bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling and Capturing Users' Actions in CSCL Systems for Collaboration Analysis Purposes
Authors: Duque Rafael , Bravo Crescencio , Gallardo Jesús , Giraldo William Joseph , Ortega Manuel
Published: March 2009

A significant number of CSCL (Computer-Supported Collaborative Learning) environments support the learning of groups of students enabling their collaboration in solving problems. These collaborative environments usually need additional computational support to allow the automatic processing of both the actions carried out by the students and the end solution with the aim of studying the learning process and the validity of the solution proposed to the problem. This process, known as Collaboration and Interaction Analysis, is typically carried out in three phases: observation, abstraction and intervention. In this paper, we propose a methodological approach for the design of mechanisms for the observation phase. This approach provides a set of procedures enabling developers to design observation systems in CSCL environments that capture and model all the information required for comprehensive analyses of the collaboration process and the resulting solution to the problem. This methodological approach is put into practice by means of its use in the design of an observation system in the SPACE-DESIGN (SPecification and Automatic Construction of collaborative Environments of DESIGN) collaborative environment.
A Virtual Laboratory Structure for Developing Programming Labs
Authors: Prieto-Blazquez Josep , Herrera-Joancomarti Jordi , Guerrero-Roldán Ana-Elena
Published: March 2009

Virtual Laboratories in a Virtual Learning Environment are indispensable spaces for developing practical activities. This paper proposes an integrated structure for Virtual Laboratories for undergraduate degree programmes in Computer Engineering and Software Engineering. The general structure proposed is based on the experience gained in designing and developing Virtual Laboratories during the past eleven years in a virtual university. Technological, pedagogical, strategic and academic staff resources are included in the Virtual Laboratories structure. The proposed structure has been applied to different computer areas and this paper presents the special case of a Virtual Programming Laboratory. Its effectiveness has been evaluated by the students using a web questionnaire.
Towards a Generalized Architecture for the Integration of Tools in LMSs
Authors: Fontenla Gonzalez Jorge , Caeiro Rodriguez Manuel , Llamas Nistal Martin
Published: March 2009

In this article we introduce the main components of a generalized architecture to facilitate the integration of tools in LMSs. This proposal tries to improve the reuse possibilities of the tools in e-learning systems. Reusability has been suggested as a key solution to reduce the high costs of the development of educational experiences in e-learning systems. Up to now, reutilization has focused mainly on the educational contents around metadata standards, contents formats, packaging systems, etc. However, educational practices usually involve tools to facilitate the communication, collaboration and work of students and teachers as well. This proposal is part of a wider solution based on the language PoEML, in which not only the possibility of the inclusion of tools in LMSs is considered, but also the management of its utilization.
Design of a Flexible and Adaptable LMS Engine in Conformance with PoEML
Authors: Pérez-Rodríguez Roberto , Caeiro-Rodriguez Manuel , Anido-Rifon Luis
Published: March 2009

This paper describes the support of the Structural, Functional, Order and Temporal perspectives in PoEML. PoEML is a modeling language devoted to support a broad range of pedagogical approaches, from content-based, to collaborative and practical oriented. At this point, a main issue is to provide a good level of adaptability and flexibility. The final goal is to support changes in the educational process development, enabling the provision of different learning experiences depending on the learning goals, the learner needs and features, the previous results, etc. The introduced solution is based on the separation of concerns principle adopted in PoEML. Basically, the solution facilitates the use of a set of educational resources in different ways by separating the form in which such resources are organized (Structural perspective) from the decisions of what has to be done (Functional perspective) and when (Order and Temporal perspectives).
Effects of a Centered Virtual Teaching Environment on Learning Styles in the Academic Performance of College Students
Authors: Iriarte Díaz-Granados Fernando Segundo , Dominguez E. , Ricardo C. , Fontalvo H.
Published: March 2009

Based on the concept of adaptive hypermedia, the webCT platform was used to design a learning virtual environment that would allow studentsâ?? interaction of different support materials with their usual styles of learning. GA Latin Square design was used to determine the role that environment and learning styles, along with intrinsic motivation, played on academic performance, navigation patterns, and number of visits to the support materials.

The study showed an important difference in academic performance in favor of the Balanced group. Intrinsic motivation was the main explicative factor for the differences found beyond learning styles. The conclusion was that there are differences in the way of using the objects of learning, and that there are differentiated patterns to access the support material, depending on the studentsâ?? learning styles.
Supporting the Quality of Learning Objects Through Their Ranking Visualization
Authors: Morales Morgado E. M. , Gómez Aguilar D.A , García Peñalvo F. J. , Therón Sánchez R.
Published: March 2009

The quality of Learning Objects (LOs) is currently being promoted by certain tools which consider specific criteria for their evaluation; however, there is no existing methodology that considers both the value assigned to the LO itself and the percentage related to the number of evaluators who have compared the quality of resources. As in the case of various products offered through the Internet backed by an assessment of users in a unified ranking, the purpose of this paper is to suggest a proposal for the automated assessments of experts who can clearly see the best or worst aspects in LO quality.
Surface Modification of Polymers
Authors: Kang E.T. , Neoh K.G.
Published: March 2009

