Search

While many instances of GPCR dimerization have been reported for vertebrate receptors, invertebrate GPCR dimerization remains poorly investigated, with few invertebrate GPCRs having been shown to assemble as dimers. To date, no Drosophila GPCRs have been shown to assemble as dimers. To explore the evolutionary conservation of GPCR dimerization, we employed an acceptor-photobleaching FRET methodology to evaluate whether multiple subclasses of Drosophila GPCRs assembled as homodimers when heterologously expressed in HEK-293 T cells. We C-terminally tagged multiple Drosophila neuropeptide GPCRs that exhibited structural homology with a vertebrate GPCR family member previously shown to assemble as a dimer with CFP and YFP fluorophores and visualized these receptors through confocal microscopy. FRET responses were determined based on the increase in CFP emission intensity following YFP photobleaching for each receptor pair tested. A significant FRET response was observed for each receptor expressed as a homodimer pair, while non-significant FRET responses were displayed by both cytosolic CFP and YFP expressed alone, and a heterodimeric pair of receptors from unrelated families. These findings suggest that receptors exhibiting positive FRET responses assemble as homodimers at the plasma membrane and are the first to suggest that Drosophila GPCRs assemble as homodimeric complexes. We propose that GPCR dimerization arose early in metazoan evolution and likely plays an important and underappreciated role in the cellular signaling of all animals.

The acute toxicity of organophosphorus-based compounds is primarily a result of acetylcholinesterase inhibition in the central and peripheral nervous systems. The resulting cholinergic crisis manifests as seizure, paralysis, respiratory failure and neurotoxicity. Though overstimulation of muscarinic receptors is the mechanistic basis of central organophosphorus (OP) toxicities, short-term changes in synapse physiology that precede OP-induced seizures have not been investigated in detail. To study acute effects of OP exposure on synaptic function, field excitatory postsynaptic potentials (fEPSPs) were recorded from Schaffer collateral synapses in the mouse hippocampus CA1 stratum radiatum during perfusion with various OP compounds. Administration of the OPs paraoxon, soman or VX rapidly and stably depressed fEPSPs via a presynaptic mechanism, while the non-OP proconvulsant tetramethylenedisulfotetramine had no effect on fEPSP amplitudes. OP-induced presynaptic long-term depression manifested prior to interictal spiking, occurred independent of recurrent firing, and did not require NMDA receptor currents, suggesting that it was not mediated by activity-dependent calcium uptake. Pharmacological dissection revealed that the presynaptic endocannabinoid type 1 receptor (CB1R) as well as postsynaptic M1 and M3 muscarinic acetylcholine receptors were necessary for OP-LTD. Administration of CB1R antagonists significantly reduced survival in mice after a soman challenge, revealing an acute protective role for endogenous CB1R signaling during OP exposure. Collectively these data demonstrate that the endocannabinoid system alters glutamatergic synaptic function during the acute response to OP acetylcholinesterase inhibitors.

Identifying useful mathematical models of physical systems is an essential part of computational modeling and simulation. Once appropriate models are identified, they can be used for applications such as response prediction, structural control, monitoring structural integrity, lifetime prognosis, etc. The number of models and model classes available to the modeler to represent a physical phenomenon, however, can be very large. Retaining all available models throughout a study can be computationally burdensome, so the modeler has the significant problem of identifying the valid models to be used in further studies. To address this challenge, a probabilistic framework is proposed herein for validating models by intertwining the concepts of model falsification and Bayesian model selection. Model falsification, based on the philosophy that measurements can only be used to falsify models, is used in this framework in both pre- and postprocessing steps to eliminate models and model classes, respectively, that cannot explain the measurements. This is the first study to propose a framework to integrate these two paradigms. A likelihood-bound model falsification, previously introduced by the authors, determines the validity of the initial candidate model classes, using the false discovery rate (FDR), and removes most of the incorrect ones without incurring any significant additional computational burden. Next, Bayesian model selection, which assigns posterior model class probabilities based on Bayes’ theorem, is applied to the remaining model classes to identify the model(s) and model class(es) that provide predictions that probabilistically best fit the data. Finally, a postprocessing likelihood-bound falsification checks the validity of the final model class(es). The proposed framework is first illustrated through two nonlinear structural dynamics examples that show the efficacy of the proposed framework in identifying models for these structures as well as reducing the computational burden relative to Bayesian model selection applied alone. Finally, a third example uses measurement data from experiments performed on a full-scale four-story base-isolated building at the world’s largest shake table in Japan’s “E-Defense” laboratory.

In most countries, environmental regulation focuses on local pollution, which causes damages near the emission source, while regulation on global pollutants such as greenhouse gases (GHGs) has been slow. Theoretically, local and global pollutants can either be substitutes or complements in production. A firm's response to local pollution regulation can lead greenhouse gas emissions to decrease if the firm switches energy source from oil to natural gas, or to increase if it reduces the temperature of a natural gas-fired boiler, which causes NOx emissions to fall but CO2 emissions to rise. Consequently, local pollution regulation may either intensify or reduce global warming concerns. We exploit new data on US GHG emissions and variation in local pollution regulation across US counties to estimate this relationship. We find no evidence that more stringent local pollution regulation changes GHG emissions from the non-energy sectors. The lack of a statistically detectable effect cannot be explained by a decrease in production or by firms switching production to less regulated countries, and it is true on aggregate as well as for individual polluting industries, though in some instances the coefficients are not precisely estimated. Therefore, local pollution regulation is unlikely to suffice to address global warming.

