bluuebunny/crossref_metadata_2025 huggingface dataset:
Lack of protein‐tyrosine sulfation disrupts photoreceptor outer segment morphogenesis, retinal function and retinal anatomy
Authors: Sherry David M. , Murray Anne R. , Kanan Yogita , Arbogast Kelsey L. , Hamilton Robert A. , Fliesler Steven J. , Burns Marie E. , Moore Kevin L. , Al‐Ubaidi Muayyad R.
Published: October 2010

To investigate the role(s) of protein‐tyrosine sulfation in the retina, we examined retinal function and structure in mice lacking tyrosylprotein sulfotransferases (TPST) 1 and 2. Tpst double knockout (DKO; Tpst1−/−/Tpst2 −/−) retinas had drastically reduced electroretinographic responses, although their photoreceptors exhibited normal responses in single cell recordings. These retinas appeared normal histologically; however, the rod photoreceptors had ultrastructurally abnormal outer segments, with membrane evulsions into the extracellular space, irregular disc membrane spacing and expanded intradiscal space. Photoreceptor synaptic terminals were disorganized in Tpst DKO retinas, but established ultrastructurally normal synapses, as did bipolar and amacrine cells; however, the morphology and organization of neuronal processes in the inner retina were abnormal. These results indicate that protein‐tyrosine sulfation is essential for proper outer segment morphogenesis and synaptic function, but is not critical for overall retinal structure or synapse formation, and may serve broader functions in neuronal development and maintenance.
Differential effects of short‐ and long‐term hyperhomocysteinaemia on cholinergic neurons, spatial memory and microbleedingsin vivoin rats
Authors: Pirchl Michael , Ullrich Celine , Humpel Christian
Published: October 2010

Hyperhomocysteinaemia (HHcy) has been identified as a cardiovascular risk factor for neurodegenerative brain diseases. The aim of the present study was to investigate the effects of short (5 months) or long (15 months) HHcy in Sprague–Dawley ratsin vivo. Short‐ and long‐term HHcy differentially affected spatial memory as tested in a partially baited eight‐arm radial maze. HHcy significantly reduced the number of choline acetyltransferase (ChAT)‐positive neurons in the basal nucleus of Meynert and ChAT‐positive axons in the cortex only after short‐term but not long‐term treatment, while acetylcholine levels in the cortex were decreased at both time points. Nerve growth factor (NGF) was significantly enhanced in the cortex only after 15 months of HHcy. HHcy did not affect cortical levels of amyloid precursor protein, beta‐amyloid(1‐42), tau and phospho‐tau181 and several inflammatory markers, as well as vascular RECA‐1 and laminin density. However, HHcy induced cortical microbleedings, as illustrated by intensive anti‐rat IgG‐positive spots in the cortex. In order to study the regulation of the key enzyme ChAT, organotypic rat brain slices were incubated with homocysteine, which induced a decline of ChAT that was counteracted by NGF treatment. In conclusion, our data demonstrate that chronic short‐ and long‐term HHcy differentially caused memory impairment, cholinergic dysfunction, NGF expression and vascular microbleedings.
Dissociable regulation of instrumental action within mouse prefrontal cortex
Authors: Gourley Shannon L. , Lee Anni S. , Howell Jessica L. , Pittenger Christopher , Taylor Jane R.
Published: October 2010

Evaluation of the behavioral ‘costs’, such as effort expenditure relative to the benefits of obtaining reward, is a major determinant of goal‐directed action. Neuroimaging evidence suggests that the human medial orbitofrontal cortex (mOFC) is involved in this calculation and thereby guides goal‐directed and choice behavior, but this region’s functional significance in rodents is unknown despite extensive work characterizing the role of the lateral OFC in cue‐related response inhibition processes. We first tested mice with mOFC lesions in an instrumental reversal task lacking discrete cues signaling reinforcement; here, animals were required to shift responding based on the location of the reinforced aperture within the chamber. Mice with mOFC lesions acquired the reversal but failed to inhibit responding on the previously reinforced aperture, while mice with prelimbic prefrontal cortex lesions were unaffected. When tested on a progressive ratio schedule of reinforcement, mice with prelimbic cortical lesions were unable to maintain responding, resulting in declining response levels. Mice with mOFC lesions, by contrast, escalated responding. Neither lesion affected sensitivity to satiety‐specific outcome devaluation or non‐reinforcement (i.e. extinction), and neither had effects when placed after animals were trained on a progressive ratio response schedule. Lesions of the ventral hippocampus, which projects to the mOFC, resulted in similar response patterns, while lateral OFC and dorsal hippocampus lesions resulted in response acquisition, though not inhibition, deficits in an instrumental reversal. Our findings thus selectively implicate the rodent mOFC in braking reinforced goal‐directed action when reinforcement requires the acquisition of novel response contingencies.
Feed‐forward control of preshaping in the rat is mediated by the corticospinal tract
Authors: Carmel Jason B. , Kim Sangsoo , Brus‐Ramer Marcel , Martin John H.
Published: October 2010

