bluuebunny/crossref_metadata_2025 huggingface dataset:
Modelling heterogeneity in clustered count data with extra zeros using compound Poisson random effect
Authors: Ma Renjun , Hasan M. Tariqul , Sneddon Gary
Published: May 2009

In medical and health studies, heterogeneities in clustered count data have been traditionally modeled by positive random effects in Poisson mixed models; however, excessive zeros often occur in clustered medical and health count data. In this paper, we consider a three‐level random effects zero‐inflated Poisson model for health‐care utilization data where data are clustered by both subjects and families. To accommodate zero and positive components in the count response compatibly, we model the subject level random effects by a compound Poisson distribution. Our model displays a variance components decomposition which clearly reflects the hierarchical structure of clustered data. A quasi‐likelihood approach has been developed in the estimation of our model. We illustrate the method with analysis of the health‐care utilization data. The performance of our method is also evaluated through simulation studies. Copyright © 2009 John Wiley & Sons, Ltd.
Synthesis and Spectral Studies of CdTe–Dendrimer Conjugates
Authors: Ghosh Srabanti , Saha Abhijit
Published: May 2009

In order to couple high cellular uptake and target specificity of dendrimer molecule with excellent optical properties of semiconductor nanoparticles, the interaction of cysteine-capped CdTe quantum dots with dendrimer was investigated through spectroscopic techniques. NH2-terminated dendrimer molecule quenched the photoluminescence of CdTe quantum dots. The binding constants and binding capacity were calculated, and the nature of binding was found to be noncovalent. Significant decrease in luminescence intensity of CdTe quantum dots owing to noncovalent binding with dendrimer limits further utilization of these nanoassemblies. Hence, an attempt is made, for the first time, to synthesize stable, highly luminescent, covalently linked CdTe–Dendrimer conjugate in aqueous medium using glutaric dialdehyde (G) linker. Conjugate has been characterized through Fourier transform infrared spectroscopy and transmission electron microscopy. In this strategy, photoluminescence quantum efficiency of CdTe quantum dots with narrow emission bandwidths remained unaffected after formation of the conjugate.
Fabrication of Uniform Au–Carbon Nanofiber by Two-Step Low Temperature Decomposition
Authors: Lee Myeongsoon , Hong Seong-Cheol , Kim Don
Published: May 2009

This paper presents a facile and efficient way to prepare carbon nanofibers ornamented with Au nanoparticles (Au/CNFs). Gold nanoparticles were first deposited in the channels of an anodized aluminum oxide (AAO) membrane by thermal decomposition of HAuCl4and then carbon nanofibers were produced in the same channels loaded with the Au nanoparticles by decomposition of sucrose at 230 °C. An electron microscopy study revealed that the carbon nanofibers, ~10 nm thick and 6 μm long, were decorated with Au nanoparticles with a diameter of 10 nm. This synthetic route can produce uniform Au nanoparticles on CNF surfaces without using any additional chemicals to modify the AAO channels or the CNF surfaces.
Nucleotide dependent cysteine reactivity of hGBP1 uncovers a domain movement during GTP hydrolysis
Authors: Vöpel Tobias , Kunzelmann Simone , Herrmann Christian
Published: May 2009

As a member of the dynamin superfamily human guanylate‐binding protein 1 (hGBP1) binds and hydrolyses GTP thereby undergoing structural changes which lead to self‐assembly of the protein. Here, we employ the reactivity of hGBP1 with a cysteine reactive compound in order to monitor structural changes imposed by GTP binding and hydrolysis. Positions of cysteine residues buried between the C‐terminal domain of hGBP1 and the rest of the protein are identified which report a large change of accessibility by the compound after addition of GTP. Our results indicate that nucleotide hydrolysis induces a domain movement in hGBP1, which we suggest enables further assembly of the protein.
Will mobile learning change language learning?
Authors: Kukulska-Hulme Agnes
Published: May 2009

The use of mobile phones and other portable devices is beginning to have an impact on how learning takes place in many disciplines and contexts, including language learning. Learners who are not dependent on access to fixed computers can engage in activities that relate more closely to their current surroundings, sometimes crossing the border between formal and informal learning. This creates the potential for significant change in teaching and learning practices. Taking the broader field of mobile learning as the setting within which developments in mobile-assisted language learning may be understood, the paper argues that an emphasis on mobility can lead to new perspectives and practices. The paper offers reflections on what mobile learning has to offer and considers whether it is likely to change how languages are taught and learnt. ‘Mobile learning’ is not a stable concept; therefore its current interpretations need to be made explicit. Examples of current projects and practices show an affinity between mobile and games-based learning, and can further illuminate what is distinctive and worthwhile about mobile learning.
Training future language teachers to develop online tutors’ competence through reflective analysis
Authors: Guichon Nicolas
Published: May 2009

This article sets out to identify key competencies which language tutors need to develop in order to manage synchronous online teaching. In order to aptly monitor interactions with distant learners, it is proposed that three types of regulation pertaining to socio-affective, pedagogical and multimedia aspects are required. On the one hand, this research aims at specifying these competencies and, on the other hand, it seeks to identify the relevance of reflective analysis for professional development.

The context of this study is a teacher training programme for Masters Degree students in teaching French as a foreign language that provides trainees with the opportunity of teaching online to intermediate-level students of French from a North American university via a desktop videoconferencing platform. This programme first endeavours to put trainees in a professional situation by getting them to prepare and administer sessions in order to confront them with the specific challenges of synchronous online tutoring. Second, it seeks to help them to gain insight into their own activity by developing critical thinking towards their own practice.