Genetics likely play a role in various responses to nerve agent (NA) exposure, as genetic background plays an important role in behavioral, neurological, and physiological responses. This study uses different mouse strains to identify if mouse strain differences in sarin exposure exist. In Experiment 1, basal levels of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and carboxylesterase (CE) were measured in different strains of naïve mice to account for potential pharmacokinetic determinants of individual differences. In Experiment 2, median lethal dose (MLD) levels were estimated in 8 inbred mouse strains following subcutaneous (s.c.) administration of sarin. Few strain or sex differences in esterase activity levels were observed, with the exception of erythrocyte AChE activity in the C57BL/6J strain. Both sex and strain differences in toxicity were observed, with the most resistant strains being the BALB/cByJ and FVB/NJ strains and the most sensitive strain being the DBA/2J strain. These findings can be expanded to explore pathways involved in NA response, which may provide an avenue to develop therapeutics for preventing and treating the damaging effects of NA exposure.

This paper couples a traditional hedonic model with architectural style classifications from human experts and machine learning (ML) enabled classifiers to estimate sales price premia over architectural styles, both at the building and the neighborhood-level. We find statistically and economically significant price differences for houses from distinct architectural styles across an array of specifications and modeling assumptions. Comparisons between classifications from ML models and human experts illustrate the conditions under which ML classifiers may perform at least as reliable as human experts in mass appraisal models. Hedonic estimates illustrate that the impact of architectural style on price is attenuated by properties with less well-defined styles and we find no evidence for differential price effects ofRevivalorContemporaryarchitecture for new construction.

G protein-coupled receptors are the largest superfamily of cell surface receptors in the Metazoa and play critical roles in transducing extracellular signals into intracellular responses. This action is mediated through conformational changes in the receptor following ligand binding. A number of conserved motifs have critical roles in GPCR function, and here we focus on a highly conserved motif (WxFG) in extracellular loop one (EL1). A phylogenetic analysis documents the presence of the WxFG motif in ∼90% of Class A GPCRs and the motif is represented in 17 of the 19 Class A GPCR subfamilies. Using site-directed mutagenesis, we mutagenized the conserved tryptophan residue in eight receptors which are members of disparate class A GPCR subfamilies from different taxa. The modification of the Drosophila leucokinin receptor shows that substitution of any non-aromatic amino acid for the tryptophan leads to a loss of receptor function. Additionally, leucine substitutions at this position caused similar signaling defects in the follicle-stimulating hormone receptor (FSHR), Galanin receptor (GALR1), AKH receptor (AKHR), corazonin receptor (CRZR), and muscarinic acetylcholine receptor (mACHR1). Visualization of modified receptors through the incorporation of a fluorescent tag revealed a severe reduction in plasma membrane expression, indicating aberrant trafficking of these modified receptors. Taken together, these results suggest a novel role for the WxFG motif in GPCR trafficking and receptor function.

We present a new SIngle-scintillator Neutron and Gamma-Ray spectrometer (SINGR) instrument for use with both passive and active measurement techniques. Here we discuss, the application of SINGR for planetary exploration missions; however, hydrology, nuclear non-proliferation, and resource prospecting are all potential areas where the instrument could be applied. SINGR uses an elpasolite scintillator , Cs 2YLiCl6 :Ce (CLYC), that has been shown to have high neutron efficiency even at small volumes, with a gamma-ray energy resolution of approximately 4% full-width-at-half-maximum at 662 keV. Active gamma-ray and neutron (GRNS) measurements were performed with SINGR at the NASA Goddard Space Flight Center (GSFC) Goddard Geophysical and Astronomical Observatory (GGAO) outdoor test site using a pulsed neutron generator (PNG) to interrogate geologically relevant materials (basalt and granite monuments). These experimental results, combined with simulations, demonstrate that SINGR is capable of generating neutron die-away curves that can be used to reconstruct the bulk hydrogen abundance and the depth distribution of hydrogen within the monuments. We compare our experimental results with Monte Carlo N-Particle (MCNP) 6.1 transport simulations to constrain the uncertainties in depth and hydrogen abundance from the neutron die-away data generated by SINGR. For future planetary exploration missions, SINGR provides a single detector system for interrogating the shallow subsurface to characterize the presence and abundance of hydrated phases and to provide bulk elemental analysis.

We use temporal and spatial variation to evaluate the effectiveness of nearly all (over 400) state and utility incentives that promote the installation of residential solar photovoltaic (PV) panels. Using a unique data set that values a wide array of solar incentives including cash incentives, tax credits, and solar renewable energy credits, we evaluate and compare the impact of incentives using a standardized net present value of each incentive. We pair these data the amount of new residential solar installations within each state and year to examine the relationship between incentive type and new residential PV installations. We find that each additional dollar of incentives has led to on average, an additional 500 W of additional installed capacity per thousand residential electric customers. This effect is enabled by the presence of net metering and financing availability. Direct cash incentives, when coupled with financing initiatives and net metering, drive much of the impact on installations. Results are consistent with research that shows that incentive salience may drive variation in effectiveness. Results suggest that approximately 67% of state and utility incentives, up to $1.9 billion over 11 years, were likely spent on incentives that did not increase residential solar PV installations.

The expansion of distributed solar necessitates additional research into the impacts on both utilities and their customers. In this paper we use New Jersey solar data, PJM market data, and demand profiles from a PJM utility to investigate rate and bill impacts of large-scale solar penetration. In addition to the subsidization of solar adopters by non-participants, we highlight the channels through which cross-subsidization of rate classes can arise in practice. The results of our study indicate that the fear of a utility “death spiral” may be exaggerated. Significant solar can be incorporated with only a 2% increase in non-participant bills. At high levels of penetration, distributed solar has the potential to alter the system peak hour which affects the allocation of costs across rate-classes. As the peak hour shifts to the evening when solar production diminishes, residential customers face higher distribution costs. Policy makers and utilities need to be aware of these challenges in designing the next generation of rates that are better aligned with cost causality.

