The in silico macrophage: toward a better understanding of inflammatory disease

Macrophages function as sentinel, cell-regulatory hubs capable of initiating, perpetuating and contributing to the resolution of an inflammatory response, following their activation from a resting state. Highly complex and varied gene expression programs within the macrophage enable such functional diversity. To investigate how programs of gene expression relate to the phenotypic attributes of the macrophage, the development of in silico modeling methods is needed. Such models need to cover multiple scales, from molecular pathways in cell-autonomous immunity and intercellular communication pathways in tissue inflammation to whole organism response pathways in systemic disease. Here, we highlight the potential of in silico macrophage modeling as an amenable and important yet under-exploited tool in aiding in our understanding of the immune inflammatory response. We also discuss how in silico macrophage modeling can help in future therapeutic strategies for modulating both the acute protective effects of inflammation (such as host defense and tissue repair) and the harmful chronic effects (such as autoimmune diseases).Comment: 7 pages plus 1 figur

Advanced Electro-Optic Surety Devices

The Advanced Electro-Optic Surety Devices project was initiated in march 1991 to support design laboratory guidance on electro-optic device packaging and evaluation. Sandia National Laboratory requested AlliedSignal Inc., Kansas City Division (KCD), to prepare for future packaging efforts in electro-optic integrated circuits. Los Alamos National Laboratory requested the evaluation of electro-optic waveguide devices for nuclear surety applications. New packaging techniques involving multiple fiber optic alignment and attachment, binary lens array development, silicon V-groove etching, and flip chip bonding were requested. Hermetic sealing of the electro-optic hybrid and submicron alignment of optical components present new challenges to be resolved. A 10-channel electro-optic modulator and laser amplifier were evaluated for potential surety applications

Eddy current damper for the labshare remote laboratory shake table rig

The design and performance of an eddy current damper for the Labshare remotely operated "Shake Table" multi-storey building vibration rig is described. The damper comprises stationary E-cores on either side of a copper plate attached to each storey. An approximate formula for the damper retarding force F is derived, of the form F = -kuI2 for plate velocity u and E-core current I, and a criterion for its validity is established in terms of the magnetic Reynolds number. A close fit to measurements of the force using a load cell is obtained for k = 0.401 N/(ms-1A2). This was about 12% lower than the force determined by three-dimensional (3D) finite element analysis (FEA) using ANSYS 12.1, but the error can be attributed to manufacturing imperfections. Students can use the force formula in their investigation of closed-loop control of the Shake Table vibration. More generally, a formula for the force constant k can be used for the approximate design of any similar E-core damper

Local government budgeting

"5/72/1M"This is the first publication in a new series designed to aid elected and appointed officials in local government in Missouri. The series will focus on the administrative responsibilities of local officials associated with counties, cities, towns or villages, and special districts. This first guide gives an overview of the budgetary process for all types of local governments including the constitutional and statutory requirements and the reasons for budgeting. It also points out some weaknesses in existing law and makes suggestions for improving financial reporting, as well as improving the decision-making process of budgeting. The Administrative Guide Series is the third category of publications developed by the Governmental Affairs Program, and will have new titles added over the next several years in the areas of: ( 1) governmental accounting and fiscal administration, and (2) local government administration. In addition, the Missouri Local Government Hand k Series was developed several years ago to aid local officials and now includes five publications.--ForewordIncludes bibliographical references

Transportation demand management on UNC's campus: evaluation, best practices and recommendations for reducing single-occupancy vehicle use

