bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytoprotective Effects of Geranylgeranylacetone against Retinal Photooxidative Damage
Authors: Tanito Masaki , Kwon Yong-Won , Kondo Norihiko , Bai Jie , Masutani Hiroshi , Nakamura Hajime , Fujii Junichi , Ohira Akihiro , Yodoi Junji
Published: March 2005

Exposure to excessive light induces retinal photoreceptor cell damage, leading to development and progression of various retinal diseases. We tested the effect of geranylgeranylacetone (GGA), an acyclic polyisoprenoid, on light-induced retinal damage in mice. Oral treatment with GGA (1.0 mg/d) for 5 d induced thioredoxin (Trx) and heat shock protein 72 (Hsp72) predominantly in the retinal pigment epithelium (RPE). After white light exposure (8000 lux for 2 h), the percentage of terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling-positive photoreceptor cells decreased significantly at 24 and 96 h, and the number of photoreceptor cell nuclei at 96 h and the electroretinographic amplitudes of the a- and b-waves at 4 and 10 d increased significantly in GGA-pretreated mice compared with saline-pretreated mice. Light-induced upregulations of 8-hydroxy-2-deoxyguanosine and 4-hydroxy-2-nonenal-modified protein, markers of oxidative stress, were inhibited by GGA pretreatment. To elucidate the cytoprotective mechanism of GGA and Trx, we used human K-1034 RPE cells and mouse photoreceptor-derived 661W cells. In K-1034 cells, GGA (10 μm) induced intracellular Trx, Hsp72, and extracellular Trx but not extracellular Hsp72. Extracellular Trx (0.75 nm) attenuated H2O2(200 μm)-induced cell damage in 661W cells. Pretreatment with GGA and overexpression of Trx in K-1034 cells counteracted H2O2(50 μm)-induced attenuation of cellular latex bead incorporation. Protection of phagocytotic activity through induction of Trx and possibly Hsp72 in RPE cells and elimination of oxidative stress in the photoreceptor layer through release of Trx from RPE cells may be mechanisms of GGA-mediated cytoprotection. Therefore, Trx is a neurotrophic factor released from RPE cells and plays a crucial role in maintaining photoreceptor cell integrity.
Afferents and Homotypic Neighbors Regulate Horizontal Cell Morphology, Connectivity, and Retinal Coverage
Authors: Reese Benjamin E. , Raven Mary A. , Stagg Stephanie B.
Published: March 2005

Horizontal cells are inhibitory interneurons with laterally oriented dendrites that overlap one another, contacting the pedicles of cone photoreceptors. Because of their regular spacing, the network of horizontal cells provides a uniform coverage of the retinal surface. The developmental processes establishing these network properties are undefined, but cell-intrinsic instructions and interactions with other cells have each been suggested to play a role. Here, we show that the intercellular spacing of horizontal cells is essentially independent of genetic background and is predicted by local density, suggesting that horizontal cell positioning is modulated by proximity to other horizontal cells. Dendritic field area compensates for this variation in intercellular spacing, maintaining constant dendritic coverage between strains. Functional dendritic overlap is achieved anatomically at the level of the pedicles, where horizontal cells interact with one another to establish their connectivity: the number of dendritic terminals contacting a pedicle changes, reciprocally, between neighboring horizontal cells during development based on their relative proximity to each pedicle. Cellular morphology is also shown to be regulated by the afferents themselves: afferent elimination before innervation does not alter dendritic field size nor stratification but compromises dendritic branching and prevents terminal formation. Afferent and homotypic interactions therefore generate the morphology, spacing, and connectivity of horizontal cells underlying their functional coverage of the retina.
Ca2+-Dependent Regulation of Rho GTPases Triggers Turning of Nerve Growth Cones
Authors: Jin Ming , Guan Chen-bing , Jiang Yun-ai , Chen Gang , Zhao Chun-tao , Cui Kai , Song Yuan-quan , Wu Chien-ping , Poo Mu-ming , Yuan Xiao-bing
Published: March 2005

Cytoplasmic Ca2+elevation and changes in Rho GTPase activity are both known to mediate axon guidance by extracellular factors, but the causal relationship between these two events has been unclear. Here we show that direct elevation of cytoplasmic Ca2+by extracellular application of a low concentration of ryanodine, which activated Ca2+release from intracellular stores, upregulated Cdc42/Rac, but downregulated RhoA, in cultured cerebellar granule cells and human embryonic kidney 293T cells. Chemoattractive turning of the growth cone triggered by a gradient of ryanodine was blocked by overexpression of mutant forms of Cdc42 but not of RhoA inXenopusspinal cord neurons. Furthermore, Ca2+-induced GTPase activity correlated with activation of protein kinase C and required a basal activity of Ca2+/calmodulin-dependent protein kinase II. Thus, Rho GTPases may mediate axon guidance by linking upstream Ca2+signals triggered by guidance factors to downstream cytoskeletal rearrangements.
NMDA Receptor-Dependent Regulation of Axonal and Dendritic Branching
Authors: Lee Li-Jen , Lo Fu-Sun , Erzurumlu Reha S.
Published: March 2005