Rats are used to model human corticospinal tract (CST) injury and repair. We asked whether rats possess the ability to orient their paw to the reaching target and whether the CST mediates this skill, as it does in primates. To test this ability, called preshaping, we trained rats to reach for pieces of pasta oriented either vertically or horizontally. We measured paw angle relative to the target and asked whether rats used target information attained before contact to preshape the paw, indicating feed‐forward control. We also determined whether preshaping improved with practice. We then selectively lesioned the CST in the medullary pyramid contralateral to the reaching forepaw to test whether preshaping relies on the CST. Rats significantly oriented their paw to the pasta orientation before contact, demonstrating feed‐forward control. Both preshaping and reaching efficiency improved with practice, while selective CST lesion abrogated both. The loss of preshaping was greatest for pasta oriented vertically, suggesting loss of supination, as seen with human CST injury. The degree of preshaping loss strongly correlated with the amount of skill acquired at baseline, suggesting that the CST mediates the learned component of preshaping. Finally, the amount of preshaping lost after injury strongly correlated with reduced retrieval success, showing an important functional consequence for preshaping. We have thus demonstrated, for the first time, preshaping in the rat and dependence of this skill on the CST. Understanding the basis for this skill and measuring its recovery after injury will be important for studying higher‐level motor control in rats.
MRI predictors of long‐term evolution in amyotrophic lateral sclerosis
Authors: Agosta Federica , Pagani Elisabetta , Petrolini Melissa , Sormani Maria P. , Caputo Domenico , Perini Michele , Prelle Alessandro , Salvi Fabrizio , Filippi Massimo
Published: October 2010

We investigated whether conventional and diffusion tensor (DT) magnetic resonance imaging (MRI) features of the corticospinal tract (CST) contribute to the prediction of the long‐term clinical evolution in patients with amyotrophic lateral sclerosis (ALS). Brain conventional and DT MRI were obtained from 18 healthy subjects and 24 patients with sporadic ALS. Mean diffusivity (MD) and fractional anisotropy (FA) of the CST were obtained. Patients were scanned at baseline, then entered a longitudinal clinical follow‐up. The ALS Functional Rating scale (ALSFRS) progression rate during follow‐up was estimated. Patients were followed up prospectively for a median period of 3.4 years. Two patients were lost at follow‐up and eight died during the observation period. The mean ALSFRS progression rate was 0.7/month (range = 0.0–2.0/month). At baseline, ALS patients showed significantly increased MD and decreased FA of the CST compared with controls. CST FA was associated with ALSFRS progression rate. ALSFRS deterioration rate and CST FA were independent predictors of survival in ALS patients. Survival at year 3 was 42% in patients with CST FA ≤ 0.56 compared with 90% in patients with CST FA > 0.56. This study shows that more severe CST DT MRI abnormalities predict a poorer long‐term clinical outcome in ALS patients. DT MRI of the brain has the potential to offer in vivo markers of disease severity.
Dynamics of Strongly Nonlinear Kinks and Solitons in a Two‐Layer Fluid
Authors: Gorshkov K. , Ostrovsky L. A. , Soustova I.
Published: October 2010

Perturbation theory is developed for interaction of strongly nonlinear solitary waves close to the limiting, tabletop solitons (Π‐solitons). The method is based on representing each soliton as a compound of two kinks so that the interaction of N solitons is treated as the interaction of 2N kinks. As an example the Miyata–Choi–Camassa equations for a two‐layer fluid is considered. Equations for kink coordinates are obtained and analyzed. Some nontrivial features of two‐soliton interaction characteristic of the strongly nonlinear case are established.
Maximum Likelihood Estimation of a Multi-Dimensional Log-Concave Density
Authors: Cule Madeleine , Samworth Richard , Stewart Michael
Published: October 2010

Let X1,…,Xn be independent and identically distributed random vectors with a (Lebesgue) density f. We first prove that, with probability 1, there is a unique log-concave maximum likelihood estimator f^n of f. The use of this estimator is attractive because, unlike kernel density estimation, the method is fully automatic, with no smoothing parameters to choose. Although the existence proof is non-constructive, we can reformulate the issue of computing f^n in terms of a non-differentiable convex optimization problem, and thus combine techniques of computational geometry with Shor’s r-algorithm to produce a sequence that converges to f^n. An R version of the algorithm is available in the package LogConcDEAD—log-concave density estimation in arbitrary dimensions. We demonstrate that the estimator has attractive theoretical properties both when the true density is log-concave and when this model is misspecified. For the moderate or large sample sizes in our simulations, f^n is shown to have smaller mean integrated squared error compared with kernel-based methods, even when we allow the use of a theoretical, optimal fixed bandwidth for the kernel estimator that would not be available in practice. We also present a real data clustering example, which shows that our methodology can be used in conjunction with the expectation–maximization algorithm to fit finite mixtures of log-concave densities.
A Geometric Characterization of Optimal Designs for Regression Models with Correlated Observations
Authors: Holland-Letz Tim , Dette Holger , Pepelyshev Andrey
Published: October 2010

