697 research outputs found
Letter from T. S. Pendergrass
Letter concerning a copy of a report from a session of the State Legislature
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Advances in understanding large-scale responses of the water cycle to climate change
Globally, thermodynamics explains an increase in atmospheric water vapor with warming of around 7%/Ā°C near to the surface. In contrast, global precipitation and evaporation are constrained by the Earth's energy balance to increase at ā¼2ā3%/Ā°C. However, this rate of increase is suppressed by rapid atmospheric adjustments in response to greenhouse gases and absorbing aerosols that directly alter the atmospheric energy budget. Rapid adjustments to forcings, cooling effects from scattering aerosol, and observational uncertainty can explain why observed global precipitation responses are currently difficult to detect but are expected to emerge and accelerate as warming increases and aerosol forcing diminishes. Precipitation increases with warming are expected to be smaller over land than ocean due to limitations on moisture convergence, exacerbated by feedbacks and affected by rapid adjustments. Thermodynamic increases in atmospheric moisture fluxes amplify wet and dry events, driving an intensification of precipitation extremes. The rate of intensification can deviate from a simple thermodynamic response due to ināstorm and largerāscale feedback processes, while changes in largeāscale dynamics and catchment characteristics further modulate the frequency of flooding in response to precipitation increases. Changes in atmospheric circulation in response to radiative forcing and evolving surface temperature patterns are capable of dominating water cycle changes in some regions. Moreover, the direct impact of human activities on the water cycle through water abstraction, irrigation, and land use change is already a significant component of regional water cycle change and is expected to further increase in importance as water demand grows with global population
Investigating the relationship between mitochondrial genetic variation and cardiovascular-related traits to develop a framework for mitochondrial phenome-wide association studies
BACKGROUND: Mitochondria play a critical role in the cell and have DNA independent of the nuclear genome. There is much evidence that mitochondrial DNA (mtDNA) variation plays a role in human health and disease, however, this area of investigation has lagged behind research into the role of nuclear genetic variation on complex traits and phenotypic outcomes. Phenome-wide association studies (PheWAS) investigate the association between a wide range of traits and genetic variation. To date, this approach has not been used to investigate the relationship between mtDNA variants and phenotypic variation. Herein, we describe the development of a PheWAS framework for mtDNA variants (mt-PheWAS). Using the Metabochip custom genotyping array, nuclear and mitochondrial DNA variants were genotyped in 11,519 African Americans from the Vanderbilt University biorepository, BioVU. We employed both polygenic modeling and association testing with mitochondrial single nucleotide polymorphisms (mtSNPs) to explore the relationship between mtDNA variants and a group of eight cardiovascular-related traits obtained from de-identified electronic medical records within BioVU. RESULTS: Using polygenic modeling we found evidence for an effect of mtDNA variation on total cholesterol and type 2 diabetes (T2D). After performing comprehensive mitochondrial single SNP associations, we identified an increased number of single mtSNP associations with total cholesterol and T2D compared to the other phenotypes examined, which did not have more significantly associated SNPs than would be expected by chance. Among the mtSNPs significantly associated with T2D we identified variant mt16189, an association previously reported only in Asian and European-descent populations. CONCLUSIONS: Our replication of previous findings and identification of novel associations from this initial study suggest that our mt-PheWAS approach is robust for investigating the relationship between mitochondrial genetic variation and a range of phenotypes, providing a framework for future mt-PheWAS
Apathy Is Associated With Ventral Striatum Volume in Schizophrenia Spectrum Disorder
Apathy is prevalent in schizophrenia, but its etiology has received little investigation. The ventral striatum (VS), a key brain region involved in motivated behavior, has been implicated in studies of apathy. We therefore evaluated whether apathy is associated with volume of the VS on MRI in 23 patients with schizophrenia using voxel-based morphometry. Results indicated that greater self-reported apathy severity was associated with smaller volume of the right VS even when controlling for age, gender, depression, and total gray matter volume. The finding suggests that apathy is related to abnormality of brain circuitry subserving motivated behavior in patients with schizophrenia