Simulating the nonlinear behavior of complex systems requires significant computational effort. Despite the rapid progress in computing technology, the demand is still strong for more efficient simulation methods in diverse structural dynamics fields such as nonlinear system identification and nonlinear system reliability. In addition to efficiency, algorithmic stability and accuracy must be addressed in the development of new simulation procedures. In this paper, a method to treat localized nonlinearities in a structure efficiently and accurately is proposed. The method is conditionally stable. The system equations are separated into a state-invariant linear part and a state-dependent nonlinear part that is considered to be external pseudo-forces that act on the linear system. The response of the system is obtained by fixed point iterations in which the pseudo-forces are updated until convergence. In addition to the one time-step-ahead prediction form, the novel idea of multiple time-step-ahead prediction is proposed. The effect of this approach is investigated and shown to increase algorithm efficiency and stability. To perform the numerical integration, time-stepping schemes like the exponential first-order hold method can be used to the advantage of efficiency and accuracy. To increase the accuracy and stability of the method, a novel second-order hold equivalent is derived and implemented. The efficiency, stability, and accuracy of the method are demonstrated in numerical examples. Finally, the method is applied to the earthquake-induced motion of a 20-story building with local nonlinearities.

We examine a new mechanism by which environmental regulation can increase efficiency: intra-firm knowledge spillovers due to environmental regulation. County-level non-attainment of the National Ambient Air Quality Standards creates spatial variation in the degree of regulatory stringency, as states impose stronger environmental regulation in non-attainment counties. We use this spatial variation to examine how the efficiency of electricity generators responds to increases in regulation. We show that, in response to increased regulatory stringency, electricity generators find technical efficiency enhancements and then transfer these enhancements to other units within their fleet. We find that a change in regulatory stringency translates to within-firm spillovers of 3–4%, and that these gains occur at least 3 years after the increase in regulatory stringency.

Understanding how animals move in a complex habitat mosaic is critical to biodiversity conservation as deforested lands and secondary rainforests accumulate in landscapes previously dominated by primary forests. To visualize the spatiotemporal dynamics of secondary forest recovery after pasture abandonment, we formed a conceptual model predicting avian space use during a temporal sequence beginning with deforestation and continuing through regrowth of old secondary forest. We tested five predictions of the model at the Biological Dynamics of Forest Fragments Project near Manaus, Brazil, using 73 radio-tagged understory insectivores of three species: two woodcreepers (Glyphorynchus spirurus, Xiphorhynchus pardalotus) and a terrestrial antthrush (Formicarius colma). Both woodcreepers provided evidence to support all predictions except that of greater path tortuosity in primary forest. Woodcreepers using secondary forest had larger home ranges, larger core areas, and faster movement rates than in primary forest. Further, the proportion of all species' core areas in primary forest exceeded the proportion of home ranges in primary forest. Formicarius colma showed a fundamentally different pattern than the woodcreepers: it essentially avoided secondary forest until 27–31 years after pasture abandonment, at which point movements were indistinguishable from those in primary forest. Formicarius colma and other terrestrial insectivores show implastic spatiotemporal responses to recovering secondary growth, which we suspect contributes to the sensitivity of this guild to forest disturbance. Quantifying the value of marginal (and economically inconsequential) habitats such as secondary forest will be essential as land managers strive to maintain species persistence and connectivity in increasingly heterogeneous tropical landscapes.

We examine how a population's age distribution and a growing divide between the ethnic composition of older and young generations is likely to affect support for higher education funding. Using detailed survey data on voter preferences for higher education funding and precinct-level vote returns from locally-funded community college bond referenda in California, we find that older voters are significantly less supportive of higher education funding than younger voters and that support among older non-Hispanic white voters is particularly weak when those voters reside in a jurisdiction where the college-age population is more heavily Hispanic.

This paper utilizes a newly created index for colocalization to estimate the determinants of industrial agglomeration within a single urban area. Our new index directly incorporates the location of individual establishments while controlling for the Modifiable Areal Unit Problem (MAUP) in order to create this measure of spatial similarity between two industries. We estimate that proximity to transportation infrastructure and consumers as well as knowledge spillovers largely explain patterns of agglomeration. We find a smaller role for input–output linkages and consumption externalities for retail and consumer service industries.

Using detailed trip-level taxi and for-hire-vehicle data and new incident-level complaints data, we study how the entry of Uber and Lyft has affected the quality of taxi services in New York City. In a panel setting with 263 NYC taxi-zones over the time period from 2014 to 2017, we find that increased competition measured by the number of daily Uber/Lyft trips in a given taxi-zone has led to more complaints regarding a variety of service quality dimensions such as unsafe driving, rude behavior and fare refusal. Our results are robust to accounting for potential simultaneity in the determination of complaints and Uber and Lyft penetration.

Since Gamson's (1975) landmark study of social movement organizations, scholars have debated whether it is more advantageous to concentrate on a narrow or diverse set of issues. This paper recasts this debate in terms of organizational survival. Drawing on ideas from theories of category spanning and social movements, we argue that an organization that occupies a distinct niche conveys its purpose more effectively, which increases its chances of survival when compared to more diverse SMOs. Using a longitudinal dataset on environmental social movement organizations (ESMOs), we find organizations that span multiple and distant issue categories are significantly more likely to disband, compared to those with a more specialized focus. Other characteristics of ESMOs affect their survival rate in ways that are strikingly similar to for-profits and other types of nonprofits. Larger and more complex ESMOs benefit from economies of scale, while younger, less established organizations are more likely to perish.

