bluuebunny/crossref_metadata_2025 huggingface dataset:
Prospective Evaluation of the Prevalence and Clinical Significance of Positive Autoantibodies After Pediatric Liver Transplantation
Authors: Avitzur Yaron , Ngan Bo Y , Lao Michelle , Fecteau Annie , Ng Vicky Lee
Published: July 2007

Background and Objectives:

De novo autoimmune hepatitis (AIH) recently was recognized as an important cause of late graft dysfunction after pediatric liver transplantation (LT). However, the significance of isolated elevation of autoantibodies in children after LT without history of prior autoimmune liver disease scarcely has been studied. The aim of the present study was to determine the prevalence and risk factors for autoantibodies production in pediatric LT recipients and to assess the impact of isolated elevation of autoantibodies over time on graft function.

Methods:

Sixty‐eight children without history of autoimmune disease were recruited over the course of 1 year into this cross‐sectional study. A single blood specimen was drawn at study entry to determine titers of autoantibodies. Clinical and laboratory assessment and medical history were obtained at study entry as well. Patients were then divided into positive and negative autoantibodies groups, and prospectively followed for 18 months for evidence of abnormal liver function tests.

Results:

One or more autoantibodies were detected in 18 (26%) patients. Anti‐smooth muscle was the most common (n = 13) antibody. Time since transplant (>4 years) was the only risk factor identified for the presence of autoantibodies (univariate risk ratio, 3.3; 95% confidence interval, 1.2–9). During the follow‐up period, 5 patients with positive autoantibody screen developed de novo AIH (n = 3) or chronic rejection (n = 2), compared with 0 in the negative autoantibody group. Children with positive autoantibody screen were at higher risk for development of de novo AIH or chronic rejection (univariate risk ratio 13.9; 95% confidence interval, 1.7–111;P= 0.004).

Conclusions:

Positive autoantibodies are common in children after LT and their presence may denote a higher risk for the development of de novo AIH or chronic rejection over time.
Combination of Helicobacter pylori Strain and Tumor Necrosis Factor‐α Polymorphism of the Host Increases the Risk of Peptic Ulcer Disease in Children
Authors: Wilschanski Michael , Schlesinger Yechiel , Faber Joseph , Rudensky Berl , Ohnona Fred S , Freier Serem , Rahman Elena , Refael Shira , Halle David
Published: July 2007

Background:

Helicobacter pylori infection is probably acquired in childhood and causes a vigorous immune response. It is unclear why only a subgroup of infected children develops peptic ulcer disease. We have previously reported that iceA1 strains tend to be associated with duodenal disease in children. However, the pathogenesis probably does not depend solely on the H pylori strain but also on the variability of the host response.

Objectives:

The aim of this study was to assess the significance of tumor necrosis factor‐α (TNF‐α) promoter polymorphism in relation to infection with H pylori strains in children.

Methods:

A total of 113 antral biopsies of H pylori–positive children (ages 2–18 years) were analyzed. Of these, 23 had duodenal disease, including erosive duodenitis and/or duodenal ulceration, and 90 had gastritis only. H pylori infection was diagnosed by bacterial culture and histology. Patient genomic DNA extracted from the antral biopsy was used to characterize the genetic polymorphism of TNF‐α promoter at nucleotide positions −308 and −238 by polymerase chain reaction–based restriction fragment‐length polymorphism. All H pylori strains were examined for cytotoxin‐associated gene A and induced‐by‐contact‐with‐epithelium gene (iceA1).

Results:

A total of 31% of children with duodenal disease were infected with iceA1 positive strains and had the −238 G to A polymorphism in the TNF‐α gene vs only 1.6% of children with gastritis alone (P < 0.0005).

Conclusions:

The combination of bacterial iceA1 and TNF‐α 238 G to A polymorphism may be a risk factor for peptic ulcer disease in children infected with H pylori. Larger studies are needed to confirm this association.
Increased Mucosal Expression of Toll‐like Receptor (TLR)2 and TLR4 in Coeliac Disease
Authors: Szebeni Beáta , Veres Gábor , Dezsőfi Antal , Rusai Krisztina , Vannay Ádám , Bokodi Géza , Vásárhelyi Barna , Korponay‐Szabó IR , Tulassay Tivadar , Arató András
Published: July 2007

Objectives:

The dysregulation of adaptive immunity is extensively investigated in celiac disease (CD). Recent data also suggest, however, the implication of innate immunity in CD. Toll‐like receptors (TLRs) play a central role in the initiation or maintenance of innate immune responses. The aim of this study was to characterise the expression of TLR2, TLR3, and TLR4 in duodenal biopsy samples taken from children with CD and from controls.

