bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibitory Effect of Lamotrigine on A‐type Potassium Current in Hippocampal Neuron–Derived H19‐7 Cells
Authors: Huang Chin‐Wei , Huang Chao‐Ching , Liu Yen‐Chin , Wu Sheng‐Nan 
Published: July 2004

Summary:  Purpose: We investigated the effects of lamotrigine (LTG) on the rapidly inactivating A‐type K+ current (IA) in embryonal hippocampal neurons. Methods: The whole‐cell configuration of the patch‐clamp technique was applied to investigate the ion currents in cultured hippocampal neuron–derived H19‐7 cells in the presence of LTG. Effects of various related compounds on IA in H19‐7 cells were compared. Results: LTG (30 μM–3 mM) caused a reversible reduction in the amplitude of IA. The median inhibitory concentration (IC50) value required for the inhibition of IA by LTG was 160 μM. 4‐Aminopyridine (1 mM), quinidine (30 μM), and capsaicin (30 μM) were effective in suppressing the amplitude of IA, whereas tetraethylammonium chloride (1 mM) and gabapentin (100 μM) had no effect on it. The time course for the inactivation of IA was changed to the biexponential process during cell exposure to LTG (100 μM). LTG (300 μM) could shift the steady‐state inactivation of IA to a more negative membrane potential by approximately −10 mV, although it had no effect on the slope of the inactivation curve. Moreover, LTG (100 μM) produced a significant prolongation in the recovery of IA inactivation. Therefore in addition to the inhibition of voltage‐dependent Na+ channels, LTG could interact with the A‐type K+ channels to suppress the amplitude of IA. The blockade of IA by LTG does not simply reduce current magnitude, but alters current kinetics, suggesting a state‐dependent blockade. LTG might have a higher affinity to the inactivated state than to the resting state of the IA channel. Conclusions: This study suggests that in hippocampal neurons, during exposure to LTG, the LTG‐mediated inhibition of these K+ channels could be one of the ionic mechanisms underlying the increased neuronal excitability.
Differential Effects of Antiepileptic Drugs on Sexual Function and Reproductive Hormones in Men with Epilepsy: Interim Analysis of a Comparison between Lamotrigine and Enzyme‐inducing Antiepileptic Drugs
Authors: Herzog Andrew G. , Drislane Frank W. , Schomer Donald L. , Pennell Page B. , Bromfield Edward B. , Kelly Kevin M. , Farina Erin L. , Frye Cheryl A. 
Published: July 2004

Summary:  Purpose: We compared sexual function and reproductive hormone levels among men with localization‐related epilepsy (LRE) taking various antiepileptic drugs (AEDs) and normal controls (NC). Methods: Subjects were 63 men with LRE [enzyme‐inducing (EI) AEDs, 36; lamotrigine (LTG), 18; no AEDs, 9] and 18 NC. Sexual interest and function (S‐score), hormone levels [bioactive testosterone (BAT) and estradiol (BAE)], hormone ratios [BAT/BAE], and gonadal efficiency [BAT/luteinizing hormone (LH)] were compared among the groups. Results: S‐scores, BAT levels, BAT/BAE, and BAT/LH were significantly lower in the EIAED group than in NC or LTG groups. Sex hormone–binding globulin (SHBG) was significantly higher in the EIAED group than in all other groups. Of men with LRE, 23.8% had abnormally low S‐scores: 33.3% taking EIAEDs, 5.5% taking LTG, and 22.2% taking no AEDs (p < 0.01). BAT was low in 55.6% taking EIAEDs as compared with 33.3% taking LTG and 33.3% taking no AEDs (p < 0.05). Among men with low S‐scores, 86.7% had low BAT as compared with 33.3% of men with normal scores (p < 0.01). BAT decline with age was greater among men with LRE than in controls (3.75 vs. 1.80 ng/dl/yr). The slope showed no significant difference among LRE groups. However, 89% of 40‐ to 50‐year‐old men taking EIAEDs had low BAT as compared with 33% taking LTG and 33% taking no AED (p < 0.01). Conclusions: Sexual function, BAT levels, BAT/BAE, and gonadal efficiency are greater with LTG than with EIAED. Abnormally low BAT levels are reached at an earlier age with EIAEDs than with LTG.
John Hughlings‐Jackson's Writings on the Auditory Aura and Localization of the Auditory Cortex
Authors: Hogan R. Edward , Kaiboriboon Kitti 
Published: July 2004

