bluuebunny/crossref_metadata_2025 huggingface dataset:
The Modified Sudden Death Test: Planning Life Tests with a Limited Number of Test Positions
Authors: Pascual FG , Meeker WQ
Published: May 2009

We present modified sudden death test (MSDT) plans to address the problem of limited testing positions in life tests. A single MSDT involves testing k specimens simultaneously until the rth failure. The traditional sudden death test (SDT) is a special case when r=1. The complete MSDT plan consists of g single MSDTs run in sequence. When r>1, there can be up to r−1 idle test positions at any time. We propose testing “standby” specimens in the idle positions and use simulation to gage the improvement over the basic MSDT plan. We evaluate test plans with respect to the asymptotic variance of maximum likelihood estimators of quantities of interest, total experiment duration, and sample size. In contrast to traditional experimental plans, shorter total testing time and smaller sample sizes are possible under MSDT plans.
Qualitative Assessment of Failure in Bolted Connections: Maximum Stress Criterion
Authors: Patton-Mallory M , Pellicane PJ , Smith FW
Published: May 2009

This paper presents information regarding the distribution of critical stresses and regions where failure is likely to initiate in single bolt wood connections loaded in tension. Predicted stresses are the results of a three-dimensional numerical analysis of a connection consisting of a single steel pin and a wood member with a hole. Stresses of particular interest are: parallel-to-grain compression and shear and perpendicular-to-grain tension. Failure location is determined by considering the regions of the member where the material capacity is exceeded in at least one of the three aforementioned stresses. No stress interaction is assumed in this analysis.

A recently developed and verified three-dimensional (3-D) finite element model was used in this study. Important features of this model include a trilinear constitutive model of the nonlinear behavior of wood and a mechanism to describe the contact between the pin and the hole with changing connection load. The connection geometries studied included a single ratio of end distance to pin diameter (e∕d=4) and three bolt aspect ratios (length of bolt in wood member/bolt diameter) (l∕d=2,5,and7).

Stress contours are illustrated on the 3-D wood member surface, on the contact surface, and on planes of symmetry. Pin and wood deformations are also illustrated.

The results show that for connections with an (l∕d)=2, stresses are nearly uniform through the wood member thickness with negligible pin yielding. For connections with the larger bolt aspect ratios, considerably more pin bending and yielding is predicted with nonuniform stress distributions through the member thickness. The maximum stress failure criterion is found to be useful for comparing numerically predicted stress distributions to failure modes observed experimentally. By making these comparisons, it is possible to make qualitative interpretations of the critical stress states to indicate the regions where failure is likely to occur.
Qualitative Assessment of Failure in Bolted Connections: Tsai-Wu Criterion
Authors: Patton-Mallory M , Pellicane PJ , Smith FW
Published: May 2009

In a companion paper, a characterization is presented of stress fields in a single-shear bolted connection subjected to tension loading. Numerous stress contours are presented that illustrate the magnitude of the parallel-to-grain compression and shear stresses, as well as the perpendicular-to-grain tension stresses. In addition, regions of potential failure in the selected specimens are identified based on a maximum stress failure criterion.

The work presented in this paper represents additional efforts to identify the effect of stress interactions on the strength of the previously mentioned connections. The Tsai-Wu criterion, quantified by its failure index, is used as the tool to identify stress interactions between the aforementioned stress components. Connection geometries similar to those discussed in the companion paper [end distance/bolt diameter (e∕d)=4; and length of bolt in main member/bolt diameter (aspect ratio) (l∕d)=2,5,and7] are studied. In addition, several other geometries are discussed that illustrate the effects of changing aspect ratio and end distance.

A number of significant findings are reached in this study. As is the case in the companion study, all connections with (l∕d)=2 have nearly uniform distributions of the Tsai-Wu failure index (FI) through the specimen thickness. No significant pin bending is associated with this geometry. Connections with l∕d>4 have a failure mode (interpreted from the numerical model) that includes substantial pin bending due to steel yielding, wood crushing, and localized cracking.
Wnt5a Induces Simultaneous Cortical Axon Outgrowth and Repulsive Axon Guidance through Distinct Signaling Mechanisms
Authors: Li Li , Hutchins B. Ian , Kalil Katherine
Published: May 2009

Wnts are morphogens that also function as axon guidance molecules.In vivoWnt5a gradients via Ryk receptors were found to repel cortical axons into developing callosal and corticospinal pathways. Here, using dissociated cortical cultures, we found that bath-applied Wnt5a increased axon outgrowth. In turning assays, Wnt5a gradients simultaneously increased axon outgrowth and induced repulsive turning, a potential mechanism for propelling cortical axonsin vivo. We found that axon outgrowth is mediated by Ryk, whereas axon repulsion requires both Ryk and Frizzled receptors. Both receptors mediate Wnt-evoked fluctuations in intracellular calcium, which is required for increased axon outgrowth and repulsion by Wnt5a. However, whereas increased axon outgrowth involves calcium release from stores through IP3 receptors as well as calcium influx through TRP channels, axon repulsion is mediated by TRP channels without involvement of IP3 receptors. These results reveal distinct signaling mechanisms underlying Wnt5a-induced axon outgrowth and repulsive guidance.
The Basal Forebrain Cholinergic System Is Required Specifically for Behaviorally Mediated Cortical Map Plasticity
Authors: Ramanathan Dhakshin , Tuszynski Mark H. , Conner James M.
Published: May 2009