Patients and Methods:

Duodenal biopsy specimens were collected from 16 children with untreated CD, 9 children with treated CD, and 10 controls. The mRNA expression of TLR2, TLR3, and TLR4 was determined by semiquantitative reverse transcription‐polymerase chain reaction. Protein levels of TLRs were determined by Western blot.

Results:

We found higher TLR2 and TLR4 mRNA expression and protein levels in the duodenal mucosa of children with treated CD and untreated CD compared with controls. TLR2 and TLR4 mRNA expression and protein levels were even higher in the duodenal mucosa of children with treated CD than in untreated CD. TLR3 mRNA expression was increased in the duodenal mucosa of children with treated CD compared with untreated CD and controls. We were able to detect TLR3 protein only in the biopsy specimens of treated patients with CD.

Conclusions:

The alteration of TLR2 and TLR4 expression in the duodenal mucosa of patients with CD supports the potential implication of innate immune system in the pathomechanism of this disease.
Therapeutic Endoscopy for Nonvariceal Gastrointestinal Bleeding
Authors: Kay Marsha H , Wyllie Robert
Published: July 2007

The evaluation and management of acute gastrointestinal bleeding in infants, children, and adolescents is a reason for emergency consultation frequently cited by pediatric gastroenterologists. After stabilization of the patient's condition, endoscopic evaluation remains the most rapid and accurate method to identify the origin of acute bleeding in the majority of lesions in the pediatric age group. Several endoscopic techniques may be applied to bleeding lesions to achieve hemostasis. Familiarity with the various techniques and with the specifics of their use is essential for the pediatric endoscopist. This review focuses on the endoscopic management of acute nonvariceal bleeding in infants and children.
Parameter estimation and prediction for the course of a single epidemic outbreak of a plant disease
Authors: Kleczkowski A , Gilligan C.A
Published: July 2007

Many epidemics of plant diseases are characterized by large variability among individual outbreaks. However, individual epidemics often follow a well-defined trajectory which is much more predictable in the short term than the ensemble (collection) of potential epidemics. In this paper, we introduce a modelling framework that allows us to deal with individual replicated outbreaks, based upon a Bayesian hierarchical analysis. Information about ‘similar’ replicate epidemics can be incorporated into a hierarchical model, allowing both ensemble and individual parameters to be estimated. The model is used to analyse the data from a replicated experiment involving spread ofRhizoctonia solanion radish in the presence or absence of a biocontrol agent,Trichoderma viride. The rate of primary (soil-to-plant) infection is found to be the most variable factor determining the final size of epidemics. Breakdown of biological control in some replicates results in high levels of primary infection and increased variability. The model can be used to predict new outbreaks of disease based upon knowledge from a ‘library’ of previous epidemics and partial information about the current outbreak. We show that forecasting improves significantly with knowledge about the history of a particular epidemic, whereas the precision of hindcasting to identify the past course of the epidemic is largely independent of detailed knowledge of the epidemic trajectory. The results have important consequences for parameter estimation, inference and prediction for emerging epidemic outbreaks.
When individual behaviour matters: homogeneous and network models in epidemiology
Authors: Bansal Shweta , Grenfell Bryan T , Meyers Lauren Ancel
Published: July 2007