Summary: Purpose:To relate John Hughlings‐Jackson's findings of the auditory aura to his ideas about the “dreamy state,” and localization of primary auditory cortex.Methods:We reviewed Hughlings‐Jackson's writings on the auditory aura and his integration of the auditory aura into his description of the “dreamy state.”  To integrate Hughlings‐Jackson's postulations about the auditory aura and David Ferrier's localization of primary auditory cortex, we also reviewed Ferrier's localization of auditory cortex in animals.Results:Hughlings‐Jackson described three cases of the auditory aura, which he integrated with his concept of the “dreamy state” (now known as mesial temporal epilepsy). In doing so, he described the current concept of elementary and complex auditory auras. Hughlings‐Jackson also associated the auditory aura with seizures that began in the “auditory centre of Ferrier.” Whereas Ferrier showed respect and admiration for Hughlings‐Jackson's work as a whole, he did not integrate Hughlings‐Jackson's ideas of localization of the auditory epileptic aura with his work in localizing the primary auditory cortex in animals.Conclusions:Hughlings‐Jackson outlined the modern concept of elementary and complex auditory auras and correctly correlated it with primary auditory cortex. The history of Hughlings‐Jackson's auditory aura reflects the history of his ideas of epilepsy as a whole, which closely parallel our modern concepts of focal epilepsy.
Surgical Treatment of Temporoparietooccipital Cortical Dysplasia in Infants: Report of Two Cases
Authors: Daniel Roy Thomas , Meagher‐Villemure Kathleen , Roulet Eliane , Villemure Jean‐Guy 
Published: July 2004

Summary:  Purpose: Extensive multilobar cortical dysplasia in infants commonly is first seen with catastrophic epilepsy and poses a therapeutic challenge with respect to control of epilepsy, brain development, and psychosocial outcome. Experience with surgical treatment of these lesions is limited, often not very encouraging, and holds a higher operative risk when compared with that in older children and adults. Methods: Two infants were evaluated for surgical control of catastrophic epilepsy present since birth, along with a significant psychomotor developmental delay. Magnetic resonance imaging showed multilobar cortical dysplasia (temporoparietooccipital) with a good electroclinical correlation. They were treated with a temporal lobectomy and posterior (parietooccipital) disconnection. Results: Both infants had excellent postoperative recovery and at follow‐up (1.5 and 3.5 years) evaluation had total control of seizures with a definite “catch up” in their development, both motor and cognitive. No long‐term complications have been detected to date. Conclusions: The incorporation of disconnective techniques in the surgery for extensive multilobar cortical dysplasia in infants has made it possible to achieve excellent seizure results by maximizing the extent of surgical treatment to include the entire epileptogenic zone. These techniques decrease perioperative morbidity, and we believe would decrease the potential for the development of long‐term complications associated with large brain excisions.
Local contributions to the Euler–Poincaré characteristic of a set
Authors: JERNOT J. P. , JOUANNOT‐CHESNEY P. , LANTUEJOUL C. 
Published: July 2004

SummaryThe Euler–Poincaré characteristic (EPC) of a polyconvex subset X of Rd can be evaluated by covering the subset with an auxiliary tessellation, measuring its contribution within each cell of the tessellation and adding all contributions. Two different ways are proposed to define the contribution of a cell to the EPC of X. These contributions turn out to be related by duality formulae. Finally, three applications are given: the measurement of the EPC on adjacent fields, the measurement of the EPC on discretized images and the detection of defects in atomic structures.
Combining intensity, edge and shape information for 2D and 3D segmentation of cell nuclei in tissue sections
Authors: WÄHLBY C. , SINTORN I.‐M. , ERLANDSSON F. , BORGEFORS G. , BENGTSSON E. 
Published: July 2004