We consider the problem of optimal design of experiments for random-effects models, especially population models, where a small number of correlated observations can be taken on each individual, whereas the observations corresponding to different individuals are assumed to be uncorrelated. We focus on c-optimal design problems and show that the classical equivalence theorem and the famous geometric characterization of Elfving from the case of uncorrelated data can be adapted to the problem of selecting optimal sets of observations for the n individual patients. The theory is demonstrated by finding optimal designs for a linear model with correlated observations and a non-linear random-effects population model, which is commonly used in pharmaco-kinetics.
Modelling Non-Homogeneous Poisson Processes with Almost Periodic Intensity Functions
Authors: Shao Nan , Lii Keh-Shin
Published: October 2010

We propose a model for the analysis of non-stationary point processes with almost periodic rate of occurrence. The model deals with the arrivals of events which are unequally spaced and show a pattern of periodicity or almost periodicity, such as stock transactions and earthquakes. We model the rate of occurrence of a non-homogeneous Poisson process as the sum of sinusoidal functions plus a baseline. Consistent estimates of frequencies, phases and amplitudes which form the sinusoidal functions are constructed mainly by the Bartlett periodogram. The estimates are shown to be asymptotically normally distributed. Computational issues are discussed and it is shown that the frequency estimates must be resolved with order o(T−1) to guarantee the asymptotic unbiasedness and consistency of the estimates of phases and amplitudes, where T is the length of the observation period. The prediction of the next occurrence is carried out and the mean-squared prediction error is calculated by Monte Carlo integration. Simulation and real data examples are used to illustrate the theoretical results and the utility of the model.
Viewing Tax Policy Through Party-Colored Glasses: What German Politicians Believe
Authors: Heinemann Friedrich , Janeba Eckhard
Published: October 2010

The process of globalization has an important impact on national tax policies. Most of the literature does not focus directly on the political decision-making process and assumes that the desired tax policy is responding to objective underlying tradeoffs. Based on an original survey of members of the German national parliament (Bundestag) in 2006/07, we document a strong ideological bias among policy-makers with respect to the perceived mobility of international tax bases (real capital and paper profits). Ideology also influences, directly and indirectly, the perceived national autonomy in tax setting and preferences for a European Union minimum tax for companies. There seems little consensus as to what the efficiency costs of capital taxation in open economies are, even though our survey falls in a period of extensive debate about, and actual adoption of, a company tax reform bill in Germany.
PACAP‐regulated phenylethanolamineN‐methyltransferase gene expression
Authors: Tai Tze Chun , Wong‐Faull David C. , Claycomb Robert , Aborn Jennifer L. , Wong Dona Lee
Published: October 2010

J. Neurochem.(2010)115, 1195–1205.

Pituitary adenylate cyclase activating polypeptide (PACAP) induces the proximal −893 bp of rat phenylethanolamineN‐methyltransferase (PNMT) gene promoter in PC12 cells via PACAP type I receptors. Deletion mutation analysis suggested that the initial −392 bp of promoter, containing early growth response protein (Egr‐1), specificity protein 1 (Sp1) and activator protein 2 (AP‐2) binding sites (−165, −168 and −103 bp, respectively), was sufficient for PACAP activation. Egr‐1 and AP‐2 involvement was supported by PACAP induction of their mRNA and protein. Mutation of the Egr‐1, Sp1 and AP‐2 elements showed that the Egr‐1 site was essential for PACAP stimulation. Mutation of the −103 bp AP‐2 site partially reduced PACAP activation of the promoter. Mutation of two upstream AP‐2 sites at −573 and −650 bp, separately or in tandem, also prevented promoter induction by PACAP. siRNA knock‐down of Egr‐1 and AP‐2 suppressed promoter activation for the −893 bp construct. Egr‐1 siRNA knock‐down also eliminated the residual activation observed for the −103 bp AP‐2 mutant construct, suggesting that Egr‐1 and AP‐2 through respective −165 and −650/−573/−103 bp sites cooperatively stimulate the promoter. PACAP responses appear orchestrated through cAMP‐protein kinase A and phospholipase C signaling as MDL12,330A, H89 and U73122, respectively, inhibited promoter induction by PACAP and reduced PACAP‐stimulation of Egr‐1, AP‐2 and PNMT mRNA and protein and Egr‐1 and AP‐2 protein/DNA complex formation. Findings are the first to show that PACAP stimulates PNMT promoter‐driven gene expression via PACAP type I receptors and cAMP‐protein kinase A and phospholipase C signaling, recruiting Egr‐1 and AP‐2 as cooperative regulators, and the first to associate the transcription factor AP‐2 to PACAP‐mediated gene induction.
Interferon‐β induces apoptosis in human SH‐SY5Y neuroblastoma cells through activation of JAK–STAT signaling and down‐regulation of PI3K/Akt pathway
Authors: Dedoni Simona , Olianas Maria C. , Onali Pierluigi
Published: October 2010