Many applications require polymeric materials to be in contact with other materials or with specific environments. In this respect, the surface and interface properties of polymers cannot be overemphasized. This article describes, reviews, and updates the three most common surface modification techniques for synthetic polymers, viz, (i) plasma modification, (ii) surface grafting and graft polymerization, and (iii) chemical modification and reaction. Plasma modification involves surface energetic interactions, as well as plasma polymerization and deposition. Surface modification via grafting and graft polymerization generally involves the “grafting to” and “grafting from” approaches. The latter approach has been made even more versatile by the development of surface‐initiated controlled radical polymerizations in the late 1990s. Chemical modification of polymer surfaces includes ozone treatment, chemical and electrochemical redox reactions, sulfonation and halogenation, photochemical reactions, biologically influenced modification, and layer‐by‐layer coating. Finally, the effects of physical structures of modified surfaces are briefly discussed.
“Click” Chemistry in Macromolecular Synthesis
Authors: Binder Wolfgang H. , Zirbs Ronald
Published: March 2009

“Click” chemistry is a valuable tool in polymer science for the efficient linkage of functional entities, oligomers or polymers, yielding access to functional homo‐, block‐, star‐, graft‐polymers as well as higher polymeric architectures (dendrimers, hyperbranched polymers, supramolecular polymers, gels, polymer brushes). Besides other efficient “click” reactions, the copper‐(I)‐catalyzed 1,3‐dipolar‐azide/alkyne cycloaddition reaction has emerged as the method of choice to this and related purposes. Main advantage in relation to conventional linking reactions are (1) quantitative yields, (2) mild reaction conditions, (3) solvent and substrate insensitivity, and (4) high yielding reactions under both homogeneous and heterogeneous reaction conditions. The article describes basics of the reaction as well as applications in polymer science and technology.
Assessing the literacy skills of adult immigrants and adult English language learners
Authors: Wrigley Heide Spruck , Chen Jing , White Sheida , Soroui Jaleh
Published: March 2009

This chapter examines the characteristics and performance of adult immigrants and adult English language learners on the National Assessment of Adult Literacy. These factors are related to key social outcomes such as involvement in the labor force, income, and welfare participation, and the data reported can be used in making decisions about program planning, as well as in implementation of adult ESOL programs and services.
Best practices for teaching the “whole” adult ESL learner
Authors: Schwarzer David
Published: March 2009

Based on adult second‐language acquisition research and whole‐language principles, this chapter describes some best practices for teaching adults in ESL classrooms.
Journaling in an adult ESL literacy program
Authors: Larrotta Clarena
Published: March 2009

This chapter focuses on journal writing in adult ESL as a practice to promote literacy development and community building.
Final thoughts on community in adult ESL
Authors: Larrotta Clarena
Published: March 2009

This chapter discusses underlying themes and emergent issues related to community building and the learning and teaching of adult ESL.
The influence of heightened body‐awareness on walking through apertures
Authors: Lopresti‐Goodman Stacy , Kallen Rachel W. , Richardson Michael J. , Marsh Kerry L. , Johnston Lucy
Published: March 2009

The reported study measured the ratio between aperture‐width and hip‐width that marked the critical transition from frontal walking to body rotation for male and female participants. Half of the participants of each sex wore form‐fitting lycra clothes and half loose‐fitting jogging suits. Participants wearing the form‐fitting clothing reported heightened body awareness relative to those wearing the loose‐fitting clothing. For male participants this difference was reflected in a smaller aperture‐to‐hip ratio in the form‐fitting than loose‐fitting clothing condition. That is, males walked frontally through smaller apertures when wearing form‐fitting than when wearing loose‐fitting clothing. For females there was no difference in walking action as a function of clothing style. Results are discussed in terms of the perception of action opportunities in the environment, the influence of body awareness on such perception and sex differences. Copyright © 2009 John Wiley & Sons, Ltd.
Expert testimony in recovered memory trials: Effects on mock jurors' opinions, deliberations and verdicts
Authors: Buck Julie A. , Warren Amye R.
Published: March 2009

The current study examined the impact of adversarial expert testimony on deliberations and verdicts in a mock trial involving recovered memories of child sexual abuse. Participants (N = 238) were randomly assigned to one of the six conditions in a 2 (Defense Expert: absent or present) × 3 (Plaintiff Expert: absent, general or specific/therapist) factorial design. After reading the mock trial transcript, participants completed a questionnaire and deliberated to reach a jury verdict. The defense expert's statements effectively reduced the number of pro‐plaintiff verdicts and the plaintiff's credibility. These effects were not mitigated by the plaintiff experts, suggesting that the plaintiff experts may only confirm jurors' prior pro‐repression beliefs. Copyright © 2009 John Wiley & Sons, Ltd.
Characterizing visual behaviour in a lineup task
Authors: Mansour Jamal K. , Lindsay R. C. L. , Brewer Neil , Munhall K. G.
Published: March 2009

Eye tracking was used to monitor participants' visual behaviour while viewing lineups in order to determine whether gaze behaviour predicted decision accuracy. Participants viewed taped crimes followed by simultaneous lineups. Participants (N = 34) viewed 4 target‐present and 4 target‐absent lineups. Decision time, number of fixations and duration of fixations differed for selections vs. non‐selections. Correct and incorrect selections differed only in terms of comparison‐type behaviour involving the selected face. Correct and incorrect non‐selections could be distinguished by decision time, number of fixations and duration of fixations on the target or most‐attended face and comparisons. Implications of visual behaviour for judgment strategy (relative vs. absolute) are discussed. Copyright © 2009 John Wiley & Sons, Ltd.
Catalytic Deoxygenation of 1,2‐Propanediol to Give n‐Propanol
Authors: Schlaf Marcel , Ghosh Prasenjit , Fagan Paul J. , Hauptman Elisabeth , Bullock R. Morris
Published: March 2009

