bluuebunny/crossref_metadata_2025 huggingface dataset:
Leg symptoms of healthy people and their treatment with compression hosiery
Authors: Blättler W , Kreis N , Lun B , Winiger J , Amsler F
Published: September 2008

Objectives

Occasional leg symptoms, like feelings of heaviness and tension, and occupational or evening oedema are considered typical features of a venous disorder but show low specificity in epidemiological and observational studies. We evaluated the prevalence and nature of such symptoms in subjects with no history or signs of venous disease and investigated the optimal strength that medical compression stockings (MCS) should exert in order to alleviate the symptoms and to prevent leg swelling.

Methods

Specifically designed questionnaires were used to assess the symptoms of 40 healthy employees of a factory producing MCS. Lower leg volumes were quantified in the morning and evening. Calf size hosiery providing documented ankle pressures of 4–9 (mean 7.3), 12–18 (mean 14.9) and 18–22 (mean 19.5) mmHg, respectively, were tested in a prospective, open-label, randomized trial lasting three weeks. Endpoints were the relief of symptoms, prevention of vesperal oedema and comfort in wearing the stockings.

Results

Sixty-five percent of the participants reported at least occasional leg symptoms and oedema. Somatic-type symptoms (i.e. pain, heaviness, swelling, unattractive legs) were present in two, psychic-type symptoms (i.e. leg- and personality-related unrest and stress) in 17 and both components in seven of the 40 subjects. MCS exerting 15 and 20 mmHg prevented the symptoms and oedema. Stockings providing <10 mmHg were ineffective and those providing >19 mmHg were not well-tolerated. The effect on the somatic-type symptoms was strongly correlated with the amount of lower leg volume which could be reduced by wearing stockings ( P = 0.005). No correlation was found between the efficacy of compression and the emotional component of the symptoms.

Conclusion

The cause of occasional pain in the legs of apparently healthy people is unknown. Some features of the syndrome reflect an emotional disorder while others mirror venous insufficiency. MCS of 15 mmHg effectively relieve the symptoms resembling venous insufficiency, prevent oedema and are well-tolerated.
Analysis and Design of a Type of Retractable Roof Structure
Authors: Mao Decan , Luo Yaozhi
Published: September 2008

This paper is concerned with the analysis and design of radially retractable roof structures (RRS). This new type of structure consists of a foldable lattice of angulated beams connected by scissor hinges to which cover plates or membranes are attached. However, the current design has two obvious shortcomings. First of all, there is a lack of a convenient way to keep all the pivots of an angulated beam within the boundary of its corresponding RRS plate. Secondly, the stiffness of the RRS is too small to resist external loads, which limits the practical application of this structure. This paper aims to tackle these two problems. Based on the analytical formulae given by previous studies, we propose a corresponding design method for the RRS plates and thus the designers can easily figure out plates which fit perfectly together for an RRS. To increase the stiffness of the RRS, a few support conditions for the RRS are discussed and then the structural behavior of numerical simulated models under different support conditions is investigated. Moreover, some measures to increase the stiffness of the RRS are proposed, providing additional choice to the designers. Physical model is built to demonstrate the design concepts and show that the geometrical and mechanical analysis is correct.
Cyclic Performance of Concrete Filled Steel Tubular Columns after Exposure to Fire: Analysis and Simplified Model
Authors: Han Lin Hai , Lin Xiao Kang , Yang You Fu
Published: September 2008

A mechanics model is developed in this paper for concrete filled steel tubular (CFST) columns subjected to constant axial load and cyclically increasing flexural loading after exposure to ISO-834 standard fire. The predicted cyclic responses for the composite columns are in good agreement with the test results. Based on the theoretical model, parametric analysis was performed on the behaviours of moment ( M) versus curvature ( ϕ) response, and lateral load ( P) versus lateral displacement (Δ) relationship for the composite columns after exposure to fire. Finally, simplified hysteretic models for the moment ( M) versus curvature ( ϕ) response, and the lateral load ( P) versus lateral displacement (Δ) relationship were suggested.
The effect of intron length on exon creation ratios during the evolution of mammalian genomes
Authors: Roy Meenakshi , Kim Namshin , Xing Yi , Lee Christopher
Published: September 2008

Recent studies report that alternatively spliced exons tend to occur in longer introns, which is attributed to the length constraints for splice site pairing for the two major splicing mechanisms, intron definition versus exon definition. Using genome-wide studies of EST and microarray data from human and mouse, we have analyzed the distribution of various subsets of alternatively spliced exons, based on their inclusion level and evolutionary history, versus increasing intron length. Alternative exons may be included in either a major or minor fraction of all transcripts (known as major-form and minor-form exons, respectively). We find that major-form exons are seven- to eightfold more likely to be contained in short introns (<400 nt) than minor-form exons, which occur preferentially in longer introns. Since minor-form exons are more likely to be novel (∼75%), this implied that novel exons arise more frequently in longer introns. To test this hypothesis, we used whole genome alignments to classify exons according to their phylogenetic age. We find that older exons, i.e., exons that are conserved in all mammals, predominate at shorter intron lengths, for both major- and minor-form exons. In contrast, exons that arose recently during primate evolution are more prevalent at longer intron lengths (>1000 nt). This suggests that the observed correlation of longer intron lengths with alternatively spliced exons may be at least partly due to biases in the probability of exon creation, which is higher in long introns.
From the Editor…
Authors: Keller L. Robin
Published: September 2008