J. Neurochem. (2010) 115, 1421–1433.

Type I interferons (IFNs) are known to cause neuropsychiatric side effects, which have been proposed to be mediated by either peripheral actions or activation of glial cells. In the present study, we have investigated whether these cytokines could act directly on neuronal cells and regulate signaling pathways involved in cell death. In human SH‐SY5Y neuroblastoma cells, type I IFNs rapidly stimulated tyrosine phosphorylation of Janus kinase and signal transducer and activator of transcription (STAT) through type I IFN receptor. Prolonged exposure to IFN‐β induced apoptotic cell death accompanied by cytochrome C release, cleavage of caspases 9, 7, 3 and poly‐(ADP ribose) polymerase and DNA fragmentation. Janus kinase inhibition reduced IFN‐β‐stimulated TyK2 and STAT1 phosphorylation, STAT1 transcriptional activity, induction of double‐stranded RNA‐activated protein kinase (PKR) and caspase cleavage. PKR induction was associated with enhanced PKR activity and chemical inhibition of PKR reduced IFN‐stimulated caspase activation. Moreover, long‐term IFN‐β treatment led to down‐regulation of phosphatidylinositol 3‐kinase/Akt signaling and IFN‐β‐induced apoptosis was attenuated in cells expressing constitutively active Akt. Similarly, in mouse primary neurons IFN‐β induced STAT phosphorylation, caspase 3 cleavage and inhibition of Akt signaling. Thus, type I IFNs can directly impair neuronal survival by regulating multiple signaling molecules promoting the intrinsic apoptotic pathway. This effect may contribute to the cytokine neurotoxicity.
Regulation of protein phosphatase 2A methylation by LCMT1 and PME‐1 plays a critical role in differentiation of neuroblastoma cells
Authors: Sontag Jean‐Marie , Nunbhakdi‐Craig Viyada , Mitterhuber Martina , Ogris Egon , Sontag Estelle
Published: October 2010

J. Neurochem. (2010) 115, 1455–1465.

Neuritic alterations are a major feature of many neurodegenerative disorders. Methylation of protein phosphatase 2A (PP2A) catalytic C subunit by the leucine carboxyl methyltransferase (LCMT1), and demethylation by the protein phosphatase methylesterase 1, is a critical PP2A regulatory mechanism. It modulates the formation of PP2A holoenzymes containing the Bα subunit, which dephosphorylate key neuronal cytoskeletal proteins, including tau. Significantly, we have reported that LCMT1, methylated C and Bα expression levels are down‐regulated in Alzheimer disease‐affected brain regions. In this study, we show that enhanced expression of LCMT1 in cultured N2a neuroblastoma cells, which increases endogenous methylated C and Bα levels, induces changes in F‐actin organization. It promotes serum‐independent neuritogenesis and development of extended tau‐positive processes upon N2a cell differentiation. These stimulatory effects can be abrogated by LCMT1 knockdown and S‐adenosylhomocysteine, an inhibitor of methylation reactions. Expression of protein phosphatase methylesterase 1 and the methylation‐site L309Δ C subunit mutant, which decrease intracellular methylated C and Bα levels, block N2a cell differentiation and LCMT1‐mediated neurite formation. Lastly, inducible and non‐inducible knockdown of Bα in N2a cells inhibit process outgrowth. Altogether, our results establish a novel mechanistic link between PP2A methylation and development of neurite‐like processes.
Regulation and role of cyclin‐dependent kinase activity in neuronal survival and death
Authors: Hisanaga Shin‐ichi , Endo Ryo
Published: October 2010

J. Neurochem. (2010) 115, 1309–1321.

Cyclin‐dependent kinase (Cdk)5 is a proline‐directed Ser/Thr protein kinase that functions mainly in neurons and is activated by binding to a regulatory subunit, p35 or p39. Kinase activity is mainly determined by the amount of p35 available, which is controlled by a balance between synthesis and degradation. Kinase activity is also regulated by Cdk5 phosphorylation, but the activity of phosphorylated Cdk5 is in contrast to that of cycling Cdks. Cdk5 is a versatile protein kinase that regulates multiple neuronal activities including neuronal migration and synaptic signaling. Further, Cdk5 plays a role in both survival and death of neurons. Long‐term inactivation of Cdk5 triggers cell death, and the survival activity of Cdk5 is apparent when neurons suffer from stress. In contrast, hyper‐activation of Cdk5 by p25 promotes cell death, probably by reactivating cell‐cycle machinery in the nucleus. The pro‐death activity is suppressed by membrane association of Cdk5 via myristoylation of p35. Appropriate activity, localization, and regulation of Cdk5 may be critical for long‐term survival of neurons, which is more than 80 years in the case of humans.
Mapping the English Lake District: a literary GIS
Authors: Cooper David , Gregory Ian N
Published: October 2010

To date, much of the work that uses Geographical Information Systems (GIS) to study human geographies applies a social science paradigm to quantitative data. There is a growing recognition of the need, however, to test whether GIS can be used to map out the qualitative ‘data’ provided by the articulation of subjective spatial experiences. This paper expands the conceptual possibilities opened up by the use of GIS technology through an exploration of the theoretical potentiality of literary GIS. Drawing on work carried out as part of an interdisciplinary project, ‘Mapping the Lakes’, the paper focuses on the ways in which GIS can be used to explore the spatial relationships between two textual accounts of tours of the English Lake District: the proto‐Picturesque journey undertaken by the poet, Thomas Gray, in the autumn of 1769; and Samuel Taylor Coleridge’s self‐consciously post‐Picturesque ‘circumcursion’ of August 1802. Alongside this text‐specific focus, the paper also draws on recent spatial literary criticism to reflect, more generally, on the critical possibilities and problems associated with the digital mapping of space and place in literature. Ultimately, the paper seeks to open up methodological and critical space for the ongoing development of literary GIS.
A Mock Circulatory System With Physiological Distribution of Terminal Resistance and Compliance: Application for Testing the Intra‐Aortic Balloon Pump
Authors: Kolyva Christina , Biglino Giovanni , Pepper John R. , Khir Ashraf W.
Published: October 2010