The data elicited for this research derive from the tutor trainees’ interpretations of their own practice when confronted with the film of their own situated activity. The episodes chosen by the trainees to feed the self-confrontation process constitute significant units because by being told and commented upon, they elucidate how and to what extent competencies are built. Three discursive strategies have been identified and used to organise the content analysis of the data: description; expression of a difficulty; reflective review of the activity. The strategies used by trainees to verbalise their own activity can inform teacher educators about the constraints of the work situation and about the resources trainees need to deploy to face up to this unknown professional situation.

Results indicate that trainees concentrate particularly on pedagogical aspects that distance and faulty technology have rendered complex. The encountered difficulties are equally distributed between a repertoire of competencies pertaining to language teaching and competencies more directly linked with online teaching. Finally, this study has enabled us to assess the potential of self-confrontation for teacher practice and leads us to propose directions for improving this training device.
Efficient Graph Packing via Game Colouring
Authors: KIERSTEAD H. A. , KOSTOCHKA A. V.
Published: May 2009

The game colouring number gcol(G) of a graphGis the leastksuch that, if two players take turns choosing the vertices of a graph, then either of them can ensure that every vertex has fewer thankneighbours chosen before it, regardless of what choices the other player makes. Clearly gcol(G) ≤ Δ(G)+1. Sauer and Spencer [20] proved that if two graphsG1andG2onnvertices satisfy 2Δ(G1)Δ(G2) <nthen they pack,i.e., there is an embedding ofG1into the complement ofG2. We improve this by showing that if (gcol(G1)−1)Δ(G2)+(gcol(G2)−1)Δ(G1) <nthenG1andG2pack. To our knowledge this is the first application of colouring games to a non-game problem.
Environmental and population externalities
Authors: JÖST FRANK , QUAAS MARTIN F.
Published: May 2009

We analyze the external effects that arise in the decisions of firms on polluting emissions and in the decisions of parents on the number of births in an optimal control model with three stock variables representing population, economic capital, and pollution. We distinguish two different types of households, which represent opposite ends of a spectrum of potential familial structures: ‘dynastic households’, in which the family sticks together forever and ‘micro-households’, in which children leave their parent's household immediately after birth. We show that the decision of parents on the number of births involves an externality that is qualitatively different for both types of familial structure. Hence, population policy should be different, according to the type of household. A first best result may be obtained in the case of dynastic households if an appropriate tax on the household size is applied, or, in the case of micro-households, if an appropriate tax on children is applied.
Psychologische Interventionen bei demenziellen Erkrankungen
Authors: Fischer-Terworth Christian , Probst Paul , Glanzmann Peter G. , Knorr Carolin C.
Published: May 2009

Hintergrund: In verschiedenen Krankheitsstadien einer Demenz nehmen psychologische Interventionen einen zentralen Stellenwert bei der günstigen Beeinflussung kognitiver, behavioraler und psychopathologischer Symptome ein. Die Wirksamkeit dieser Ansätze wurde bisher nicht hinreichend systematisch in randomisierten kontrollierten Studien untersucht. Methode: Zur Erfassung des Forschungsstands über evidenzbasierte psychologische Therapien bei Demenz wurde eine Recherche in MEDLINE, PsycInfo, Psyndex und der Cochrane-Database durchgeführt. Eingeschlossen in die Evaluation wurden systematische Reviews, randomisierte kontrollierte Studien und kontrollierte Studien. Ergebnisse: Innerhalb der Vielzahl von Therapiemethoden zeigen sich hohe Evidenzlevels für (a) kognitive Verhaltenstherapie zur Behandlung behavioraler und psychopathologischer Symptome, insbesondere von Depressivität und (b) Psychoedukation und kognitiv-behaviorale Psychotherapie für Angehörige bei der Reduktion psychischer Belastung und psychopathologischer Symptome bei Angehörigen und Patienten. Moderate Evidenz besteht für die Anwendung von (a) kognitiver Stimulation zur Stabilisierung kognitiver Funktionen bei leichter bis mittelschwerer Alzheimer-Demenz und (b) Musiktherapie bei der kurzfristigen Reduktion von Agitation und anderer behavioraler und psychopathologischer Symptome bei mittelschwerer bis schwerer Demenz. Nur bedingt wirksam zur Reduktion behavioraler und psychopathologischer Symptome sind verschiedene Ansätze sensorischer Therapie. Zunehmende Evidenz zeigt sich für die Bedeutung einer milieutherapeutischen Umweltgestaltung. Diskussion: Weitere randomisierte kontrollierte Studien zu psychologischen Interventionen bei verschiedenen Demenzformen und -stadien mit größeren Fallzahlen sind dringend erforderlich.
Instrumente zur klinischen Diagnostik von selbstverletzendem Verhalten
Authors: Nitkowski Dennis , Petermann Franz
Published: May 2009

Zur Erfassung selbstverletzenden Verhaltens liegen mehrere diagnostische Instrumente vor, die bislang primär in der Forschung verwendet wurden. Mit diesem Überblicksartikel soll geklärt werden, wie nützlich sieben Verfahren zur klinischen Diagnostik unter den Aspekten Gütekriterien und klinische Relevanz sind. Die Verfahren weisen in Hinblick auf die Kriterien eine unterschiedliche Eignung auf. Bei zwei Instrumenten bestehen Unschärfen in der Abgrenzung gegenüber Suizidversuchen. Es wird aufgezeigt, in welchen Phasen des diagnostischen Prozesses die Verfahren aufgrund ihrer Eigenschaften am besten einzusetzen sind.
False Memories in the DRM Paradigm
Authors: Sugrue Katrina , Strange Deryn , Hayne Harlene
Published: May 2009