Given rates of deforestation, disturbance, and secondary forest accumulation in tropical rainforests, there is a great need to quantify habitat use and movement among different habitats. This need is particularly pronounced for animals most sensitive to disturbance, such as insectivorous understory birds. Here we use multistate capture–recapture models with radiotelemetry data to determine the successional stage at which within-day movement probabilities of Amazonian birds in secondary forest are similar to those in primary forest. We radio-tracked three common understory insectivore species in primary and secondary forest at the Biological Dynamics of Forest Fragments project near Manaus, Brazil: two woodcreepers, Glyphorynchus spirurus (n = 19) and Xiphorhynchus pardalotus (n = 18), and the terrestrial antthrush Formicarius colma (n = 19). Forest age was a strong predictor of fidelity to a given habitat. All three species showed greater fidelity to primary forest than to 8–14-year-old secondary forest, indicating the latter’s relatively poor quality. The two woodcreeper species used 12–18-year-old secondary forest in a manner comparable to continuous forest, but F. colma avoided moving even to 27–31-year-old secondary forest—the oldest at our site. Our results suggest that managers concerned with less sensitive species can assume that forest reserves connected by 12–18-year-old secondary forest corridors are effectively connected. On the other hand, >30 years are required after land abandonment before secondary forest serves as a primary forest-like conduit for movement by F. colma; more sensitive terrestrial insectivores may take longer still.

The nuclear materials environment has been increasing significantly in complexity over the past couple of decades. The prevention of attacks from nuclear weapons is becoming more difficult, and nuclear forensics is a deterrent by providing detailed information on any type of nuclear event for proper attribution. One component of the nuclear forensic analysis is a measurement of the neutron spectrum. As an example, the neutron component provides information on the composition of the weapons, whether boosting is involved or the mechanisms used in creating a supercritical state. As 6Li has a large cross-section for thermal neutrons, the lithium battery is a primary candidate for assessing the neutron spectrum after detonation. The absorption process for 6Li yields tritium, which can be measured at a later point after the nuclear event, as long as the battery can be processed in a manner to successfully extract the tritium content. In addition, measuring the activated constituents after exposure provides a means to reconstruct the incident neutron spectrum. The battery consists of a spiral or folded layers of material that have unique, energy dependent interactions associated with the incident neutron flux. A detailed analysis on the batteries included a pre-irradiated mass spectrometry analysis to be used as input for neutron spectrum reconstruction. A set of batteries were exposed to a hard neutron spectrum delivered by the University of Massachusetts, Lowell research reactor Fast Neutron Irradiator (FNI). The gamma spectra were measured from the batteries within a few days and within a week after the exposure to obtain sufficient data on the activated materials in the batteries. The activity was calculated for a number of select isotopes, indicating the number of associated neutron interactions. The results from tritium extraction are marginal. A measurable increase in detected particles (gammas and betas) below 50 keV not self-attenuated by the battery was observed, yet as the spectra are coarse, the gamma information is not separable from tritium spectra. The activation analysis was successful, and the incident neutron spectrum was reconstructed using materials found in lithium batteries.

Recently, RMD has investigated the use of CLYC (Cs2LiYCl6 :Ce), a new and emerging scintillation material, in a gamma–neutron coded aperture imaging system based on RMD׳s commercial RadCam TM instrument. CLYC offers efficient thermal neutron detection, fast neutron detection capabilities, excellent pulse shape discrimination (PSD), and gamma-ray energy resolution as good as 4% at 662 keV. PSD improves the isolation of higher energy gammas from thermal neutron interactions (>3 MeV electron equivalent peak), compared to conventional pulse height techniques. The scintillation emission time in CLYC provides the basis for PSD; where neutron interactions result in a slower emission rise and decay components while gamma interactions result in a faster emission components. By creating a population plot based on the ratio of the decay tail compared to the total integral amplitude (PSD ratio), discrimination of gammas, thermal neutrons, and fast neutrons is possible. Previously, we characterized the CLYC-based RadCam system for imaging gammas and neutrons using a layered W-Cd coded aperture mask and employing only pulse height discrimination. In this paper, we present the latest results which investigate gamma-neutron imaging capabilities using PSD. An FPGA system is used to acquire the CLYC–PSPMT last dynode signals, determine a PSD ratio for each event, and compare it to a calibrated PSD cutoff. Each event is assigned either a gamma (low) or neutron (high) flag signal which is then correlated with the imaging information for each event.

Renewable portfolio standards (RPSs) have become a popular tool for state governments to promote renewable electricity generation and to decrease carbon dioxide emissions within a state or region. Renewable portfolio standards are a policy tool likely to persist for many decades due to the long term goals of many state RPSs and the likely creation of a federal RPS alongside any comprehensive climate change bill. Even though RPSs have become a popular policy tool, there is little empirical evidence about their costs. Using the temporal and regional variation in RPS requirements, I estimate the long-run price elasticity of supply of renewable electricity generation to be 2.67 (95% CI of 1.74, 3.60). Using my preferred elasticity estimate, I calculate the marginal cost of abatement from RPSs is at least $11 per ton of CO2 compared to a marginal cost of abatement of $3 per ton in the Regional Greenhouse Gas Initiative.