The basal forebrain cholinergic system has been implicated in the reorganization of adult cortical sensory and motor representations under many, but not all, experimental conditions. It is still not fully understood which types of plasticity require the cholinergic system and which do not. In this study, we examine the hypothesis that the basal forebrain cholinergic system is required for eliciting plasticity associated with complex cognitive processing (e.g., behavioral experiences that drive cortical reorganization) but is not required for plasticity mediated under behaviorally independent conditions. We used established experimental manipulations to elicit two distinct forms of plasticity within the motor cortex: facial nerve transections evoke reorganization of cortical motor representations independent of behavioral experience, and skilled forelimb training induces behaviorally dependent expansion of forelimb motor representations. In animals that underwent skilled forelimb training in conjunction with a facial nerve lesion, cholinergic mechanisms were required for mediating the behaviorally dependent plasticity associated with the skilled motor training but were not necessary for mediating plasticity associated with the facial nerve transection. These results dissociate the contribution of cholinergic mechanisms to distinct forms of cortical plasticity and support the hypothesis that the forebrain cholinergic system is selectively required for modulating complex forms of cortical plasticity driven by behavioral experience.
Response Disengagement on a Spatial Self-Ordered Sequencing Task: Effects of Regionally Selective Excitotoxic Lesions and Serotonin Depletion within the Prefrontal Cortex
Authors: Walker Susannah C. , Robbins Trevor W. , Roberts Angela C.
Published: May 2009

Prefrontal cortex (PFC) is critical for self-ordered response sequencing. Patients with frontal lobe damage are impaired on response sequencing tasks, and increased blood flow has been reported in ventrolateral and dorsolateral PFC in subjects performing such tasks. Previously, we have shown that large excitotoxic lesions of the lateral PFC (LPFC) and orbitofrontal cortex FC (OFC), but not global prefrontal dopamine depletion, markedly impaired marmoset performance on a spatial self-ordered sequencing task (SSOST). To determine whether LPFC or OFC was responsible for the previously observed impairments and whether the underlying neural mechanism was modulated by serotonin, the present study compared the effects of selective LPFC and OFC excitotoxic lesions and 5,7-DHT-induced PFC serotonin depletions in marmosets on SSOST performance. Severe and long-lasting impairments in SSOST performance, including robust perseverative responding, followed LPFC but not OFC lesions. The deficit was ameliorated by task manipulations that precluded perseveration. Depletions of serotonin within LPFC and OFC had no effect, despite impairing performance on a visual discrimination reversal task, thus providing further evidence for differential monaminergic regulation of prefrontal function. In the light of the proposed attentional control functions of ventrolateral PFC and the failure of LPFC-lesioned animals to disengage from the immediately preceding response, it is proposed that this deficit may be due to a failure to attend to and register that a response has been made and thus should not be repeated. However, 5-HT does not appear to be implicated in this response inhibitory capacity.
A Genetically Mediated Bias in Decision Making Driven by Failure of Amygdala Control
Authors: Roiser Jonathan P. , de Martino Benedetto , Tan Geoffrey C. Y. , Kumaran Dharshan , Seymour Ben , Wood Nicholas W. , Dolan Raymond J.
Published: May 2009

Genetic variation at the serotonin transporter-linked polymorphic region (5-HTTLPR) is associated with altered amygdala reactivity and lack of prefrontal regulatory control. Similar regions mediate decision-making biases driven by contextual cues and ambiguity, for example the “framing effect.” We hypothesized that individuals hemozygous for the short (s) allele at the 5-HTTLPR would be more susceptible to framing. Participants, selected as homozygous for either the long (la) or s allele, performed a decision-making task where they made choices between receiving an amount of money for certain and taking a gamble. A strong bias was evident toward choosing the certain option when the option was phrased in terms of gains and toward gambling when the decision was phrased in terms of losses (the frame effect). Critically, this bias was significantly greater in the ss group compared with the lala group. In simultaneously acquired functional magnetic resonance imaging data, the ss group showed greater amygdala during choices made in accord, compared with those made counter to the frame, an effect not seen in the lala group. These differences were also mirrored by differences in anterior cingulate–amygdala coupling between the genotype groups during decision making. Specifically, lala participants showed increased coupling during choices made counter to, relative to those made in accord with, the frame, with no such effect evident in ss participants. These data suggest that genetically mediated differences in prefrontal–amygdala interactions underpin interindividual differences in economic decision making.
Cystatin B Deficiency Sensitizes Neurons to Oxidative Stress in Progressive Myoclonus Epilepsy, EPM1
Authors: Lehtinen Maria K. , Tegelberg Saara , Schipper Hyman , Su Haixiang , Zukor Hillel , Manninen Otto , Kopra Outi , Joensuu Tarja , Hakala Paula , Bonni Azad , Lehesjoki Anna-Elina
Published: May 2009