Heterogeneity in host contact patterns profoundly shapes population-level disease dynamics. Many epidemiological models make simplifying assumptions about the patterns of disease-causing interactions among hosts. In particular, homogeneous-mixing models assume that all hosts have identical rates of disease-causing contacts. In recent years, several network-based approaches have been developed to explicitly model heterogeneity in host contact patterns. Here, we use a network perspective to quantify the extent to which real populations depart from the homogeneous-mixing assumption, in terms of both the underlying network structure and the resulting epidemiological dynamics. We find that human contact patterns are indeed more heterogeneous than assumed by homogeneous-mixing models, but are not as variable as some have speculated. We then evaluate a variety of methodologies for incorporating contact heterogeneity, including network-based models and several modifications to the simple SIR compartmental model. We conclude that the homogeneous-mixing compartmental model is appropriate when host populations are nearly homogeneous, and can be modified effectively for a few classes of non-homogeneous networks. In general, however, network models are more intuitive and accurate for predicting disease spread through heterogeneous host populations.
Assessing the risk of bluetongue to UK livestock: uncertainty and sensitivity analyses of a temperature-dependent model for the basic reproduction number
Authors: Gubbins Simon , Carpenter Simon , Baylis Matthew , Wood James L.N , Mellor Philip S
Published: July 2007

Since 1998 bluetongue virus (BTV), which causes bluetongue, a non-contagious, insect-borne infectious disease of ruminants, has expanded northwards in Europe in an unprecedented series of incursions, suggesting that there is a risk to the large and valuable British livestock industry. The basic reproduction number,R0, provides a powerful tool with which to assess the level of risk posed by a disease. In this paper, we computeR0for BTV in a population comprising two host species, cattle and sheep. Estimates for each parameter which influencesR0were obtained from the published literature, using those applicable to the UK situation wherever possible. Moreover, explicit temperature dependence was included for those parameters for which it had been quantified. Uncertainty and sensitivity analyses based on Latin hypercube sampling and partial rank correlation coefficients identified temperature, the probability of transmission from host to vector and the vector to host ratio as being most important in determining the magnitude ofR0. The importance of temperature reflects the fact that it influences many processes involved in the transmission of BTV and, in particular, the biting rate, the extrinsic incubation period and the vector mortality rate.
Granular temperature as an energy dissipation mechanism in bodies of the Solar System
Authors: Kadish Jon , Rougier Esteban , Munjiza Ante , Barber J.R
Published: July 2007

There is theoretical and observational evidence that asteroids and comets are conglomerations of particles ranging in size from dust grains to boulders. It is well known that energy added to such systems is dissipated by friction, plasticity and fracture. In addition to these physical phenomena, we find that energy can be dissipated in the form of particle kinetic energy due to random velocity distributions. ‘Dissipation’ in this manner is measured by what is called a granular temperature owing to its similarities with kinetic gas theory. This work has implications on our understanding of the growth of asteroids and comets.
A Silurian ‘marrellomorph’ arthropod
Authors: Siveter Derek J , Fortey Richard A , Sutton Mark D , Briggs Derek E.G , Siveter David J
Published: July 2007

Xylokorys chledophilia, a new arthropod with three-dimensionally preserved soft tissues, is described from the Herefordshire (Silurian) Lagerstätte of England. The head and trunk are covered by a relatively featureless ovoid carapace, which comprises a domed central part and a flange-like border. The head bears five pairs of appendages. The first is uniramous, with dorsal and ventral projections distally. Appendages two to four are biramous and each endopod terminates in two projections. Appendage five is possibly biramous. The hypostome is very long and subrectangular in outline. There are approximately 35 pairs of biramous trunk appendages. Each exopod comprises a long slender shaft bearing numerous fine filaments; each endopod comprises a ribbon-like shaft bearing paddle-like endites. Morphological comparisons and cladistic analyses ofX. chledophiliaindicate affinity withVachonisia rogerifrom the Lower Devonian Hunsrück Slate, within the marrellomorphs, but assignment to Marrellomorpha is provisional pending revision of other members of this clade.Xylokorysis the first ‘marrellomorph’ to be reported from the Silurian. It is interpreted as a benthic particle filter feeder, which may also have consumed prey items.
Genome-wide analyses reveal properties of redundant and specific promoter occupancy within theETSgene family
Authors: Hollenhorst Peter C. , Shah Atul A. , Hopkins Christopher , Graves Barbara J.
Published: July 2007