SummaryThough much is known about the cellular and molecular components of the circadian clock, output pathways that couple clock cells to overt behaviors have not been identified. We conducted a screen for circadian-relevant neurons in the Drosophila brain and report here that cells of the pars intercerebralis (PI), a functional homolog of the mammalian hypothalamus, comprise an important component of the circadian output pathway for rest:activity rhythms. GFP reconstitution across synaptic partners (GRASP) analysis demonstrates that PI cells are connected to the clock through a polysynaptic circuit extending from pacemaker cells to PI neurons. Molecular profiling of relevant PI cells identified the corticotropin-releasing factor (CRF) homolog, DH44, as a circadian output molecule that is specifically expressed by PI neurons and is required for normal rest:activity rhythms. Notably, selective activation or ablation of just six DH44+ PI cells causes arrhythmicity. These findings delineate a circuit through which clock cells can modulate locomotor rhythms.

In previous studies (Zhang and Johnson, 2012, 2013) [1,2], the authors proposed a substructure identification method for shear structures. This method is extended herein to accommodate more complicated plane frame building structures. Via a model reduction technique, a multi-story multi-bay plane frame is converted into a beam-like model, having one translational and two rotational degrees-of-freedom (DOFs) for each floor. Based on this model, an inductive substructure identification method is formulated, using the cross power spectral densities between the frame floor horizontal accelerations and a reference response, to identify the equivalent story stiffness and damping parameters of the frame from top to bottom inductively. An identification error analysis reveals how structural responses affect the identification accuracy. Exploiting this result, a reference selection rule is proposed to select the best reference response and further improve the identification accuracy. Finally, a five-story two-bay frame structure is used to demonstrate the efficacy of the proposed substructure identification, very accurately identifying the structural parameters even under the influence of large measurement noise; based on the estimated parameters, a hypothesis testing method is used to detect and locate structural damage, simulated by stiffness reduction of some columns.

The Tiebout model assumes that individuals sort to the jurisdiction which best matches their fiscal preferences. However, there is a paucity of reliable estimates for the impact of tax changes on household mobility. We utilize a state mandated school finance reform and temporal differences in vacation home densities to provide a unique test of this fundamental Tiebout assumption. The results show that changes in property taxes explain a significant amount of the variation in vacation home growth; a 3–4 mil decrease in property tax rates is associated with an increase of approximately one vacation home per square kilometer.

A computationally efficient method for the reanalysis of the damped generalized eigenvalue problems associated with linear dynamical systems with local damping and stiffness modifications is developed. No restrictions are imposed on the damping of the system and the modifications in the damping and the stiffness can be independent of each other. The application of the developed method to the undamped generalized eigenvalue problem with mass and stiffness modifications is also discussed. The proposed method achieves up to three orders of magnitude gains in computational efficiency compared to the conventional solution procedures.

Robbing and dodging is a well-documented food protective behaviour in rats. Recently, we demonstrated that a simple cybernetic rule, gaining and maintaining a preferred interanimal distance, can account for much of the variability in dodging by rats. In this paper, the field cricket, Teleogryllus oceanicus, was used to test whether or not the same or similar cybernetic rules are used by animals of different lineages and body plans. Pairs of female crickets were tested in a circular arena with a clear glass surface. A small food pellet was given to one of the crickets and the attempts to rob the food by the other were videotaped from beneath. The results show that, although crickets, unlike rats, use a variety of defensive strategies, all of the cases in which they use evasion to protect a portable food item conform to the same cybernetic rules used by rats.

We construct the location quotient (LQ) from a discrete data generating process and formally test its statistical properties. First, we show that the LQ is typically unbiased, but exhibits finite sample bias when assuming a Poisson distribution. Second, we determine the accuracy of statistical tests, which depends of both sample size as well as desired confidence levels. After constructing LQs using County Business Patterns (2000) data, we find improved accuracy in statistical tests when one increases spatial as well as industrial aggregation. Results show a clear tradeoff between precise statistical inference and power in detecting industrial concentration.

We introduce a non-parametric microdata based test for industrial specialization and apply it to a single urban area. Our test employs establishment densities for specific industries, a population counterfactual, and a new correction for multiple hypothesis testing to determine the statistical significance of specialization across both places and industries. Results highlight patterns of specialization that are extremely varied, with downtown places specializing in a number of service sector industries, while suburban places specialize in both manufacturing and service industries. Business service industries are subject to more specialization than non-business service industries while the manufacturing sector contains the lowest representation of industries with specialized places. Finally, we compare results for specialization with localization and show that both measures contribute to our understanding of industry and place specific agglomerative forces.

The CMOS solid-state photomultiplier (SSPM) is an array of Geiger avalanche photodiodes (GPD) read out in parallel. These devices are not susceptible to magnetic fields, less expensive to fabricate than many other photodetector technologies, compact, and allow for on-chip integration of signal processing circuits. A number of nuclear detection applications require detector sizes on the order of 1 cm. Standard silicon fabrication technology limits the size of the SSPM die, and tiling of the silicon die can result in large-area devices but results in dead space between die for bonding purposes. Radiation Monitoring Devices (RMD) has fabricated 1×1 cm SSPM arrays on a single die. The size of these devices is large enough to provide an alternative detector for scintillation detector applications compared to photomultiplier tubes. Although the size increases the dark noise, we will demonstrate that the large-area SSPM can provide a PMT-like response for 22Na gamma rays using an LYSO crystal. Each of the noise terms associated with the large-area SSPM is discussed, quantifying the cross talk and after pulse multipliers, which are scaling factors to the gain to account for the additional output charge from the SSPM. The excess noise factor associated with cross talk and after pulsing has a linear dependence on the multiplier term. The signal and noise terms have been compiled to provide the best operating voltage of roughly 6 V above breakdown for a 1×1 cm CMOS SSPM to be operated with a short integration time (