In the rodent trigeminal principal nucleus (PrV), trigeminal afferent terminals and postsynaptic cells form discrete modules (“barrelettes”) that replicate the patterned array of whiskers and sinus hairs on the snout. Barrelette neurons of the PrV relay whisker-specific patterns to the contralateral thalamus and, subsequently, to the primary somatosensory barrel cortex. Genetic impairment of NMDA receptor (NMDAR) function blocks development of barrelettes in the PrV. Underlying cellular and functional defects are not known. Here, we examined morphological differentiation of whisker afferents, dendritic differentiation of barrelette cells, and their electrophysiological properties in mice with genetic perturbations of the essential subunit NR1 of NMDARs. We show that inNR1gene knock-down (KD) and knock-out mice, whisker afferents begin their embryonic development normally but, over time, fail to segregate into patches, and instead they develop exuberant terminal arbors spanning most of the PrV. PostnatalNR1KD barrelette cells, with significantly reduced NMDA currents, retain their membrane and synaptic properties but develop longer dendrites with no orientation preference. These results indicate that NMDARs regulate growth of presynaptic terminal arbors and postsynaptic dendritic branching, thereby leading to consolidation of synapses and patterning of presynaptic and postsynaptic elements.
Physiological Changes in Glucose Differentially Modulate the Excitability of Hypothalamic Melanin-Concentrating Hormone and Orexin NeuronsIn Situ
Authors: Burdakov Denis , Gerasimenko Oleg , Verkhratsky Alexei
Published: March 2005

The physiological signaling mechanisms that link normal variations in body energy status to the activity of arousal- and metabolism-regulating brain centers are not well understood. The melanin-concentrating hormone (MCH) and orexin/hypocretin types of neurons of the lateral hypothalamus (LH) exert opposing effects on arousal and metabolism. We examined whether shifts in brain extracellular glucose that correspond to physiological changes in blood glucose can alter the electrical output of neurochemically and biophysically defined LH cells in mouse brain slices. Here, we show that physiologically relevant concentrations of glucose dose-dependently enhance the electrical excitability of MCH neurons by inducing depolarization and increasing membrane resistance. We also demonstrate that the same physiological shifts in glucose have the opposite effects on the electrical activity of orexin neurons. We propose that these direct actions of glucose on the arousal- and metabolism-regulating LH neurons play a key role in the translation of normal variations in body energy resources into appropriate changes in arousal and metabolism.
Calcium-Stimulated Adenylyl Cyclases Modulate Ethanol-Induced Neurodegeneration in the Neonatal Brain
Authors: Maas James W. , Indacochea Ricardo A. , Muglia Lisa M. , Tran Timothy T. , Vogt Sherri K. , West Tim , Benz Ann , Shute Amanda A. , Holtzman David M. , Mennerick Steven , Olney John W. , Muglia Louis J.
Published: March 2005

Fetal alcohol exposure results in cognitive and neurobehavioral deficits, but the effects of modifying genetic loci on the severity of these sequelas have not been well characterized. Although the cAMP signaling pathway has been shown to be an important modulator of ethanol sensitivity in adult mice, its potential role in modulating ethanol-induced neurodegeneration has not been examined. Adenylyl cyclases (ACs) 1 and 8 produce cAMP in response to intracellular calcium elevation and modulate several aspects of neuronal function, including ethanol sensitivity. AC1 and AC8 are expressed widely throughout the brain of neonatal mice, and genetic deletion of both AC1 and AC8 in double-knock-out (DKO) mice enhances ethanol-induced neurodegeneration in the brains of neonatal mice. In addition, ethanol treatment induces significantly greater levels of caspase-3 activation in the brains of DKO mice compared with wild-type (WT) mice, reflecting higher numbers of apoptotic neurons. Administration of the NMDA receptor antagonist MK801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine hydrogen maleate] or the GABAAreceptor potentiator phenobarbital, which mimics components of the effects of ethanol on neurons, results in significantly greater neurodegeneration in the brains of neonatal DKO mice than WT mice. Furthermore, loss of a single calcium-stimulated AC isoform potentiates neurodegeneration after administration of ethanol, MK801, or phenobarbital. In contrast, the levels of physiological cell death, death after hypoxia/ischemia, and excitotoxic cell death are not increased in the brains of DKO mice. Thus, AC1 and AC8 are critical modulators of neurodegeneration induced by activity blockade in the neonatal brain and represent genetic loci that may potentially modify the severity of fetal alcohol syndrome.
Interactions between Ephrin-B and Metabotropic Glutamate 1 Receptors in Brain Tissue and Cultured Neurons
Authors: Calò L. , Bruno V. , Spinsanti P. , Molinari G. , Korkhov V. , Esposito Z. , Patanè M. , Melchiorri D. , Freissmuth M. , Nicoletti F.
Published: March 2005