The conservation of in vitro DNA-binding properties within families of transcription factors presents a challenge for achieving in vivo specificity. To uncover the mechanisms regulating specificity within theETSgene family, we have used chromatin immunoprecipitation coupled with genome-wide promoter microarrays to query the occupancy of three ETS proteins in a human T-cell line. Unexpectedly, redundant occupancy was frequently detected, while specific occupancy was less likely. Redundant binding correlated with housekeeping classes of genes, whereas specific binding examples represented more specialized genes. Bioinformatics approaches demonstrated that redundant binding correlated with consensus ETS-binding sequences near transcription start sites. In contrast, specific binding sites diverged dramatically from the consensus and were found further from transcription start sites. One route to specificity was found—a highly divergent binding site that facilitates ETS1 and RUNX1 cooperative DNA binding. The specific and redundant DNA-binding modes suggest two distinct roles for members of the ETS transcription factor family.
Identification of a tyrosinase (TYR) exon 4 deletion in albino ferrets (Mustela putorius furo)
Authors: Blaszczyk W. M. , Distler C. , Dekomien G. , Arning L. , Hoffmann K.‐P. , Epplen J. T.
Published: July 2007

Albinism is due to a lack of pigmentation in hair, skin and eye, and has been shown to occur in several animal species. Mutations of the tyrosinase (TYR) gene account for albinism in domestic cats, rabbits, cattle, mice and rats. In this study, we demonstrate that a TYR mutation accounts for albinism in the ferret (Mustela putorius furo). The coding sequence of the five exons of TYR was determined in genomic DNA from wild‐type pigmented ‘sable’ coloured and albino ferrets. It was not possible to amplify TYR exon 4 in albino ferrets originating from different breeds. The deletion of exon 4 in albino ferrets was confirmed by Southern blot hybridization of genomic DNA from albino and pigmented ferrets. This is the first report of a deletion of a TYR exon in a non‐human mammal.
Organic phosphorus speciation and pedogenesis: analysis by solution 31P nuclear magnetic resonance spectroscopy
Authors: McDowell R. W. , Cade‐Menun B. , Stewart I.
Published: July 2007

Changes in phosphorus (P) during soil development are central to the understanding of labile P for plant productivity and soil P management. We used NaOH‐EDTA extraction with 31P nuclear magnetic resonance spectroscopy (31P NMR), sequential P fractionation, and general soil chemical characterization to better our understanding of P dynamics within two chronosequences (Manawatu and Reefton) and one Basalt maturity sequence under original native vegetation. With time, orthophosphate and orthophosphate monoesters tended to increase with organic C to a maximum of about two‐thirds of NaOH‐EDTA‐extractable P in young soils (16 000 years in the Reefton chronosequence), but gradually declined thereafter to about one‐third of NaOH‐EDTA‐extractable P in the oldest soils (130 000 years old). This coincided with a depletion of P from primary minerals (e.g. apatite) and readily available P for plant production. This depletion of inorganic P resulted in a greater reliance on organic P cycling via mineralization, hence the depletion of the normally recalcitrant monoester‐P pool. Concomitantly, the build‐up of labile P species (diesters and pyrophosphate) and scyllo‐ over myo‐inositol hexakisphosphate occurred as soils developed, and might be attributed to microbial activity, including scavenging for P. This work highlights the importance of organic P cycling during pedogenesis.
Community‐wide character displacement in New Zealand skinks
Authors: Montoya Isabel , Burns K.C.
Published: July 2007

Aim To test for community‐wide character displacement in New Zealand skinks.

Location Four small islands in the New Zealand archipelago.

Methods (1) We conducted a field experiment on a single island to evaluate whether prey size selection is correlated with lizard body size. We pitfall trapped 69 skinks from three species, measured several aspects of their morphology and presented each animal with a variety of different‐sized prey in a food choice experiment. (2) We tested whether the morphological characteristics associated with prey size selection were evenly partitioned in four island skink communities using null models.

Results Prey size selection was associated with skink morphology; larger skinks consumed larger prey. Null model analyses showed support for evenly displaced body sizes on one island, weak support on one island and no support on two islands.