All of the papers in this issue focus on the value of obtaining information about uncertainties. We begin with an article by J. Eric Bickel on “The Relationship Between Perfect and Imperfect Information in a Two-Action Risk-Sensitive Problem.” Next, is an article by Philippe Delquié on “The Value of Information and Intensity of Preference.” Our third article, which uses an example of an oilfield decision to demonstrate an approach to “Valuing Future Information Under Uncertainty Using Polynomial Chaos,” is by Michael Prange, William J. Bailey, Benoit Couët, Hugues Djikpesse, Margaret Armstrong, Alain Galli, and David Wilkinson. In the final article, Thomas Eppel and Detlof von Winterfeldt describe the calculation of value of information about the contents of waste storage tanks in “Value-of-Information Analysis For Nuclear Waste Storage Tanks.” Since information is the topic of this issue, our trivia question is about the late Jacob Marschak, from whom I learned about the economics of information and about clarity of thought.
Simulation-Based Optimization of Virtual Nesting Controls for Network Revenue Management
Authors: van Ryzin Garrett , Vulcano Gustavo
Published: September 2008

Virtual nesting is a popular capacity control strategy in network revenue management. In virtual nesting, products (itinerary-fare-class combinations) are mapped (“indexed”) into a relatively small number of “virtual classes” on each resource (flight leg) of the network. Nested protection levels are then used to control the availability of these virtual classes; specifically, a product request is accepted if and only if its corresponding virtual class is available on each resource required. Bertsimas and de Boer proposed an innovative simulation-based optimization method for computing protection levels in a virtual nesting control scheme [Bertsimas, D., S. de Boer. 2005. Simulation-based booking-limits for airline revenue management. Oper. Res. 53 90–106]. In contrast to traditional heuristic methods, this simulation approach captures the true network revenues generated by virtual nesting controls. However, because it is based on a discrete model of capacity and demand, the method has both computational and theoretical limitations. In particular, it uses first-difference estimates, which are computationally complex to calculate exactly. These gradient estimates are then used in a steepest-ascent-type algorithm, which, for discrete problems, has no guarantee of convergence.

In this paper, we analyze a continuous model of the problem that retains most of the desirable features of the Bertsimas-de Boer method, yet avoids many of its pitfalls. Because our model is continuous, we are able to compute gradients exactly using a simple and efficient recursion. Indeed, our gradient estimates are often an order of magnitude faster to compute than first-difference estimates, which is an important practical feature given that simulation-based optimization is computationally intensive. In addition, because our model results in a smooth optimization problem, we are able to prove that stochastic gradient methods are at least locally convergent. On several test problems using realistic networks, the method is fast and produces significant performance improvements relative to the protection levels produced by heuristic virtual nesting schemes. These results suggest it has good practical potential.
Socio‐economic status and handedness in two large cohorts of French adults
Authors: Faurie Charlotte , Bonenfant Sébastien , Goldberg Marcel , Hercberg Serge , Zins Marie , Raymond Michel
Published: September 2008

Left‐and right‐handers have coexisted since the Palaeolithic age. Hand preference is heritable. Moreover, there is extensive evidence of an association between left‐handedness and several fitness costs. In this context, the persistence of the polymorphism is interesting. Here, we explore the associations between socio‐economic status and handedness, analysing data from two large cohorts of adult men and women. Such associations are relevant to an evolutionary approach, as the socio‐economic and the reproductive value are related. Our results partly support the hypothesis that left‐handers have a socio‐economic status advantage, countervailing the health issues. Although the models explain a small proportion of the variance observed, the frequency of left‐handedness is significantly higher: (1) among women of higher educational level; (2) among categories of higher income; and (3) among individuals who have a higher position in the company. The importance of these findings for the evolution of the polymorphism of handedness is discussed.
Nutrition Education and Support Program for Community-Dwelling Adults With Intellectual Disabilities
Authors: Humphries Kathleen , Traci Meg Ann , Seekins Tom
Published: September 2008

To test the efficacy, acceptability, and appropriateness of a nutrition education and support program, 4 community-based group homes for adults with intellectual or developmental disabilities participated in a pilot intervention with extended baseline period and pre–post-test design. Adults (N = 32) with intellectual or developmental disabilities, 20 direct service staff, 4 managers of group homes, and 2 health specialists at private service providers participated in the intervention, consisting of a system of nutrition supports in nutrition education and guidelines, menu and meal planning, grocery shopping, and cooking designed for the special needs of this population. Positive impacts were found using the program, including fidelity measures, food systems changes and acceptability to users, planned and served foods, and cost changes associated with implementation.
Embedded, Constant Time Delay Instruction by Peers Without Disabilities in General Education Classrooms
Authors: Jameson J. Matt , McDonnell John , Polychronis Shamby , Riesen Tim
Published: September 2008