We examined the interaction between ephrins and metabotropic glutamate (mGlu) receptors in the developing brain and cultured neurons. EphrinB2 coimmunoprecipitated with mGlu1a receptors, in all of the brain regions examined, and with mGlu5 receptors in the corpus striatum. In striatal slices, activation of ephrinB2 by a clustered form of its target receptor, EphB1, amplified the mGlu receptor-mediated stimulation of polyphosphoinositide (PI) hydrolysis. This effect was abolished in slices treated with mGlu1 or NMDA receptor antagonists but was not affected by pharmacological blockade of mGlu5 receptors. An interaction among ephrinB2, mGlu1 receptor, and NMDA was supported by the following observations: (1) the NR1 subunit of NMDA receptors coimmunoprecipitated with mGlu1a receptors and ephrinB2 in striatal lysates; (2) clustered EphB1 amplified excitatory amino acid-stimulated PI hydrolysis in cultured granule cells grown under conditions that favored the expression of mGlu1a receptors; and (3) clustered EphB1 amplified the enhancing effect of mGlu receptor agonists on NMDA toxicity in cortical cultures, and its action was sensitive to mGlu1 receptor antagonists. Finally, fluorescence resonance energy transfer and coclustering analysis in human embryonic kidney 293 cells excluded a physical interaction between ephrinB2 and mGlu1a (or mGlu5 receptors). A functional interaction between ephrinB and mGlu1 receptors, which likely involves adaptor or scaffolding proteins, might have an important role in the regulation of developmental plasticity.
Regulation of Motoneuron Excitability via Motor Endplate Acetylcholine Receptor Activation
Authors: Nakanishi Stan T. , Cope Timothy C. , Rich Mark M. , Carrasco Dario I. , Pinter Martin J.
Published: March 2005

Motoneuron populations possess a range of intrinsic excitability that plays an important role in establishing how motor units are recruited. The fact that this range collapses after axotomy and does not recover completely until after reinnervation occurs suggests that muscle innervation is needed to maintain or regulate adult motoneuron excitability, but the nature and identity of underlying mechanisms remain poorly understood. Here, we report the results of experiments in which we studied the effects on rat motoneuron excitability produced by manipulations of neuromuscular transmission and compared these with the effects of peripheral nerve axotomy. Inhibition of acetylcholine release from motor terminals for 5-6 d with botulinum toxin produced relatively minor changes in motoneuron excitability compared with the effect of axotomy. In contrast, the blockade of acetylcholine receptors with α-bungarotoxin over the same time interval produced changes in motoneuron excitability that were statistically equivalent to axotomy. Muscle fiber recordings showed that low levels of acetylcholine release persisted at motor terminals after botulinum toxin, but endplate currents were completely blocked for at least several hours after daily intramuscular injections of α-bungarotoxin. We conclude that the complete but transient blockade of endplate currents underlies the robust axotomy-like effects of α-bungarotoxin on motoneuron excitability, and the low level of acetylcholine release that remains after injections of botulinum toxin inhibits axotomy-like changes in motoneurons. The results suggest the existence of a retrograde signaling mechanism located at the motor endplate that enables expression of adult motoneuron excitability and depends on acetylcholine receptor activation for its normal operation.
Endothelial Nitric Oxide Synthase Regulates Brain-Derived Neurotrophic Factor Expression and Neurogenesis after Stroke in Mice
Authors: Chen Jieli , Zacharek Alex , Zhang Chunling , Jiang Hao , Li Yi , Roberts Cynthia , Lu Mei , Kapke Alissa , Chopp Michael
Published: March 2005

Here, we investigate the effects of endothelial nitric oxide synthase (eNOS) on angiogenesis, neurogenesis, neurotrophic factor expression, and neurological functional outcome after stroke. Wild-type and eNOS knock-out (eNOS-/-) mice were subjected to permanent occlusion of the right middle cerebral artery.eNOS-/-mice exhibited more severe neurological functional deficit after stroke than wild-type mice. Decreased subventricular zone (SVZ) progenitor cell proliferation and migration, measured using bromodeoxyuridine, Ki-67, nestin, and doublecortin immunostaining in the ischemic brain, and decreased angiogenesis, as demonstrated by reduced endothelial cell proliferation, vessel perimeter, and vascular density in the ischemic border, were evident ineNOS-/-mice compared with wild-type mice. eNOS-deficient mice also exhibited a reduced response to vascular endothelial growth factor (VEGF)-induced angiogenesis in a corneal assay. ELISAs showed thateNOS-/-mice have decreased brain-derived neurotrophic factor (BDNF) expression but not VEGF and basic fibroblast growth factor in the ischemic brain compared with wild-type mice. In addition, cultured SVZ neurosphere formation, proliferation, telomerase activity, and neurite outgrowth but not cell viability fromeNOS-/-mice were significantly reduced compared with wild-type mice. BDNF treatment of SVZ cells derived fromeNOS-/-mice restored the decreased neurosphere formation, proliferation, neurite outgrowth, and telomerase activity in culturedeNOS-/-SVZ neurospheres. SVZ explant cell migration also was significantly decreased ineNOS-/-mice compared with wild-type mice. These data indicate that eNOS is not only a downstream mediator for VEGF and angiogenesis but also regulates BDNF expression in the ischemic brain and influences progenitor cell proliferation, neuronal migration, and neurite outgrowth and affects functional recovery after stroke.
ets-2 Promotes the Activation of a Mitochondrial Death Pathway in Down's Syndrome Neurons
Authors: Helguera Pablo , Pelsman Alejandra , Pigino Gustavo , Wolvetang Ernst , Head Elizabeth , Busciglio Jorge
Published: March 2005