Prior research using the Deese-Roediger-McDermott paradigm has shown that participants are more likely to report the critical lures when long lists are presented. In this experiment, we evaluated two potential explanations for this list-length effect. Ten-year-old children and adults studied 7- or 14-word lists. After recalling each list, participants were then asked to report any other words that they had thought about, but had not reported, during the recall phase. We found that long lists were more likely to activate the critical lure and that short lists did not facilitate source monitoring. On the basis of our findings, we conclude that, for both age groups, the list-length effect was due primarily to list-related differences in activation of the critical lure.
Nutrient regime regulates complex transcriptional start site usage within a Pseudoalteromonas chitinase gene cluster
Authors: Delpin Marina W , Goodman Amanda E
Published: May 2009

The chitinase gene cluster of the marine bacterium Pseudoalteromonas sp. S91, chiABC, which produces the major chitinases of this sp., was transcribed as an operon and from each individual gene. chiA, chiB and chiC were found to possess multiple transcriptional start points (TSPs), the use of which was determined by the nutrient regime used for S91 growth. In minimal medium containing glutamate, chiA, chiB and chiC each used 3, 1 and 1 TSP, respectively. Upon the addition of the chitin monomer N-acetylglucosamine, the number of chiA TSPs was unaffected. However, chiB used an additional 4 TSPs, and chiC used four new TSPs excluding the TSP used in glutamate only. In addition, the cluster was transcribed as an operon from TSP A1 of chiA. All TSPs were potentially associated with either a σ70- or σ54-dependent promoter. Under the growth conditions used, no TSPs were detected for chiB or chiC in S91CX, a chiA transposon mutant. The transcription of the S91 chiABC gene cluster produced at least four polycistronic mRNAs. In addition, the occurrence of operon transcription of chiABC, and identification of an additional 12 putative TSPs within the gene cluster, gave an indication that each gene appeared to be transcribed from more than one promoter region upstream of each in-frame translation start codon. Questions arose regarding the reason for this complexity of transcription within the gene cluster, leading to a re-evaluation of the Chi protein domains. By bioinformatic review, ChiA, ChiB and ChiC were found to potentially possess additional putative domains.
Can the black box be cracked? The augmentation of microbial ecology by high-resolution, automated sensing technologies
Authors: Shade Ashley , Carey Cayelan C , Kara Emily , Bertilsson Stefan , McMahon Katherine D , Smith Matthew C
Published: May 2009

Automated sensing technologies, ‘ASTs,’ are tools that can monitor environmental or microbial-related variables at increasingly high temporal resolution. Microbial ecologists are poised to use AST data to couple microbial structure, function and associated environmental observations on temporal scales pertinent to microbial processes. In the context of aquatic microbiology, we discuss three applications of ASTs: windows on the microbial world, adaptive sampling and adaptive management. We challenge microbial ecologists to push AST potential in helping to reveal relationships between microbial structure and function.
Multiple Genes Influence BMI on Chromosome 7q31–34: The NHLBI Family Heart Study
Authors: Laramie Jason M. , Wilk Jemma B. , Williamson Sally L. , Nagle Michael W. , Latourelle Jeanne C. , Tobin Jennifer E. , Province Michael A. , Borecki Ingrid B. , Myers Richard H.
Published: May 2009

The National Heart, Lung, and Blood Institute Family Heart Study (FHS) genome‐wide linkage scan identified a region of chromosome 7q31–34 with a lod score of 4.9 for BMI at D7S1804 (131.9 Mb). We report the results of linkage and association to BMI in this region for two independent FHS samples. The first sample includes 225 FHS pedigrees with evidence of linkage to 7q31–34, using 1,132 single‐nucleotide polymorphisms (SNPs) and 7 microsatellites. The second represents a case–control sample (318 cases; BMI >25 and 325 controls; BMI <25) derived from unrelated FHS participants who were not part of the genome scan. The latter set was genotyped for 606 SNPs, including 37 SNPs with prior evidence for association in the linked families. Although variance components linkage analysis using only SNPs generated a peak lod score that coincided with the original linkage scan at 131.9 Mb, a conditional linkage analysis showed evidence of a second quantitative trait locus (QTL) near 143 cM influencing BMI. Three SNPs (rs161339, rs12673281, and rs1993068) located near the three genes pleiotrophin (PTN), diacylglycerol (DAG) kinase iota (DGKι), and cholinergic receptor, muscarinic 2 (CHRM2) demonstrated significant association in both linked families (P = 0.0005, 0.002, and 0.03, respectively) and the case–control sample (P = 0.01, 0.0003, and 0.03, respectively), regardless of the genetic model tested. These findings suggest that several genes may be associated with BMI in the 7q31–34 region.
Genome‐wide Association Study and Follow‐up Analysis of Adiposity Traits in Hispanic Americans: The IRAS Family Study
Authors: Norris Jill M. , Langefeld Carl D. , Talbert Matthew E. , Wing Maria R. , Haritunians Talin , Fingerlin Tasha E. , Hanley Anthony J.G. , Ziegler Julie T. , Taylor Kent D. , Haffner Steven M. , Chen Yii‐Der I. , Bowden Donald W. , Wagenknecht Lynne E.
Published: May 2009