A thin layer angiogenesis assay: a modified basement matrix assay for assessment of endothelial cell differentiation
BACKGROUND: Basement matrices such as Matrigelā¢ and Geltrexā¢ are used in a variety of cell culture assays of anchorage-dependent differentiation including endothelial cell tube formation assays. The volumes of matrix recommended for these assays (approximately 150 Ī¼l/cm(2)) are costly, limit working distances for microscopy, and require cell detachment for subsequent molecular analysis. Here we describe the development and validation of a thin-layer angiogenesis (TLA) assay for assessing the angiogenic potential of endothelial cells that overcomes these limitations. RESULTS: Geltrexā¢ basement matrix at 5 Ī¼l/cm(2) in 24-well (10 Ī¼l) or 96-well (2 Ī¼l) plates supports endothelial cell differentiation into tube-like structures in a comparable manner to the standard larger volumes of matrix. Since working distances are reduced, high-resolution single cell microscopy, including DIC and confocal imaging, can be used readily. Using MitoTracker dye we now demonstrate, for the first time, live mitochondrial dynamics and visualise the 3-dimensional network of mitochondria present in differentiated endothelial cells. Using a standard commercial total RNA extraction kit (Qiagen) we also show direct RNA extraction and RT-qPCR from differentiated endothelial cells without the need to initially detach cells from their supporting matrix. CONCLUSIONS: We present here a new thin-layer assay (TLA) for measuring the anchorage-dependent differentiation of endothelial cells into tube-like structures which retains all the characteristics of the traditional approach but with the added benefit of a greatly lowered cost and better compatibility with other techniques, including RT-qPCR and high-resolution microscopy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12860-014-0041-5) contains supplementary material, which is available to authorized users
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ASPEN computer simulations of the mixed waste treatment project baseline flowsheet
The treatment and disposal of mixed waste (i.e., waste containing both hazardous and radioactive components) is a challenging waste- management problem of particular concern to Department of Energy (DOE) sites throughout the United States. Traditional technologies used for destroying hazardous wastes must be re- evaluated for their ability to handle mixed wastes, and, in some cases, new technologies must be developed. The Mixed Waste Treatment Project (MWTP), a collaborative effort between Lawrence Livermore National Laboratory (LLNL), Los Alamos National Laboratory, and Pacific Northwest Laboratory (PNL), was established by the DOE`s Waste Operations Program (EM-30) to develop and analyze alternative mixed waste treatment approaches. One of the MWTP`s initiatives, and the objective of this study, was to develop flowsheets for prototype, integrated, mixed-waste treatment facilities that can serve as models for sites developing their own treatment strategies. Evaluation of these flowsheets is being facilitated through the use of computer modeling. The objectives of the flowsheet simulations are to compare process effectiveness and costs of alternative flowsheets and to determine if commercial process-simulation software could be used on the large, complex process of an integrated mixed waste processing facility. Flowsheet modeling is needed to evaluate many aspects of proposed flowsheet designs. A major advantage of modeling the complete flowsheet is the ability to define the internal recycle streams, thereby making it possible to evaluate the impact of one operation on the whole plant. Many effects that can be seen only in this way. Modeling also can be used to evaluate sensitivity and range of operating conditions, radioactive criticality, and relative costs of different flowsheet designs. Further, the modeled flowsheets must be easily modified so that one can examine how alternative technologies and varying feed streams affect the overall integrated process
Diverse Convergent Evidence in the Genetic Analysis of Complex Disease: Coordinating Omic, Informatic, and Experimental Evidence to Better Identify and Validate Risk Factors