This study investigated the effects of a training package (written manual, individual training session, and ongoing verbal feedback) on middle school peer tutors' use of embedded, constant time delay procedures and on the learning outcomes for students with significant cognitive disabilities in general education settings. The study data showed that peer tutors could be trained quickly and efficiently to accurately use constant time delay and embedded instructional techniques in general education settings. The data also showed that peer tutors delivering embedded, constant time delay instruction in general education settings resulted in skill acquisition for students with significant cognitive disabilities. In addition, teacher and peer tutor measures were positive about the social validity of the procedures and outcomes of the peer-delivered embedded instructional package.
Slow-light dispersion in coupled periodic waveguides
Authors: Sukhorukov Andrey A. , Lavrinenko Andrei V. , Chigrin Dmitry N. , Pelinovsky Dmitry E. , Kivshar Yuri S.
Published: September 2008

Periodic waveguides bring a new twist to the typical waveguiding problems of the intermediate case between photonic crystal waveguides and photonic wires or ridge waveguides. We develop an asymptotic theory applicable for a broad class of coupled periodic waveguide structures and use the analytical expressions to identify the generic types of dispersion in the vicinity of a photonic band edge, where the group velocity of light is reduced. We show that the dispersion can be controlled by the longitudinal shift between the waveguides. We also demonstrate through finite-difference time-domain simulations examples of spatial and temporal pulse dynamics in association with different types of slow-light dispersion.
Simultaneous Measurement of Serum Testosterone and Dihydrotestosterone by Liquid Chromatography–Tandem Mass Spectrometry
Authors: Shiraishi Steve , Lee Paul W N , Leung Andrew , Goh Victor H H , Swerdloff Ronald S , Wang Christina
Published: September 2008

Background: Recent reports have described inherent problems with androgen immunoassays compared with mass spectrometry analyses.

Methods: We developed a method for measuring serum testosterone (T) and 5α-dihydrotestosterone (DHT) simultaneously via liquid–liquid extraction followed by liquid chromatography–tandem mass spectrometry (LC-MS/MS) with positive-mode electrospray ionization.

Results: The DHT and T calibrators showed a linear response from 0.069 nmol/L to 34.4 nmol/L and 69.3 nmol/L, respectively. T interference in the DHT assay and vice versa were negligible. Within- and between-run imprecision values were <5% for both analytes. Percent recoveries of T and DHT spiked into samples at concentrations spanning the calibration curve were 100%–113% and 98%–107%, respectively. The lower limit of quantification was 0.069 nmol/L for both steroids. Serum T concentrations measured by LC-MS/MS were different from those obtained by RIA, especially at lower T concentrations. Serum DHT concentrations measured by LC-MS/MS were markedly lower than those generated by RIA because of the nonselectivity of the RIA without chromatography. The reference intervals (mean ± 2 SDs) determined for T and DHT were 9.2–33.7 nmol/L and 0.47–2.65 nmol/L, respectively, for 113 healthy adult men and 0.33–2.02 nmol/L and 0.09–0.91 nmol/L, respectively, for 133 healthy premenopausal women.

Conclusions: We have developed and validated a selective and precise method for simultaneous measurements of serum T and DHT that can be adopted for routine measurements of these androgens in health and disease in men and women.
Neuronal Source of Plasma Dopamine
Authors: Goldstein David S , Holmes Courtney
Published: September 2008

Background: Determinants of plasma norepinephrine (NE) and epinephrine concentrations are well known; those of the third endogenous catecholamine, dopamine (DA), remain poorly understood. We tested in humans whether DA enters the plasma after corelease with NE during exocytosis from sympathetic noradrenergic nerves.

Methods: We reviewed plasma catecholamine data from patients referred for autonomic testing and control subjects under the following experimental conditions: during supine rest and in response to orthostasis; intravenous yohimbine (YOH), isoproterenol (ISO), or glucagon (GLU), which augment exocytotic release of NE from sympathetic nerves; intravenous trimethaphan (TRI) or pentolinium (PEN), which decrease exocytotic NE release; or intravenous tyramine (TYR), which releases NE by nonexocytotic means. We included groups of patients with pure autonomic failure (PAF), bilateral thoracic sympathectomies (SNS-x), or multiple system atrophy (MSA), since PAF and SNS-x are associated with noradrenergic denervation and MSA is not.

Results: Orthostasis, YOH, ISO, and TYR increased and TRI/PEN decreased plasma DA concentrations. Individual values for changes in plasma DA concentrations correlated positively with changes in NE in response to orthostasis (r = 0.72, P < 0.0001), YOH (r = 0.75, P < 0.0001), ISO (r = 0.71, P < 0.0001), GLU (r = 0.47, P = 0.01), and TYR (r = 0.67, P < 0.0001). PAF and SNS-x patients had low plasma DA concentrations. We estimated that DA constitutes 2%–4% of the catecholamine released by exocytosis from sympathetic nerves and that 50%–90% of plasma DA has a sympathoneural source.

Conclusions: Plasma DA is derived substantially from sympathetic noradrenergic nerves.
A Personalized Approach to Cancer Treatment: How Biomarkers Can Help
Authors: Duffy Michael J , Crown John
Published: September 2008

Background: The present approach to cancer treatment is often referred to as “trial and error” or “one size fits all.” This practice is inefficient and frequently results in inappropriate therapy and treatment-related toxicity. In contrast, personalized treatment has the potential to increase efficacy and decrease toxicity.