We investigated candidate genomic regions associated with computed tomography (CT)–derived measures of adiposity in Hispanics from the Insulin Resistance Atherosclerosis Study Family Study (IRASFS). In 1,190 Hispanic individuals from 92 families 3 from the San Luis Valley, Colorado and San Antonio, Texas, we measured CT‐derived visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and visceral:subcutaneous ratio (VSR). A genome‐wide association study (GWAS) was completed using the Illumina HumanHap 300 BeadChip (∼317K single‐nucleotide polymorphisms (SNPs)) in 229 individuals from the San Antonio site (stage 1). In total, 297 SNPs with evidence for association with VAT, SAT, or VSR, adjusting for age and sex (P < 0.001), were genotyped in the remaining 961 Hispanic samples. The entire Hispanic cohort (n = 1,190) was then tested for association, adjusting for age, sex, site of recruitment, and admixture estimates (stage 2). In stage 3, additional SNPs were genotyped in four genic regions showing evidence of association in stage 2. Several SNPs were associated in the GWAS (P < 1 × 10−5) and were confirmed to be significantly associated in the entire Hispanic cohort (P < 0.01), including: rs7543757 for VAT, rs4754373 and rs11212913 for SAT, and rs4541696 and rs4134351 for VSR. Numerous SNPs were associated with multiple adiposity phenotypes. Targeted analysis of four genes whose SNPs were significant in stage 2 suggests candidate genes for influencing the distribution (RGS6) and amount of adiposity (NGEF). Several candidate loci, including RGS6 and NGEF, are associated with CT‐derived adipose fat measures in Hispanic Americans in a three‐stage genetic association study.
Ultrasonography to Quantify Hepatic Fat Content: Validation by 1H Magnetic Resonance Spectroscopy
Authors: Edens Mireille A. , van Ooijen Peter M.A. , Post Wendy J. , Haagmans Mark J.F. , Kristanto Wisnumurti , Sijens Paul E. , van der Jagt Erik J. , Stolk Ronald P.
Published: May 2009

An abundance of fat stored within the liver, or steatosis, is the beginning of a broad hepatological spectrum, usually referred to as fatty liver disease (FLD). For studies on FLD, quantitative hepatic fat ultrasonography would be an appealing study modality. Objective of this study was to develop a technique for quantifying hepatic fat content by ultrasonography and validate this using proton magnetic resonance spectroscopy (1H MRS) as gold standard. Eighteen white volunteers (BMI range 21.0–42.9) were scanned by both ultrasonography and 1H MRS. Altered ultrasound characteristics, present in the case of FLD, were assessed using a specially developed software program. Various attenuation and textural based indices of FLD were extracted from ultrasound images. Using linear regression analysis, the predictive power of several models (consisting of both attenuation and textural based measures) on log 10–transformed hepatic fat content by 1H MRS were investigated. The best quantitative model was compared with a qualitative ultrasonography method, as used in clinical care. A model with four ultrasound characteristics could modestly predict the amount of liver fat (adjusted explained variance 43.2%, P = 0.021). Expanding the model to seven ultrasound characteristics increased adjusted explained variance to 60% (P = 0.015), with r = 0.789 (P < 0.001). Comparing this quantitative model with qualitative ultrasonography revealed a significant advantage of the quantitative model in predicting hepatic fat content (P < 0.001). This validation study shows that a combination of computer‐assessed ultrasound measures from routine ultrasound images can be used to quantitatively assess hepatic fat content.
Revealing Uncertainty for Information Visualization
Authors: Skeels Meredith , Lee Bongshin , Smith Greg , Robertson George G.
Published: May 2009

Uncertainty in data occurs in domains ranging from natural science to medicine to computer science. By developing ways to include uncertainty in our information visualizations, we can provide more accurate depictions of critical data sets so that people can make more informed decisions. One hindrance to visualizing uncertainty is that we must first understand what uncertainty is and how it is expressed. We reviewed existing work from several domains on uncertainty and created a classification of uncertainty based on the literature. We empirically evaluated and improved upon our classification by conducting interviews with 18 people from several domains, who self-identified as working with uncertainty. Participants described what uncertainty looks like in their data and how they deal with it. We found commonalities in uncertainty across domains and believe our refined classification will help us in developing appropriate visualizations for each category of uncertainty.
Adaptation to audiovisual asynchrony modulates the speeded detection of sound
Authors: Navarra Jordi , Hartcher-O'Brien Jessica , Piazza Elise , Spence Charles
Published: May 2009

The brain adapts to asynchronous audiovisual signals by reducing the subjective temporal lag between them. However, it is currently unclear which sensory signal (visual or auditory) shifts toward the other. According to the idea that the auditory system codes temporal information more precisely than the visual system, one should expect to find some temporal shift of vision toward audition (as in the temporal ventriloquism effect) as a result of adaptation to asynchronous audiovisual signals. Given that visual information gives a more exact estimate of the time of occurrence of distal events than auditory information (due to the fact that the time of arrival of visual information regarding an external event is always closer to the time at which this event occurred), the opposite result could also be expected. Here, we demonstrate that participants' speeded reaction times (RTs) to auditory (but, critically, not visual) stimuli are altered following adaptation to asynchronous audiovisual stimuli. After receiving “baseline” exposure to synchrony, participants were exposed either to auditory-lagging asynchrony (VA group) or to auditory-leading asynchrony (AV group). The results revealed that RTs to sounds became progressively faster (in the VA group) or slower (in the AV group) as participants' exposure to asynchrony increased, thus providing empirical evidence that speeded responses to sounds are influenced by exposure to audiovisual asynchrony.
Inhibition of human tumor growth in mice by an oncolytic herpes simplex virus designed to target solely HER-2-positive cells
Authors: Menotti Laura , Nicoletti Giordano , Gatta Valentina , Croci Stefania , Landuzzi Lorena , De Giovanni Carla , Nanni Patrizia , Lollini Pier-Luigi , Campadelli-Fiume Gabriella
Published: May 2009