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Deoxygenation of 1,2‐propanediol (1.0 M in sulfolane) catalyzed by bis(dicarbonyl)(μ‐hydrido)(pentamethylcyclopentadiene)ruthenium trifluoromethanesulfonate ({[Cp*Ru(CO)2]2(μ‐H)}+OTf−) (0.5 mol%) at 110 °C under hydrogen (750 psi) in the presence of trifluoromethanesulfonic acid (HOTf) (60 mM) gives n‐propanol as the major product, indicating high selectivity for deoxygenation of the internal hydroxy group over the terminal hydroxy group of the diol. The deoxygenation of 1,2‐propanediol is strongly influenced by the concentration of acid, giving faster rates and proceeding to higher conversions as the concentration of HOTf is increased. Propionaldehyde was observed as an intermediate, being formed through acid‐catalyzed dehydration of 1,2‐propanediol. This aldehyde is hydrogenated to n‐propanol through an ionic pathway involving protonation of the aldehyde, followed by hydride transfer from the neutral hydride, dicarbonyl(pentamethylcyclopentadiene)ruthenium hydride [Cp*Ru(CO)2H]. The proposed mechanism for the deoxygenation/hydrogenation reaction involves formation of a highly acidic dihydrogen complex [Cp*Ru(CO)2(η2‐H2)]+ OTf−.
Transition Metal‐Catalysed, Direct and Site‐Selective N1‐, C2‐ or C3‐Arylation of the Indole Nucleus: 20 Years of Improvements
Authors: Joucla Lionel , Djakovitch Laurent
Published: March 2009

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The direct and site‐selective transition metal‐catalysed N1‐, C2‐ or C3‐arylations of indoles have been the subject of almost continuous improvements since their discovery in early 1980s. This research area is mainly motivated by the biological relevance of this class of compounds in order to propose catalytic alternative syntheses to the well known methodologies involving the formation of the indole ring like the Fischer, Larock, Cacchi, Lautens etc. reactions. Since the late 1990s it has experienced new impulses related to the intensive development of catalytic CH activation. Today, through the intensive studies of Buchwald and Hartwig, the N1‐arylation of indoles has reached sufficient maturity for both academic and industrial applications. On the other hand, the selective C2‐ or C3‐arylation of indoles, initiated by Ohta in the middle 1980s, has become a hot research area these last years following the reports of Sames. Surprisingly, only few reports concern the use of heterogeneous catalysts; however, the application of these emerging methodologies seems to be related to the discovery of industrially attractive systems.
Capillary forces between two solid spheres linked by a concave liquid bridge: Regions of existence and forces mapping
Authors: Megias‐Alguacil David , Gauckler Ludwig J.
Published: March 2009

This article focuses on the capillary interactions arising when two spherical particles are connected by a concave liquid bridge. This scenario is found in many situations where particles are partially wetted by a liquid, like liquid films stabilized with nanoparticles. We analyze different parameters governing the liquid bridge: interparticle separation, wetting angle and liquid volume. The results are compiled in a liquid volume‐wetting angle diagram in which the regions of existence (stability) or inexistence (instability) of the bridge are outlined and the possible maximum and minimal particle distances for which the liquid bridge may be found. Calculations of the capillary forces discriminate those conditions for which such force is repulsive or attractive. The results are plotted in form of maps that allow an easy understanding of the stability of a liquid bridge and the conditions at which it may be produced for the two particle model. © 2009 American Institute of Chemical Engineers AIChE J, 2009
Impact of vitamin D deficiency on the clinical presentation and prognosis of patients with newly diagnosed multiple myeloma
Authors: Ng Alvin C. , Kumar Shaji K. , Rajkumar S. Vincent , Drake Matthew T.
Published: March 2009

Vitamin D is a fundamental mediator of skeletal metabolism. It also has important nonskeletal actions. We hypothesized that vitamin D deficiency may play an important role in skeletal morbidity and clinical outcomes in MM. We studied 148 newly diagnosed MM patients from January 1, 2004 through December 31, 2008 who had a serum 25‐hydroxyvitamin D [25(OH)D] obtained within 14 days of diagnosis. Subjects with vitamin D deficiency [25(OH)D level less than 50 nmol/L (20 ng/mL)] had higher mean values of serum C‐reactive protein (CRP) (2.40 mg/L vs. 0.84 mg/L, P = 0.02) and creatinine (1.75 mg/dL vs. 1.24 mg/dL, P = 0.03) and lower serum albumin values (3.12 g/dL vs. 3.39 g/dL, P = 0.003) compared to subjects without vitamin D deficiency. The prevalence of vitamin D deficiency increased in parallel with International Staging System (ISS): 16% of subjects in Stage I, 20% in Stage II, and 37% in Stage III (P = 0.03) were vitamin D deficient. No differences were detected between the two groups in terms of skeletal morbidity. Association of vitamin D deficiency with higher serum CRP, serum creatinine and ISS stage at time of diagnosis suggests that vitamin D deficiency may portend poorer outcomes in subjects with MM. Am. J. Hematol. 2009. © 2009 Wiley‐Liss, Inc.
Does being an orphan decrease the nutritional status of Luo children?
Authors: Zidron Amy M. , Juma Elizabeth , Ice Gillian H.
Published: March 2009