The progressive myoclonus epilepsies, featuring the triad of myoclonus, seizures, and ataxia, comprise a large group of inherited neurodegenerative diseases that remain poorly understood and refractory to treatment. TheCystatin Bgene is mutated in one of the most common forms of progressive myoclonus epilepsy, Unverricht–Lundborg disease (EPM1).Cystatin Bknockout in a mouse model of EPM1 triggers progressive degeneration of cerebellar granule neurons. Here, we report impaired redox homeostasis as a key mechanism by which Cystatin B deficiency triggers neurodegeneration. Oxidative stress induces the expression of Cystatin B in cerebellar granule neurons, and EPM1 patient-linked mutation of theCystatin Bgene promoter impairs oxidative stress induction ofCystatin Btranscription. Importantly,Cystatin Bknockout or knockdown sensitizes cerebellar granule neurons to oxidative stress-induced cell death. The Cystatin B deficiency-induced predisposition to oxidative stress in neurons is mediated by the lysosomal protease Cathepsin B. We uncover evidence of oxidative damage, reflected by depletion of antioxidants and increased lipid peroxidation, in the cerebellum ofCystatin Bknock-out micein vivo. Collectively, our findings define a pathophysiological mechanism in EPM1, whereby Cystatin B deficiency couples oxidative stress to neuronal death and degeneration, and may thus provide the basis for novel treatment approaches for the progressive myoclonus epilepsies.
Photostimulation of Retrotrapezoid Nucleus Phox2b-Expressing NeuronsIn VivoProduces Long-Lasting Activation of Breathing in Rats
Authors: Abbott Stephen B. G. , Stornetta Ruth L. , Fortuna Michal G. , Depuy Seth D. , West Gavin H. , Harris Thurl E. , Guyenet Patrice G.
Published: May 2009

The retrotrapezoid “nucleus” (RTN), located in the rostral ventrolateral medullary reticular formation, contains a bilateral cluster of ∼1000 glutamatergic noncatecholaminergic Phox2b-expressing propriobulbar neurons that are activated by CO2in vivoand by acidificationin vitro. These cells are thought to function as central respiratory chemoreceptors, but this theory still lacks a crucial piece of evidence, namely that stimulating these particular neurons selectivelyin vivoincreases breathing. The present study performed in anesthetized rats seeks to test whether this expectation is correct. We injected into the left RTN a lentivirus that expresses the light-activated cationic channel ChR2 (channelrhodopsin-2) (H134R mutation; fused to the fluorescent protein mCherry) under the control of the Phox2-responsive promoter PRSx8. Transgene expression was restricted to 423 ± 38 Phox2b-expressing neurons per rat consisting of noncatecholaminergic and C1 adrenergic neurons (3:2 ratio). Photostimulation delivered to the RTN regionin vivovia a fiberoptic activated the CO2-sensitive neurons vigorously, produced a long-lasting (t1/2= 11 s) increase in phrenic nerve activity, and caused a small and short-lasting cardiovascular stimulation. Selective lesions of the C1 cells eliminated the cardiovascular response but left the respiratory stimulation intact. In rats with C1 cell lesions, the mCherry-labeled axon terminals originating from the transfected noncatecholaminergic neurons were present exclusively in the lower brainstem regions that contain the respiratory pattern generator. These results provide strong evidence that the Phox2b-expressing noncatecholaminergic neurons of the RTN region function as central respiratory chemoreceptors.
Identification of Flap Structure-Specific Endonuclease 1 as a Factor Involved in Long-Term Memory Formation of Aversive Learning
Authors: Saavedra-Rodríguez Lorena , Vázquez Adrinel , Ortiz-Zuazaga Humberto G. , Chorna Nataliya E. , González Fernando A. , Andrés Lissette , Rodríguez Karen , Ramírez Fernando , Rodríguez Alan , de Ortiz Sandra Peña
Published: May 2009

We previously proposed that DNA recombination/repair processes play a role in memory formation. Here, we examined the possible role of thefen-1gene, encoding a flap structure-specific endonuclease, in memory consolidation of conditioned taste aversion (CTA). Quantitative real-time PCR showed that amygdalarfen-1mRNA induction was associated to the central processing of the illness experience related to CTA and to CTA itself, but not to the central processing resulting from the presentation of a novel flavor. CTA also increased expression of the Fen-1 protein in the amygdala, but not the insular cortex. In addition, double immunofluorescence analyses showed that amygdalar Fen-1 expression is mostly localized within neurons. Importantly, functional studies demonstrated that amygdalar antisense knockdown offen-1expression impaired consolidation, but not short-term memory, of CTA. Overall, these studies define thefen-1endonuclease as a new DNA recombination/repair factor involved in the formation of long-term memories.
Dopaminergic Response to Drug Words in Cocaine Addiction
Authors: Goldstein Rita Z. , Tomasi Dardo , Alia-Klein Nelly , Honorio Carrillo Jean , Maloney Thomas , Woicik Patricia A. , Wang Ruiliang , Telang Frank , Volkow Nora D.
Published: May 2009

When exposed to drug conditioned cues (stimuli associated with the drug), addicted individuals experience an intense desire for the drug, which is associated with increased dopamine cell firing. We hypothesized that drug-related words can trigger activation in the mesencephalon, where dopaminergic cells are located. During functional magnetic resonance imaging (fMRI), 15 individuals with cocaine use disorders and 15 demographically matched healthy control subjects pressed buttons for color of drug-related versus neutral words. Results showed that the drug words, but not neutral words, activated the mesencephalon in the cocaine users only. Further, in the cocaine users only, these increased drug-related mesencephalic responses were associated with enhanced verbal fluency specifically for drug words. Our results for the first time demonstrate fMRI response to drug words in cocaine-addicted individuals in mesencephalic regions as possibly associated with dopaminergic mechanisms and with conditioning to language (in this case drug words). The correlation between the brief verbal fluency test, which can be easily administered (crucial for clinical studies), and fMRI cue reactivity could be used as a biomarker of neurobiological changes in addiction.
Acquisition of a Simple Motor Skill: Task-Dependent Adaptation Plus Long-Term Change in the Human Soleus H-Reflex
Authors: Thompson Aiko K. , Chen Xiang Yang , Wolpaw Jonathan R.
Published: May 2009