Oncolytic virotherapy exploits the ability of viruses to infect, replicate into, and kill tumor cells. Among the viruses that entered clinical trials are HSVs. HSVs can be engineered to become tumor-specific by deletion of selected genes or retargeting to tumor-specific receptors. A clinically relevant surface molecule is HER-2, hyperexpressed in one fourth of mammary and ovary carcinomas, and associated with high metastatic ability. As a previously undescribed strategy to generate HSV recombinants retargeted to HER-2 and detargeted from natural receptors, we replaced the Ig-folded core in the receptor-binding virion glycoprotein gD with anti-HER-2 single-chain antibody. The recombinant entered cells solely via HER-2 and lysed HER-2–positive cancer cells. Because of the high specificity, its safety profile in i.p. injected mice was very high, with a LD
50
>5 × 10
8
pfu, a figure at least 10,000-fold higher than that of corresponding WT-gD carrying virus (LD
50
≈ 5 × 10
4
pfu). When administered intratumorally to nude mice bearing HER-2–hyperexpressing human tumors, it strongly inhibited progressive tumor growth. The results provide a generally applicable strategy to engineer HSV recombinants retargeted to a wide range of receptors for which a single-chain antibody is available, and show the potential for retargeted HSV to exert target-specific inhibition of human tumor growth. Therapy with HER-2-retargeted oncolytic HSV could be effective in combined or sequential protocols with monoclonal antibodies and small inhibitors, particularly in patients resistant to HER-2-targeted therapy because of alterations in HER-2 signaling pathway, or against brain metastases inaccessible to anti-HER-2 antibodies.
Turbulence-driven instabilities limit insect flight performance
Authors: Combes Stacey A. , Dudley Robert
Published: May 2009

Environmental turbulence is ubiquitous in natural habitats, but its effect on flying animals remains unknown because most flight studies are performed in still air or artificially smooth flow. Here we show that variability in external airflow limits maximum flight speed in wild orchid bees by causing severe instabilities. Bees flying in front of an outdoor, turbulent air jet become increasingly unstable about their roll axis as airspeed and flow variability increase. Bees extend their hindlegs ventrally at higher speeds, improving roll stability but also increasing body drag and associated power requirements by 30%. Despite the energetic cost, we observed this stability-enhancing behavior in 10 euglossine species from 3 different genera, spanning an order of magnitude in body size. A field experiment in which we altered the level of turbulence demonstrates that flight instability and maximum flight speed are directly related to flow variability. The effect of environmental turbulence on flight stability is thus an important and previously unrecognized determinant of flight performance.
Evidence for remembering when events occurred in a rodent model of episodic memory
Authors: Zhou Wenyi , Crystal Jonathon D.
Published: May 2009

The content of episodic memory consists of representations of unique past events. Episodic memories are grounded in a temporal framework (i.e., we remember when an event occurred). It has recently been argued that episodic-like memory in rats is qualitatively different from human episodic memory because, rather than remembering when an earlier past event occurred, rats used the cue of how long ago it occurred. We asked, therefore, whether rats remember the time of day at which they encountered a distinctive event, in addition to what occurred and where it happened. Rats were tested in the morning and afternoon, on separate days. A distinctive flavor (chocolate) was replenished at a daily-unique location at only one of these times. The interval between first and second daily opportunities to eat (study and test, respectively) was constant. Rats adjusted their revisits to the chocolate location at different times of day by using time of day rather than the cue of how long ago an event occurred. Two lines of evidence suggest that rats remembered the time at which the distinctive event occurred. First, under conditions in which the time of test (but not time of study) was novel, rats immediately transferred their knowledge of the chocolate contingency to the new test time. Second, under conditions in which predictions for study and test times were put in conflict, rats again used study time. Our results suggest that, at the time of memory assessment, rats remember when a recent episode occurred, similar to human episodic memory.
Contact-induced grammaticalization
Authors: Matthews Stephen , Yip Virginia
Published: May 2009

It is widely acknowledged that developments in bilingual individuals parallel, and ultimately underlie, those taking place in the course of contact-induced change. In this paper we address the poorly understood relationship between the individual and community-level processes, focusing on the process of grammaticalization in circumstances of language contact and the corresponding developmental processes in bilingual acquisition. The phenomena chosen for discussion are drawn from Singapore Colloquial English (SCE) and from the Hong Kong Bilingual Corpus (Yip & Matthews 2000, 2007). Parallel developments in SCE and bilingual acquisition are analysed as cases of contact-induced grammaticalization as defined by Heine and Kuteva (2003; 2005), with some modifications. The emergence of already as a marker of aspect presents a case of ‘ordinary’ contact-induced grammaticalization, while the development of grammatical functions of give represents a case of replica grammaticalization. One implication of these findings is that bilingual first language acquisition is a possible route for substrate influence, both in general and specifically in the development of contact languages such as pidgins and creoles.
Tone inventories and tune-text alignments
Authors: Gooden Shelome , Drayton Kathy-Ann , Beckman Mary E.
Published: May 2009