Down's syndrome (DS) is characterized by mental retardation and development of Alzheimer's disease (AD). Oxidative stress and mitochondrial dysfunction are both related to neurodegeneration in DS. Several genes in chromosome 21 have been linked to neuronal death, including the transcription factor ets-2. Cortical cultures derived from normal and DS fetal brains were used to study the role of ets-2 in DS neuronal degeneration. ets-2 was expressed in normal human cortical neurons (HCNs) and was markedly upregulated by oxidative stress. When overexpressed in normal HCNs, ets-2 induced a stereotyped sequence of apoptotic changes leading to neuronal death. DS HCNs exhibit intracellular oxidative stress and increased apoptosis after the first week in culture (Busciglio and Yankner, 1995). ets-2 levels were increased in DS HCNs, and, between 7 and 14 din vitro, DS HCNs showed increased bax, cytoplasmic translocation of cytochromecand apoptosis inducing factor, and active caspases 3 and 7, consistent with activation of an apoptotic mitochondrial death pathway. Degeneration of DS neurons was reduced by dominant-negative ets-2, suggesting that increased ets-2 expression promotes DS neuronal apoptosis. In the human brain, ets-2 expression was found in neurons and astrocytes. Strong ets-2 immunoreactivity was observed in DS/AD and sporadic AD brains associated with degenerative markers such as bax, intracellular Aβ, and hyperphosphorylated tau. Thus, in DS/AD and sporadic AD brains, converging pathological mechanisms leading to chronic oxidative stress and ets-2 upregulation in susceptible neurons may result in increased vulnerability by promoting the activation of a mitochondrial-dependent proapoptotic pathway of cell death.
Western Attractions
Authors: NICHOLS ROGER L.
Published: March 2005

North America,and in particular the United States, has fascinated Europeans as the place of the "exotic other " for at least the last two centuries. This article surveys American and European art, novels,radio programs, Western films, and television Westerns from the 1820s to the present. It posits that the presence of Indians, fictional Western heroes,gunmen,and a perceived general level of violence made frontier and Western America more colorful and exciting than similar circumstances and native people in other parts of the world. This resulted in a continuing interest in the fictional aspect of the American frontier and Western historical experiences.
In The Shadow Of Yung Wing
Authors: RHOADS EDWARD J. M.
Published: March 2005

The Chinese Educational Mission (CEM) was one of the �rst efforts at "self-strengthening," China's late nineteenth-century attempt at modernization. Beginning in 1872, the Qing government sent 120 boys to live and study in New England for extended periods. The mission was the brainchild of Yung Wing (1828-1912), known as a pioneering Chinese in America. This article contends that Zeng Laishun (ca. 1826-1895), the CEM's original interpreter, was no less a pioneer. It examines Zeng's education in Singapore, New Jersey, and New York; his early career as, successively, a missionary assistant, a businessman, and a teacher at a naval school in China; his concurrent roles as the English translator for the CEM in the United States and (with his family) as a cultural interpreter of China to New England's elite; and brie�y, following his return to China in 1874, his association with Li Hongzhang as his chief English secretary.
Wants, Wages, And Workers
Authors: BANKOFF GREG
Published: March 2005

A need for workers posed a dilemma for the new U.S. administration in the Philippines anxious to demonstrate its progressive intentions and distance itself from the compulsion that had characterized public works during the previous regime. Instead, it turned to the market to �nd both an ideologically acceptable and a practically realizable solution. Commencing with an investigation of extrafamilial work relations during the Spanish period, this article traces the nature and extent of the labor shortage at the turn of the twentieth century. It then discusses the important role of unions before evaluating government policy in the light of subsequent events. In one sense, the American Philippines was the �rst truly modern state in Southeast Asia, infused by the logic of capitalism and informed by market mechanisms.
Culture And Poverty
Authors: KRAINZ THOMAS A.
Published: March 2005

Scholars have increasingly focused on the ideological motivations for national Progressive Era welfare policies by examining a few eastern or midwestern cities; relief efforts in rural communities and the American West have been largely overlooked. What shaped local Progressive Era relief policies was not new social welfare ideas but, rather, local circumstances-economies, settlement patterns, environmental conditions, religious beliefs, kinship ties, philanthropic practices, and local of�cials' decisions. Because these circumstances varied from county to county, stark differences appear when examining local relief practices. Who received aid, assistance levels, durations on relief, and types of aid varied considerably between two rural Colorado counties, Costilla and Lincoln. Local circumstances also affected attempts to transform annuities and rations on the Ute Mountain Ute Indian Reservation into a form of poor relief. The decentralized nature of America's welfare state allowed these dramatic differences in relief practices to become a de�ning element of the Progressive Era.
Λέξις ηθική (ethical style) in book III of Aristotle'sRhetoric? The uses of ηθικόϛ in the aristotelian corpus.
Authors: Woerther Frédérique
Published: March 2005