Main conclusions Results showed mixed support for community‐wide character displacement in New Zealand skinks. Differences in body sizes appear to reflect the use of different‐sized prey. Even differentiation in body sizes on one island suggests that species coexistence is facilitated by interspecific differences in prey size selection. However, little support was found on other islands, suggesting that other factors, such as interspecific differences in habitat selection and/or diurnal activity patterns, may interact with differences in prey size selection to promote coexistence among New Zealand skinks.
Chloroplast‐generated reactive oxygen species are involved in hypersensitive response‐like cell death mediated by a mitogen‐activated protein kinase cascade
Authors: Liu Yidong , Ren Dongtao , Pike Sharon , Pallardy Stephen , Gassmann Walter , Zhang Shuqun
Published: July 2007

Plant defense against pathogens often includes rapid programmed cell death known as the hypersensitive response (HR). Recent genetic studies have demonstrated the involvement of a specific mitogen‐activated protein kinase (MAPK) cascade consisting of three tobacco MAPKs, SIPK, Ntf4 and WIPK, and their common upstream MAPK kinase (MAPKK or MEK), NtMEK2. Potential upstream MAPKK kinases (MAPKKKs or MEKKs) in this cascade include the orthologs of Arabidopsis MEKK1 and tomato MAPKKKα. Activation of the SIPK/Ntf4/WIPK pathway induces cell death with phenotypes identical to pathogen‐induced HR at macroscopic, microscopic and physiological levels, including loss of membrane potential, electrolyte leakage and rapid dehydration. Loss of membrane potential in NtMEK2DD plants is associated with the generation of reactive oxygen species (ROS), which is preceded by disruption of metabolic activities in chloroplasts and mitochondria. We observed rapid shutdown of carbon fixation in chloroplasts after SIPK/Ntf4/WIPK activation, which can lead to the generation of ROS in chloroplasts under illumination. Consistent with a role of chloroplast‐generated ROS in MAPK‐mediated cell death, plants kept in the dark do not accumulate H2O2 in chloroplasts after MAPK activation, and cell death is significantly delayed. Similar light dependency was observed in HR cell death induced by tobacco mosaic virus, which is known to activate the same MAPK pathway in an N‐gene‐dependent manner. These results suggest that activation of the SIPK/Ntf4/WIPK cascade by pathogens actively promotes the generation of ROS in chloroplasts, which plays an important role in the signaling for and/or execution of HR cell death in plants.
Quantitative phosphoproteomic analysis of plasma membrane proteins reveals regulatory mechanisms of plant innate immune responses
Authors: Nühse Thomas S. , Bottrill Andrew R. , Jones Alexandra M.E. , Peck Scott C.
Published: July 2007

Advances in proteomic techniques have allowed the large‐scale identification of phosphorylation sites in complex protein samples, but new biological insight requires an understanding of their in vivo dynamics. Here, we demonstrate the use of a stable isotope‐based quantitative approach for pathway discovery and structure–function studies in Arabidopsis cells treated with the bacterial elicitor flagellin. The quantitative comparison identifies individual sites on plasma membrane (PM) proteins that undergo rapid phosphorylation or dephosphorylation. The data reveal both divergent dynamics of different sites within one protein and coordinated regulation of homologous sites in related proteins, as found for the PM H+‐ATPases AHA1, 2 and 3. Strongly elicitor‐responsive phosphorylation sites may reflect direct regulation of protein activity. We confirm this prediction for RbohD, an NADPH oxidase that mediates the rapid production of reactive oxygen species (ROS) in response to elicitors and pathogens. Plant NADPH oxidases are structurally distinct from their mammalian homologues, and regulation of the plant enzymes is poorly understood. On RbohD, we found both unchanging and strongly induced phosphorylation sites. By complementing an RbohD mutant plant with non‐phosphorylatable forms of RbohD, we show that only those sites that undergo differential regulation are required for activation of the protein. These experiments demonstrate the potential for use of quantitative phosphoproteomics to determine regulatory mechanisms at the molecular level and provide new insights into innate immune responses.
Place‐selective firing contributes to the reverse‐order reactivation of CA1 pyramidal cells during sharp waves in open‐field exploration
Authors: Csicsvari Jozsef , O'Neill Joseph , Allen Kevin , Senior Timothy
Published: July 2007

