Dissonance
Nonprofits compete with collaborators and collaborate with competitors regularly. Collaboration, a long-standing normatively preferred strategy for nonprofits, is utilized as modus operandi without thought to the potential unintended consequences. While competition, long deemed a dirty, word for nonprofits is a necessary but undesirable reality, avoided without consideration to the potential benefits. Nonprofits leaders may not be willing to explicitly acknowledge the use of competition as an operational strategy, which makes room for cognitive dissonance to impact the study of nonprofits. This piece identifies impacts of cognitive dissonance offering direction for future research exploring the interactive nature of competing with collaborators.Sports Innovation Institute, IUPUI
Lilly Family School of Philanthropy, IUPU
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Learning cell states from high-dimensional single-cell data
Recent developments in single-cell measurement technologies have yielded dramatic increases in throughput (measured cells per experiment) and dimensionality (measured features per cell). In particular, the introduction of mass cytometry has made possible the simultaneous quantification of dozens of protein species in millions of individual cells in a single experiment. The raw data produced by such high-dimensional single-cell measurements provide unprecedented potential to reveal the phenotypic heterogeneity of cellular systems. In order to realize this potential, novel computational techniques are required to extract knowledge from these complex data.
Analysis of single-cell data is a new challenge for computational biology, as early development in the field was tailored to technologies that sacrifice single-cell resolution, such as DNA microarrays. The challenges for single-cell data are quite distinct and require multidimensional modeling of complex population structure. Particular challenges include nonlinear relationships between measured features and non-convex subpopulations.
This thesis integrates methods from computational geometry and network analysis to develop a framework for identifying the population structure in high-dimensional single-cell data. At the center of this framework is PhenoGraph, and algorithmic approach to defining subpopulations, which when applied to healthy bone marrow data was shown to reconstruct known immune cell types automatically without prior information. PhenoGraph demonstrated superior accuracy, robustness, and efficiency, compared to other methods.
The data-driven approach becomes truly powerful when applied to less characterized systems, such as malignancies, in which the tissue diverges from its healthy population composition. Applying PhenoGraph to bone marrow samples from a cohort of acute myeloid leukemia (AML) patients, the thesis presents several insights into the pathophysiology of AML, which were extracted by virtue of the computational isolation of leukemic subpopulations. For example, it is shown that leukemic subpopulations diverge from healthy bone marrow but not without bound: Leukemic cells are apparently free to explore only a restricted phenotypic space that mimics normal myeloid development. Further, the phenotypic composition of a sample is associated with its cytogenetics, demonstrating a genetic influence on the population structure of leukemic bone marrow.
The thesis goes on to show that functional heterogeneity of leukemic samples can be computationally inferred from molecular perturbation data. Using a variety of methods that build on PhenoGraph's foundations, the thesis presents a characterization of leukemic subpopulations based on an inferred stem-like signaling pattern. Through this analysis, it is shown that surface phenotypes often fail to reflect the true underlying functional state of the subpopulation, and that this functional stem-like state is in fact a powerful predictor of survival in large, independent cohorts.
Altogether, the thesis takes the existence and importance of cellular heterogeneity as its starting point and presents a mathematical framework and computational toolkit for analyzing samples from this perspective. It is shown that phenotypic and functional heterogeneity are robust characteristics of acute myeloid leukemia with clinically significant ramifications
Scaling up Payments for Watershed Services: Recommendations for Increasing Participation in Watershed Conservation Among Non-Industrial Private Forest Landowners in the Sebago Lake Watershed, Maine
Payments for Watershed Services (PWS) programs are receiving attention throughout the U.S. as a
policy option to secure water quality in a cost effective manner. PWS programs face many challenges
in implementation; prominent among them is designing a program that generates interest and
participation among the suppliers of water quality, upstream private landowners. This report seeks to
inform the development of a PWS program in Southeast Maine by examining the system of
incentives needed to encourage private forest owners to adopt conservation best management
practices that enhance water quality downstream. While focused on the Sebago Lake watershed,
which provides drinking water for the Greater Portland area, this project approaches the localized
study as a specific case to identify biophysical, institutional, economic and social factors that favor or
limit the scaling up of PWS schemes. This analysis combines a systematic review of literature on
landowner preferences to existing incentive programs, interviews with program administrators from
PWS schemes throughout the U.S., and interviews with key stakeholders in Southeast Maine. This
report provides a set of recommendations organized around: segmentation of landowners; targeting
and positioning PWS programs; selecting attractive program attributes; and leveraging effective
outreach channels and tactics. Key recommendations include: co-create program attributes with
landowners; encourage peer to peer communication to build support and awareness; provide a
portfolio of financial and non-financial incentives to increase interest; and partner with existing
conservation organizations to add capabilities and resources.Master of ScienceNatural Resources and EnvironmentUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/90874/1/scaling_up_watershed_services_2012.pd
Chimeric antigen receptor–T cell therapy manufacturing: modelling the effect of offshore production on aggregate cost of goods