Idealized modeling of most engineering structures yields linear mathematical models, i.e. , linear ordinary or partial differential equations. However, features like nonlinear dampers and/or springs can render nonlinear an otherwise linear model. Often, the connectivity of these nonlinear elements is confined to only a few degrees-of-freedom (DOFs) of the structure. In such cases, treating the entire structure as nonlinear results in very computationally expensive solutions. Moreover, if system parameters are uncertain, their stochastic nature can render the analysis even more computationally costly. This paper presents an approach for computing the response of such systems in a very efficient manner. The proposed solution procedure first segregates the DOFs appearing in the nonlinear and/or stochastic terms from those DOFs that involve only linear deterministic operations. Second, the responses of nonlinear/stochastic terms are determined using a non-standard form of a nonlinear Volterra integral equation (NVIE). Finally, the responses of the remaining DOFs are computed through a convolution approach using the fast Fourier transform to further increase the computational efficiency. Three examples are presented to demonstrate the efficacy and accuracy of the proposed method. It is shown that, even for moderately sized systems (∼1000 DOFs), the proposed method is about three orders of magnitude faster than a conventional Monte Carlo sampling method ( i.e. , solving the system of ODEs repeatedly).

The compact, robust nature of the CMOS solid-state photomultiplier (SSPM) allows the creation of small, low-power scintillation-based radiation measurement devices. Monitoring space radiation including solar protons and secondary neutrons generated from high-energy protons impinging on spacecraft is required to determine the dose to astronauts. Small size and highly integrated design are desired to minimize consumption of payload resources. RMD is developing prototype radiation measurement and personal dosimeter devices using emerging scintillation materials coupled to CMOS SSPM’s for multiple applications. Spectroscopic measurements of high-energy protons and gamma-rays using tissue-equivalent, inorganic scintillators coupled to SSPM devices demonstrate the ability of an SSPM device to monitor the dose from proton and heavy ion particles, providing real time feedback to astronauts. Measurement of the dose from secondary neutrons introduces additional challenges due to the need to discriminate neutrons from other particle types and to accurately determine their energy deposition. We present strategies for measuring neutron signatures and assessing neutron dose including simulations of relevant environments and detector materials.

Solid-state photomultipliers (SSPMs) are a compact, lightweight, potentially low-cost alternative to a photomultiplier tube for a variety of scintillation detector applications, including digital-dosimeter and medical-imaging applications. Manufacturing SSPMs with a commercial CMOS process provides the ability for rapid prototyping, and facilitates production to reduce the cost. RMD designs CMOS SSPM devices that are fabricated by commercial foundries. This work describes the characterization and performance of these devices for scintillation detector applications. This work also describes the terms contributing to device noise in terms of the excess noise of the SSPM, the binomial statistics governing the number of pixels triggered by a scintillation event, and the background, or thermal, count rate. The fluctuations associated with these terms limit the resolution of the signal pulse amplitude. We explore the use of pixel-level signal conditioning, and characterize the performance of a prototype SSPM device that preserves the digital nature of the signal. In addition, we explore designs of position-sensitive SSPM detectors for medical imaging applications, and characterize their performance.

We have designed position sensitive solid-state photomultipliers (PS-SSPM) using a complementary metal-oxide–semiconductor (CMOS) process. While only needing four signal output channels to readout, the device provides spatial information on the micro-pixel level. Four variations of the PS-SSPM were fabricated, however, we only show the characterization results from two. These two PS-SSPMs were characterized for their energy and coincidence timing resolution, spatial resolution, and scintillator array imaging. Each PS-SSPM is 1.5×1.5 mm2, however, each device has different micro-pixel geometries and a different micro-pixel electrical readout for event position sensing. The FWHM energy resolution at 511 keV was measured as a function of bias using a 1×1×20 mm3 LYSO crystal. The energy resolution was ∼13–14% for both PS-SSPM designs. The LYSO scintillator coincidence timing resolution was measured with results ranging from 2.1 to 1.0 ns between the two PS-SSPMs. Spatial resolution studies were conducted using a focused (∼15 μm beam spot diameter) pulsed 635 nm diode laser. For each PS-SSPM, its X and Y FWHM spatial resolution was measured to be 70 μm. Lastly, we demonstrate the PS-SSPM imaging capabilities using a LYSO scintillator array having 500×500 μm2 pixels.

Experiments and simulations using various solid-state photomultiplier (SSPM) designs have been performed to evaluate pixel layouts and explore design choices. SPICE simulations of a design for position-sensing SSPMs showed charge division in the resistor network, and anticipated timing performance of the device. The simulation results predict good position information for resistances in the range of 1–5 kΩ and 150-Ω preamplifier input impedance. Back-thinning of CMOS devices can possibly increase the fill factor to 100%, improve spectral sensitivity, and allow for the deposition of anti-reflective coatings after fabrication. We report initial results from back illuminating a CMOS SSPM, and single Geiger-mode avalanche photodiode (GPD) pixels, thinned to 50 μm.

The arrestins are a family of molecules that terminate signaling from many different G protein-coupled receptors, by inhibiting the association between receptor and downstream effectors. We recently employed a human betaarrestin2-GFP fusion protein to explore the dynamics of different neuropeptide receptors in Drosophila and have previously used a betaarrestin translocation assay to identify ligands at orphan receptors. Here, we report that the Drosophila arrestin encoded by kurtz functions in a similar fashion and can be employed to investigate GPCR-arrestin associations. Specifically, a GFP-krz fusion protein, upon co-expression with various Drosophila peptide receptors, an amine receptor, and a mammalian peptide receptor translocates to the plasma membrane in specific response to ligand application. This molecular phenotype is exhibited in a mammalian cell line as well as in a Drosophila cell line. Notably, the details of receptor-arrestin associations in terms of endocytotic patterns are functionally conserved between the mammalian arrestins and kurtz. Furthermore, we report that kurtz mutants exhibit hypersensitivity to osmotic stress, implicating GPCR desensitization as an important feature of the endocrine events that shape this stress response.