The “hybrid” prosodic systems described for several Caribbean creoles challenge typologies that dichotomize between “intonation languages” and “tone languages” or between “stress” and “pitch-accent” languages. A more nuanced differentiation emerges if languages are compared in terms of questions concerning tone inventory and tune-text alignment, such as: Are the tunes of short utterances composed primarily of tone patterns specified to contrast words or of intonation patterns that are morphemes in their own right? What determines tune-text alignment at the lowest levels of the prosodic hierarchy? Should tones be anchored to rhythmically prominent syllables within focused constituents? This paper explores these questions for several languages with “hybrid” prosodic systems including some where the hybrid nature cannot plausibly be attributed to language contact.
Subsystem interface and tone typology in Papiamentu
Authors: Rivera-Castillo Yolanda
Published: May 2009

This paper looks at the relations between tone and features from other phonological subsystems in Papiamentu. It proposes that the interaction of tonal features with features from stress and intonational subsystems provides important clues about the typological classification of Papiamentu as a tone language. Moreover, the taxis of tones, or their organization in the string, also provides a better understanding of this language. Papiamentu fits the description of tone-restricted languages but also exhibits features of intonational systems.
Automated Measurement of Facial Expression in Infant–Mother Interaction: A Pilot Study
Authors: Messinger Daniel S. , Mahoor Mohammad H. , Chow Sy‐Miin , Cohn Jeffrey F.
Published: May 2009

Automated facial measurement using computer vision has the potential to objectively document continuous changes in behavior. To examine emotional expression and communication, we used automated measurements to quantify smile strength, eye constriction, and mouth opening in two 6‐month‐old infant‐mother dyads who each engaged in a face‐to‐face interaction. Automated measurements showed high associations with anatomically based manual coding (concurrent validity); measurements of smiling showed high associations with mean ratings of positive emotion made by naive observers (construct validity). For both infants and mothers, smile strength and eye constriction (the Duchenne marker) were correlated over time, creating a continuous index of smile intensity. Infant and mother smile activity exhibited changing (nonstationary) local patterns of association, suggesting the dyadic repair and dissolution of states of affective synchrony. The study provides insights into the potential and limitations of automated measurement of facial action.
Development of Shyness: Relations With Children's Fearfulness, Sex, and Maternal Behavior
Authors: Eggum Natalie D. , Eisenberg Nancy , Spinrad Tracy L. , Reiser Mark , Gaertner Bridget M. , Sallquist Julie , Smith Cynthia L.
Published: May 2009

The relations of childhood fearfulness (observed and adult reported) and adult‐reported shyness at 18 (n = 256) and 30 (n = 230) months of age were assessed. Fear was positively related to shyness concurrently and longitudinally, but slightly more consistently at 18 months. The moderating roles of observed maternal sensitivity and children's sex in the relation between 18‐month fearfulness and 30‐month shyness, and between 18‐ and 30‐month shyness, were tested. The positive relation between mother‐reported fearfulness and shyness was strongest for sons of insensitive mothers but was not significant for daughters of sensitive, average, or insensitive mothers. The positive relation between mother‐reported 18‐ and 30‐month shyness was strongest for sons of insensitive mothers and for daughters of sensitive mothers. Moreover, when using scores of fear or shyness that were independent of each other, 18‐month mother‐reported fearfulness continued to interact with sex and sensitivity to predict 30‐month shyness; however, the positive relation between Time 1 and Time 2 shyness was consistent across sex and levels of sensitivity.
A Comparative Study of Arm‐Restraint Methodology: Differential Effects of Mother and Stranger Restrainers on Infants' Distress Reactivity at 6 and 9 Months of Age
Authors: Porter Christin L. , Jones Blake L. , Evans Cortney A. , Robinson Clyde C.
Published: May 2009

This study examined both differential patterns and the stability of infants' (N = 70) distress reactivity across mother and stranger arm‐restraint conditions when infants were 6 and 9 months of age. Reactivity measures included observational variables for the rise, intensity, and duration of infant distress as well as motor activities associated with escape behaviors. Correlation analyses revealed that infant behaviors during arm restraint were modestly stable across conditions and over time; however, mean comparisons also showed that infants' distress responses appear to be sensitive to protocol parameters (whether restrainer is mother or stranger). At 6 months of age, infants cried more during maternal restraint than with strangers and exhibited escape behaviors more frequently with mothers. Findings further indicate that infants' distress reactivity undergoes developmental alterations from 6 to 9 months of age, with infants crying more quickly, reaching peak intensity of distress faster, and displaying more distress at 9 months compared to 6 months. These changes in infants' reactivity were particularly accentuated during maternal compared to stranger restraint conditions at 9 months of age.
Tumor Necrosis Factor-Receptor–associated Factor-4 Is a Positive Regulator of Transforming Growth Factor-β Signaling That Affects Neural Crest Formation
Authors: Kalkan Tuzer , Iwasaki Yasuno , Park Chong Yon , Thomsen Gerald H.
Published: May 2009