A mock circulatory system (MCS) was designed to replicate a physiological environment for in vitro testing and was assessed with the intra‐aortic balloon pump (IABP). The MCS was comprised of an artificial left ventricle (LV), connected to a 14‐branch polyurethane‐compound aortic model. Physiological distribution of terminal resistance and compliance according to published data was implemented with capillary tubes of different sizes and syringes of varying air volume, respectively, fitted at the outlets of the branches. The ends of the aortic branches were connected to a common tube representing the venous system and an overhead reservoir provided atrial pressure. An IABP operating a 40‐cc balloon was set to counterpulsate with the LV. Total arterial compliance of the system was 0.94 mL/mm Hg and total arterial resistance was 20.3 ± 3.3 mm Hg/L/min. At control, physiological flow distribution was achieved and both mean and phasic aortic pressure and flow were physiological. With the IABP, aortic pressure exhibited the major features of counterpulsation: diastolic augmentation during inflation, inflection point at onset of deflation, and end‐diastolic reduction at the end of deflation. The contribution of balloon inflation and deflation was also evident on the aortic flow pattern. This MCS was verified to be suitable for IABP testing and with further adaptations it could be used for studying other hemodynamic problems and ventricular assist devices.
Total Migraine Freedom, a Potential Primary Endpoint to Assess Acute Treatment in Migraine: Comparison to the Current FDA Requirement Using the Complete Rizatriptan Study Database
Authors: Rodgers Anthony J. , Hustad Carolyn M. , Cady Roger K. , Martin Vincent T. , Winner Paul , Ramsey Karen E. , Ho Tony W.
Published: October 2010

Objective.— To examine total migraine freedom (TMF), defined as pain freedom and absence of associated symptoms, using rizatriptan clinical trial data and to explore advantages of TMF as a single primary composite efficacy endpoint.

Background.— The FDA has set a higher regulatory hurdle for registration of new migraine agents requiring both pain freedom (or relief) and absence of each associated symptom (phonophobia, photophobia, and nausea).

Methods.— Twelve studies representing phase III + efficacy/safety studies of rizatriptan 10 mg in adults treating migraine were included in the meta‐analysis. The percentage of patients achieving TMF at 2 hours by study and combined by treatment group was summarized by treatment paradigm (early/mild pain, moderate/severe, menstrual migraine). To demonstrate the impact of the strict migraine regulatory hurdle on clinical trial design and to compare it to TMF, simulation via bootstrap sampling was used.

Results.— Odds ratios (rizatriptan vs placebo, all P < .001) for TMF were 6.2 (95% CI: [4.9, 7.7]) for moderate/severe, 2.7 (95% CI: [1.8, 4.0]) for menstrual, and 3.1 (95% CI: [2.4, 4.0]) for early/mild. Most with moderate/severe migraine reported photophobia and/or phonophobia at baseline, but only half had nausea. Simulation results showed a substantial loss of power analyzing absence of pain and each symptom compared with the composite TMF endpoint across all treatment paradigms.

Conclusion.— Rizatriptan 10 mg was superior to placebo in achieving TMF at 2 hours post‐dose across all treatment paradigms. Given that the majority of patients with migraine do not exhibit all 3 associated symptoms, the TMF endpoint has significant advantages vs establishing efficacy on pain and each symptom individually.
The Fluid Symbol of Mixed Race
Authors: Zack Naomi
Published: October 2010

Philosophers have little to lose in making practical proposals. If the proposals are enacted, the power of ideas to change the world is affirmed. If the proposals are rejected, there is new material for theoretical reflection. During the 1990s, I believed that broad public recognition of mixed race, particularly black and white mixed race, would contribute to an undoing of rigid and racist, socially constructed racial categories. I argued for such recognition in my first book, Race and Mixed Race (Zack 1993), a follow-through anthology, American Mixed Race (Zack 1995), and numerous articles, especially the essay, “Mixed Black and White Race and Public Policy,” which appeared first in Hypatia in 1995.1 I also delivered scores of public and academic lectures and presentations on this subject, all of which expressed the following in varied forms and formats: Race is an idea that lacks the biological foundation it is commonly assumed to have. There is need for broad education about this absence of foundation; mixed-race identities should be recognized, especially black–white identities.
Idealizing Morality
Authors: Tessman Lisa
Published: October 2010