Transportation Demand Management (TDM) is an increasingly popular response to growing concern over traffic congestion, pollution and parking shortages. Instead of simply increasing the supply of roads and parking spaces when congestion peaks and parking is hard to find, transportation planners and public officials have turned to strategies to decrease demand for the facilities. TDM is designed to reduce the demand for single-occupancy vehicles through a set of strategies aimed at changing travel behavior. These strategies can include incentives, disincentives, policies and regulations, land-use planning practices or transit choice improvements. State and local governments, as well as individual employers, are implementing TDM programs to help solve congestion problems in their region. Universities and colleges serve as residential and employment centers for great numbers of people. Increased car usage and the parking facilities to accommodate them can be seen as a threat to the peaceful, people-friendly feel of many college campuses. Whereas many local jurisdictions engage in TDM to reduce traffic congestion, many universities' primary motivation for TDM lies in parking shortages. "Multiple factors - lack of land for new parking lots, the high costs of building parking structures, pressure from surrounding communities, and the desire to preserve air quality and campus green space" - are leading many universities toward implementing TDM programs (Toor and Havlick 2004, 3). Many campuses struggle with the problem of increased demand for parking and financial or physical inability to construct new facilities. These universities often conclude that it is more feasible for them to manage demand for parking than it is to construct more. Universities often resemble small, compact cities, complete with residences, concentrated employment, sports facilities, cultural venues and central open space. These types of campuses are particularly well-suited for TDM programs because of their density of employment and residences. TDM programs on campuses are often run by transportation and parking or planning departments and include a wide variety of strategies to reduce single-occupancy vehicle trips and demand for parking. What is unique and challenging for universities is to create programs that will appeal to both students and employees, who have different motivations and needs. Examples of campus TDM strategies include universal transit passes, raising parking rates, campus shuttles, carshares for use during the day for employees and twenty-four hours a day for students, and campus bike-share programs. Most universities have some combination of TDM strategies, and others have comprehensive multi-modal programs that integrate many. This study examines the Commuter Alternative Program, the TDM program at the University of North Carolina at Chapel Hill, which has been integral in reducing the number of single-occupancy vehicles arriving to the campus. In addition, the TDM programs at Duke University, the University of Washington, the University of British Columbia, and Cornell University are featured as case studies. The case studies include descriptions of the TDM programs at each university, successes, limitations and best practices. A comparison of the five universities reveals similarities and differences, common approaches and conflicting strategies.Master of City and Regional Plannin

Modeling the Dietary Pesticide Exposures of Young Children

A stepped approach was used to assess the exposures of 1 1/2 – 4 1/2-year-old children in the United Kingdom to residues of pesticides (dithiocarbamates; phosmet; carbendazim) found in apples and pears. The theoretical possibility that the acute reference dose (ARD) was being exceeded for a particular pesticide/fruit was tested by applying a combination of maximal variability and maximum measured residue relative to an average-body-weight consumer. The actual risk was then quantified by stochastically modeling consumption, from dietary survey data, with individual body weights, against published residue results for 2000–2002 and the variability of residue distribution within batches. The results, expressed as numbers of children per day likely to ingest more than the ARD, were in the range of 10–226.6 children per day, depending upon the pesticide and year of sampling. The implications for regulatory action are discussed

Kinetic and Spectroscopic Analysis of the Catalytic Role of H79 in the Methionine Aminopeptidase from \u3cem\u3eEscherichia coli\u3c/em\u3e

To gain insight into the role of the strictly conserved histidine residue, H79, in the reaction mechanism of the methionyl aminopeptidase from Escherichia coli (EcMetAP-I), the H79A mutated enzyme was prepared. Co(II)-loaded H79A exhibits an overall \u3e7000-fold decrease in specific activity. The almost complete loss of activity is primarily due to a \u3e6000-fold decrease in kcat. Interestingly, the Km value obtained for Co(II)-loaded H79A was approximately half the value observed for wild-type (WT) EcMetAP-I. Consequently, kcat/Km values decreased only 3000-fold. On the other hand, the observed specific activity of Mn(II)-loaded H79A EcMetAP-I decreased by ∼2.6-fold while kcat decreased by ∼3.5-fold. The observed Km value for Mn(II)-loaded H79A EcMetAP-I was ∼1.4-fold larger than that observed for WT EcMetAP-I, resulting in a kcat/Km value that is lower by ∼3.4-fold. Metal binding, UV−vis, and EPR data indicate that the active site is unperturbed by mutation of H79, as suggested by X-ray crystallographic data. Kinetic isotope data indicate that H79 does not transfer a proton to the newly forming amine since a single proton is transferred in the transition state for both the WT and H79A EcMetAP-I enzymes. Therefore, H79 functions to position the substrate by hydrogen bonding to either the amine group of the peptide linkage or a backbone carbonyl group. Together, these data provide new insight into the catalytic mechanism of EcMetAP-I

Forestry Bulletin No. 25: Silviculture of Southern Bottomland Hardwoods

The potential of southern bottomland hardwood types is clear, for they, along with the cypress, occupy about 37 million acres and compromise more than half of the hardwood stumpage in the south.https://scholarworks.sfasu.edu/forestrybulletins/1021/thumbnail.jp

Statistics of selectively neutral genetic variation

Random models of evolution are instrumental in extracting rates of microscopic evolutionary mechanisms from empirical observations on genetic variation in genome sequences. In this context it is necessary to know the statistical properties of empirical observables (such as the local homozygosity for instance). Previous work relies on numerical results or assumes Gaussian approximations for the corresponding distributions. In this paper we give an analytical derivation of the statistical properties of the local homozygosity and other empirical observables assuming selective neutrality. We find that such distributions can be very non-Gaussian.Comment: 4 pages, 4 figure