In omic research, such as genome wide association studies, researchers seek to repeat their results in other datasets to reduce false positive findings and thus provide evidence for the existence of true associations. Unfortunately this standard validation approach cannot completely eliminate false positive conclusions, and it can also mask many true associations that might otherwise advance our understanding of pathology. These issues beg the question: How can we increase the amount of knowledge gained from high throughput genetic data? To address this challenge, we present an approach that complements standard statistical validation methods by drawing attention to both potential false negative and false positive conclusions, as well as providing broad information for directing future research. The Diverse Convergent Evidence approach (DiCE) we propose integrates information from multiple sources (omics, informatics, and laboratory experiments) to estimate the strength of the available corroborating evidence supporting a given association. This process is designed to yield an evidence metric that has utility when etiologic heterogeneity, variable risk factor frequencies, and a variety of observational data imperfections might lead to false conclusions. We provide proof of principle examples in which DiCE identified strong evidence for associations that have established biological importance, when standard validation methods alone did not provide support. If used as an adjunct to standard validation methods this approach can leverage multiple distinct data types to improve genetic risk factor discovery/validation, promote effective science communication, and guide future research directions
Deep Brain Stimulation Targeting the Fornix for Mild Alzheimer Dementia: Design of the ADvance Randomized Controlled Trial
Background: There are currently few available treatments and no cure for Alzheimer disease (AD), a growing public health burden. Animal models and an open-label human trial have indicated that deep brain stimulation (DBS) of memory circuits may improve symptoms and possibly slow disease progression. The ADvance trial was designed to examine DBS of the fornix as a treatment for mild AD. Methods: ADvance is a randomized, double-blind, placebo-controlled, delayed-start, multicenter clinical trial conducted at six sites in the US and one site in Canada. Eighty-five subjects initially consented to be screened for the trial. Of these, 42 subjects who met inclusion and exclusion criteria were implanted with DBS leads anterior to the columns of the fornix bilaterally. They were randomized 1:1 to DBS off or DBS on groups for the initial 12 months of follow-up. After 1 year, all subjects will have their devices turned on for the remainder of the study. Postimplantation, subjects will return for 13 follow-up visits over 48 months for cognitive and psychiatric assessments, brain imaging (up to 12 months), and safety monitoring. The primary outcome measures include Alzheimer\u27s Disease Assessment Scale -- cognitive component (ADAS-cog-13), Clinical Dementia Rating sum of boxes (CDR-SB), and cerebral glucose metabolism measured with positron emission tomography. This report details the study methods, baseline subject characteristics of screened and implanted participants, and screen-to-baseline testā¬āretest reliability of the cognitive outcomes. Results: Implanted subjects had a mean age of 68.2 years, were mostly male (55%), and had baseline mean ADAS-cog-13 and CDR-SB scores of 28.9 (SD, 5.2) and 3.9 (SD, 1.6), respectively. There were no significant differences between screened and implanted or nonimplanted subjects on most demographic or clinical assessments. Implanted subjects had significantly lower (better) ADAS-cog-11 (17.5 vs 21.1) scores, but did not differ on CDR-SB. Scores on the major outcome measures for the trial were consistent at screening and baseline. Conclusion: ADvance was successful in enrolling a substantial group of patients for this novel application of DBS, and the study design is strengthened by rigorous subject selection from seven sites, a double-blind placebo-controlled design, and extensive open-label follow-up
Cyborg Activism: Exploring the reconfigurations of democratic subjectivity in Anonymous
This article develops the concept of cyborg activism as novel configuration of democratic subjectivity in the Information Age by exploring the online collectivity Anonymous as a prototype. By fusing elements of human/machine and organic/digital the cyborg disrupts modern logics of binary thinking. Cyborg activism emerges as the reconfiguration of equality/hierarchy, reason/emotion, and nihilism/idealism. Anonymous demonstrates how through the use of contingent and ephemeral digital personae hierarchies in cyborg activism prove more volatile than in face-to-face settings. Emotions appear as an essential part of a politics of passion, which enables pursuing laughter and joy, expressing anger, and experiencing empowerment as part of a reasoned, strategic politics. Anonymousā political content reconfigures nihilist sentiments, frustration, and political disenchantment on the one hand with idealist world views on the other. This enables the cohabitation and partial integration of a great diversity of political claims rooted in various ideologies
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