Abstract In Aristotle's works, the adjective ηθικός has two principal meanings: it can, namely, refer to (1) whatever is relative to ήθος, or (2) whatever is capable of expressing ήθος. This latter sense is what the present study proposes initially to delineate, by endeavoring to evaluate precisely the nature and meaning of ήθος as it is implied in each use of the adjective. This analysis will permit a subsequent isolation of the of the particular senses illustrated in the three occurrences of ηθικός which appear in the passages of the Rhetoric devoted to the λέξις of oratory. (Rhet. III, 7, 1408 a 11, 1408 a 25, et III, 1413 b 10). In effect: (1) when the notion of λέξις ηθική involves the ήθος of the speaker, the semantic extension of this latter term exhibits certain divergences, not only with regard to the way it is characterized in the rest of the treatise, as in the definition of πίστις εν τώι ήθει τού λέγοντος, but also with regard to the doctrine in the Ethics; (2) the way in which Rhet. III, 12 conceives of υπόκρισις—with which λέξις ηθική has close and privileged associations—implies a traditional, non-Aristotelian conception of ήθος. Taking into accound the discordant character of the three above-mentioned instances provides a new resource for critical studies devoted to questions about the dating and unity of the Rhetoric.
Cicero as a Reporter of Aristotelian and Theophrastean Rhetorical Doctrine
Authors: Fortenbaugh William W.
Published: March 2005

Abstract This article is based on a general principle: the study of a fragmentary author should begin with a study of the sources. The particular subject is Cicero as a source for Theophrastus' rhetorical doctrine. The works On Invention, On the Orator andOrator are considered one after the other. The reliability of Cicero is tested by comparing what is said about Aristotle with what we read in the existingRhetoric. Grounds for caution will be found. In the case of Theophrastus, we shall discover that Cicero does have value as a source, but his value should not be overstated. The reports are often quite general and sometimes they involve Ciceronian additions.
Vives's De ratione dicendi: Structure, Innovations, Problems
Authors: Mack Peter
Published: March 2005

Abstract This paper presents a critical assessment of Vives's major rhetorical treatise, De ratione dicendi (1533). In terms of structure it shows that the first book is concerned with the linguistic basis of style, that the second deals with the qualities of style, the four aims of rhetoric, decorum and disposition and that the third presents guidance on composing ten genres of writing practised by humanists. The paper describes Vives's original contributions to the analysis of the linguistic basis of style, the qualities of style, emotional manipulation, decorum, and the composition of history and commentary. In assessing Vives's work it makes comparisons with rhetoric texts by Agricola, Erasmus, Melanchthon, and Ramus. It finds that Vives's reform of rhetoric is based in his encyclopaedic grasp of human learning but that this very encyclopaedism can cause weaknesses in his discussions of particular topics. De ratione dicendi tells us a great deal about Vives's perceptiveness and breadth of reading but, with only three sixteenth century editions, it was not a successful textbook.
Primary Erythromelalgia in a Child Responding to Intravenous Lidocaine and Oral Mexiletine Treatment
Authors: Nathan Aruna , Rose John B. , Guite Jessica W. , Hehir David , Milovcich Karen
Published: March 2005

Erythromelalgia is a rare, chronic, debilitating condition characterized by redness, warmth, and severe burning pain of the distal extremities. The feet are more commonly affected than the hands. Pain is precipitated by increases in temperature and by exercise. Patients often obtain relief by immersing the affected extremity in cold water. The pain is often refractory to treatment. For many patients, multiple pain medications have been useless in achieving complete relief of pain symptoms. Previous reports of erythromelalgia among adolescents indicated prolonged relief of pain with sodium nitroprusside infusions, epidural infusions of local anesthetics, or gabapentin treatment. We present a case of an 11-year-old, white, male child with primary erythromelalgia, whose initial symptoms started in his preschool years and whose childhood was marked by escalating episodes of pain with warmth and redness of his feet, precipitated especially by increases in temperature and by activity. All conventional pain management techniques had failed to relieve our patient of his symptoms, and he obtained some relief only by soaking his affected extremities in ice water. He had experienced minimal benefit from seeing a pain psychologist, who helped him develop techniques to cope with the pain. At the time of presentation, the patient's episodes of pain had increased to 15 to 20 per day, and there was evidence of chronic immersion injury to the skin of his feet. Before his most recent hospitalization, the pain had spread to involve his hands as well. The patient was overwhelmed with anxiety and could not participate in school or social activities at the time of admission. During his current hospitalization, he did show some therapeutic response to sodium nitroprusside infusion, which unfortunately had to be discontinued because of side effects and because his family desired to leave the ICU environment, which was stressful to the patient. He also had some response to lumbar epidural infusion of local anesthetics, which could not be continued because he found the motor blockade that accompanied his analgesia intolerable. However, intravenous lidocaine infusion, with subsequent transition to oral mexiletine therapy, proved very effective in reducing the frequency and severity of the pain episodes. The patient was discharged from the hospital with oral mexiletine therapy and has been monitored at the pain management clinic. He returned to and completed school, attended summer camp, and enjoys an active happy life. He walks without precipitating pain in his feet and sleeps 9 to 10 hours every night. He has needed to soak his feet on only 4 occasions in the 6 months since his discharge from the hospital. His quality of life has improved significantly. He has shown no evidence of liver toxicity, and his mexiletine levels have been stable.
Hypospadias in Washington State: Maternal Risk Factors and Prevalence Trends
Authors: Porter Michael P. , Faizan M. Khurram , Grady Richard W. , Mueller Beth A.
Published: March 2005

Objective. Maternal risk factors for hypospadias are poorly defined, and there is debate about temporal trends in hypospadias prevalence. We examined select maternal characteristics as possible risk factors for hypospadias among male offspring and evaluated yearly prevalence rates in Washington State.