The HIV/AIDS pandemic is creating a generation of orphaned children in Africa. The number of orphans will continue to increase long after the HIV/AIDS crisis has peaked; therefore, it is important to determine how best to assist these children. Current studies investigating the impact of orphanhood have conflicting results and conclusions. Several studies report that orphans are at a disadvantage and are more likely to suffer from malnutrition, whereas other studies report no difference between the nutritional status of orphans and nonorphans. Four hundred eleven Luo children (mean age 9 ± 1 years) were recruited to participate in a study investigating the impact of orphanhood on nutritional status. Participants underwent an interview, anthropometric measurements, testing for anemia, a clinical history, and a physical exam. Anthropometric variables and hemoglobin level were compared across groups using a t‐test. The reference population used for comparison of anthropometric variables is the 2000 CDC growth reference data. All analyses were gender specific, and the effect of length of orphanhood was also investigated. The data presented here suggest that there is no significant difference between the nutritional status of orphaned and nonorphaned Luo children. This study supports research indicating there is little, if any, difference in nutritional indicators between orphans and nonorphans. Orphans may live in households with higher socioeconomic statuses than nonorphans. Luo orphans may not be at higher risk for poor nutritional status than nonorphans; therefore, interventions targeted at this age group should include both orphaned and nonorphaned children. Am. J. Hum. Biol., 2009. © 2009 Wiley‐Liss, Inc.
A geometric morphometric approach to the quantification of population variation in sub‐Saharan African crania
Authors: Franklin Daniel , Cardini Andrea , Oxnard Charles E.
Published: March 2009

We report here on new data examining cranial variation in 18 modern human sub‐Saharan African populations. Previously, we investigated variation within southern Africa; we now extend our analyses to include a series of Central, East, and West African crania, to further knowledge of the relationships between, and variation and regional morphological patterning in, those populations. The sample comprises 377 male individuals; the three‐dimensional coordinates of 96 landmarks are analyzed using Procrustes‐based methods. Interpopulation variation is examined by calculating shape distances between groups, which are compared using resampling statistics and parametric tests. Phenotypic variance, as a proxy for genetic variance, is measured and compared across populations. Principal components and cluster analyses are employed to explore relationships between the populations. Shape differences are visualized using three‐dimensional rendered models. Observed disparity patterns imply a mix of differences and similarities across populations, with no apparent support for genetic bottlenecks, which is likely a consequence of migrations that may have influenced differences in cranial form; supporting data are found in recent molecular studies. The Pygmy sample had the most distinctive cranial morphology; characteristically small in size with marked prognathism. These features characterized, although less strongly, the neighboring Bateke, and are possibly related to similar selective pressures in conjunction with interbreeding. Small cranial size is also involved in the considerable distinctiveness of the San and Khoikhoi. The statistical procedures applied in this study afford a powerful and robust means of quantifying and visualizing the magnitude and pattern of cranial variation between sub‐Saharan African populations. Am. J. Hum. Biol., 2010. © 2009 Wiley‐Liss, Inc.
Short‐ and long‐term consequences of early parental loss in the historical population of the Krummhörn (18th and 19th century)
Authors: Willführ Kai P.
Published: March 2009

The impact of the early loss of one's father or one's mother on the survival and age at death of children was investigated on the basis of a historical reconstitution of families from the Krummhörn (East Frisia/Ostfriesland; Germany) with the aid of Kaplan‐Meier plots and the Cox regression. In our analyses, we took into account the changed situation of the family after the death of a parent by incorporating the surviving spouse's remarriage or relationships with stepparents. We find that the impact on survival of the children was sex‐specific and also depended on whether and at what point in time during childhood their father or mother had died. As expected, children's immediate survival was strongly affected by maternal loss. A few results can be construed as survival diminishing long‐term consequences of the early loss of a parent. Daughters who lost their fathers before their first birthday proved to have increased mortality over a longer period of their youth. The age at death of daughters was also lowered if they had to live with a step‐mother during early childhood. To interpret these results, three hypotheses, including an (intrinsic) trade‐off, compensation and a selection scenario, were tested. Other approaches, which are based, for example, on the extrinsic trade‐off between mating effort and parental investment of the surviving parent, also appear to be suitable as an explanation for the long‐term consequences, which eventually draws the conclusion that the compensation scenario is the most likely explanation for the consequences of early parental loss. Am. J. Hum. Biol., 2009. © 2009 Wiley‐Liss, Inc.
A linkage search for joint panic disorder/bipolar genes
Authors: Logue Mark W. , Durner Martina , Heiman Gary A. , Hodge Susan E. , Hamilton Steven P. , Knowles James A. , Fyer Abby J. , Weissman Myrna M.
Published: March 2009

There is comorbidity and a possible genetic connection between Bipolar disease (BP) and panic disorder (PD). Genes may exist that increase risk to both PD and BP. We explored this possibility using data from a linkage study of PD (120 multiplex families; 37 had ≥1 BP member). We calculated 2‐point lodscores maximized over male and female recombination fractions by classifying individuals with PD and/or BP as affected (PD + BP). Additionally, to shed light on possible heterogeneity, we examine the pedigrees containing a bipolar member (BP+) separately from those that do not (BP−), using a Predivided‐Sample Test (PST). Linkage evidence for common genes for PD + BP was obtained on chromosomes 2 (lodscore = 4.6) and chromosome 12 (lodscore = 3.6). These locations had already been implicated using a PD‐only diagnosis, although at both locations this was larger when a joint PD + BP diagnosis was used. Examining the BP+ families and BP− families separately indicates that both BP+ and BP− pedigrees are contributing to the peaks on chromosomes 2 and 12. However, the PST indicates different evidence of linkage is obtained from BP+ and BP− pedigrees on chromosome 13. Our findings are consistent with risk loci for the combined PD + BP phenotype on chromosomes 2 and 12. We also obtained evidence of heterogeneity on chromosome 13. The regions on chromosomes 12 and 13 identified here have previously been implicated as regions of interest for multiple psychiatric disorders, including BP. © 2009 Wiley‐Liss, Inc.
Role of n‐type voltage‐dependent calcium channels in autoimmune optic neuritis
Authors: Gadjanski Ivana , Boretius Susann , Williams Sarah K. , Lingor Paul , Knöferle Johanna , Sättler Muriel B. , Fairless Richard , Hochmeister Sonja , Sühs Kurt‐Wolfram , Michaelis Thomas , Frahm Jens , Storch Maria K. , Bähr Mathias , Diem Ricarda
Published: March 2009

Objective

The aim of this study was to investigate the role of voltage‐dependent calcium channels (VDCCs) in axon degeneration during autoimmune optic neuritis.

