Discouraging Federal actions that reduce the value of private property: evaluating procedural and financial approaches

A regulatory taking occurs when a court concludes that a government action has taken private property for a public use without paying just compensation to the owner--a violation of the fifth amendment. Often, the remedy is a monetary award whose value is determined by the court. ; In recent years there has been considerable interest in creating a statutory complement to the constitutional law of takings. Some believe that a statutory scheme, using procedural financial approaches, would discourage federal regulatory activities that reduce the value of privately owned property. The procedural approach would require federal agencies to evaluate the property value effects of proposed actions before undertaking them. The financial approach would require that federal agencies pay from their own budgets for any compensation awards that result from their decisions. ; This paper compares the existing procedural and financial approaches to the ones proposed. It describes the model of agency incentives and the regulatory environment implicitly assumed by these proposals and compares them to the literature on regulatory decision making and administrative law. Finally, the paper discusses some of the institutional factors likely to affect the outcome of the proposed reforms, including the role of the courts in enforcing analysis requirements, the extent of agency discretion, and the federal budget process.Environmental protection

Do statistical myths and urban legends matter for the sustainability of strategy research? : the case of moderation analysis

Statistical and methodological myths and urban legends (MULs) are perpetuated truisms which in reality are not true. It is widely believed that MULs can perpetuate incorrect methodological decisions, lead to misapplications of analyses, produce inaccurate inferences and provide errant guidelines for reviewers and editors who decide on the merit of manuscripts. However, other than identifying the practices that can lead to MULs and documenting their likely existence, few if any studies have considered their implications for theory development. In the present study, we test whether an MUL associated with using hierarchical linear regression analysis to test moderation can lead to differences in findings and influence conclusions: we address two questions in particular: (1) Did strategy scholars employing hierarchical linear regression interpret and make conclusions regarding main effect coefficients separately from significant interaction terms and (2) would the findings change if such an interpretation would have been made jointly with significant interactions? Based on a content analysis of SMJ articles, we find that MULs are present with respect to testing moderation and that they could adversely influence results and proposed implications for theory and knowledge development. We find that MULs matter in strategic management research and could shape the sustainability of its knowledge base

Assessing dose–response relationships for endocrine disrupting chemicals (EDCs): a focus on non-monotonicity

The fundamental principle in regulatory toxicology is that all chemicals are toxic and that the severity of effect is proportional to the exposure level. An ancillary assumption is that there are no effects at exposures below the lowest observed adverse effect level (LOAEL), either because no effects exist or because they are not statistically resolvable, implying that they would not be adverse. Chemicals that interfere with hormones violate these principles in two important ways: dose–response relationships can be non-monotonic, which have been reported in hundreds of studies of endocrine disrupting chemicals (EDCs); and effects are often observed below the LOAEL, including all environmental epidemiological studies examining EDCs. In recognition of the importance of this issue, Lagarde et al. have published the first proposal to qualitatively assess non-monotonic dose response (NMDR) relationships for use in risk assessments. Their proposal represents a significant step forward in the evaluation of complex datasets for use in risk assessments. Here, we comment on three elements of the Lagarde proposal that we feel need to be assessed more critically and present our arguments: 1) the use of Klimisch scores to evaluate study quality, 2) the concept of evaluating study quality without topical experts’ knowledge and opinions, and 3) the requirement of establishing the biological plausibility of an NMDR before consideration for use in risk assessment. We present evidence-based logical arguments that 1) the use of the Klimisch score should be abandoned for assessing study quality; 2) evaluating study quality requires experts in the specific field; and 3) an understanding of mechanisms should not be required to accept observable, statistically valid phenomena. It is our hope to contribute to the important and ongoing debate about the impact of NMDRs on risk assessment with positive suggestions

The Domain Interface of the Human Glutamate Transporter EAAT1 Mediates Chloride Permeation

AbstractThe concentration of glutamate within the glutamatergic synapse is tightly regulated by the excitatory amino-acid transporters (EAATs). In addition to their primary role of clearing extracellular glutamate, the EAATs also possess a thermodynamically uncoupled Cl− conductance. Several crystal structures of an archaeal EAAT homolog, GltPh, at different stages of the transport cycle have been solved. In a recent structure, an aqueous cavity located at the interface of the transport and trimerization domains has been identified. This cavity is lined by polar residues, several of which have been implicated in Cl− permeation. We hypothesize that this cavity opens during the transport cycle to form the Cl− channel. Residues lining this cavity in EAAT1, including Ser-366, Leu-369, Phe-373, Arg-388, Pro-392, and Thr-396, were mutated to small hydrophobic residues. Wild-type and mutant transporters were expressed in Xenopus laevis oocytes and two-electrode voltage-clamp electrophysiology, and radiolabeled substrate uptake was used to investigate function. Significant alterations in substrate-activated Cl− conductance were observed for several mutant transporters. These alterations support the hypothesis that this aqueous cavity at the interface of the transport and trimerization domains is a partially formed Cl− channel, which opens to form a pore through which Cl− ions pass. This study enhances our understanding as to how glutamate transporters function as both amino-acid transporters and Cl− channels

Constitutive Ion Fluxes and Substrate Binding Domains of Human Glutamate Transporters

Application of L-glutamate activates ionic currents in voltage-clamped Xenopus oocytes expressing cloned human excitatory amino acid transporters (EAATs). However, even in the absence of L-glutamate, the membrane conductance of oocytes expressing EAAT1 was significantly increased relative to oocytes expressing EAAT2 or control oocytes. Whereas transport mediated by EAAT2 is blocked by the non-transported competitive glutamate analog kainate (K = 14 μM), EAAT1 is relatively insensitive (K \u3e 3 mM). Substitution of a block of 76 residues from EAAT2 into EAAT1, in which 18 residues varied from EAAT1, conferred high affinity kainate binding to EAAT1, and application of kainate to oocytes expressing the chimeric transporter blocked a pre-existing monovalent cation conductance that displayed a permeability sequence K \u3e Na \u3e Li choline. The results identify a structural domain of glutamate transporters that influences kainate binding and demonstrate the presence of a constitutive ion-selective pore in the transporter

Glycine transport inhibitors for the treatment of pain.