Implicit in feminist and other critiques of ideal theorizing is a particular view of what normative theory should be like. Although I agree with the rejection of ideal theorizing that oppression theorists (and other theorists of justice) have advocated, the proposed alternative of nonideal theorizing is also problematic. Nonideal theorizing permits one to address oppression by first describing (nonideal) oppressive conditions, and then prescribing the best action that is possible or feasible given the conditions. Borrowing an insight from the “moral dilemmas debate”—namely that moral wrongdoing or failure can be unavoidable—I suggest that offering (only) action-guidance under nonideal conditions obscures the presence and significance of unavoidable moral failure. An adequate normative theory should be able to issue a further, non-action-guiding evaluative claim, namely that the best that is possible under oppressive conditions is not good enough, and may constitute a moral failure. I find exclusively action-guiding nonideal theory to be both insufficiently nonidealizing (because it idealizes the moral agent by falsely characterizing the agent as always able to avoid moral wrongdoing) and meanwhile too strongly adapted to the nonideal (because normative expectations are lowered and detrimentally adapted to options that, while the best possible, are still unacceptable).
Feminist Epistemology at Hypatia's 25th Anniversary1
Authors: Longino Helen
Published: October 2010

This essay surveys twenty-five years of feminist epistemology in the pages ofHypatia. Feminist contributions have addressed the affective dimensions of knowledge; the natures of justification, rationality, and the cognitive agent; and the nature of truth. They reflect thinking from both analytic and continental philosophical traditions and offer a rich tapestry of ideas from which to continue challenging tradition and forging analytical tools for the problems ahead.
Confronting an Impasse: Reflections on the Past and Future of Beauvoir Scholarship
Authors: Simons Margaret
Published: October 2010

Hypatia's twenty-fifth anniversary in 2009, coming on the heels of Simone de Beauvoir's 100th birthday in 2008, provides an ideal moment to reflect on the past and future of research on Beauvoir's philosophy—the subject of two pastHypatiaissues. Reviewing these early issues in the light of more recent publications reveals both the progress in Beauvoir scholarship and a scholarly impasse that must be confronted if that progress is to continue.
Revisiting Rorty: Contributions to a Pragmatist Feminism
Authors: Dieleman Susan
Published: October 2010

In this paper, I contribute to the ongoing investigation of the similarities and dissimilarities between feminism and pragmatism—a project explored more than fifteen years ago in the Hypatia special issue on Feminism and Pragmatism (1993)—by looking at the value of Richard Rorty's work for feminist theorists and activists. In this paper, I defend Rorty against three central feminist criticisms: 1) that Rorty's defense of liberal irony relies upon a problematic delineation between public and private, 2) that Rorty's endorsement of reform over revolution is too conservative to be of use for feminism, and 3) that the role of the ironist in social progress is not useful for, nor does it accurately reflect the history of, the feminist movement. I argue that these criticisms can be mitigated by being located within the broader context of Rorty's philosophical and political commitments, which we are now in a better position to understand and thus revisit. More specifically, I contend that bringing together Rorty's private discourse of redescription with his public discourse of justification provides for feminists new methods for animating social progress. I conclude by offering examples of how adopting a Rortyan perspective would be well-suited to achieving further feminist aims.
Life Cycle Assessment of Water Supply Plans in Mediterranean Spain
Authors: Muñoz Ivan , Milà‐i‐Canals Llorenç , Fernández‐Alba Amadeo R.
Published: October 2010

Life cycle assessment (LCA) was used to compare the current water supply planning in Mediterranean Spain, the so‐called AGUA Programme, with its predecessor, the Ebro river water transfer (ERWT). Whereas the ERWT was based on a single interbasin transfer, the AGUA Programme excludes new transfers and focuses instead on different types of resources, including seawater and brackish water desalination and wastewater reuse, among others. The study includes not only water supply but the whole anthropic cycle of water, from water abstraction to wastewater treatment. In addition to standard LCA impact categories, a specific impact category focusing on freshwater resources is included, which takes into account freshwater scarcity in the affected water catchments. In most impact categories the AGUA Programme obtains similar or even lower impact scores than ERWT. Concerning impacts on freshwater resources, the AGUA Programme obtains an impact score 49% lower than the ERWT. Although the current water planning appears to perform better in many impact categories than its predecessor, this study shows that water supply in Spanish Mediterranean regions is substantially increasing its energy intensity and that Mediterranean basins suffer a very high level of water stress due to increasing demand and limited resources.
A High‐Resolution Statistical Model of Residential Energy End Use Characteristics for the United States
Authors: Min Jihoon , Hausfather Zeke , Lin Qi Feng
Published: October 2010

The absence of detailed information on residential energy end use characteristics for the United States has in the past presented an impediment to the effective development and targeting of residential energy efficiency programs. This article presents a framework for modeling space heating, cooling, water heating, and appliance energy end uses, fuels used, and carbon emissions at a zip code–level resolution for the entire United States. It combines a regression‐based statistical model derived from Residential Energy Consumption Survey data with U.S. census 2000 five‐digit zip code level information, climate division–level temperature data, and other sources. The results show large variations in energy use characteristics both between and within different regions of the country, with particularly notable differences in the magnitude of and distribution by fuel of residential energy use in urban and rural areas. The results are validated against residential energy sales data and have useful implications for both residential energy efficiency planning and further study of variations in use patterns.
Design Space Characterization for Meeting Cost and Carbon Reduction Goals
Authors: Mutchek Michele A. , Williams Eric D.
Published: October 2010