Activity-dependent plasticity occurs throughout the CNS. However, investigations of skill acquisition usually focus on cortex. To expand the focus, we analyzed in humans the development of operantly conditioned H-reflex change, a simple motor skill that develops gradually and involves plasticity in both the brain and the spinal cord. Each person completed 6 baseline and 24 conditioning sessions over 10 weeks. In each conditioning session, the soleus H-reflex was measured while the subject was or was not asked to increase (HRup subjects) or decrease (HRdown subjects) it. When the subject was asked to change H-reflex size, immediate visual feedback indicated whether a size criterion had been satisfied. Over the 24 conditioning sessions, H-reflex size gradually increased in six of eight HRup subjects and decreased in eight of nine HRdown subjects, resulting in final sizes of 140 ± 12 and 69 ± 6% of baseline size, respectively. The final H-reflex change was the sum of within-session (i.e., task-dependent) adaptation and across-session (i.e., long-term) change. Task-dependent adaptation appeared within four to six sessions and persisted thereafter, averaging +13% in HRup subjects and −15% in HRdown subjects. In contrast, long-term change began after 10 sessions and increased gradually thereafter, reaching +27% in HRup subjects and −16% in HRdown subjects. Thus, the acquisition of H-reflex conditioning consists of two phenomena, task-dependent adaptation and long-term change, that together constitute the new motor skill. In combination with previous data, this new finding further elucidates the interaction of plasticity in brain and spinal cord that underlies the acquisition and maintenance of motor skills.
The Effect of Microsaccades on the Correlation between Neural Activity and Behavior in Middle Temporal, Ventral Intraparietal, and Lateral Intraparietal Areas
Authors: Herrington Todd M. , Masse Nicolas Y. , Hachmeh Karim J. , Smith Jackson E. T. , Assad John A. , Cook Erik P.
Published: May 2009

It is widely reported that the activity of single neurons in visual cortex is correlated with the perceptual decision of the subject. The strength of this correlation has implications for the neuronal populations generating the percepts. Here we asked whether microsaccades, which are small, involuntary eye movements, contribute to the correlation between neural activity and behavior. We analyzed data from three different visual detection experiments, with neural recordings from the middle temporal (MT), lateral intraparietal (LIP), and ventral intraparietal (VIP) areas. All three experiments used random dot motion stimuli, with the animals required to detect a transient or sustained change in the speed or strength of motion. We found that microsaccades suppressed neural activity and inhibited detection of the motion stimulus, contributing to the correlation between neural activity and detection behavior. Microsaccades accounted for as much as 19% of the correlation for area MT, 21% for area LIP, and 17% for VIP. While microsaccades only explain part of the correlation between neural activity and behavior, their effect has implications when considering the neuronal populations underlying perceptual decisions.
Molecular Basis of the Interactions of the Nogo-66 Receptor and Its Homolog NgR2 with Myelin-Associated Glycoprotein: Development of NgROMNI-Fc, a Novel Antagonist of CNS Myelin Inhibition
Authors: Robak Laurie A. , Venkatesh Karthik , Lee Hakjoo , Raiker Stephen J. , Duan Yuntao , Lee-Osbourne Jane , Hofer Thomas , Mage Rose G. , Rader Christoph , Giger Roman J.
Published: May 2009

Myelin-associated glycoprotein (MAG) is a sialic acid-binding Ig-family lectin that functions in neuronal growth inhibition and stabilization of axon–glia interactions. The ectodomain of MAG is comprised of five Ig-like domains and uses neuronal cell-type-specific mechanisms to signal growth inhibition. We show that the first three Ig-like domains of MAG bind with high affinity and in a sialic acid-dependent manner to the Nogo-66 receptor-1 (NgR1) and its homolog NgR2. Domains Ig3–Ig5 of MAG are sufficient to inhibit neurite outgrowth but fail to associate with NgR1 or NgR2. Nogo receptors are sialoglycoproteins comprised of 8.5 canonical leucine-rich repeats (LRR) flanked by LRR N-terminal (NT) and C-terminal (CT)-cap domains. The LRR cluster is connected through a stalk region to a membrane lipid anchor. The CT-cap domain and stalk region of NgR2, but not NgR1, are sufficient for MAG binding, and when expressed in neurons, exhibit constitutive growth inhibitory activity. The LRR cluster of NgR1 supports binding of Nogo-66, OMgp, and MAG. Deletion of disulfide loop Cys309–Cys336of NgR1 selectively increases its affinity for Nogo-66 and OMgp. A chimeric Nogo receptor variant (NgROMNI) in which Cys309–Cys336is deleted and followed by a 13 aa MAG-binding motif of the NgR2 stalk, shows superior binding of OMgp, Nogo-66, and MAG compared with wild-type NgR1 or NgR2. Soluble NgROMNI(NgROMNI-Fc) binds strongly to membrane-bound inhibitors and promotes neurite outgrowth on both MAG and CNS myelin substrates. Thus, NgROMNI-Fc may offer therapeutic opportunities following nervous system injury or disease where myelin inhibits neuronal regeneration.
The Anatomy of Object Recognition—Visual Form Agnosia Caused by Medial Occipitotemporal Stroke
Authors: Karnath Hans-Otto , Rüter Johannes , Mandler André , Himmelbach Marc
Published: May 2009