Concentrated patches of recent trembling aspen (Populus tremuloides) mortality covered 56,091 ha of Colorado forests in 2006. Mortality has progressed rapidly. Area affected increased 58% between 2005 and 2006 on the Mancos-Dolores Ranger District, San Juan National Forest, where it equaled nearly 10% of the aspen cover type. In four stands that were measured twice, incidence of mortality increased from 7–9% in 2002/2003 to 31–60% in 2006. Mortality generally decreased with increasing elevation over the primary elevation range of aspen and occurred on less steep slopes than healthy aspen. Slope-weighted mean aspects of aspen cover type were northern at low elevations and generally southern at high elevations. Relative frequency of mortality was generally highest on southern to western aspects. In 31 stands measured in detail, mortality ranged from 0 to 100% (mean 32%) and was negatively correlated with stand density (P = 0.033). Size of trees affected was strongly correlated with amount of current mortality (P Agents that typically kill mature trees in aspen stands were unimportant in this mortality. Instead, a group of interchangeable, usually secondary agents was most commonly associated with mortality, including Cytospora canker (usually caused by Valsa sordida), aspen bark beetles (Trypophloeus populi and Procryphalus mucronatus), poplar borer (Saperda calcarata), and bronze poplar borer (Agrilus liragus). The rapidity of mortality, mortality agents involved, and probably other causal factors distinguish this phenomenon from the long-term loss of aspen cover usually attributed to successional processes operating in an altered disturbance regime (and often exacerbated by ungulate browsing). Our data are consistent with a hypothesis that (a) predisposing factors include stand maturation, low density, southern aspects and low elevations; (b) a major inciting factor was the recent, acute drought accompanied by high temperatures, and; (c) contributing factors and proximate agents of mortality are the common biotic agents observed. On sites with poor regeneration and weak root systems, clones may die, resulting in the long-term loss of aspen forest cover.

There has been tremendous growth in the development of statistical methods to quantify the spatial concentration of industrial activity. With these methodological advancements has come increased complexity in the construction of a ’better’ measure of agglomeration. The research presented here tests the power and size properties of commonly used agglomeration indices through a series of simulations. Results provide evidence that a simple Gini coecient has greater power in detecting statistical significant agglomeration for an industry and that the commonly used Ellison and Glaeser (1997) and Duranton and Overman (2005) indices may have incorrect size properties when industries concentrate in rural areas or when a study area is polycentric. Results highlight that continuous measures of agglomeration have greater statistical power and are not subject to bias from data aggregation. Conclusions suggest that applied researchers have limited gains and may even be worse o when incorporating complex agglomeration indices beyond a simple Gini coecient.

DNA fragmentation factors (DFF) form protein complexes consisting of nuclease DFF40/CAD and inhibitory chaperon DFF45/ICAD. Although activated caspase-3 has been shown to cleave DFF complexes with the release of active DFF40 and DNA fragmentation, the organ-specific mechanisms of DFF turnover during liver injury accompanied by massive apoptosis are unclear. In this study, we investigated hepatic profile of DFF40-immunopositive proteins in two models of liver injury in rats: acute ischemia/reperfusion (I/R) and chronic alcohol administration. We show that DFF40-like proteins occur in intact rat liver mainly as a 52 kDa protein. Hepatic I/R induced caspase-3 activation and a time-dependent accumulation of DFF40-positive protein fragments (40 kDa and 20 kDa), most likely via specific caspase-3 cleavage as evidenced by in vitro digestion of intact liver tissue with recombinant caspase-3. In addition, immunoprecipitation with DFF40 followed by western blot with active caspase-3 antibody revealed the presence of active caspase-3 in DFF40-immunopositive 20 kDa proteins. Chronic alcohol administration in rats also resulted in a dose-dependent fragmentation of DFF40 proteins similar to I/R injury. Liver immunohistochemistry showed an up-regulation of DFF40-immunopositive proteins with nuclear co-localization of DFF40 with histone H1 following acute I/R. Collectively, these data demonstrate that DFF40 immunopositive proteins exist in the liver as distinct, tissue-specific molecular forms that may be processed by caspase-3 during both acute and chronic liver injury.

SummaryThe neuropeptide Pigment-Dispersing Factor (PDF) is a principle transmitter regulating circadian locomotor rhythms in Drosophila. We have identified a Class II (secretin-related) G protein-coupled receptor (GPCR) that is specifically responsive to PDF and also to calcitonin-like peptides and to PACAP. In response to PDF, the PDF receptor (PDFR) elevates cAMP levels when expressed in HEK293 cells. As predicted by in vivo studies, cotransfection of Neurofibromatosis Factor 1 significantly improves coupling of PDFR to adenylate cyclase. pdfr mutant flies display increased circadian arrhythmicity, and also display altered geotaxis that is epistatic to that of pdf mutants. PDFR immunosignals are expressed by diverse neurons, but only by a small subset of circadian pacemakers. These data establish the first synapse within the Drosophila circadian neural circuit and underscore the importance of Class II peptide GPCR signaling in circadian neural systems.