Methods. We performed a population-based, case-control study using linked birth-hospital discharge data from Washington State for 1987–1997 and prevalence data for 1987–2002. All cases of hypospadias were identified on the basis of International Classification of Diseases, Ninth Revision, codes from the birth hospitalization (N = 2155). Five control subjects were randomly selected for each case subject from the remaining singleton births, frequency matched according to year of birth (N = 10775). Maternal and infant characteristics were ascertained from the birth certificate. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Yearly prevalence was determined by dividing the total number of hypospadias cases by the number of male singleton live births for each year.

Results. The risk of delivering an affected male infant increased with advancing maternal age; relative to women <20 years of age, those >40 years of age were at greatest risk (OR: 1.70; 95% CI: 1.17–2.48). Infants of nonwhite women were generally at decreased risk. Infants born to women with preexisting diabetes mellitus were at greater risk than those born to women without diabetes (OR: 2.18; 95% CI: 1.03–4.60); however, this was not observed for infants born to women with gestational diabetes. The birth prevalence of hypospadias in 2002 was 5.0 cases per 1000 male births, not significantly different from that in 1987.

Conclusion. Older maternal age, white race, and preexisting diabetes were associated with increased risk of hypospadias among male offspring. The prevalence of hypospadias in Washington State did not increase significantly between 1987 and 2002.
Homeostasis Model Assessment Is More Reliable Than the Fasting Glucose/Insulin Ratio and Quantitative Insulin Sensitivity Check Index for Assessing Insulin Resistance Among Obese Children and Adolescents
Authors: Keskin Mehmet , Kurtoglu Selim , Kendirci Mustafa , Atabek M. Emre , Yazici Cevat
Published: March 2005

Objective. Simple fasting methods to measure insulin resistance, such as the homeostasis model assessment (HOMA), fasting glucose/insulin ratio (FGIR), and quantitative insulin sensitivity check index (QUICKI) methods, have been widely promoted for adult studies but have not been evaluated formally among children and adolescents. The aim of this study was to compare the HOMA, FGIR, and QUICKI methods for measuring insulin resistance, expressed by oral glucose tolerance test (OGTT) results, among obese children and adolescents.

Methods. Fifty-seven pubertal obese children and adolescents (30 girls and 27 boys; mean age, 12.04 ± 2.90 years; mean BMI: 29.57 ± 5.53) participated in the study. All participants underwent an OGTT. Blood samples were obtained 0, 30, 60, 90, and 120 minutes after oral glucose administration for glucose and insulin measurements, and 2 separate groups were studied, according to the presence or absence of insulin resistance. HOMA, FGIR, and QUICKI methods were studied for validation of insulin resistance determined with the OGTT for these groups.

Results. The groups consisted of 25 obese children and adolescents with insulin resistance (14 girls and 11 boys; mean age: 12.88 ± 2.88 years; mean BMI: 31.29 ± 5.86) and 32 subjects without insulin resistance (16 girls and 16 boys; mean age: 11.38 ± 2.79 years; mean BMI: 28.23 ± 4.94). There were significant differences in the mean HOMA (6.06 ± 4.98 and 3.42 ± 3.14, respectively) and QUICKI (0.313 ± 0.004 and 0.339 ± 0.004, respectively) values between the 2 groups. Sensitivity and specificity calculations based on insulin resistance with receiver operating characteristic curve analysis indicated that HOMA had high sensitivity and specificity for measuring insulin resistance.

Conclusions. As a measure of insulin resistance among children and adolescents, HOMA is more reliable than FGIR and QUICKI. The present HOMA cutoff point for diagnosis of insulin resistance is 3.16. The HOMA cutoff point of >2.5 is valid for adults but not for adolescents.
Gödel, Tarski, Church, and The Liar
Authors: Serény György
Published: March 2005

The fact that Gödel's famous incompleteness theorem and the archetype of all logical paradoxes, that of the Liar, are related closely is, of course, not only well known, but is a part of the common knowledge of the community of logicians. Indeed, almost every more or less formal treatment of the theorem makes a reference to this connection. Gödel himself remarked in the paper announcing his celebrated result (cf. [7]):

The analogy between this result and Richard's antinomy leaps to the eye;

there is also a close relationship with the ‘liar’ antinomy, since … we are

… confronted with a proposition which asserts its own unprovability.