Smart irrigation controllers (SICs) can save water by adapting watering schedules to climate and soil conditions. The potential benefit of SICs is particularly high in southwestern U.S. states, where the arid climate makes water scarcer and increases watering needs of landscapes. A number of studies have tested the ability of SICs to save water in residential and small commercial settings. Results generally show overall savings, but there is substantial variability, including cases of increased water use. Though there are many controllers on the market, we argue there is a further need for optimization of design and field performance. To inform the technology development process, we develop a design for environment method, which overlays economic and environmental performance parameters under different operating conditions. This method is applied to characterize design goals for controller price and water savings that SICs must meet to yield life cycle carbon dioxide reductions and economic savings in southwestern U.S. states, accounting for regional variability in electricity and water prices and carbon overhead. Results from applying the model to SICs in the Southwest suggest that some areas are significantly easier to design for. One concept to realize improved design in practice is to build out the controller market in a staged set of niches, starting from a more favorable area then moving toward more challenging conditions.
Exposure to Traffic and Risk of Hospitalization Due to Injuries
Authors: Segui‐Gomez Maria , Lopez‐Valdes Francisco J. , Guillen‐Grima Francisco , Smyth Ernesto , Llorca Javier , de Irala Jokin
Published: October 2010

Research on the risk of motor vehicle injuries and their relationship with the amount of travel has been only partially analyzed. The few individual exposure assessments are related to very specific subsets of the driving and traveling populations. This study analyzes the relationship between kilometers traveled and hospitalization due to motor vehicle injuries. Twelve thousand three hundred and sixty nine Spanish university graduates from the Seguimiento Universidad de Navarra multipurpose cohort study were evaluated. They had not been hospitalized due to motor vehicle injuries at baseline and were followed up to eight years. Biannual questionnaires allowed for self‐reporting of kilometers traveled in motor vehicles, together with incidence of hospitalization. Covariates in the Cox regression models included age and gender and baseline use of safety belt while driving, driving a vehicle with driver‐side airbag, driving a motorcycle, and drinking and driving. There were 49,766 participant‐years with an average yearly travel of 7,828 km per person‐year. Thirty‐six subjects reported a first hospitalization event during this time. The adjusted hazard ratio per additional kilometer traveled was 1.00005 (95% confidence interval 1.000013 to 1.000086). Even the smallest of reductions in the amount of kilometers traveled (from an average of 3,250 km per year to 1,000) has a statistically significant protective effect on the likelihood of sustaining hospitalization due to motor vehicle injury (aHR 0.9, 95% CI 0.78 to 0.98). In light of current policies aimed to reduce motorized traffic due to environmental concerns, it may be appropriate to consider the additional health benefit related to reductions in injuries.
Bank Risk Taking at the Onset of the Current Banking Crisis
Authors: Fortin Rich , Goldberg Gerson M. , Roth Greg
Published: October 2010

We analyze bank governance, share ownership, CEO compensation, and bank risk taking in the period leading to the current banking crisis. Using a sample of large U.S. bank holding companies (BHCs), we find that BHCs with greater managerial control, achieved through various corporate governance mechanisms, take less risk. BHCs that pay CEOs high base salaries also take less risk, while BHCs that grant CEOs more in stock options or that pay CEOs higher bonuses take more risk. The evidence is generally consistent with BHC managers exhibiting greater risk aversion than outside shareholders, but with several factors affecting managers’ risk‐taking incentives.
The Effect of Labor Market Demand on U.S. CEO Pay Since 1980
Authors: Nagel Gregory L.
Published: October 2010

This paper shows that the rise in U.S. chief executive officer (CEO) pay from 1980 to 2003 is only partially explained by competition for profit‐producing talent in the labor market. This conclusion is obtained by removing unintended data biases from tests of the only theoretical model in the literature that relates labor market competition (measured by large firm size) to CEO pay level. When the biases are removed or minimized, no more than 33% of the 600+ percentage rise in large‐firm CEO pay since 1980 is explained by a corresponding increase in large firm size.
The Impact on Interest Rates of Unemployment Announcements and Their Revisions
Authors: Gunderson James E. , Sterbenz Frederic P.
Published: October 2010

The announced changes in monthly employment reports and in weekly new unemployment claim reports are based on new levels and on revisions to previous levels. We analyze the effect on interest rates of surprises to these two separate components of the changes. We find that for weekly reports the effect on interest rates of the new level is greater than the effect of the revisions. For monthly employment reports, the two components’ effects have similar strength.
Estimating Volatility Persistence in Oil Prices Under Structural Breaks
Authors: Ewing Bradley T. , Malik Farooq
Published: October 2010

Policy makers and financial market participants are interested in knowing how shocks affect the volatility of oil prices over time. We accurately compute the volatility persistence by incorporating endogenously determined structural breaks into a GARCH model. Contrary to previous findings, we find that oil shocks dissipate very quickly but have a strong initial impact. Understanding this behavior is not only important for derivative valuation and hedging decisions but for broader financial markets and the overall economy, for which there are significant consequences.
Empirical Evidence of the Existence of Investable Premiums in Emerging Market Investable Stocks
Authors: Girard Eric C.
Published: October 2010