We report the first experimental results on a high-gain harmonic-generation (HGHG) free-electron laser (FEL) operating in the ultraviolet. An 800 nm seed from a Ti-Sapphire laser has been used to produce saturated amplified output at the 266 nm third-harmonic. The results confirm the advantages of the HGHG FEL: stable central wavelength, narrow bandwidth and small pulse energy fluctuation. The harmonic output at 88 nm, which accompanies the 266 nm radiation, has been used in an ion pair imaging experiment in chemistry.

The DUV-FEL facility has been in operation in the High Gain Harmonic Generation (HGHG) mode producing a 266-nm output from 177-MeV electrons for 1 year. In this paper, we present preliminary results of the Chirped Pulse Amplification (CPA) of the HGHG radiation. In the normal HGHG process, a 1-ps electron beam is seeded by a chirped 9 ps long, 800-nm Ti:Sapphire laser. The electron beam sees only a narrow fraction of the seed laser bandwidth. However, in the CPA case, the seed laser pulse length is reduced to 1 ps, and the electron beam sees the full bandwidth. We introduce an energy chirp on the electron beam to match the chirp of the seed pulse, enabling the resonant condition for the whole beam. We present measurements of the spectrum bandwidth for various chirp conditions.

Neuroprotective effects of estrogens are demonstrated consistently in the cerebral cortex, but not in subcortical areas. In the present study, transient middle cerebral artery occlusions (MCAO) were induced for various duration, and protective effects of estrogen treatment on the cerebral cortex and subcortex were evaluated. MCAO was induced for 30, 40 or 60 min in ovariectomized rats. Animals were treated with 17β-estradiol (E2) or vehicle (OVX) 2 h before MCAO and sacrificed 24 h after the indicated duration of MCAO. Ischemic lesion was evaluated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin and eosin staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. E2 treatment reduced the magnitude and delayed the appearance of the total ischemic lesion area and largely prevented TUNEL staining in the cortex. In the subcortex, E2 treatment prevented the ischemic lesion in the 30-min group, reduced lesion area in the 40-min group, but had no effect on ischemic lesion area in the 60-min group. E2 treatment significantly decreased apoptotic cell number in the subcortical area at 30 and 40 min, but not at 60 min of MCAO. This study demonstrated that estrogen treatment can protect the cerebral subcortex in a severity-dependent manner, suggesting that the lack of protective effects of estrogen treatment in the subcortex is not due to the lack of estrogen receptors. Further, this study indicates that estrogens could be used as a neuroprotectant to prolong the therapeutic window of thrombolysis and prolong the time of cerebral circulation intervention for neurosurgical procedure.

The Deep Ultra Violet FEL (DUV-FEL) experiment is being commissioned in the Source Development Laboratory at NSLS in Brookhaven National Laboratory. The goal of the project is to produce coherent radiation below 100 nm wavelength using High-Gain Harmonic Generation utilizing a seed laser. As a first step of this experiment, self-amplified spontaneous emission (SASE) has been achieved at 400 and 266 nm with electron beam energies at 140 and 171.7 MeV. As an intermediate stage of the experiment, direct seeding with the 266 nm laser also has been accomplished. We report the measurements of the SASE and direct seeding. We measure the FEL properties for various electron beam conditions and discuss the performance of the FEL.

VISA (Visible to Infrared SASE Amplifier) is a high-gain self-amplified spontaneous emission FEL, which achieved saturation at 840 nm within a single-pass 4-m undulator. A gain length shorter than 18 cm has been obtained, yielding the gain of 2 ×108 at saturation. The FEL performance, including spectral, angular, and statistical properties of SASE radiation, has been characterized for different electron beam conditions. The results are compared to 3-D SASE FEL theory and start-to-end numerical simulations of the entire injector, transport, and FEL system. Detailed agreement between simulations and experimental results is obtained over the wide range of the electron beam parameters.© 2003 Elsevier Science B.V. All rights reserved.

The Deep Ultra-Violet Free Electron Laser (DUVFEL) at the National Synchrotron Light Source consists of a 5 MeV photoinjector, a 200 MeV S-band linear accelerator, a four-magnet chicane compressor and a 10 m wiggler with a 3.9 cm period. The commissioning of the SDL accelerator was completed recently and it is routinely producing a high-quality electron beam with a peak current of ∼400 A and a normalised emittance of 3–4 mm mrad. The first SASE lasing of the DUV FEL has been demonstrated at both 266 and 400 nm. The gain length of the SASE experiments was measured to be 66 cm in both cases and up to 20 nJ per pulse was obtained. A laser seeded FEL at 266 nm is in the very early stages of commissioning and amplification of the laser seed has been observed. The goal of the seeded laser FEL is to saturate the FEL and thereby generate sufficient third harmonic at 89 nm for experimental applications. Here we report the observation and measurements of SASE at 400 and 266 nm and the first results of seeded FEL.

Visible to Infrared SASE Amplifier is a free electron laser (FEL) designed to saturate at a radiation wavelength of 800 nm within a 4 m long, strong focusing undulator. Large gain is achieved by driving the FEL with 72 MeV, high brightness beam of BNL's accelerator test facility. We present measurements that demonstrate saturation in addition to the frequency spectrum of the FEL radiation. Energy, gain length and spectral characteristics are compared and shown to agree with simulation and theoretical predictions.

A model is presented to explain the light-current–voltage characteristics of composite light-emitting structures. These structures are composed of a conducting polymer matrix impregnated with a sheet of inorganic quantum dot nanocrystals. Such structures were reported to exhibit emission characteristics which were extremely promising but, at the same time, not explicable using available models. We present a generalized model that can describe the salient observed characteristics.