Methods

Calcium ion (Ca2+) influx into the optic nerve (ON) through VDCCs was investigated in a rat model of optic neuritis using manganese‐enhanced magnetic resonance imaging and in vivo calcium imaging. After having identified the most relevant channel subtype (N‐type VDCCs), we correlated immunohistochemistry of channel expression with ON histopathology. In the confirmatory part of this work, we performed a treatment study using ω‐conotoxin GVIA, an N‐type specific blocker.

Results

We observed that pathological Ca2+influx into ONs during optic neuritis is mediated via N‐type VDCCs. By analyzing the expression of VDCCs in the inflamed ONs, we detected an upregulation of α1B, the pore‐forming subunit of N‐type VDCCs, in demyelinated axons. However, high expression levels were also found on macrophages/activated microglia, and lower levels were detected on astrocytes. The relevance of N‐type VDCCs for inflammation‐induced axonal degeneration and the severity of optic neuritis was corroborated by treatment with ω‐conotoxin GVIA. This blocker led to decreased axon and myelin degeneration in the ONs together with a reduced number of macrophages/activated microglia. These protective effects were confirmed by analyzing the spinal cords of the same animals.

Interpretation

We conclude that N‐type VDCCs play an important role in inflammation‐induced axon degeneration via two mechanisms: First, they directly mediate toxic Ca2+influx into the axons; and second, they contribute to macrophage/microglia function, thereby promoting secondary axonal damage. Ann Neurol 2009;66:81–93
Vascular endothelial growth factor gene transfer for diabetic polyneuropathy: A randomized, double‐blinded trial
Authors: Ropper Allan H. , Gorson Kenneth C. , Gooch Clifton L. , Weinberg David H. , Pieczek Ann , Ware James H. , Kershen Joshua , Rogers Adam , Simovic Drasko , Schratzberger Peter , Kirchmair Rudolf , Losordo Douglas
Published: March 2009

Objective

Randomized, blinded trial of intramuscular gene transfer using plasmid vascular endothelial growth factor (VEGF) to treat diabetic polyneuropathy.

Methods

Diabetic patients with polyneuropathy were randomized to receive a VEGF‐to‐placebo ratio of 3:1. Three sets of injections were given at eight standardized sites adjacent to the sciatic, peroneal, and tibial nerves of one leg. Primary outcomes were change in symptom score at 6 months and a prespecified overall clinical and electrophysiological improvement score. Secondary outcomes were differences in symptoms, examination scores, visual analog pain scale, nerve conduction, and quantitative sensory testing.

Results

Thirty‐nine patients received plasmid VEGF and 11 received placebo. Mean symptom score improved in both legs at 6 months, favoring VEGF over placebo (−1.2 ± 0.5 vs −0.9 ± 0.5; p < 0.01 after adjustment for change in the untreated leg) and compared with the untreated leg (−0.7 ± 0.5; p = 0.02). The region of sensory loss and visual analog pain scale improved in the treated group (−1.5 vs −0.5; p = 0.01). Twelve of 39 VEGF versus 2 of 11 placebo patients met criterion for overall improvement. Other measures including nerve conduction potentials did not improve. There were 84 adverse events in VEGF patients, and 22 were serious; there were 51 events in placebo patients, and 2 were serious.

Interpretation

Intramuscular plasmid VEGF gene transfer improved diabetic neuropathic symptoms, meeting primary end‐point criteria for efficacy but not affecting most secondary measures. Treatment was associated with more serious adverse events that did not reach statistical significance. These results are not conclusive but may justify further clinical study. Ann Neurol 2009;65:386–393
Insulin‐like growth factor‐1 and neurotrophin‐3 gene therapy prevents motor decline in an X‐linked adrenoleukodystrophy mouse model
Authors: Mastroeni Roberto , Bensadoun Jean‐Charles , Charvin Delphine , Aebischer Patrick , Pujol Aurora , Raoul Cédric
Published: March 2009

X‐linked adrenoleukodystrophy (X‐ALD) is the most common inherited peroxisomal disorder characterized by a progressive demyelination of the central nervous system. The marked loss of myelin and oligodendrocytes observed in the disease prompted us to evaluate the therapeutic potential of insulin‐like growth factor‐1 and neurotrophin‐3, two potent inducers of myelin formation and oligodendrocyte survival. Viral vectors engineered to produce insulin‐like growth factor‐1 or neurotrophin‐3 were administrated into the cerebrospinal fluid of an X‐linked adrenoleukodystrophy mouse model. We show that viral‐based, long‐lasting delivery of insulin‐like growth factor‐1 and neurotrophin‐3 significantly halts the progression of the disease and leads to potent protective effect against the demyelination process. Ann Neurol 2009;66:117–122
A novel Nav1.7 mutation producing carbamazepine‐responsive erythromelalgia
Authors: Fischer Tanya Z. , Gilmore Elaine S. , Estacion Mark , Eastman Emmanuella , Taylor Sean , Melanson Michel , Dib‐Hajj Sulayman D. , Waxman Stephen G.
Published: March 2009

Objective

Human and animal studies have shown that Nav1.7 sodium channels, which are preferentially expressed within nociceptors and sympathetic neurons, play a major role in inflammatory and neuropathic pain. Inherited erythromelalgia (IEM) has been linked to gain‐of‐function mutations of Nav1.7. We now report a novel mutation (V400M) in a three‐generation Canadian family in which pain is relieved by carbamazepine (CBZ).