SummaryWe present a region‐based segmentation method in which seeds representing both object and background pixels are created by combining morphological filtering of both the original image and the gradient magnitude of the image. The seeds are then used as starting points for watershed segmentation of the gradient magnitude image. The fully automatic seeding is done in a generous fashion, so that at least one seed will be set in each foreground object. If more than one seed is placed in a single object, the watershed segmentation will lead to an initial over‐segmentation, i.e. a boundary is created where there is no strong edge. Thus, the result of the initial segmentation is further refined by merging based on the gradient magnitude along the boundary separating neighbouring objects. This step also makes it easy to remove objects with poor contrast. As a final step, clusters of nuclei are separated, based on the shape of the cluster. The number of input parameters to the full segmentation procedure is only five. These parameters can be set manually using a test image and thereafter be used on a large number of images created under similar imaging conditions. This automated system was verified by comparison with manual counts from the same image fields. About 90% correct segmentation was achieved for two‐ as well as three‐dimensional images.
Experimental secondary electron spectra under SEM conditions
Authors: JOY D. C. , PRASAD M. S. , MEYER H. M. 
Published: July 2004

SummarySecondary electron spectra have been collected from both pure elements and from compounds examined under conditions approximating those found in a scanning electron microscope. Despite the presence of substantial surface contamination these spectra are found to be reproducible and characteristic of the underlying material. Typically the peak in such spectra is found to be at an energy of about 5 eV, and 50% of the total secondary electron emission falls within the range 0–12 eV. These data may be of value for the design of detectors for scanning microscopy and might have applications for microanalysis.
An attempt to artificially select Strongyloides ratti for resistance to the host immune response
Authors: Wilkes C. P. , Viney M. E. 
Published: July 2004

SUMMARY Previous work has selected Heligmosomoides polygyrus for increased survival and reproduction in hosts with prior exposure to H. polygyrus, and therefore ‘immune’ to this parasite. We investigated whether Strongyloides ratti would respond similarly to selection for survival and reproduction in S. ratti‐immune hosts. During 32 generations of selection, there appeared to be an initial, brief response to this selection, but this was not sustained and, eventually, the immune‐selected line died out. Specific measures of the response to selection at generations 6, 12 and 25 did not detect any significant response to selection. Therefore, we have failed to select a line of S. ratti for increased resistance to its host immune response.
Analysis of Ehrlichia ruminantium‐specific T1/T2 responses during vaccination with a protective killed vaccine and challenge of goats
Authors: Esteves I. , Vachiéry N. , Martinez D. , Totté P. 
Published: July 2004

SUMMARYEhrlichia ruminantium is an obligate intracellular bacterium that causes heartwater in ruminants and for which T‐cell‐mediated immunity is believed to play an important role in protection. To better characterize protective cellular immunity, E. ruminantium‐specific IFN‐γ and IL‐4 recall responses in major T‐cell subsets were analysed by flow cytometry during immunization of goats with a killed vaccine and following a virulent challenge. The killed vaccine elicited both CD8+ and CD4+ subsets to produce cytoplasmic IFN‐γ in the absence of IL‐4, thus indicating a biased T1 response. The relative capacity of CD8+ T‐cells to produce IFN‐γ was significantly higher than CD4+ T‐cells but the final contribution of both subsets was comparable. Circulating ER‐specific CD4 and CD8 effectors substantially decreased in numbers after the booster injection and could not be detected in most animals during challenge, which warrants further investigation in immune compartments other than blood. Since IFN‐γ inhibits the growth of the pathogen in target cells, the information provided in this study on E. ruminantium‐specific T1 responses will be valuable to develop cellular tools for the identification of potential protective antigens.
Managing a Portfolio of Interdependent New Product Candidates in the Pharmaceutical Industry
Authors: Blau Gary E. , Pekny Joseph F. , Varma Vishal A. , Bunch Paul R. 
Published: July 2004