The influential model on visual information processing by Milner and Goodale (1995) has suggested a dissociation between action- and perception-related processing in a dorsal versus ventral stream projection. It was inspired substantially by the observation of a double dissociation of disturbed visual action versus perception in patients with optic ataxia on the one hand and patients with visual form agnosia (VFA) on the other. Unfortunately, almost all cases with VFA reported so far suffered from inhalational intoxication, the majority with carbon monoxide (CO). Since CO induces a diffuse and widespread pattern of neuronal and white matter damage throughout the whole brain, precise conclusions from these patients with VFA on the selective role of ventral stream structures for shape and orientation perception were difficult. Here, we report patient J.S., who demonstrated VFA after a well circumscribed brain lesion due to stroke etiology. Like the famous patient D.F. with VFA after CO intoxication studied by Milner, Goodale, and coworkers (Goodale et al., 1991, 1994; Milner et al., 1991; Servos et al., 1995; Mon-Williams et al., 2001a,b; Wann et al., 2001; Westwood et al., 2002; McIntosh et al., 2004; Schenk and Milner, 2006), J.S. showed an obvious dissociation between disturbed visual perception of shape and orientation information on the one side and preserved visuomotor abilities based on the same information on the other. In both hemispheres, damage primarily affected the fusiform and the lingual gyri as well as the adjacent posterior cingulate gyrus. We conclude that these medial structures of the ventral occipitotemporal cortex are integral for the normal flow of shape and of contour information into the ventral stream system allowing to recognize objects.
Massage Accelerates Brain Development and the Maturation of Visual Function
Authors: Guzzetta Andrea , Baldini Sara , Bancale Ada , Baroncelli Laura , Ciucci Francesca , Ghirri Paolo , Putignano Elena , Sale Alessandro , Viegi Alessandro , Berardi Nicoletta , Boldrini Antonio , Cioni Giovanni , Maffei Lamberto
Published: May 2009

Environmental enrichment (EE) was shown recently to accelerate brain development in rodents. Increased levels of maternal care, and particularly tactile stimulation through licking and grooming, may represent a key component in the early phases of EE. We hypothesized that enriching the environment in terms of body massage may thus accelerate brain development in infants. We explored the effects of body massage in preterm infants and found that massage accelerates the maturation of electroencephalographic activity and of visual function, in particular visual acuity. In massaged infants, we found higher levels of blood IGF-1. Massage accelerated the maturation of visual function also in rat pups and increased the level of IGF-1 in the cortex. Antagonizing IGF-1 action by means of systemic injections of the IGF-1 antagonist JB1 blocked the effects of massage in rat pups. These results demonstrate that massage has an influence on brain development and in particular on visual development and suggest that its effects are mediated by specific endogenous factors such as IGF-1.
X11-Like Protein Deficiency Is Associated with Impaired Conflict Resolution in Mice
Authors: Sano Yoshitake , Ornthanalai Veravej G. , Yamada Kazuyuki , Homma Chihiro , Suzuki Hitomi , Suzuki Toshiharu , Murphy Niall P. , Itohara Shigeyoshi
Published: May 2009

Understanding how emotion is generated, how conflicting emotions are regulated, and how emotional states relate to sophisticated behaviors is a crucial challenge in brain research. Model animals showing selective emotion-related phenotypes are highly useful for examining these issues. Here, we describe a novel mouse model that withdraws in approach-avoidance conflicts. X11-like (X11L)/Mint2 is a neuronal adapter protein with multiple protein-protein interaction domains that interacts with several proteins involved in modulating neuronal activity. X11L-knock-out (KO) mice were subordinate under competitive feeding conditions. X11L-KO mice lost significantly more weight than cohoused wild-type mice without signs of decreased motivation to eat or physical weakness. In a resident-intruder test, X11L-KO mice showed decreased intruder exploration behavior. Moreover, X11L-KO mice displayed decreased marble-burying, digging and burrowing behaviors, indicating aberrant ethological responses to attractive stimuli. In contrast, X11L-KO mice were indistinguishable from wild-type mice in the open field, elevated plus maze, and light/dark transition tests, which are often used to assess anxiety-like behavior. Neurochemical analysis revealed a monoamine imbalance in several forebrain regions. The defective ethological responses and social behaviors in X11L-KO mice were rescued by the expression of X11L under aCamk2apromoter using the Tet-OFF system during development. These findings suggest that X11L is involved in the development of neuronal circuits that contribute to conflict resolution.
Calpain-Mediated N-Cadherin Proteolytic Processing in Brain Injury
Authors: Jang You-Na , Jung Yi-Sook , Lee Soo Hwan , Moon Chang-Hyun , Kim Chang-Hoon , Baik Eun Joo
Published: May 2009

Neural-cadherin (N-cadherin), a member of the classical cadherin family of transmembrane glycoproteins, mediates cellular recognition and cell–cell adhesion through calcium-dependent homophilic interactions and plays important roles in the development and maintenance of the nervous system. Metalloproteinase is known to cleave N-cadherin, which is further cleaved by γ-secretase. The intracellular domain of N-cadherin interacts with β-catenin, and β-catenin stability is critical for cell–cell adhesion and cell survival. In the present study, we showed that N-cadherin is cleaved specifically by calpain, resulting in the generation of a novel 110 kDa fragment. The cleavage occurred in ischemic brain lesions andin vitroneural cells in the presence of NMDA and ionomycin, and was restored by calpain inhibitors but not matrix metalloproteinase or γ-secretase inhibitors. Calpain directly cleaved N-cadherin inin vitrocalpain assays, and calpain inhibitors prevented its cleavage in a dose-dependent manner. Using N-cadherin deletion mutants, we found that calpain cleavage sites exist in at least four regions of the cytoplasmic domain. Treatment with NMDA induced neuronal death, and it suppressed the expression of surface N-cadherin and the N-cadherin/β-catenin interaction, effects that were prevented by calpain inhibitor. Furthermore, calpain-mediated N-cadherin cleavage significantly affected cell–cell adhesion, AKT signaling, the N-cadherin/β-catenin interaction and the Wnt target gene expressions through the accumulation of nuclear β-catenin.
Prevalence of IGF1 deficiency in prepubertal children with isolated short stature
Authors: Edouard T , Grünenwald S , Gennero I , Salles J P , Tauber M
Published: May 2009