Methods

We extracted genomic DNA from blood samples of eight members of the family, and the sequence ofSCN9Acoding exons was compared with the reference Nav1.7 complementary DNA. Wild‐type Nav1.7 and V400M cell lines were then analyzed using whole‐cell patch‐clamp recording for changes in activation, deactivation, steady‐state inactivation, and ramp currents.

Results

Whole‐cell patch‐clamp studies of V400M demonstrate changes in activation, deactivation, steady‐state inactivation, and ramp currents that can produce dorsal root ganglia neuron hyperexcitability that underlies pain in these patients. We show that CBZ, at concentrations in the human therapeutic range, normalizes the voltage dependence of activation and inactivation of this inherited erythromelalgia mutation in Nav1.7 but does not affect these parameters in wild‐type Nav1.7.

Interpretation

Our results demonstrate a normalizing effect of CBZ on mutant Nav1.7 channels in this kindred with CBZ‐responsive inherited erythromelalgia. The selective effect of CBZ on the mutant Nav1.7 channel appears to explain the ameliorative response to treatment in this kindred. Our results suggest that functional expression and pharmacological studies may provide mechanistic insights into hereditary painful disorders. Ann Neurol 2009;65:733–741
Circulating endothelial microparticles as a marker of cerebrovascular disease
Authors: Jung Keun‐Hwa , Chu Kon , Lee Soon‐Tae , Park Hee‐Kwon , Bahn Jae‐Jun , Kim Dong‐Hyun , Kim Jin‐Hee , Kim Manho , Kun Lee Sang , Roh Jae‐Kyu
Published: March 2009

Objective

Circulating endothelial microparticles (EMPs) have been reported to reflect vascular damage. Detailed profiling of these blood endothelial markers may adumbrate the pathogenesis of stroke or enable determination of the risk for stroke. We investigated EMP profiles in patients at risk for cerebrovascular disease.

Methods

We prospectively examined 348 consecutive patients: 73 patients with acute stroke and 275 patients with vascular risk factors but no stroke events. We quantified various types of EMPs by flow cytometry using CD31, CD42b, annexin V (AV), and CD62E antibodies in the peripheral blood of patients. This method allowed fractionation of CD31+/CD42b−, CD31+/AV+, and CD62E+ EMPs. Clinical and laboratory factors associated with EMPs were assessed.

Results

Recent ischemic episodes were found to be more strongly associated with greater CD62E+ EMP levels than with levels of other phenotypes. Increased National Institutes of Health Stroke Scale scores and infarct volumes in acute stroke patients were significantly associated with greater CD62E+ EMP levels. In the risk factor group, patients with extracranial arterial stenosis had greater CD62E+ EMP levels, whereas those with intracranial arterial stenosis had greater CD31+/CD42b− and CD31+/AV+ EMP levels. The ratio of CD62E+ to CD31+/CD42b− or CD31+/AV+ EMP level significantly discriminated extracranial and intracranial arterial stenosis.

Interpretation

Circulating EMP phenotypic profiles reflect distinct phenotypes of cerebrovascular disease and are markers of vascular pathology and an increased risk for ischemic stroke. Ann Neurol 2009;66:191–199
Advances in the basic and clinical science of migraine
Authors: Charles Andrew
Published: March 2009

Migraine continues to be an elephant in the room of medicine: massively common and a heavy burden on patients and their healthcare providers, yet the recipient of relatively little attention for research, education, and clinical resources. Its visibility is gradually increasing, however, as advances in genetics, imaging, epidemiology, and pharmacology produce a more definitive understanding of the condition, and identify more specific and effective treatments. Rapid evolution of concepts regarding its prevalence, pathophysiology, and clinical management is leading to growing recognition of migraine as a fundamentally important disorder of the nervous system. Ann Neurol 2009;65:491–498
Specific central nervous system recruitment of HLA‐G+ regulatory T cells in multiple sclerosis
Authors: Huang Yu‐Hwa , Zozulya Alla L. , Weidenfeller Christian , Metz Imke , Buck Dorothea , Toyka Klaus V. , Brück Wolfgang , Wiendl Heinz
Published: March 2009

Objective

We have recently described a novel population of natural regulatory T cells (Treg) that are characterized by the expression of HLA‐G and may be found at sites of tissue inflammation (HLA‐Gpos Treg). Here we studied the role of these cells in multiple sclerosis (MS), a prototypic autoimmune inflammatory disorder of the central nervous system (CNS).

Methods

Sixty‐four patients with different types of MS, 9 patients with other neurological diseases, and 20 healthy donors were included in this study. Inflamed brain lesions from 5 additional untreated MS patients were examined. HLA‐Gpos Treg were analyzed in the cerebrospinal fluid (CSF) by flow cytometry and in inflammatory demyelinating lesions of MS brain specimens by immunohistochemistry. Functional capacity was accessed and transmigration was determined using an in vitro model of the human blood‐brain barrier (BBB).

Results

HLA‐Gpos Treg were found enriched in the inflamed CSF of MS patients and in inflammatory demyelinating lesions of MS brain specimens. HLA‐Gpos Treg showed a strong propensity to transmigrate across BBB, which was vigorously driven by inflammatory chemokines, and associated with a gain of suppressive capacity upon transmigration. CSF‐derived HLA‐Gpos Treg of MS patients represented a population of activated central memory activated T cells with an upregulated expression of inflammatory chemokine receptors and exhibiting full suppressive capacity. Unlike natural FoxP3‐expressing Treg, HLA‐Gpos Treg derived from peripheral blood were functionally unimpaired in MS.