Content: We reviewed the literature relevant to prognostic, predictive, and toxicity-related markers in cancer, with particular attention to systematic reviews, prospective randomized trials, and guidelines issued by expert panels. To achieve personalized treatment for cancer, we need markers for determining prognosis, predicting response to therapy, and predicting severe toxicity related to treatment. Among the best-validated prognostic markers currently available are serum concentrations of α-fetoprotein (AFP), human chorionic gonadotropin (hCG), and lactate dehydrogenase (LDH) for patients with nonseminoma germ cell tumors and tissue concentrations of both urokinase plasminogen activator and plasminogen activator inhibitor 1 (PAI-1) for breast cancer patients. Clinically useful therapy predictive markers are estrogen and progesterone receptors to select patients with breast cancer for treatment with endocrine therapy and human epidermal growth factor receptor 2 (HER-2) to select breast cancer patients for treatment with trastuzumab (Herceptin). Markers available for identifying drug-induced adverse reactions include thiopurine methyltransferase (TPMT) to predict toxicity from thiopurines in the treatment of acute lymphoblastic leukemia and uridine diphosphate glucuronyltransferase to predict toxicity from irinotecan in the treatment of colorectal cancer.

Conclusions: Validated prognostic, predictive, and toxicity markers should help cancer treatment move from the current trial-and-error approach to more personalized treatment.
Monographs on drugs which are frequently analyzed in therapeutic drug monitoring / Arzneimittel-Monographien für Medikamente, die regelmäßig im Rahmen des Therapeutic Drug Monitorings analysiert werden
Authors: Rentsch Working group “Drug Monitoring” of the SSCC: Katharina , Eap Chin Bin , Fathi Marc , Grignaschi Nathalie , Magnin Jean-Luc , Thormann Wolfgang , Todesco Liliane , Werner Dominique
Published: September 2008

In addition to the monographs which have been published recently by the working group “Drug Monitoring” of the Swiss Society of Clinical Chemistry (SSCC) [1, 2], new monographs have been written. The aim of these monographs is to provide an overview on the information which is important for the request and interpretation of the results. Therefore, the targeted readers are laboratory health professionals and the receivers of the reports. In this series, aminoglycoside as well as glycopeptide antibiotics are presented. In addition, two antimycotic drugs, which are regularly quantified in sera of intensive care patients, are described. Also, the monograph on mebendazole is shown. This drug is often used in high doses for the treatment of infections with Echinococcus multilocularis for which the measurement of drug concentrations in serum is recommended. Information on the indication for therapeutic drug monitoring (TDM), protein binding, metabolic pathways and enzymes involved, elimination half-life and elimination routes, and therapeutic or toxic concentrations is provided. Because pre-analytical considerations are of particular importance for therapeutic drug monitoring, there is also information given at which time the determination of the drug concentration is reasonable and when steady-state concentrations are reached after changing the dose. Furthermore, the stability of the drug and its metabolite(s) after blood sampling is described. For readers with a specific interest, references to important publications are provided. The number of the monographs will be continuously increased. The updated files are presented on the homepage of the SSCC (www.sscc.ch). We hope that these monographs are helpful for the better handling of therapeutic drug monitoring and we are looking forward to comments by the readers.
Laboranalytik im Rahmen klinischer Studien unter Berücksichtigung der ICH-GCP-Leitlinie / Laboratory testing in clinical trials under consideration of the ICH-GCP guideline
Authors: Nordmann Stephan , Wieland Eberhard
Published: September 2008

Klinische Studien sind für die Einführung und Zulassung neuer Arzneimittel unverzichtbar. In den letzten Jahren haben sich die Regeln weltweit und damit auch die gesetzlichen Normen in Deutschland verschärft. Das Arzneimittelgesetz (AMG) hat die Inhalte der international harmonisierten Leitlinie zur Guten Klinischen Praxis (ICH-GCP) übernommen, welche die ethischen und qualitativen Bedingungen zur Durchführung klinischer Studien beschreiben. Da Laboruntersuchungen Bestandteil fast aller klinischen Studien zur Arzneimittelprüfung sind, gelten diese Normen auch für die Laboranalytik im Rahmen klinischer Studien. Unter Berücksichtigung dieser Normen und Gesetze ist zu fordern, dass Laboratorien und Laborärzte schon bei der Planung von klinischen Studien gehört werden sollten. Darüber hinaus sollte das Labor vor dem Beginn einer Studie in einem Prüfzentrum informiert werden. Am besten sollte ein getrennter Laborvertrag abgeschlossen werden und die Laborleistungen für klinische Studien separat nach der Gebührenordnung für Ärzte (GOÄ) honoriert werden. Die Vorlage von Ringversuchszertifikaten und die Bereitstellung eines Leistungsverzeichnisses nach Abschluss einer Studie reichen nach der Meinung der Autoren nicht aus, um dem AMG gerecht zu werden und um das Laborpersonal ausreichend juristisch abzusichern.
Histone Deacetylase Inhibitors Decrease Cocaine But Not Sucrose Self-Administration in Rats
Authors: Romieu Pascal , Host Lionel , Gobaille Serge , Sandner Guy , Aunis Dominique , Zwiller Jean
Published: September 2008