Background/aims

‘Primary IGF1 deficiency (IGFD)’ is defined by low levels of IGF1 without a concomitant impairment in GH secretion in the absence of secondary cause. The aims of this study were to evaluate the prevalence of non-GH deficient IGFD in prepubertal children with isolated short stature (SS) and to describe this population.

Methods

This retrospective study included all children with isolated SS seen in our Pediatric Endocrinology Unit from January 2005 to December 2007. Children were included based on the following criteria: i) SS with current height SDS ≤ −2.5, ii) age≥2 years, and iii) prepubertal status. Exclusion criteria were: i) identified cause of SS and ii) current or past therapy with rhGH. IGF1-deficient children were defined as children without GH deficiency and with IGF1 levels below or equal to −2 SDS.

Results

Among 65 children with isolated SS, 13 (20%) had low IGF1 levels, consistent with a diagnosis of primary IGFD, four of which were born small for gestational age and nine were born appropriate for gestational age. When compared with non-IGFD children, IGFD children had higher birth weight (−0.7 vs −1 SDS, P=0.02) and birth height (−1.7 vs −2 SDS, P=0.04) and more delayed bone age (2.6 vs 1.7 years, P=0.03).

Conclusion

The prevalence of primary IGFD was 20% in children with isolated SS. Concerning the pathophysiology, our study emphasizes that IGFD in some children may be secondary to nutritional deficiency or to maturational delay.
Polymorphic Genes of Major Effect: Consequences for Variation, Selection and Evolution in Arabidopsis thaliana
Authors: Stinchcombe John R , Weinig Cynthia , Heath Katy D , Brock Marcus T , Schmitt Johanna
Published: May 2009

The importance of genes of major effect for evolutionary trajectories within and among natural populations has long been the subject of intense debate. For example, if allelic variation at a major-effect locus fundamentally alters the structure of quantitative trait variation, then fixation of a single locus can have rapid and profound effects on the rate or direction of subsequent evolutionary change. Using an Arabidopsis thaliana RIL mapping population, we compare G-matrix structure between lines possessing different alleles at ERECTA, a locus known to affect ecologically relevant variation in plant architecture. We find that the allele present at ERECTA significantly alters G-matrix structure—in particular the genetic correlations between branch number and flowering time traits—and may also modulate the strength of natural selection on these traits. Despite these differences, however, when we extend our analysis to determine how evolution might differ depending on the ERECTA allele, we find that predicted responses to selection are similar. To compare responses to selection between allele classes, we developed a resampling strategy that incorporates uncertainty in estimates of selection that can also be used for statistical comparisons of G matrices.
Epigenetic Inheritance and the Missing Heritability Problem
Authors: Slatkin Montgomery
Published: May 2009

Epigenetic phenomena, and in particular heritable epigenetic changes, or transgenerational effects, are the subject of much discussion in the current literature. This article presents a model of transgenerational epigenetic inheritance and explores the effect of epigenetic inheritance on the risk and recurrence risk of a complex disease. The model assumes that epigenetic modifications of the genome are gained and lost at specified rates and that each modification contributes multiplicatively to disease risk. The potentially high rate of loss of epigenetic modifications causes the probability of identity in state in close relatives to be smaller than is implied by their relatedness. As a consequence, the recurrence risk to close relatives is reduced. Although epigenetic modifications may contribute substantially to average risk, they will not contribute much to recurrence risk and heritability unless they persist on average for many generations. If they do persist for long times, they are equivalent to mutations and hence are likely to be in linkage disequilibrium with SNPs surveyed in genomewide association studies. Thus epigenetic modifications are a potential solution to the problem of missing causality of complex diseases but not to the problem of missing heritability. The model highlights the need for empirical estimates of the persistence times of heritable epialleles.
Assessment of Sleep-Disordered Breathing in Pediatric Neuromuscular Diseases
Authors: Katz Sherri L.
Published: May 2009

This is a summary of the presentation on the assessment of sleep-disordered breathing in pediatric neuromuscular diseases, presented as part of the program on pulmonary management of pediatric patients with neuromuscular disorders at the 30th annual Carrell-Krusen Neuromuscular Symposium on February 20, 2008.
Equipment Options for Cough Augmentation, Ventilation, and Noninvasive Interfaces in Neuromuscular Respiratory Management
Authors: Boitano Louis J.
Published: May 2009

This is a summary of the presentation on equipment options for cough augmentation, ventilation, and noninvasive interfaces in neuromuscular respiratory management presented as part of the program on pulmonary management of pediatric patients with neuromuscular disorders at the 30th annual Carrell-Krusen Neuromuscular Symposium on February 20, 2008.
Airway Clearance in Duchenne Muscular Dystrophy
Authors: Kravitz Richard M.
Published: May 2009