Interpretation

In MS, HLA‐Gpos Treg may serve to control potentially destructive immune responses directly at the sites of CNS inflammation and to counterbalance inflammation once specifically recruited to the CNS. Ann Neurol 2009
The neuropathology of probable Alzheimer disease and mild cognitive impairment
Authors: Schneider Julie A. , Arvanitakis Zoe , Leurgans Sue E. , Bennett David A.
Published: March 2009

Objective

Mixed pathologies are common in older persons with dementia. Little is known about mixed pathologies in probable Alzheimer disease (AD) and about the spectrum of neuropathology in mild cognitive impairment (MCI). The objective of this study was to investigate single and mixed common age‐related neuropathologies in persons with probable AD and MCI.

Methods

The study included 483 autopsied participants from the Religious Orders Study and the Rush Memory and Aging Project with probable AD (National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association criteria), MCI (amnestic and nonamnestic), or no cognitive impairment. We excluded 41 persons with clinically possible AD and 14 with other dementias. We documented the neuropathology of AD (National Institute on Aging–Reagan criteria), macroscopic cerebral infarcts, and neocortical Lewy body (LB) disease.

Results

Of 179 persons (average age, 86.9 years) with probable AD, 87.7% had pathologically confirmed AD, and 45.8% had mixed pathologies, most commonly AD with macroscopic infarcts (n = 54), followed by AD with neocortical LB disease (n = 19) and both (n = 8). Of the 134 persons with MCI, 54.4% had pathologically diagnosed AD (58.7% amnestic; 49.2% nonamnestic); 19.4% had mixed pathologies (22.7% amnestic; 15.3% nonamnestic). Macroscopic infarcts without pathologically diagnosed AD accounted for 4.5% of probable AD, 13.3% of amnestic MCI, and 18.6% of nonamnestic MCI. Pure neocortical LB disease was uncommon in all persons with cognitive impairment (<6%). Microscopic infarcts (without macroscopic infarcts) were common as a mixed pathology, but rarely accounted for a clinical diagnosis of probable AD (n = 4) or MCI (n = 3).

Interpretation

Clinically diagnosed probable AD and MCI, even amnestic MCI, are pathologically heterogeneous disorders, with many persons exhibiting mixed pathologies. Ann Neurol 2009;66:200–208
Schutzgruppengesteuerte Oberflächenchemie – Organisation und temperaturinduzierte Kupplung von 4,4′‐Di(tert‐Butoxycarbonylamino)biphenyl auf Metalloberflächen
Authors: Boz Serpil , Stöhr Meike , Soydaner Umut , Mayor Marcel
Published: March 2009

Wie die Perlen einer Kette wurden molekulare Bausteine auf einer Oberfläche vororganisiert, um sie anschließend miteinander zu verbinden. Dabei wurde sowohl die supramolekulare Anordnung der Reaktanten als auch die anschließende thermische Aktivierung zur Verknüpfung von der Schutzgruppe bestimmt.

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Biotin–Avidin as a Protease‐Responsive Cap System for Controlled Guest Release from Colloidal Mesoporous Silica
Authors: Schlossbauer Axel , Kecht Johann , Bein Thomas
Published: March 2009

Regelbare Freisetzung: Wenn Avidin als „Deckel“ an biotinyliertem kolloidalem mesoporösem Silica angebracht wird, können seine vier Untereinheiten einzeln an Biotin‐Gruppierungen an der Oberfläche binden (siehe Bild). Das erhaltene Material ist ein vielversprechender Kandidat für die Entwicklung intelligenter Detergenzien oder Wirkstofftransportsysteme. Die Deckel können durch kontrollierte enzymatische Hydrolyse geöffnet werden, um Gastmoleküle freizusetzen.

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Selective Isomerization of Epoxides to Allylic Alcohols Catalyzed by TiO2‐Supported Gold Nanoparticles
Authors: Raptis Christos , Garcia Hermenegildo , Stratakis Manolis
Published: March 2009

Ringöffnungs‐ReakTiO2nen: Goldnanopartikel auf TiO2 vermitteln die heterogenkatalysierte Isomerisierung von Epoxiden zu Allylalkoholen nach einem konzertierten Mechanismus (siehe Schema). Die Reaktion liefert die Produkte in hohen Ausbeuten und mit bemerkenswerter Selektivität.

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Solution‐Based Direct Growth of Organic Crystals on an Active Channel Region for Printable Bottom‐Contact Organic Field‐Effect Transistors
Authors: Hong Jung‐Pyo , Lee Seonghoon
Published: March 2009

Wachstum und Selbstorganistation organischer Kristalle zwischen Source(S)‐ und Drain(D)‐Elektrode lieferten – unter Verwendung einer Mikropipette und isothermem Abdampfen des Lösungsmittels in einem Zwei‐Flüssigkeiten‐System – organisch‐kristalline Transistoren (siehe Mikroskopieaufnahme unter polarisiertem Licht). Die Methode ähnelt dem Tintenstrahldruck und dürfte für die kostengünstige Fabrikation gedruckter Elektroniken in großem Maßstab geeignet sein.