Regulation of gene expression is known to contribute to the long-term adaptations taking place in response to drugs of abuse. Recent studies highlighted the regulation of gene transcription in neurons by chromatin remodeling, a process in which posttranslational modifications of histones play a major role. To test the involvement of epigenetic regulation on drug-reinforcing properties, we submitted rats to the cocaine operant self-administration paradigm. Using the fixed ratio 1 schedule, we found that the histone deacetylase (HDAC) inhibitors trichostatin A and phenylbutyrate dose-dependently reduced cocaine self-administration. Under the progressive ratio schedule, both trichostatin A and depudecin significantly reduced the breaking point, indicating that HDAC inhibition attenuated the motivation of rats for cocaine. Conversely, HDAC inhibition did not decrease self-administration for the natural reinforcer sucrose. This observation was correlated with measurements of HDAC activity in the frontal cortex, which was inhibited in response to cocaine, but not to sucrose self-administration. Control experiments showed that the decrease in the motivation for the drug was not attributable to a general motivational dysfunction because trichostatin A had no adverse effect on locomotion during the habituation session or on cocaine-induced hyperlocomotion. It was not attributable to anhedonia because the inhibitor had no effect on the sucrose preference test. In contrast, trichostatin A completely blocked the cocaine-induced behavioral sensitization. Together, the data show that epigenetic regulation of gene transcription in adult brain is able to influence a motivated behavior and suggest that HDAC inhibition may counteract the neural sensitization leading to drug dependence.
Growth of White Matter in the Adolescent Brain: Role of Testosterone and Androgen Receptor
Authors: Perrin Jennifer S. , Hervé Pierre-Yves , Leonard Gabriel , Perron Michel , Pike G. Bruce , Pitiot Alain , Richer Louis , Veillette Suzanne , Pausova Zdenka , Paus Tomáš
Published: September 2008

The growth of white matter during human adolescence shows a striking sexual dimorphism; the volume of white matter increases with age slightly in girls and steeply in boys. Here, we provide evidence supporting the role of androgen receptor (AR) in mediating the effect of testosterone on white matter. In a large sample of typically developing adolescents (n= 408, 204 males), we used magnetic resonance imaging and acquired T1-weighted and magnetization transfer ratio (MTR) images. We also measured plasma levels of testosterone and genotyped a functional polymorphism in the AR gene, namely the number of CAG repeats in exon 1 believed to be inversely proportional to the AR transcriptional activity. We found that the testosterone-related increase of white-matter volume was stronger in male adolescents with the lower versus higher number of CAG repeats in the AR gene, with testosterone explaining, respectively, 26 and 8% of variance in the volume. The MTR results suggest that this growth is not related to myelination; the MTR decreased with age in male adolescents. We speculate that testosterone affects axonal caliber rather than the thickness of the myelin sheath.
Goal Representations Dominate Superior Colliculus Activity during Extrafoveal Tracking
Authors: Hafed Ziad M. , Krauzlis Richard J.
Published: September 2008

The primate superior colliculus (SC) has long been known to be involved in saccade generation. However, SC neurons also exhibit fixation-related and smooth-pursuit-related activity. A parsimonious explanation for these seemingly disparate findings is that the SC contains a map of behaviorally relevant goal locations, rather than just a motor map for saccades and fixation. This explanation predicts that SC activity should reflect the behavioral goal, even when the behavioral response is not fixation or saccades, and even if the goal does not correspond to a visual stimulus. We tested this prediction by using a tracking task that dissociates the stimulus and goal locations. In this task, monkeys tracked the invisible midpoint between two peripheral bars, such that the visual stimuli were peripheral but the goal was foveal/parafoveal. We recorded from SC neurons representing peripheral locations associated with the stimulus or central locations associated with the goal. Most neurons with peripheral response fields did not respond differently during tracking than during passive viewing of the stimulus under fixation; most neurons with central response fields responded more during tracking than during fixation, despite the lack of a visual stimulus. Moreover, the spatial distribution of activity during tracking was larger than that during fixation or tracking of a foveal stimulus, suggesting that the greater spatial uncertainty about the invisible goal corresponded to more widespread SC activity. These results demonstrate the flexibility with which activity across the SC represents the location, as well as the spatial precision, of behaviorally relevant goals for multiple eye movements.
Amplification of Transducer Gain by Angiotensin II-Mediated Enhancement of Cortical Actin Density in Osmosensory Neurons
Authors: Zhang Zizhen , Bourque Charles W.
Published: September 2008