On the linear track, the recent firing sequences of CA1 place cells recur during sharp wave/ripple patterns (SWRs) in a reverse temporal order [Foster & Wilson (2006) Nature, 440, 680–683]. We have found similar reverse‐order reactivation during SWRs in open‐field exploration where the firing sequence of cells varied before each SWR. Both the onset times and the firing patterns of cells showed a tendency for reversed sequences during SWRs. These effects were observed for SWRs that occurred during exploration, but not for those during longer immobility periods. Additionally, reverse reactivation was stronger when it was preceded by higher speed (> 5 cm/s) run periods. The trend for reverse‐order SWR reactivation was not significantly different in familiar and novel environments, even though SWR‐associated firing rates of both pyramidal cells and interneurons were reduced in novel environments as compared with familiar. During exploration‐associated SWRs (eSWR) place cells retain place‐selective firing [O'Neill et al. (2006) Neuron, 49, 143–155]. Here, we have shown that each cell's firing onset was more delayed and firing probability more reduced during eSWRs the further the rat was from the middle of the cell's place field; that is, cells receiving less momentary place‐related excitatory drive fired later during SWR events. However, even controlling for place field distance, the recent firing of cells was still significantly correlated with SWR reactivation sequences. We therefore propose that both place‐related drive and the firing history of cells contribute to reverse reactivation during eSWRs.
Aerosolization of mycobacteria and legionellae during dental treatment: low exposure despite dental unit contamination
Authors: Dutil Steve , Veillette Marc , Mériaux Anne , Lazure Louis , Barbeau Jean , Duchaine Caroline
Published: July 2007

Dental unit waterlines (DUWL) support growth of a dense microbial population that includes pathogens and hypersensitivity‐inducing bacteria, such as Legionella spp. and non‐tuberculous mycobacteria (NTM). Dynamic dental instruments connected to DUWL generate aerosols in the work environment, which could allow waterborne pathogens to be aerosolized. The use of the real‐time quantitative polymerase chain reaction (qPCR) provides a more accurate estimation of exposure levels compared with the traditional culture approach. Bioaerosol sampling was performed 13 times in an isolated dental treatment room according to a standardized protocol that included four dental prophylaxis treatments. Inhalable dust samples were taken at the breathing zone of both the hygienist and patient and outside the treatment room (control). Total bacteria as well as Legionella spp. and NTM were quantified by qPCR in bioaerosol and DUWL water samples. Dental staff and patients are exposed to bacteria generated during dental treatments (up to 4.3 E + 05 bacteria per m3 of air). Because DUWL water studied was weakly contaminated by Legionella spp. and NTM, their aerosolization during dental treatment was not significant. As a result, infectious and sensitization risks associated with legionellae and NTM should be minimal.
Occupying the Margins: Labour Integration and Social Exclusion in Artisanal Mining in Tanzania
Authors: Fisher Eleanor
Published: July 2007

This article examines the marginal position of artisanal miners in sub‐Saharan Africa, and considers how they are incorporated into mineral sector change in the context of institutional and legal integration. Taking the case of diamond and gold mining in Tanzania, the concept of social exclusion is used to explore the consequences of marginalization on people's access to mineral resources and ability to make a living from artisanal mining. Because existing inequalities and forms of discrimination are ignored by the Tanzanian state, the institutionalization of mineral titles conceals social and power relations that perpetuate highly unequal access to resources. The article highlights the complexity of these processes, and shows that while legal integration can benefit certain wealthier categories of people, who fit into the model of an ‘entrepreneurial small‐scale miner’, for others adverse incorporation contributes to socio‐economic dependence, exploitation and insecurity. For the issue of marginality to be addressed within integration processes, the existence of local forms of organization, institutions and relationships, which underpin inequalities and discrimination, need to be recognized.
K+M‐Current Regulates the Transition to Seizures in Immature and Adult Hippocampus
Authors: Qiu Cuie , Johnson Brian N. , Tallent Melanie K.
Published: July 2007

Summary

Purpose:Loss‐of‐function mutations in Kv7.2 or Kv7.3 K+channel subunits underlies the neonatal epilepsy benign familial neonatal convulsions (BFNC). These two subunits interact to form a functional K+channel that underlies the M‐current (IM), a voltage‐dependent noninactivating K+current. In BFNC, seizures begin shortly after birth, and spontaneously remit in the first few months of life. The nature of this window of vulnerability is unclear. We address this issue using a hippocampal slice model, to study the effects of IMblockade or augmentation on epileptiform activity.

Methods:We used the Mg++‐free seizure model in adult and immature (P8‐P15) acute rat hippocampal slices. We recorded from both CA1 and CA3 regions using extracellular and intracellular methods.