This is a summary of the presentation on airway clearance in neuromuscular disorders presented as part of the program on airway clearance in Duchenne muscular dystrophy at the 30th annual Carrell-Krusen Neuromuscular Symposium on February 20, 2008.
Initiating Noninvasive Management of Respiratory Insufficiency in Neuromuscular Disease
Authors: Benditt Joshua O.
Published: May 2009

This is a summary of the presentation on initiating noninvasive management of respiratory insufficiency in neuromuscular disease, presented as part of the program on pulmonary management of pediatric patients with neuromuscular disorders at the 30th annual Carrell-Krusen Neuromuscular Symposium on February 20, 2008.
A 2009 Perspective on the 2004 American Thoracic Society Statement, “Respiratory Care of the Patient With Duchenne Muscular Dystrophy”
Authors: Finder Jonathan D.
Published: May 2009

This is a summary of the presentation “A 2009 Perspective on the 2004 American Thoracic Society Statement, ‘Respiratory Care of the Patient With Duchenne Muscular Dystrophy,’” presented as part of the program on pulmonary management of pediatric patients with neuromuscular disorders at the 30th annual Carrell-Krusen Neuromuscular Symposium on February 20, 2008.
Selves and identities in narrative and discourse. Michael Bamberg, Anna de Fina and Deborah Schiffrin (eds) (2007)
Authors: Block David
Published: May 2009

Selves and identities in narrative and discourse. Michael Bamberg, Anna de Fina and Deborah Schiffrin (eds) (2007) Studies in Narrative 9. Amsterdam: John Benjamins, pp. x + 355. ISBN 978 90 272 2649 5
Lingüística Aplicada del Español. Manel Lacorte (ed.) (2007)
Authors: Guijarro-Fuentes Pedro
Published: May 2009

Lingüística Aplicada del Español. Manel Lacorte (ed.) (2007) Madrid: Arco Libros. pp. 560 ISBN 84 7635 663 3
Defining and investigating monolingualism
Authors: Ellis Elizabeth M
Published: May 2009

Some may find it strange to see a special journal issue on monolingualism. After all, is it not bilinguals and multilinguals who present the more interesting questions? It certainly seems so, for research has concentrated on their linguistic, psycholinguistic and sociolinguistic make-up. The implication of this is that monolingualism is the norm, and that bilingualism and multilingualism constitute abnormal states which merit investigation; even though this idea sits oddly with the belief of most linguists that the majority of the world’s population is bi- or multilingual, and that therefore monolingualism may be the exception rather than the norm. There is little systematic investigation of monolingualism: Romaine pointed out in 1995 that she would find it strange to see a book with the title ‘Monolingualism’. This special issue of Sociolinguistic Studies carries just such a title, and the papers it includes represent an attempt to explore the phenomenon of monolingualism from a number of different perspectives. In this introduction I will outline why a simple definition of monolingualism is neither easy to establish nor useful, and also why it is important to come to an understanding of it as a particular kind of ‘lingualism’ (Cruz Ferreira p.c.). I then review ways in which monolingualism has been represented thus far in the literature, outline some possible research questions and end by introducing the contributions to this volume.
Two processes of reproducing monolingualism in South Korea
Authors: Park Joseph Sung-Yul
Published: May 2009

Using the notion of language ideology as a primary tool, this article identifies mono-lingualism as an ideological construct. It demonstrates how language ideologies may reproduce monolingualism by erasing elements of the sociolinguistic field that do not fit with the monolingual vision of a society, a process that has particular significance in the context of globalization, in which the spread of global languages and transnational movement of speakers constantly challenge the idea of state monolingualism. The case in point for this article is South Korea, which, despite a recent emphasis on English language learning, appears to maintain its traditional image of a highly monolingual society. I argue that this monolingualism is not an absence of English, but an erasure of the presence of English, accomplished through language ideological work. To illustrate this point, I outline two ideologies – externalization, which frames Korean uses of English as un-Korean (thus as something in which ‘real’ Koreans would not engage), and self-deprecation, which frames them as ‘bad English’ (thus as not English at all) – and explain how they are employed in Korean discourses of English to deny the possibility of Korean-English bilingualism in Korean society.
‘Who can tell, mon ami?’
Authors: Planchenault Gaëlle
Published: May 2009

French stylization can frequently be observed in the English-speaking media under the form of faked French accents or performed personas as is the case with Poirot’s TV character. In the popular ITV drama adaptation of the well-known eponymous novels of Agatha Christie, dialogues in English are peppered with French words. This paper will analyse the functions of these tokens of bilingualism and will show that they are used as a form of ethnosymbolism (Haarmann 1986). In this article, I argue that the actor’s performance is a representation of the foreign language and culture for a mainly monolingual audience. For Androutsopoulos (2007: 222), it is a matter of ‘styling ethnic otherness for majority audiences’. I relate the staging of salient linguistic traits to folk linguistics and more particularly to the beliefs a speech community carries on another speech community and its ways of speaking. In order to identify popular conceptions regarding transfers from L1 French, the lines of the Belgian sleuth are analysed on lexical, pragmatic and syntactic levels.
Book Reviews
Authors: Garbutt Joanna
Published: May 2009

The language of police interviewing: A critical analysis Georgina Heydon (2005) Basingstoke: Palgrave Macmillan 240 pp. ISBN 1–4039–1726–4 Communicating rights: The language of arrest and detention Frances Rock (2007) Basingstoke: Palgrave Macmillan 256 pp. ISBN 978–0230013315
Analyzing linguistic data: A practical introduction to statistics using. R. Harald Baayen (2008)
Authors: Larson-Hall Jenifer
Published: May 2009