Osmosensory neurons transduce osmotic signals into a neural spike code that commands behavioral and endocrine responses that mediate body fluid homeostasis. Although changes in osmoregulatory reflex gain are known to occur under physiological and pathological conditions, the basis for this modulation is unknown. Here, we show that angiotensin II amplifies osmosensory transduction by enhancing the proportional relationship between osmolality, receptor potential, and action potential firing in rat supraoptic nucleus neurons. This effect is mediated by a phospholipase C- and protein kinase C-dependent increase in cellular mechanosensitivity that is associated with a rapid increase in cortical actin filament density. Preventing this increase with cytochalasin D eliminated the enhancement of mechanosensitivity, whereas enhancing actin filament density with jasplakinolide potentiated mechanosensitivity and occluded the effects of angiotensin II. These results indicate that a receptor-mediated increase in cortical actin density can enhance osmosensitivity in acutely isolated supraoptic neurons.
Emergence of Novel Representations in Primary Motor Cortex and Premotor Neurons during Associative Learning
Authors: Zach Neta , Inbar Dorrit , Grinvald Yael , Bergman Hagai , Vaadia Eilon
Published: September 2008

Neurons in the motor areas of cortex play a key role in associating sensory instructions with movements. However, their ability to acquire and maintain representations of novel stimulus features, especially when these features are behaviorally relevant, remains unknown. We investigated neuronal changes in these areas during and after associative learning, by training monkeys on a novel reaching task that required associating target colors with movement directions. Before and after learning, the monkeys performed a well known center-out task. We found that during learning, up to 48% of the neurons developed learning-related responses, differentiating between the associative task and the center-out task, although movement kinematics were the same. After learning, on returning to the center-out task in which color was irrelevant, many of these neurons maintained their response to the associative task; they displayed novel sensitivity to the color of the target that was relevant during learning. These neuronal responses prevailed in both the primary motor cortex and the ventral and dorsal premotor cortices, without degrading the information that the neurons firing carried about movement direction. Our results show that motor cortical neurons can rapidly develop and maintain sensitivities to novel arbitrary sensory features such as color, when such features are behaviorally relevant.
Direct Cortical Inputs Erase Long-Term Potentiation at Schaffer Collateral Synapses
Authors: Izumi Yukitoshi , Zorumski Charles F.
Published: September 2008

Long-term potentiation (LTP), a synaptic mechanism thought to underlie memory formation, has been studied extensively at hippocampal Schaffer collateral (SC) synapses. The SC pathway transmits information to area CA1 that originates in entorhinal cortex and is processed by the dentate gyrus and area CA3. CA1 also receives direct excitatory input from entorhinal cortex via the perforant path (PP), but the role of this cortical input is less certain. Here, we report that low-frequency stimulation of PP inputs to CA1 has no lasting effect on basal SC transmission, but effectively depotentiates SC synapses that have undergone LTP in a manner that can be reversed by subsequent high-frequency stimulation of SC inputs. This depotentiation does not require NMDA receptors, group I metabotropic glutamate receptors, or L-type calcium channels, but involves adenosine acting at A1receptors. Given the limited storage capacity of the hippocampus, these observations provide a mechanism by which input from cortex can help to reset synaptic transmission in the hippocampus and facilitate additional information processing.
Decreased Striatal Dopamine Release Underlies Increased Expression of Long-Term Synaptic Potentiation at Corticostriatal Synapses 24 h after 3-Nitropropionic-Acid-Induced Chemical Hypoxia
Authors: Akopian Garnik , Crawford Cynthia , Beal M. Flint , Cappelletti Maurand , Jakowec Michael W. , Petzinger Giselle M. , Zheng Ling , Gheorghe Stacey L. , Reichel Carmela M. , Chow Robert , Walsh John P.
Published: September 2008

The striatum is particularly sensitive to the irreversible inhibitor of succinate dehydrogenase 3-nitropropionic acid (3-NP). In the present study, we examined early changes in behavior and dopamine and glutamate synaptic physiology created by a single systemic injection of 3-NP in Fischer 344 rats. Hindlimb dystonia was seen 2 h after 3-NP injections, and rats performed poorly on balance beam and rotarod motor tests 24 h later. Systemic 3-NP increased NMDA receptor-dependent long-term potentiation (LTP) at corticostriatal synapses over the same time period. The 3-NP-induced corticostriatal LTP was not attributable to increased NMDA receptor number or function, because 3-NP did not change MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine] binding or NMDA/AMPA receptor current ratios. The LTP seen 24 h after 3-NP was D1receptor dependent and reversed by exogenous addition of dopamine or a D2receptor agonist to brain slices. HPLC and fast-scan cyclic voltammetry revealed a decrease in dopamine content and release in rats injected 24 h earlier with 3-NP, and much like the enhanced LTP, dopamine changes were reversed by 48 h. Tyrosine hydroxylase expression was not changed, and there was no evidence of striatal cell loss at 24–48 h after 3-NP exposure. Sprague Dawley rats showed similar physiological responses to systemic 3-NP, albeit with reduced sensitivity. Thus, 3-NP causes significant changes in motor behavior marked by parallel changes in striatal dopamine release and corticostriatal synaptic plasticity.
Identification of Stem Cells During Prepubertal Spermatogenesis via Monitoring of Nucleostemin Promoter Activity
Authors: Ohmura Masako , Naka Kazuhito , Hoshii Takayuki , Muraguchi Teruyuki , Shugo Haruhiko , Tamase Akira , Uema Noriyuki , Ooshio Takako , Arai Fumio , Takubo Keiyo , Nagamatsu Go , Hamaguchi Isao , Takagi Minoru , Ishihara Masahiko , Sakurada Kazuhiro , Miyaji Hiromasa , Suda Toshio , Hirao Atsushi
Published: September 2008