Highly regulated industries such as pharmaceuticals and agrochemicals face the challenge of maintaining a 0continuous stream of new products. This is difficult because of low probabilities of technical success, high development costs, uncertain market impact, a scarcity of good new product ideas, and limited human and capital resources available to develop them. The problem of evaluating and selecting which new products to develop and then of sequencing or of scheduling them is complicated further by the presence of dependencies between products both in the market place and in the development process itself.This study proposes a portfolio management approach that selects a sequence of projects, which maximizes the expected economic returns at an acceptable level of risk for a given level of resources in a new product development pipeline. A probabilistic network model of distinct activities is used to capture all the activities and resources required in the “process” of developing a new drug. A prioritization scheme suggesting sequences for developing new independent drug candidates with unlimited resources is generated with a conventional bubble chart approach. These sequences initiate a genetic algorithm (GA)‐based search for the optimal sequence in the presence of product dependencies and limited resources. By statistically evaluating the sequences generated during the GA search using a discrete event simulation model, it is possible to construct an economic reward‐risk frontier that illustrates the trade‐offs between expected rewards and risks. The model ideally is suited to answer various “what if” questions relative to changes in the resource level on pipeline performance.The methodology is illustrated with an industrially motivated case study, involving nine interdependent new product candidates targeting three diseases. The dramatic results yield a candidate sequence with an expected return 28 percent higher than the sequence suggested by the bubble chart approach at almost the same level of risk. The synergism among the candidate dependencies, pipeline resources, and economic and technical uncertainties demonstrates the necessity of a computationally intensive approach if the best development strategy is to be realized.
Visualizing the Self: Exploring the Potential Benefits and Drawbacks for New Product Evaluation
Authors: Dahl Darren W. , Hoeffler Steve 
Published: July 2004

This study examines the role of visual processing in new product evaluation. The primary goal of this research was to provide insights into the role of visualization content (self‐related versus others‐related images) in product evaluation as it differentially relates to two separate types of products—incremental products and really new products. This study's results show that for incremental products, visualizing with self‐related images (versus others‐related images) led to higher evaluations. In this context, it seems that familiarity with the product category from which an incremental product extension is generated enables individuals to produce images easily where they can see themselves using the new product. In some sense, self‐related visualization might be thought of as a form of surrogate experience with the new product. The ability to self‐reference during evaluation provides positive benefits to the evaluation outcome.Contrasting this result, this study's findings showed that for really new product introductions the previously identified benefits of self‐visualization were not realized. Confirming this study's prediction, the advantage of self‐visualization over others‐related visualization was lost. This is attributed to consumer difficulty in visualizing the full application of a really new product to their current consumption behavior. Of further interest, this study's results also showed that in the case of really new products others‐related visualization facilitated higher evaluations than self‐visualization.The mediating role of visualization‐based evaluation difficulty provides further explanation for these findings. Self‐related images are shown to be difficult to imagine in a really new product context, whereas imagining others utilizing the really new product is shown to be significantly easier. Perhaps individuals can see the benefits and better understand the novel applications of a really new product when visually simulating someone else using it but have more trouble imagining the applicability of the innovation in their own life. These findings are integrated into a discussion of the managerial implications and the potential avenues for future research in the area.
Organizational Learning and New Product Introductions
Authors: Michael Steven C. , Palandjian Tracy Pun 
Published: July 2004

Organizational learning widely is believed to be important to competitive performance of companies. The purpose of this article is to examine how organizations learn from their experiences in new product introductions. Theory suggests that organizations will display a “competency trap” that reduces their ability to learn from organizational experience. Often initial success can cause a firm to rely on a single or a few experiences to develop routines, discounting later experiences. Therefore it is expected that organizations will have trouble learning from experience.The theory was tested by examining all new product introductions in the U.S. shampoo industry from 1974–1987. The dynamic nature of the business—the average brand survives about two years—made this an attractive research venue. Using the econometric technique of survival time modeling, a model was fitted of survival of brands as a function of organizational experience and organizational experience squared. The model also included controls for financial resources available to the firm and the level of first year's advertising. The model confirmed the general hypothesis that firms' brands are less successful the more experience they have. This study interprets this as evidence of a competency trap in new product introductions.The results broadly are supportive of the hypothesis that organizations find it harder to learn from experience as experience grows. Untangling the source of this problem is a goal of further research. For practice, the article suggests caution to brand managers in experienced companies. There is no guarantee that firms grow in their ability to build brands; results here suggest the opposite. Formal reviews of the new product, its process, and its performance by senior managers for lessons learned is desirable. Management of individuals and organizations may facilitate learning from experience. For managing individuals, often product success brings about a reassignment of successful personnel; care should be taken to insure that individuals' learning is captured by the new product organization before reassignment. On the organizational level, formal brand management may be a highly effective method for managing an ongoing stable of long‐lived brands but may be a poor choice in a dynamic market like shampoo. Companies may explore new organizational structures and departments to conceive and to develop new products since the skills required for managing ongoing brands may be different from creating new ones.
Magnaporthe grisea interactions with the model grass Brachypodium distachyon closely resemble those with rice (Oryza sativa)
Authors: ROUTLEDGE ANDREW P. M. , SHELLEY GREG , SMITH JOEL V. , TALBOT NICHOLAS J. , DRAPER JOHN , MUR LUIS A. J. 
Published: July 2004