Opioids, local anesthetics, anticonvulsant drugs, antidepressants, and non-steroidal anti-inflammatory drugs (NSAIDs) are used to provide pain relief but they do not provide adequate pain relief in a large proportion of chronic pain patients and are often associated with unacceptable side effects. Inhibitory glycinergic neurotransmission is impaired in chronic pain states, and this provides a novel target for drug development. Inhibitors of the glycine transporter 2 (GlyT2) enhance inhibitory neurotransmission and show particular promise for the treatment of neuropathic pain. N-arachidonyl-glycine (NAGly) is an endogenous lipid that inhibits glycine transport by GlyT2 and also shows potential as an analgesic, which may be further exploited in drug development. In this review we discuss the role of glycine neurotransmission in chronic pain and future prospects for the use of glycine transport inhibitors in the treatment of pain.NHMRC Grant: 104596

Directed Mutagenesis in Structure Activity Studies of Neurotransmitter Transporters

18 page(s

Galaxy Zoo: Disentangling the Environmental Dependence of Morphology and Colour

We analyze the environmental dependence of galaxy morphology and colour with two-point clustering statistics, using data from the Galaxy Zoo, the largest sample of visually classified morphologies yet compiled, extracted from the Sloan Digital Sky Survey. We present two-point correlation functions of spiral and early-type galaxies, and we quantify the correlation between morphology and environment with marked correlation functions. These yield clear and precise environmental trends across a wide range of scales, analogous to similar measurements with galaxy colours, indicating that the Galaxy Zoo classifications themselves are very precise. We measure morphology marked correlation functions at fixed colour and find that they are relatively weak, with the only residual correlation being that of red galaxies at small scales, indicating a morphology gradient within haloes for red galaxies. At fixed morphology, we find that the environmental dependence of colour remains strong, and these correlations remain for fixed morphology \textit{and} luminosity. An implication of this is that much of the morphology--density relation is due to the relation between colour and density. Our results also have implications for galaxy evolution: the morphological transformation of galaxies is usually accompanied by a colour transformation, but not necessarily vice versa. A spiral galaxy may move onto the red sequence of the colour-magnitude diagram without quickly becoming an early-type. We analyze the significant population of red spiral galaxies, and present evidence that they tend to be located in moderately dense environments and are often satellite galaxies in the outskirts of haloes. Finally, we combine our results to argue that central and satellite galaxies tend to follow different evolutionary paths.Comment: 19 pages, 18 figures. Accepted for publication in MNRA

Identification of a 3rd Na+ binding site of the glycine transporter, GlyT2

The Na+/Cl- dependent glycine transporters GlyT1 and GlyT2 regulate synaptic glycine concentrations. Glycine transport by GlyT2 is coupled to the co-transport of three Na+ ions, whereas transport by GlyT1 is coupled to the co-transport of only two Na+ ions. These differences in ion-flux coupling determine their respective concentrating capacities and have a direct bearing on their functional roles in synaptic transmission. The crystal structures of the closely related bacterial Na+-dependent leucine transporter, LeuTAa, and the Drosophila dopamine transporter, dDAT, have allowed prediction of two Na+ binding sites in GlyT2, but the physical location of the third Na+ site in GlyT2 is unknown. A bacterial betaine transporter, BetP, has also been crystallized and shows structural similarity to LeuTAa. Although betaine transport by BetP is coupled to the co-transport of two Na+ ions, the first Na+ site is not conserved between BetP and LeuTAa, the so called Na1' site. We hypothesized that the third Na+ binding site (Na3 site) of GlyT2 corresponds to the BetP Na1' binding site. To identify the Na3 binding site of GlyT2, we performed molecular dynamics (MD) simulations. Surprisingly, a Na+ placed at the location consistent with the Na1' site of BetP spontaneously dissociated from its initial location and bound instead to a novel Na3 site. Using a combination of MD simulations of a comparative model of GlyT2 together with an analysis of the functional properties of wild type and mutant GlyTs we have identified an electrostatically favorable novel third Na+ binding site in GlyT2 formed by Trp263 and Met276 in TM3, Ala481 in TM6 and Glu648 in TM10

Galaxy Zoo: The large-scale spin statistics of spiral galaxies in the Sloan Digital Sky Survey

We re-examine the evidence for a violation of large-scale statistical isotropy in the distribution of projected spin vectors of spiral galaxies. We have a sample of $\sim 37,000$ spiral galaxies from the Sloan Digital Sky Survey, with their line of sight spin direction confidently classified by members of the public through the online project Galaxy Zoo. After establishing and correcting for a certain level of bias in our handedness results we find the winding sense of the galaxies to be consistent with statistical isotropy. In particular we find no significant dipole signal, and thus no evidence for overall preferred handedness of the Universe. We compare this result to those of other authors and conclude that these may also be affected and explained by a bias effect.Comment: Accepted for publication in MNRAS. 8 pages, 5 figure