Computation of Single-Cell Metabolite Distributions Using Mixture Models

Metabolic heterogeneity is widely recognised as the next challenge in our understanding of non-genetic variation. A growing body of evidence suggests that metabolic heterogeneity may result from the inherent stochasticity of intracellular events. However, metabolism has been traditionally viewed as a purely deterministic process, on the basis that highly abundant metabolites tend to filter out stochastic phenomena. Here we bridge this gap with a general method for prediction of metabolite distributions across single cells. By exploiting the separation of time scales between enzyme expression and enzyme kinetics, our method produces estimates for metabolite distributions without the lengthy stochastic simulations that would be typically required for large metabolic models. The metabolite distributions take the form of Gaussian mixture models that are directly computable from single-cell expression data and standard deterministic models for metabolic pathways. The proposed mixture models provide a systematic method to predict the impact of biochemical parameters on metabolite distributions. Our method lays the groundwork for identifying the molecular processes that shape metabolic heterogeneity and its functional implications in disease.Comment: 5 Figures, 3 Table

Case report of a cervical myelomalacia caused by a thoracolumbar intradural disc herniation leading to intracranial hypotension

A 50-year-old patient was admitted with symptoms of intracranial hypotension. MRI revealed a cervical myelomalacia caused by engorged epidural veins leading to a stenosis of the spinal canal. This condition is rarely described in patients with hydrocephalus and ventricular shunts suffering from chronic overdrainage. However, the reason in this patient was a CSF leak caused by an intradural disc herniation at T12/L1. After surgery, symptoms resolved and the cervical myelomalacia and the swollen epidural veins disappeared on postoperative MRI. In patients with engorged cervical epidural veins without a ventricular shunt, a CSF leak has to be considered

A Life Cycle Analysis System to Support D and D, Pollution Prevention, and Asset Recovery

This paper describes a life cycle analysis system (LCAS) developed to support US Department of Energy (DOE) decision-making regarding deactivation and decommissioning (D and D), pollution prevention (P2), and asset recovery, and its deployment to analyze the disposition of facilities and capital assets. Originally developed for use at the Oak Ridge East Tennessee Technology Park, this approach has been refined through application at Ohio Operations Office sites and is now being deployed at a number of DOE sites. Programs such as National Metals Recycle, the D and D Focus Area, P2, and Asset Utilization are successfully using the system to make better decisions resulting in lower cost to the taxpayer and improved environmental quality. The LCAS consists of a user-friendly, cost-effective, and analytically-sound decision-aiding process and a complementary suite of automated tools to handle data administration and multiple criteria life cycle analysis (LCA). LCA is a systematic and comprehensive process for identifying, assessing, and comparing alternatives for D and D, P2, and asset recovery at government sites, and for selecting and documenting a preferred alternative. An LCA includes all of the impacts (benefits and costs) that result from a course of action over the entire period of time affected by the action. The system also includes visualizations that aid communication and help make decision-making transparent. The LCAS has three major components related to data collection, decision alternative assessment, and making the decisions. Each component is discussed in-depth using the example of deployment of the LCAS to support asset recovery

Persistence of the impact of the Hood River Conservation Project on typical and peak loads three years after weatherization

The Hood River Conservation Project (HRCP) was a major residential retrofit demonstration project, operated by Pacific Power & Light Company (Pacific Power) between 1984 and 1988, and funded by the Bonneville Power Administration (Bonneville). The project was designed to install as many cost-effective retrofit measures in as many electrically heated homes as possible in the community of Hood River, Oregon. The Pacific Power HRCP planners statistically selected a special group of 320 Hood River homes that represented a cross-section of the community. The end-use loads (electric space heating, electric water heating, and woodfuel space heating) and the interior temperatures of these homes were monitored for one year before weatherization and three years after weatherization. After more than four years of submetered data collection, 220 single-family, detached homes were available for analysis in the second load study. Weather was normalized for the four heating seasons by matching one day from the pre-program year with one day from each postretrofit year

Heat flow and calculus on metric measure spaces with Ricci curvature bounded below - the compact case

We provide a quick overview of various calculus tools and of the main results concerning the heat flow on compact metric measure spaces, with applications to spaces with lower Ricci curvature bounds. Topics include the Hopf-Lax semigroup and the Hamilton-Jacobi equation in metric spaces, a new approach to differentiation and to the theory of Sobolev spaces over metric measure spaces, the equivalence of the L^2-gradient flow of a suitably defined "Dirichlet energy" and the Wasserstein gradient flow of the relative entropy functional, a metric version of Brenier's Theorem, and a new (stronger) definition of Ricci curvature bound from below for metric measure spaces. This new notion is stable w.r.t. measured Gromov-Hausdorff convergence and it is strictly connected with the linearity of the heat flow.Comment: To the memory of Enrico Magenes, whose exemplar life, research and teaching shaped generations of mathematician

The Life Cycle Analysis Toolbox

The life cycle analysis toolbox is a valuable integration of decision-making tools and supporting materials developed by Oak Ridge National Laboratory (ORNL) to help Department of Energy managers improve environmental quality, reduce costs, and minimize risk. The toolbox provides decision-makers access to a wide variety of proven tools for pollution prevention (P2) and waste minimization (WMin), as well as ORNL expertise to select from this toolbox exactly the right tool to solve any given P2/WMin problem. The central element of the toolbox is a multiple criteria approach to life cycle analysis developed specifically to aid P2/WMin decision-making. ORNL has developed numerous tools that support this life cycle analysis approach. Tools are available to help model P2/WMin processes, estimate human health risks, estimate costs, and represent and manipulate uncertainties. Tools are available to help document P2/WMin decision-making and implement programs. Tools are also available to help track potential future environmental regulations that could impact P2/WMin programs and current regulations that must be followed. An Internet-site will provide broad access to the tools

韓国南部の水田における農業用殺虫剤撒布の数種蚊に対する毒性

A study carried out in rural areas of South Korea has revealed that farmer pesticide applications of fenitrothion, fenthion and certain other organophosphorus materials are highly toxic to mosquito larvae. The rates of application (0.3 to 0.9kg/ha), although not highly residual, are from 4 to 8 times higher than those required for Cu. tritaeniorhynchus control. The commonly used knapsack sprayer provides very thorough coverage on small (≤ 1ha) farmer plots. Application by power equipment and helicopters also provides excellent larval control. In comparison to previous years, the marked increase in pesticide usage may be a partial explanation for the much lower incidence of Japanese encephalitis in rural area.韓国南部の農村で行なった研究から,農民が撒布するフェニトロチオン,バイテックス及びその他の二,三の有機燐剤は蚊の幼虫に対して極めて有効であることがわかった.0.3-0.9kg/haの撒布は,残留性は大きくないけれども,コガタアカイエカの防除に必要な量の4-8倍に達する.普通に用いられている背負式噴霧機は狭い区画(1ha以下)に徹底して撒布するのに便利である.動力噴霧機やヘリコプターによる撒布もまた蚊の防除に優れた効果を示す.前年までと比較して,殺虫剤の使用量が増加したことが,農村での日本脳炎患者数の減少の1つの原因かもしれない