This paper shows that portfolios of more investable securities bear a premium when compared to portfolios of less investable stocks, reflecting compensation for local risk factors. The investable premium is overwhelmingly priced across 3,782 companies traded in 29 emerging markets from 1988 to 2006. The investable premium impacts stock returns at least as much as other fundamental premiums such as size, value, momentum, and loads on political, economic, and financial risk factors. The impact of the investable premium on emerging stocks returns has increased in strength, implying that foreign ownership has greater influence on local markets in recent years.
Volatility Risk Premium, Risk Aversion, and the Cross‐Section of Stock Returns
Authors: Nyberg Peter , Wilhelmsson Anders
Published: October 2010

We test if innovations in investor risk aversion are a priced factor in the stock market. Using 25 portfolios sorted on book‐to‐market and size as test assets, our new factor together with the market factor explains 64% of the variation in average returns compared to 60% for the Fama‐French model. The new factor is generally significant with an estimated risk premium close to its time series mean also when industry portfolios and portfolios sorted on previous returns are augmented to the test assets.
The AHA! Experience: Creativity Through Emergent Binding in Neural Networks
Authors: Thagard Paul , Stewart Terrence C.
Published: October 2010

Many kinds of creativity result from combination of mental representations. This paper provides a computational account of how creative thinking can arise from combining neural patterns into ones that are potentially novel and useful. We defend the hypothesis that such combinations arise from mechanisms that bind together neural activity by a process of convolution, a mathematical operation that interweaves structures. We describe computer simulations that show the feasibility of using convolution to produce emergent patterns of neural activity that can support cognitive and emotional processes underlying human creativity.
On the Observability of Purely Behavioral Sunk‐Cost Effects: Theoretical and Empirical Support for the BISC Model
Authors: Cunha Marcus , Caldieraro Fabio
Published: October 2010

There is growing interest in whether and how sunk‐cost effects for purely behavioral investments occur. In this article, we further discuss Cunha and Caldieraro’s (2009) Behavioral Investment Sunk Cost (BISC) model and reconcile Otto’s (2010) results with the BISC model predictions. We also report new data from two unpublished experiments that are consistent with the BISC model, and we discuss the conditions under which purely behavioral sunk‐cost effects are likely to be observed.
Ultrasound Assessment of Severe Dehydration in Children With Diarrhea and Vomiting
Authors: Levine Adam C. , Shah Sachita P. , Umulisa Irenee , Mark Munyaneza Richard B. , Dushimiyimana Jean Marie , Stegmann Katrina , Musavuli Juvenal , Ngabitsinze Protogene , Stulac Sara , Epino Henry M. , Noble Vicki E.
Published: October 2010

Objectives:  The objective of this study was to determine the test characteristics for two different ultrasound (US) measures of severe dehydration in children (aorta to inferior vena cava [IVC] ratio and IVC inspiratory collapse) and one clinical measure of severe dehydration (the World Health Organization [WHO] dehydration scale).

Methods:  The authors enrolled a prospective cohort of children presenting with diarrhea and/or vomiting to three rural Rwandan hospitals. Children were assessed clinically using the WHO scale and then underwent US of the IVC by a second clinician. All children were weighed on admission and then fluid‐resuscitated according to standard hospital protocols. A percent weight change between admission and discharge of greater than 10% was considered the criterion standard for severe dehydration. Receiver operating characteristic (ROC) curves were created for each of the three tests of severe dehydration compared to the criterion standard.

Results:  Children ranged in age from 1 month to 10 years; 29% of the children had severe dehydration according to the criterion standard. Of the three different measures of dehydration tested, only US assessment of the aorta/IVC ratio had an area under the ROC curve statistically different from the reference line. At its best cut‐point, the aorta/IVC ratio had a sensitivity of 93% and specificity of 59%, compared with 93% and 35% for IVC inspiratory collapse and 73% and 43% for the WHO scale.

Conclusions:  Ultrasound of the aorta/IVC ratio can be used to identify severe dehydration in children presenting with acute diarrhea and may be helpful in guiding clinical management.

ACADEMIC EMERGENCY MEDICINE 2010; 17:1035–1041 © 2010 by the Society for Academic Emergency Medicine
Recruitment and Retention of Patients into Emergency Medicine Clinical Trials
Authors: Cofield Stacey S. , Conwit Robin , Barsan William , Quinn James
Published: October 2010

The emergency medicine (EM) and prehospital environments are unlike any other clinical environments and require special consideration to allow the successful implementation of clinical trials. This article reviews the specific issues involved in EM clinical trials and provides strategies from EM and non‐EM trials to maximize recruitment and retention. While the evidence supporting some of these strategies is deficient, addressing recruitment and retention issues with specific strategies will help researchers deal with these issues in their funding applications and in turn develop the necessary infrastructure to participate in EM clinical trials.

ACADEMIC EMERGENCY MEDICINE 2010; 17:1104–1112 © 2010 by the Society for Academic Emergency Medicine