Cell and gene therapies have demonstrated excellent clinical results across a range of indications with chimeric antigen receptor (CAR)–T cell therapies among the first to reach market. Although these therapies are currently manufactured using patient-derived cells, therapies using healthy donor cells are in development, potentially offering avenues toward process improvement and patient access. An allogeneic model could significantly reduce aggregate cost of goods (COGs), potentially improving market penetration of these life-saving treatments. Furthermore, the shift toward offshore production may help reduce manufacturing costs. In this article, we examine production costs of an allogeneic CAR-T cell process and the potential differential manufacturing costs between regions. Two offshore locations are compared with regions within the United States. The critical findings of this article identify the COGs challenges facing manufacturing of allogeneic CAR-T immunotherapies, how these may evolve as production is sent offshore and the wider implication this trend could have
Vitamin C u neuropsihijatriji
Vitamins are necessary factors in human development and normal brain function. Vitamin C is a hydrosoluble compound that humans cannot produce; therefore, we are completely dependent on food intake for vitamin C. Ascorbic acid is an important antioxidative agent and is present in high concentrations in neurons and is also crucial for collagen synthesis throughout the body. Ascorbic acid has a role in modulating many essential neurotransmitters, enables neurogenesis in adult brain and protects cells against infection. While SVCT1 enables the absorption of vitamin C in the intestine, SVCT2 is primarily located in the brain. Ascorbate deficiency is classically expressed as scurvy, which is lethal if not treated. However, subclinical deficiencies are probably much more frequent. Potential fields of vitamin C therapy are in neurodegenerative, cerebrovascular and affective diseases, cancer, brain trauma and others. For example, there is some data on its positive effects in Alzheimer's disease. Various dosing regimes are used, but ascorbate is safe, even in high doses for protracted periods. Better designed studies are needed to elucidate all of the potential therapeutic roles of vitamin C.Vitamin su neophodni faktori za razvoj i normalnu funkciju mozga kod ljudi. Vitamin C je hidrosolubilno jedinjenje koje ljudski organizam ne može da sintetiše tako da smo potpuno zavisni od unosa putem hrane. Askorbinska kiselina je važno antioksidativno sredstvo i prisutna je u neuronima u visokim koncentracijama. Takođe je od ključnog značaja za sintezu kolagena u celom organizmu. Askorbinska kiselina ima ulogu u modulaciji mnogih bitnih neurotransmitera, omogućava neurogenezu u mozgu odraslog i štiti ćelije od infekcije. Dok SVCT1 omogućava apsorpciju vitamina C u crevima, SVCT2 se nalazi uglavnom u mozgu. Nedostatak askorbata klasično se ispoljava kao skorbut koji je letalan ako se ne leči, ali je supklinička deficijencija verovatno mnogo češća. Potencijalni terapijski domeni vitamina C terapije su neurodegenerativne, cerebrovaskularne i afektivne bolesti, karcinomi, traume mozga i drugi. Postoje na primer podaci o pozitivnim efektima askorbinske kiseline u Alchajmerovoj bolesti. Koriste se razni režimi doziranja, ali je askorbat pokazao bezbednost čak i u visokim dozama tokom dugih perioda. Potrebne su bolje dizajnirane studije da se razjasne sve potencijalne terapijske uloge vitamina C
High Temperature Electron Localization in dense He Gas
We report new accurate mesasurements of the mobility of excess electrons in
high density Helium gas in extended ranges of temperature and density to ascertain
the effect of temperature on the formation and dynamics of localized electron
states. The main result of the experiment is that the formation of localized
states essentially depends on the relative balance of fluid dilation energy,
repulsive electron-atom interaction energy, and thermal energy. As a
consequence, the onset of localization depends on the medium disorder through
gas temperature and density. It appears that the transition from delocalized to
localized states shifts to larger densities as the temperature is increased.
This behavior can be understood in terms of a simple model of electron
self-trapping in a spherically symmetric square well.Comment: 23 pages, 13 figure
Risk Factors for Pediatric Invasive Group A Streptococcal Disease
Invasive group A Streptococcus (GAS) infections can be fatal and can occur in healthy children. A case-control study identified factors associated with pediatric disease. Case-patients were identified when Streptococcus pyogenes was isolated from a normally sterile site, and matched controls (≥2) were identified by using sequential-digit dialing. All participants were noninstitutionalized surveillance-area residents <18 years of age. Conditional regression identified factors associated with invasive disease: other children living in the home (odds ratio [OR] = 16.85, p = 0.0002) and new use of nonsteroidal antiinflammatory drugs (OR = 10.64, p = 0.005) were associated with increased risk. More rooms in the home (OR = 0.67, p = 0.03) and household member(s) with runny nose (OR = 0.09, p = 0.002) were associated with decreased risk. Among children, household-level characteristics that influence exposure to GAS most affect development of invasive disease
Depression phenotype, inflammation and the brain: implications for future research
Inflammation is implicated in the etiology of Major Depressive Disorder (MDD). Human neuroimaging techniques are increasingly used to characterize the neural circuitry mediating actions of inflammation on mood, motivation and cognition and its relationship to MDD. In this issue, Byrne and colleagues report the first systematic review of these studies. The systematic review provides a much-needed synthesis of current research findings and highlights the role of cortical and subcortical brain structure and function. In this accompanying commentary, we highlight further points of particular relevance to future studies, including the potential advantages of functional phenotype models rather than the emphasis on mutually exclusive diagnostic categories in describing MDD and other psychiatric disorders. Novel imaging techniques will further enhance possibilities to clarify the link between inflammation and depression. New research challenges are described regarding the relationships between behavioural phenotype, brain structure and function, and peripheral inflammation
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