The transforming growth factor (TGF)-β superfamily regulates cell proliferation, apoptosis, differentiation, migration, and development. Canonical TGFβ signals are transduced to the nucleus via Smads in both major signaling branches, bone morphogenetic protein (BMP) or Activin/Nodal/TGFβ. Smurf ubiquitin (Ub) ligases attenuate these pathways by targeting Smads and other signaling components for degradation by the 26S proteasome. Here, we identify tumor necrosis factor (TNF)-receptor–associated factor-4 (TRAF4) as a new target of Smurf1, which polyubiquitylates TRAF4 to trigger its proteasomal destruction. Unlike other TRAF family members, which mediate signal transduction by TNF, interleukin, or Toll-like receptors, we find that TRAF4 potentiates BMP and Nodal signaling. In the frog Xenopus laevis, TRAF4 mRNA is stored maternally in the egg animal pole, and in the embryo it is expressed in the gastrula marginal zone, neural plate, and cranial and trunk neural crest. Knockdown of embryonic TRAF4 impairs signaling, neural crest development and neural folding, whereas TRAF4 overexpression boosts signaling and expands the neural crest. In human embryonic kidney 293 cells, small interfering RNA knockdown of Smurf1 elevates TRAF4 levels, indicating endogenous regulation of TRAF4 by Smurf1. Our results uncover new functions for TRAF4 as a Smurf1-regulated mediator of BMP and Nodal signaling that are essential for neural crest development and neural plate morphogenesis.
Dislocation of HMG-CoA Reductase and Insig-1, Two Polytopic Endoplasmic Reticulum Proteins, En Route to Proteasomal Degradation
Authors: Leichner Gil S. , Avner Rachel , Harats Dror , Roitelman Joseph
Published: May 2009

The endoplasmic reticulum (ER) glycoprotein HMG-CoA reductase (HMGR) catalyzes the rate-limiting step in sterols biosynthesis. Mammalian HMGR is ubiquitinated and degraded by the proteasome when sterols accumulate in cells, representing the best example for metabolically controlled ER-associated degradation (ERAD). This regulated degradation involves the short-lived ER protein Insig-1. Here, we investigated the dislocation of these ERAD substrates to the cytosol en route to proteasomal degradation. We show that the tagged HMGR membrane region, HMG350-HA, the endogenous HMGR, and Insig-1-Myc, all polytopic membrane proteins, dislocate to the cytosol as intact full-length polypeptides. Dislocation of HMG350-HA and Insig-1-Myc requires metabolic energy and involves the AAA-ATPase p97/VCP. Sterols stimulate HMG350-HA and HMGR release to the cytosol concurrent with removal of their N-glycan by cytosolic peptide:N-glycanase. Sterols neither accelerate dislocation nor stimulate deglycosylation of ubiquitination-defective HMG350-HA(K89 + 248R)mutant. Dislocation of HMG350-HA depends on Insig-1-Myc, whose dislocation and degradation are sterol independent. Coimmunoprecipitation experiments demonstrate sterol-stimulated association between HMG350-HA and Insig-1-Myc. Sterols do not enhance binding to Insig-1-Myc of HMG350-HA mutated in its sterol-sensing domain or of HMG350-HA(K89 + 248R). Wild-type HMG350-HA and Insig-1-Myc coimmunoprecipitate from the soluble fraction only when both proteins were coexpressed in the same cell, indicating their encounter before or during dislocation, raising the possibility that they are dislocated as a tightly bound complex.
Clathrin Functions in the Absence of the Terminal Domain Binding Site for Adaptor-associated Clathrin-Box Motifs
Authors: Collette John R. , Chi Richard J. , Boettner Douglas R. , Fernandez-Golbano Isabel M. , Plemel Rachael , Merz Alex J. , Geli Maria Isabel , Traub Linton M. , Lemmon Sandra K.
Published: May 2009

Clathrin is involved in vesicle formation in the trans-Golgi network (TGN)/endosomal system and during endocytosis. Clathrin recruitment to membranes is mediated by the clathrin heavy chain (HC) N-terminal domain (TD), which forms a seven-bladed β-propeller. TD binds membrane-associated adaptors, which have short peptide motifs, either the clathrin-box (CBM) and/or the W-box; however, the importance of the TD binding sites for these motifs has not been tested in vivo. We investigated the importance of the TD in clathrin function by generating 1) mutations in the yeast HC gene (CHC1) to disrupt the binding sites for the CBM and W-box (chc1-box), and 2) four TD-specific temperature-sensitive alleles of CHC1. We found that TD is important for the retention of resident TGN enzymes and endocytosis of α-factor; however, the known adaptor binding sites are not necessary, because chc1-box caused little to no effect on trafficking pathways involving clathrin. The Chc1-box TD was able to interact with the endocytic adaptor Ent2 in a CBM-dependent manner, and HCs encoded by chc1-box formed clathrin-coated vesicles. These data suggest that additional or alternative binding sites exist on the TD propeller to help facilitate the recruitment of clathrin to sites of vesicle formation.
Id3 Is a Direct Transcriptional Target of Pax7 in Quiescent Satellite Cells
Authors: Kumar Deepak , Shadrach Jennifer L. , Wagers Amy J. , Lassar Andrew B.
Published: May 2009