Analyzing linguistic data: A practical introduction to statistics using. R. Harald Baayen (2008) New York: Cambridge University Press, xiii, 353 pp ISBN 978–0-521–70918–7 – ISBN 978–0-521–88259–0
Projéteis com Resistência do Ar Quadrática na Velocidade
Authors: Ferreira G. F. Leal
Published: May 2009

A solução aproximada do problema do movimento de projétil com resistência do ar quadrática na velocidade, obtida em 1719 por Johann Bernoulli, é comparada com soluções integradas numerica mente a partir de uma primeira integral analítica da velocidade horizontal em termos do ângulo que o vetor velocidade faz com a horizontal, e é verificada ser adequada, pelo menos até ângulos de tiro de até 20-. Com ela resultados são obtidos em alguns casos práticos de interesse (tênis, futebol e outros) que dão elementos ao professor de física na área, para delimitar o que de prático tem o seu ensino em que a resistência do ar é ignorada.
A Lei de Beer Aplicada na Atmosfera Terrestre
Authors: Echer E. , Souza M. P. , Schuch N. J.
Published: May 2009

A Lei de Beer da transferência radiativa tem grande aplicação em problemas atmosféricos que envolvam valores de radiação solar direta. Uma síntese da física da atenuação da radiação solar pela atmosfera e da derivação da lei de Beer é apresentada neste trabalho. São apresentadas aplicações da lei de Beer no cálculo do espectro de radiação solar direta na superfície terrestre, na região do ultravioleta, considerando condições de céu limpo e apenas espalhamento Rayleigh e absorção molecular. O método de Langley foi aplicado a dados de radiação ultravioleta solar de banda larga (0,32-0,40 mim) obtidos em Santa Maria, Rio Grande do Sul, no ano de 1994, como um exemplo ilustrativo da obtenção da irradiância no topo da atmosfera e da espessura óptica atmosférica para a banda utilizada.
Introdução à eletrodinâmica atmosférica
Authors: Mendes Jr. Odim , Domingues Margarete Oliveira
Published: May 2009

A Eletrodinâmica atmosférica governa os processos físicos na Terra, afetando a vida, instalações e serviços tecnológicos. Com o objetivo de auxiliar os professores, pesquisadores e estudantes a lidarem com esta área e suas conseqüências, o ambiente eletrodinâmico é apresentado neste tutorial.
Ilustrando a Segunda Lei de Newton no Século XXI
Authors: Veit E. A. , Mors P. M. , Teodoro V. D.
Published: May 2009

Apresenta-se uma forma de ensinar a segunda Lei de Newton usando-se a modelagem computacional, de modo que, além das tradicionais situações lineares, problemas mais reais e atuais possam ser tratados. Ilustra-se com o aplicativo Modellus, que permite ao usuário (aluno ou professor) explorar modelos matemáticos baseados em equações diferenciais ou em funções. Para as situações físicas discutidas, são fornecidas as equações, parâmetros e condições iniciais necessárias, de modo que o leitor que opte por outro aplicativo tenha plenas condições de desenvolver as atividades propostas.
Introdução à Teoria Quântica de Campos: do Oscilador Harmônico ao Campo Escalar Livre
Authors: Pereira Rodrigo Gonçalves , Miranda Eduardo
Published: May 2009

As teorias quânticas de campo são fundamentais em teoria de Matéria Condensada e Física de Altas Energias. Nesse artigo mostramos como um formalismo típico de teorias de campos pode ser introduzido didaticamente, generalizando a solução do oscilador harmônico para um grande número de graus de liberdade. No limite contínuo, esse método nos leva à quantização do campo de uma corda esticada vibrante e à existência dos fônons como excitações elementares ("partículas") desse campo. O procedimento pode ser usado como introdução elementar às teorias quânticas de campo através de ferramentas ensinadas em um curso de graduação de Mecânica Quântica.
Construindo um Densímetro
Authors: Ricetti Rodrigo
Published: May 2009

Para fins didáticos, é apresentada uma maneira de construir um densímetro, aparelho utilizadopara medir a densidade de fluidos. um aparato fácil de ser construído e muito simples de serutilizado. Sua principal vantagem sobre os densímetros que comercialmente encontramos, é a suacapacidade de medir a densidade de quaisquer líquidos, operando em qualquer faixa de densidade. Outra vantagem que apresenta, é a possibilidade de fazer uma medição relativa entre quaisquerlíquidos, não fazendo apenas a medição relativa à densidade da água. Desta maneira, pode-semedir, por exemplo, a densidade do mercúrio em relação ao éter, com este instrumento. Nota-seque, desta maneira, com apenas um instrumento determina-se a densidade de qualquer líquido, nãosendo necessário dispor-se de densímetros que operem em diversas faixas de densidade, como é ocaso dos instrumentos encontrados comercialmente.
Velocidade do som no ar: um experimento caseiro com microcomputador e balde d'água
Authors: Silva Wilton Pereira da , Silva Cleide M. D. P. S. e , Fereira Tarso V. , Rocha Jerônimo S. , Silva Diogo D. P. S. e , Silva Cleiton D. P. S. e
Published: May 2009

Este artigo propõe um experimento caseiro para a determinação da velocidade do som no ar. Para tal, foi desenvolvido um programa de computador para a geração de áudio em freqüências estabelecidas pelo usuário, e também para a apresentação dos roteiros experimentais (ensino médio e superior). O experimento proposto foi realizado por diversos alunos, em suas próprias casas, e os resultados obtidos concordam com os valores esperados.