The nucleostemin (NS) gene encodes a nucleolar protein found at high levels in several types of stem cells and tumor cell lines. The function of NS is unclear but it may play a critical role in S-phase entry by stem/progenitor cells. Here we characterize NS expression in murine male germ cells. Although NS protein was highly expressed in the nucleoli of all primordial germ cells, only a limited number of gonocytes showed NS expression in neonatal testes. In adult testes, NS protein was expressed at high levels in the nucleoli of spermatogonia and primary spermatocytes but at only low levels in round spermatids. To evaluate the properties of cells expressing high levels of NS, we generated transgenic reporter mice expressing green fluorescent protein (GFP) under the control of the NS promoter (NS-GFP Tg mice). In adult NS-GFP Tg testes, GFP and endogenous NS protein expression were correlated in spermatogonia and spermatocytes but GFP was also ectopically expressed in elongated spermatids and sperm. In testes of NS-GFP Tg embryos, neonates, and 10-day-old pups, however, GFP expression closely coincided with endogenous NS expression in developing germ cells. In contrast to a previous report, our results support the existence in neonatal testes of spermatogonial stem cells with long-term repopulating capacity. Furthermore, our data show that NS expression does not correlate with cell-cycle status during prepuberty, and that strong NS expression is essential for the maintenance of germline stem cell proliferation capacity. We conclude that NS is a marker of undifferentiated status in the germ cell lineage during prepubertal spermatogenesis.

Disclosure of potential conflicts of interest is found at the end of this article.
The delayed collapse of a 42 000 ton capacity RC cement storage silo
Authors: Blight G. E.
Published: September 2008

A large silo, designed to store 42 000 metric tons of cement powder, was commissioned in 1997 and operated successfully for a period of two years. During this period, all four main compartments of the radially divided ring silo were loaded and reloaded several times to their full capacity of 16 000 tons (central cylinder) or 7000 tons (three segmental ring silos). After two years, indications of structural problems caused the silo to be put out of service while its design was reviewed. Six months later, it was decided to fill one of the 7000 ton sub-silos, which then collapsed when emptying was started from full. The current paper reviews the operating history of the silo and its design, and describes strain measurements made during the final filling, before the collapse. It is concluded that the failure was caused by construction defects that had little effect at first, as the silo initially behaved as if uncracked. As cracking progressively developed, the defects had a more and more serious effect, eventually culminating in collapse of the silo.
Cyclic response of non-seismically detailed interior RC beam–column connection with varying column tributary area
Authors: Supaviriyakit T. , Pimanmas A. , Warnitchai P.
Published: September 2008

The current paper presents a test of non-seismically detailed reinforced-concrete (RC) beam–column connections under reversed cyclic load. The tested specimens represented those of the actual mid-rise RC frame buildings designed according to the non-seismic provisions of the American Concrete Institute building code. The evaluation of ten existing RC frames was conducted to identify key structural and geometrical indices. It was found that there was correlation among structural and geometrical characteristics and the column tributary area. Hence, the column tributary area was chosen as a parameter for classifying specimens. The test results showed that specimens representing small and medium column tributary areas failed by brittle joint shear while specimens representing large column tributary areas failed by ductile flexure, even though no ductile seismic details were provided. The local bond deterioration and joint shear distress accounted for the pinched hysteretic loops. The detailed failure mechanism was investigated through a nonlinear finite element analysis. In the finite element analysis, the two-dimensional reinforced concrete plate element was used to model beam and column whereas the one-dimensional discrete joint element was used to model the interface between beam and joint face. The finite element analysis revealed that the joint shear failure of specimens representing a small to medium column tributary area resulted from the collapse of the principal diagonal concrete strut.
Workability of air-entrained lightweight concrete from rheology perspective
Authors: Chia K.-S. , Zhang M.-H.
Published: September 2008

Effects of air entrainment on rheological parameters and slump of fresh lightweight aggregate concrete were studied. Results show that yield stress and plastic viscosity of air-entrained concrete were lower than those of non-air-entrained concrete with similar superplasticiser dosage. As the entrained-air content increased, the plastic viscosity decreased whereas the yield stress remained relatively unchanged. The slump of the air-entrained concrete was significantly higher than the non-air-entrained concrete. At similar yield stress, the slump of the air-entrained concrete was higher owing to its lower plastic viscosity by air entrainment. At similar slump, the air-entrained concrete had higher yield stress and lower plastic viscosity, implying that higher shear stress is needed to initiate flow but flow resistance would be lower.
Measuring Hypothetical Bias in Choice Experiments: The Importance of Cognitive Consistency
Authors: Johansson-Stenman Olof , Svedsäter Henrik
Published: September 2008