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Wasserstoffbrücken in protischen ionischen Flüssigkeiten – Ähnlichkeiten mit Wasser
Authors: Fumino Koichi , Wulf Alexander , Ludwig Ralf
Published: March 2009

Ähnlichkeiten und Unterschiede: Die Banden in den Ferninfrarotspektren protischer ionischer Flüssigkeiten konnten intermolekularen Deformations‐ und Streckschwingungen von Wasserstoffbrücken zugeordnet werden. Die charakteristischen Beiträge im Niedrigfrequenzbereich ähneln stark denen des Wassers. Offensichtlich nehmen beide Flüssigkeiten dreidimensionale Netzwerkstrukturen ein, aber nur Wasser bildet tetraedrische Konfigurationen. EAN: Ethylammoniumnitrat, PAN: Propylammoniumnitrat, DMAN: Dimethylammoniumnitrat.

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Selective Adsorption of DNA on Chiral Surfaces: Supercoiled or Relaxed Conformation
Authors: Gan Hui , Tang Kangjian , Sun Taolei , Hirtz Michael , Li Yong , Chi Lifeng , Butz Stefan , Fuchs Harald
Published: March 2009

Adsorption bestimmt Konformation: DNA‐Moleküle gehen chiralitätsabhängige Wechselwirkungen mit Goldoberflächen ein, die mit L‐ oder D‐N‐Isobutyrylcystein modifiziert wurden. Auf der L‐Oberfläche werden die Moleküle fest adsorbiert und in eine relaxierte Konformation gezwungen, während sie auf der D‐Oberfläche ihre superhelicale Konformation als Zeichen einer schwächeren Adsorption behalten (siehe Bild).

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Palladium‐Catalyzed Oxidative Intermolecular Difunctionalization of Terminal Alkenes with Organostannanes and Molecular Oxygen
Authors: Urkalan Kaveri Balan , Sigman Matthew S.
Published: March 2009

Ein kationischer Palladiumkomplexkatalysiert die Titelreaktionen, die vermutlich über ein π‐Allyl‐ oder π‐Benzylintermediat verlaufen. Die Regioselektivität (1,2‐ oder 1,1‐Difunktionalisierung) hängt davon ab, ob die terminale Doppelbindung des Substrats konjugiert ist oder nicht (siehe Schema) und scheint vom Verhältnis der Geschwindigkeiten von β‐Hydrideliminierung und Transmetallierung bestimmt zu sein. DMA=Dimethylacetamid, Tf=Triflyl.

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Supramolecular Chiral Transcription and Recognition by Mesoporous Silica Prepared by Chiral Imprinting of a Helical Micelle
Authors: Qiu Huibin , Inoue Yoshihisa , Che Shunai
Published: March 2009

Eine Helix findet Nachahmer: Die Chiralität einer helicalen, propellerähnlichen Micelle wurde von funktionellen Gruppen auf der Oberfläche einer Mesopore von chiralem mesoporösem Siliciumdioxid übernommen. Eine derart eingeprägte supramolekulare Chiralität kann auf das Natriumsalz von Poly(propiolsäure) und auf Tetraphenylporphin‐Tetrasulfonsäure übertragen werden (siehe Bild) und wird von B‐DNA erkannt.

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Protecting‐Group‐Controlled Surface Chemistry—Organization and Heat‐Induced Coupling of 4,4′‐Di(tert‐butoxycarbonylamino)biphenyl on Metal Surfaces
Authors: Boz Serpil , Stöhr Meike , Soydaner Umut , Mayor Marcel
Published: March 2009

Like pearls on a string, molecular building blocks have been preorganized and then interlinked on a surface (see STM images). In this way both the supramolecular self‐assembly of the reactants as well as the subsequent thermal activation to release the protecting group are controlled.

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Selective Isomerization of Epoxides to Allylic Alcohols Catalyzed by TiO2‐Supported Gold Nanoparticles
Authors: Raptis Christos , Garcia Hermenegildo , Stratakis Manolis
Published: March 2009

ReacTiO2ns for rings: Gold nanoparticles supported on TiO2 are used as a novel heterogeneous catalyst for the isomerization of epoxides to allylic alcohols by a concerted mechanism (see scheme). The reaction proceeds in high yields and the product selectivity is often remarkable.

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Selective Adsorption of DNA on Chiral Surfaces: Supercoiled or Relaxed Conformation
Authors: Gan Hui , Tang Kangjian , Sun Taolei , Hirtz Michael , Li Yong , Chi Lifeng , Butz Stefan , Fuchs Harald
Published: March 2009

The right fit: Plasmid DNA molecules show chirality‐dependent interaction with gold surfaces modified by L and D N‐isobutyrylcysteine. Relaxed DNA molecules have a stronger interaction and adsorption on the L surface, while their counterparts on the D surface maintain a supercoiled conformation, indicating a weak interaction (see picture).

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Towards an Integrated Chemical Circuit
Authors: Belder Detlev
Published: March 2009

Everything on a chip: Recent developments in microfluidics enable the combination of droplet microfluidics with continuous‐flow systems (see picture). This is a promising step towards the development of integrated, complex synthesis and analysis laboratories on chips. For example, a building‐block principle could be used to integrate a multistep reaction with purification and analysis.

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Devising Boron Reagents for Orthogonal Functionalization through Suzuki–Miyaura Cross‐Coupling
Authors: Tobisu Mamoru , Chatani Naoto
Published: March 2009

Seeing the sites: The Suzuki–Miyaura reaction of substrates containing multiple coupling sites has been performed in a directed manner through the reactivity modulation of the boron moiety (see scheme). Several other strategies are also discussed.

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Correction of Errors during Protein Synthesis
Authors: Sprinzl Mathias
Published: March 2009

Quality control: The incorporation of a wrong amino acid into a growing polypeptide chain induces a correction step in which the release factor (RF1) hydrolyzes the peptide from the incorrectly matched peptidyl‐tRNA (see picture). The nascent erroneous polypeptide is released from the ribosome and degraded.

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