Pax7 is a key regulator of skeletal muscle stem cells and is required along with Pax3 to generate skeletal muscle precursors. We have identified a collection of genes induced by either Pax3 or Pax7 in C2C12 muscle cells. Two notable Pax3/7 targets are the inhibitory helix-loop-helix (HLH) proteins inhibitor of DNA binding (Id) 2 and Id3, both of which are coordinately expressed with Pax7 in quiescent satellite cells and are induced in quiescent C2C12 myogenic cells after ectopic expression of either Pax3 or Pax7. Ectopic Pax7 activates expression of a luciferase reporter driven by the Id3 promoter, and maximal induction of this reporter requires a conserved Pax7 binding site located upstream of the Id3 gene. Chromatin immunoprecipitation indicated that Pax7 is bound upstream of the Id3 promoter in quiescent satellite cells. In addition, short hairpin RNA-mediated knockdown of Pax7 expression in cultured satellite cells coordinately decreased both Id2 and Id3 expression. Together, these findings indicate that Id3 is a direct transcriptional target for Pax7 in quiescent satellite cells, and they suggest that Pax7 acts to block premature differentiation of quiescent satellite cells by inducing the expression of Id2 and Id3, which in turn may act to block either the precocious induction of myogenic basic (b)HLH proteins, the activity of myogenic bHLH proteins, or both.
Filamin A–β1 Integrin Complex Tunes Epithelial Cell Response to Matrix Tension
Authors: Gehler Scott , Baldassarre Massimiliano , Lad Yatish , Leight Jennifer L. , Wozniak Michele A. , Riching Kristin M. , Eliceiri Kevin W. , Weaver Valerie M. , Calderwood David A. , Keely Patricia J.
Published: May 2009

The physical properties of the extracellular matrix (ECM) regulate the behavior of several cell types; yet, mechanisms by which cells recognize and respond to changes in these properties are not clear. For example, breast epithelial cells undergo ductal morphogenesis only when cultured in a compliant collagen matrix, but not when the tension of the matrix is increased by loading collagen gels or by increasing collagen density. We report that the actin-binding protein filamin A (FLNa) is necessary for cells to contract collagen gels, and pull on collagen fibrils, which leads to collagen remodeling and morphogenesis in compliant, low-density gels. In stiffer, high-density gels, cells are not able to contract and remodel the matrix, and morphogenesis does not occur. However, increased FLNa-β1 integrin interactions rescue gel contraction and remodeling in high-density gels, resulting in branching morphogenesis. These results suggest morphogenesis can be “tuned” by the balance between cell-generated contractility and opposing matrix stiffness. Our findings support a role for FLNa-β1 integrin as a mechanosensitive complex that bidirectionally senses the tension of the matrix and, in turn, regulates cellular contractility and response to this matrix tension.
Randomized, Double-blind, Placebo-controlled, Dose-response, and Preclinical Safety Study of Transforaminal Epidural Etanercept for the Treatment of Sciatica
Authors: Cohen Steven P. , Bogduk Nikolai , Dragovich Anthony , Buckenmaier Chester C. , Griffith Scott , Kurihara Connie , Raymond JoLynne , Richter Philip J. , Williams Necia , Yaksh Tony L.
Published: May 2009

Background

Recent evidence implicates the inflammatory cytokine tumor necrosis factor as a major cause of radiculopathy. Yet, whereas open-label studies with systemically delivered tumor necrosis factor inhibitors have yielded positive results, a placebo-controlled study failed to demonstrate efficacy. One variable that may have contributed to poor outcomes is low drug levels at the site of nerve inflammation. To date, no studies have evaluated the efficacy or safety of epidurally administered anti-tumor necrosis factor agents.

Methods

A double-blind, placebo-controlled, dose-response study was conducted to evaluate an epidural tumor necrosis factor inhibitor. Twenty-four patients with subacute lumbosacral radiculopathy were randomly assigned to receive two transforaminal epidural injections of 2, 4, or 6 mg of entanercept 2 weeks apart in successive groups of eight. In each group, two patients received epidural saline. A parallel epidural canine safety study was conducted using the same injection doses and paradigm as in the clinical study.

Results

The animal and human safety studies revealed no behavioral, neurologic, or histologic evidence of drug-related toxicity. In the clinical arm, significant improvements in leg and back pain were collectively noted for the etanercept-treated patients, but not for the saline group, one month after treatment. One patient in the saline group (17%), six patients in the 2-mg group (100%), and four patients each in the 4-mg and 6-mg groups (67%) reported at least 50% reduction in leg pain and a positive global perceived effect one month after treatment. Six months after treatment, the beneficial effects persisted in all but one patient.

Conclusion

Epidural entanercept holds promise as a treatment for lumbosacral radiculopathy.
Localized Muscle Impedance Abnormalities in Amyotrophic Lateral Sclerosis
Authors: Tarulli Andrew W , Garmirian Lindsay P , Fogerson Patricia M , Rutkove Seward B
Published: May 2009

Objectives:

To assess changes in electrical impedance myography (EIM) parameters in amyotrophic lateral sclerosis (ALS).

Methods:

Ten patients with ALS and a cohort of normal subjects underwent EIM testing of tibialis anterior. Montages using voltage and current electrodes placed at a distance (far) and in close proximity (near) were compared. The EIM parameters, resistance (R), reactance (X), and phase (θ) in the patients with ALS, were compared with normal values.

Results:

θ measured at 50 kHz using the near montage was most sensitive to the presence of ALS, with 9 of 10 patients with ALS having smaller θ values than the calculated lower limit of normal. θ using the far montage and X using both the near and far montages were also sensitive to disease, whereas R did not seem to be useful.

Conclusion:

EIM is sensitive to muscle abnormalities in ALS, with θ measured with near montages providing the best results.