In the light of the fact that the existence of this connection is commonplace it is all the more surprising that very little can be learnt about its exact nature except perhaps that it is some kind of similarity or analogy. There is, however, a lot more to it than that. Indeed, as we shall try to show below, the general ideas underlying the three central theorems concerning internal limitations of formal deductive systems can be taken as different ways to resolve the Liar paradox. More precisely, it will turn out that an abstract formal variant of the Liar paradox, which can almost straightforwardly inferred from its original ordinary language version, is a possible common generalization of (both the syntactic and semantic versions of) Gödel's incompleteness theorem, the theorem of Tarski on the undefinability of truth, and that of Church concerning the undecidability of provability.
Local Initial Segments of The Turing Degrees
Authors: Kjos-Hanssen Bjørn
Published: March 2005

Recent results on initial segments of the Turing degrees are presented, and some conjectures about initial segments that have implications for the existence of nontrivial automorphisms of the Turing degrees are indicated.
From Foundations to Ludics
Authors: Girard Jean-Yves
Published: March 2005

Ludics [1] is a novel approach to logic—especially proof-theory. The present introduction emphasises foundational issues.

For ages, not a single disturbing idea in the area of “foundations”: the discussion is sort of ossified—as if everything had been said, as if all notions had taken their definite place, in a big cemetery of ideas. One can still refresh the flowers or regild the stone, e.g., prove technicalities, sometimes non-trivial; but the real debate is still: this paper begins with an autopsy, the autopsy of the foundational project.

Up to say 1900, the realist/dualist approach to science was dominant; during the last century some domains like physics evolved so as to become completely anti-realist; but this evolution hardly concerned logic.

By the turn of the XXth century mathematics was jeopardised by paradoxes, the most famous of them being due to Russell. Hilbert's reaction was to focus on consistency. But the reduction of paradoxes—and therefore of foundations—to solely the antinomies is highly questionable: indeed, the typical paradoxical artifacts are secret sharers, objects satisfying the formal definitions but far astray from the intended meaning, typically the Peano “curve” which contradicts our perception of dimension. Fortunately, topology has been able to show that dimension m is not the same as dimension n … but just for a second, forget this and imagine consistent mathematics in which balls in any dimension are homeomorphic: what a disaster! This exclusive focus on consistency—not to speak of the strategic failure of the Programme—should explain why logic, especially foundations lost contact with other sciences during last century.
Symmetry and Interactivity in Programming
Authors: Curien P.-L.
Published: March 2005

We recall some of the early occurrences of the notions of interactivity and symmetry in the operational and denotational semantics of programming languages. We suggest some connections with ludics.
Two Spaces Looking for a Geometer
Authors: Parisi Giorgio
Published: March 2005

In this talk I will introduce two spaces: the first space is the usual n-dimensional vector space with the unusual feature that n is a non-integer; the second space is composed of the linear matrices acting on the previous space (physicists are particularly interested in studying the limit as n goes to zero). These two spaces are not known to most mathematicians, but they are widely used by physicists. It is possible that, by extending the notion of space, they can become well defined mathematical objects.
Model Theory: Geometrical and Set-Theoretic Aspects and Prospects
Authors: Macintyre Angus
Published: March 2005

I see model theory as becoming increasingly detached from set theory, and the Tarskian notion of set-theoretic model being no longer central to model theory. In much of modern mathematics, the set-theoretic component is of minor interest, and basic notions are geometric or category-theoretic. In algebraic geometry, schemes or algebraic spaces are the basic notions, with the older “sets of points in affine or projective space” no more than restrictive special cases. The basic notions may be given sheaf-theoretically, or functorially. To understand in depth the historically important affine cases, one does best to work with more general schemes. The resulting relativization and “transfer of structure” is incomparably more flexible and powerful than anything yet known in “set-theoretic model theory”.

It seems to me now uncontroversial to see the fine structure of definitions as becoming the central concern of model theory, to the extent that one can easily imagine the subject being called “Definability Theory” in the near future.

Tarski's set-theoretic foundational formulations are still favoured by the majority of model-theorists, and evolution towards a more suggestive language has been perplexingly slow. None of the main texts uses in any nontrivial way the language of category theory, far less sheaf theory or topos theory. Given that the most notable interactions of model theory with geometry are in areas of geometry where the language of sheaves is almost indispensable (to the geometers), this is a curious situation, and I find it hard to imagine that it will not change soon, and rapidly.
Foundations and Applications: Axiomatization and Education
Authors: Lawvere F. William
Published: March 2005

Foundations and Applications depend ultimately for their existence on each other. The main links between them are education and the axiomatic method. Those links can be strengthened with the help of a categorical method which was concentrated forty years ago by Cartier, Grothendieck, Isbell, Kan, and Yoneda. I extended that method to extract some essential features of the category of categories in 1965, and I apply it here in section 3 to sketch a similar foundation within the smooth categories which provide the setting for the mathematics of change. The possibility that other methods may be needed to clarify a contradiction introduced by Cantor, now embedded in mathematical practice, is discussed in section 5.
Differential Calculus and Nilpotent Real Numbers
Authors: Kock Anders
Published: March 2005

Do there exist real numbers d with d2 = 0 (besides d = 0, of course)? The question is formulated provocatively, to stress a formalist view about existence: existence is consistency, or better, coherence.

Also, the provocation is meant to challenge the monopoly which the number system, invented by Dedekind et al., is claiming for itself as THE model of the geometric line. The Dedekind approach may be termed “arithmetization of geometry”.

We know that one may construct a number system out of synthetic geometry, as Euclid and followers did (completed in Hilbert's Grundlagen der Geometrie, [2, Chapter 3]): “geometrization of arithmetic”. (Picking two distinct points on the geometric line, geometric constructions in an ambient Euclidean plane provide structure of a commutative ring on the line, with the two chosen points as 0 and 1).