SUMMARYGermplasm of Brachypodium distachyon was inoculated with Magnaporthe grisea using either rice‐ (Guy11) or grass‐adapted (FAG1.1.1, PA19w‐06, PA31v‐01) host‐limited forms of the fungus, and interactions with varying degrees of susceptibility and resistance were identified. Ecotype ABR5 was resistant to each M. grisea strain whereas ABR1 was susceptible to all but P31vi‐01. Mendelian segregation in ABR1 × ABR5 crosses suggested that a single dominant resistance gene conferred resistance to Guy11. Microscopic analyses revealed that the aetiology of Guy11 fungal development and disease progression in ABR1 closely resembled that of rice infections. In ABR5, Guy11 pathogenesis was first suppressed at 48 h post‐inoculation, at the secondary hyphal formation stage and was coincident with cytoplasmic granulation. Resistance to strains PA31v‐01 and FAG1.1.1 was associated with a localized cell death with little callose deposition. 3,3‐Diaminobenzidine staining indicated the elicitation of cell death in B. distachyon was preceded by oxidative stress in the interacting epidermal cells and the underlying mesophyll cells. Northern blot hybridization using probes for barley genes (PR1, PR5 and PAL) indicated that each was more rapidly expressed in ABR5 challenged with Guy11 although the B. distachyon defence genes BD1 and BD8 were more quickly induced in ABR1. Such data show that B. distachyon is an appropriate host for functional genomic investigations into M. grisea pathology and plant responses.
MicroRNAs: more than a role in plant development?
Authors: LLAVE CESAR 
Published: July 2004

SUMMARYEukaryotic small RNA comprises several classes of 21–25 nucleotide non‐coding RNA, of which microRNA (miRNA) has gained a great deal of attention because it is directly involved in controlling growth and development in plants. miRNAs are processed by the RNase III‐like Dicer, although recent studies have implicated additional gene products in the step‐wise maturation of miRNAs from their primary nuclear transcripts. They function as sequence‐specific guides to trigger cleavage or translational repression of target mRNAs that have complementary sequences. Natural miRNA targets encode members of large families of transcription factors, which are collectively required for a number of developmental processes. In addition to developmental regulation, some miRNAs might be involved in specific physiological responses to several types of stresses, such as those induced by pathogen infections. Strikingly, the potyviruses, the largest group of plant RNA viruses, are able to interfere with miRNA‐guided cleavage of multiple regulatory targets in plants, thus modulating gene expression of the host cell.
Expression of a modified nucleocapsid‐protein of Tomato spotted wilt virus (TSWV) confers resistance against TSWV and Groundnut ringspot virus (GRSV) by blocking systemic spread
Authors: SCHWACH FRANK , ADAM GÜNTER , HEINZE CORNELIA 
Published: July 2004

SUMMARYTobacco transformed with a construct comprising the nucleocapsid‐protein (N) gene of Tomato spotted wilt virus (TSWV) and the 5′ non‐translated leader sequence of Plum pox virus (PPV) as a translation enhancer displays unusually broad resistance against tospoviruses. Contrary to expectations, the transgenic plants did not express a higher level of TSWV N protein than control plants harbouring the N gene without the PPV enhancer. Instead, expression of an N‐terminally elongated N protein, due to the presence of an in‐frame start codon in the PPV leader, was detected. This modified N protein was present in nucleocore and virion preparations and appears to confer resistance by interfering with systemic spread of the virus in the aerial parts of the transgenic plants, while not having an effect on primary replication.