A choice experiment eliciting environmental values with both real and hypothetical trade-offs is set up in order to test for hypothetical bias. A larger hypothetical bias was found in a between-subject than in a within-subject design, using otherwise identical scenarios, which can explain previous diverging results in the literature. We argue that people strive for consistency between their attitudes and behaviors, leading them to act in ways that correspond with their prior hypothetical statements. People hence seem to prefer to do what they say they would do, although this may not always reflect their true preferences regarding the good being valued.
Competing for Recognition through Public Good Provision
Authors: Polborn Mattias K
Published: September 2008

We consider a setting in which several groups of individuals with common interests (``clubs") compete with each other for recognition by other individuals. Depending on the context, recognition may be expressed by these other individuals joining a club, or choosing one club to admire. Clubs compete by providing a public good. Competition between clubs increases the public good provision level, and a sufficiently strong competition effect may even lead to overprovision. The model thus limits the argument for subsidies to the private providers of public goods. We discuss implications of the model for open-source software projects, university fundraising and infrastructure competition between cities.
Dual Role of Interleukin-6 in Regulating Insulin Sensitivity in Murine Skeletal Muscle
Authors: Nieto-Vazquez Iria , Fernández-Veledo Sonia , de Alvaro Cristina , Lorenzo Margarita
Published: September 2008

OBJECTIVE—Cytokines are elevated in various insulin-resistant states, including type 2 diabetes and obesity, although the contribution of interleukin-6 (IL-6) in the induction of these diseases is controversial.

RESEARCH DESIGN AND METHODS—We analyzed the impact of IL-6 on insulin action in murine primary myocytes, skeletal muscle cell lines, and mice (wild type and protein-tyrosine phosphatase 1B [PTP1B] deficient).

RESULTS—IL-6 per se increased glucose uptake by activating serine/threonine protein kinase 11 (LKB1)/AMP-activated protein kinase/protein kinase B substrate of 160 kDa (AS160) pathway. A dual effect on insulin action was observed when myotubes and mice were exposed to this cytokine: additive with short-term insulin (increased glucose uptake and systemic insulin sensitivity) but chronic exposure produced insulin resistance (impaired GLUT4 translocation to plasma membrane and defects in insulin signaling at the insulin receptor substrate 1 [IRS-1] level). Three mechanisms seem to operate in IL-6–induced insulin resistance: activation of c-Jun NH2-terminal kinase 1/2 (JNK1/2), accumulation of suppressor of cytokine signaling 3 (socs3) mRNA, and an increase in PTP1B activity. Accordingly, silencing JNK1/2 with either small interfering RNA or chemical inhibitors impaired phosphorylation of IRS-1 (Ser307), restored insulin signaling, and normalized insulin-induced glucose uptake in myotubes. When using a pharmacological approach, liver X receptor agonists overcome IL-6–induced insulin resistance by producing downregulation of socs3 and ptp1b gene expression. Finally, the lack of PTP1B confers protection against IL-6–induced insulin resistance in skeletal muscle in vitro and in vivo, in agreement with the protection against the IL-6 hyperglycemic effect observed on glucose and insulin tolerance tests in adult male mice.

CONCLUSIONS—These findings indicate the important role of IL-6 in the pathogenesis of insulin resistance and further implicate PTP1B as a potential therapeutic target in the treatment of type 2 diabetes.
Evidence That Kidney Function but Not Type 2 Diabetes Determines Retinol-Binding Protein 4 Serum Levels
Authors: Henze Andrea , Frey Simone K. , Raila Jens , Tepel Martin , Scholze Alexandra , Pfeiffer Andreas F. H. , Weickert Martin O. , Spranger Joachim , Schweigert Florian J.
Published: September 2008

OBJECTIVE— It has been suggested that retinol-binding protein 4 (RBP4) links adiposity, insulin resistance, and type 2 diabetes. However, circulating RBP4 levels are also affected by kidney function. Therefore, the aim of this study was to test whether RBP4 serum levels are primarily associated with kidney function or type 2 diabetes.

RESEARCH DESIGN AND METHODS— RBP4 serum concentration was determined by enzyme-linked immunosorbent assay in 126 nondiabetic and 104 type 2 diabetic subjects. The study population was divided according to estimated glomerular filtration rate (eGFR) into the following groups: eGFR >90 ml/min per 1.73 m2 (n = 53), 60–90 ml/min per 1.73 m2 (n = 90), 30–60 ml/min per 1.73 m2 (n = 38), and <30 ml/min per 1.73 m2 (n = 49). Each group was subdivided into nondiabetic and type 2 diabetic subjects.

RESULTS— RBP4 serum concentration was elevated (2.65 vs. 2.01 μmol/l; P < 0.001) and eGFR was reduced (56 vs. 74 ml/min per 1.73 m2; P < 0.001) in type 2 diabetic vs. nondiabetic subjects, respectively. By stratifying for eGFR, no more differences in RBP4 serum concentration were detectable between type 2 diabetic and nondiabetic subjects. A linear regression analysis revealed an influence of eGFR (r = −0.477; P < 0.001) but not A1C (r = 0.093; P = 0.185) on RBP4 serum concentration.

CONCLUSIONS— Existing human data showing elevated RBP4 levels in type 2 diabetic patients may be the result of moderate renal insufficiency rather than support for the suggestion that RBP4 links obesity to type 2 diabetes.