Starting from the geometric side, nilpotent elements are somewhat reasonable, although Euclid excluded them. The sophist Protagoras presented a picture of a circle and a tangent line; the apparent little line segment D which tangent and circle have in common, are, by Pythagoras' Theorem, precisely the points, whose abscissae d (measured along the tangent) have d2 = 0. Protagoras wanted to use this argument for destructive reasons: to refute the science of geometry.

A couple of millenia later, the Danish geometer Hjelmslev revived the Protagoras picture. His aim was more positive: he wanted to describe Nature as it was. According to him (or extrapolating his position), the Real Line, the Line of Sensual Reality, had many nilpotent infinitesimals, which we can see with our naked eyes.
The Empty Set, The Singleton, and the Ordered Pair
Authors: Kanamori Akihiro
Published: March 2005

For the modern set theorist the empty set Ø, the singleton {a}, and the ordered pair 〈x, y〉 are at the beginning of the systematic, axiomatic development of set theory, both as a field of mathematics and as a unifying framework for ongoing mathematics. These notions are the simplest building locks in the abstract, generative conception of sets advanced by the initial axiomatization of Ernst Zermelo [1908a] and are quickly assimilated long before the complexities of Power Set, Replacement, and Choice are broached in the formal elaboration of the ‘set of’f {} operation. So it is surprising that, while these notions are unproblematic today, they were once sources of considerable concern and confusion among leading pioneers of mathematical logic like Frege, Russell, Dedekind, and Peano. In the development of modern mathematical logic out of the turbulence of 19th century logic, the emergence of the empty set, the singleton, and the ordered pair as clear and elementary set-theoretic concepts serves as amotif that reflects and illuminates larger and more significant developments in mathematical logic: the shift from the intensional to the extensional viewpoint, the development of type distinctions, the logical vs. the iterative conception of set, and the emergence of various concepts and principles as distinctively set-theoretic rather than purely logical. Here there is a loose analogy with Tarski's recursive definition of truth for formal languages: The mathematical interest lies mainly in the procedure of recursion and the attendant formal semantics in model theory, whereas the philosophical interest lies mainly in the basis of the recursion, truth and meaning at the level of basic predication. Circling back to the beginning, we shall see how central the empty set, the singleton, and the ordered pair were, after all.
Computable and Continuous Partial Homomorphisms on Metric Partial Algebras
Authors: Stoltenberg-Hansen Viggo , Tucker John V.
Published: March 2005

We analyse the connection between the computability and continuity of functions in the case of homomorphisms between topological algebraic structures. Inspired by the Pour-El and Richards equivalence theorem between computability and boundedness for closed linear operators on Banach spaces, we study the rather general situation of partial homomorphisms between metric partial universal algebras. First, we develop a set of basic notions and results that reveal some of the delicate algebraic, topological and effective properties of partial algebras. Our main computability concepts are based on numerations and include those of effective metric partial algebras and effective partial homomorphisms. We prove a general equivalence theorem that includes a version of the Pour-El and Richards Theorem, and has other applications. Finally, the Pour-El and Richards axioms for computable sequence structures on Banach spaces are generalised to computable partial sequence structures on metric algebras, and we prove their equivalence with our computability model based on numerations.
Survey of the Steinhaus Tiling Problem
Authors: Jackson Steve , Mauldin R. Daniel
Published: March 2005

We survey some results and problems arising from a classic problem of Steinhaus: Is there a subset S of ℝ2 such that each isometric copy of ℤ2 (the lattice points in the plane) meets S in exactly one point.
A Universal Approach to Self-Referential Paradoxes, Incompleteness and Fixed Points
Authors: Yanofsky Noson S.
Published: March 2005

Following F. William Lawvere, we show that many self-referential paradoxes, incompleteness theorems and fixed point theorems fall out of the same simple scheme. We demonstrate these similarities by showing how this simple scheme encompasses the semantic paradoxes, and how they arise as diagonal arguments and fixed point theorems in logic, computability theory, complexity theory and formal language theory.
Finite Conformal Hypergraph Covers and Gaifman Cliques in Finite Structures
Authors: Hodkinson Ian , Otto Martin
Published: March 2005

We provide a canonical construction of conformal covers for finite hypergraphs and present two immediate applications to the finite model theory of relational structures. In the setting of relational structures, conformal covers serve to construct guarded bisimilar companion structures that avoid all incidental Gaifman cliques—thus serving as a partial analogue in finite model theory for the usually infinite guarded unravellings. In hypergraph theoretic terms, we show that every finite hypergraph admits a bisimilar cover by a finite conformal hypergraph. In terms of relational structures, we show that every finite relational structure admits a guarded bisimilar cover by a finite structure whose Gaifman cliques are guarded. One of our applications answers an open question about a clique constrained strengthening of the extension property for partial automorphisms (EPPA) of Hrushovski, Herwig and Lascar. A second application provides an alternative proof of the finite model property (FMP) for the clique guarded fragment of first-order logic CGF, by reducing (finite) satisfiability in CGF to (finite) satisfiability in the guarded fragment, GF.