Results:When M‐channels are blocked pharmacologically, the transition from interictal to ictal bursting becomes much more likely, especially in immature brain. We also show augmentation of IMis effective in stopping ictal events in immature brain, at the developmental age that approximates a human newborn in cortical development. IMappears to counter the sustained N‐methyl‐D‐aspartate (NMDA) receptor‐mediated depolarizations needed to trigger an ictal event. The increased likelihood of ictal bursting by IMblockade is not shared by other selective K+channel blockers that increase hippocampal excitability.

Conclusions:Voltage‐dependent M‐channels are activated duringinterictal bursts and contribute to burst termination. When these channels are compromised, interictal burstduration becomes sufficient to trigger the sustained depolarizations that underlie ictal bursts. This transition to ictal bursts upon IMblockade is especially likely to occur in immature hippocampus. This selective function of M‐channels likely contributes to the transient window of vulnerability to seizures that occurs with BFNC.
Effects of Noninvasive Transcutaneous Electrical Stimulation via Concentric Ring Electrodes on Pilocarpine‐induced Status Epilepticus in Rats
Authors: Besio Walter G. , Koka Kanthaiah , Cole Andrew J.
Published: July 2007

Summary

Purpose: The aim of this pilot study was to investigate the antiepileptic effects of a novel noninvasive stimulation technique, transcutaneous electrical stimulation (TcES) via scalp concentric ring electrodes, on pilocarpine‐induced status epilepticus (SE) in rats.

Methods: Five minutes after the onset of SE, TcES was administered to the experimental rat via bipolar concentric ring electrode at the CZ location. Symmetrical, biphasic, charge‐balanced, constant current, isolated pulses were applied via a custom‐made stimulator. TcES parameters ranged from 200–750 Hz, 200 or 300 μs pulse duration, and 50 or 60 mA, applied for 1 min, started with the least intense parameter set and progressively increased.

Results: TcES attenuated electrographic seizure activity and halted the progression of behavioral seizures. Interruption of seizure activity outlasted the period of stimulation and appeared to be long‐lasting. TcES treatment significantly extended the life and enhanced the survival of rats after SE.

Conclusions: Noninvasive TcES, applied 5 min after SE onset via novel concentric ring electrodes on the scalp, reduced, or abolished electrographic and behavioral seizure activity in pilocarpine‐induced SE in rats. These findings suggest that TcES may have a role in the treatment of SE.
Exchange Rates and FOMC Days
Authors: AHN SEUNG CHAN , MELVIN MICHAEL
Published: July 2007

Federal Open Market Committee (FOMC) meeting days provide a natural laboratory for exploring the effects of policy uncertainty and learning on exchange rate determination. A reasonable hypothesis is that the meeting outcomes are price‐relevant public information associated with a switch to an “informed‐trading state.” Evidence is provided by intradaily exchange rates for 10 FOMC meetings. A particularly interesting finding is that the informed‐trading regime tends to emerge during the time that the FOMC meets. An extensive search of public news indicates that the informed trading cannot be explained as the response to public information.
The Time‐Varying Phillips Correlation
Authors: BENATI LUCA
Published: July 2007

We use complex demodulation techniques to investigate changes in the correlation between real activity and inflation at the business‐cycle frequencies in the United States, the United Kingdom, the Eurozone, and 10 other Organization for Economic Cooperation and Development (OECD) countries over the post‐WWII era. Consistent with the analysis ofBall, Mankiw, and Romer (1988)we document a positive correlation between the time‐varying average gain of real activity onto inflation at the business‐cycle frequencies and inflation's Hodrick‐Prescott trend, which is compatible with New Keynesian theories emphasizing the link between trend inflation, the frequency of price adjustments, and the slope of the Phillips trade‐off.
The comparative study of two recently developed A‐scan devices: determination of central corneal thickness, anterior chamber depth and axial length
Authors: Sohajda Zoltán , Papp Júlia , Berta András , Módis László
Published: July 2007

Purpose:  The clinical use and comparison of two recently developed A‐scan ultrasound devices.

Methods:  The same investigator determined central corneal thickness (CCT), anterior chamber depth (ACD) and axial length (AL) with an OcuScan RxP (Alcon, Forth Worth, Texas, USA) and an AL‐2000 (Tomey, Erlangen, Germany) ultrasound device in 80 eyes of 40 patients. The mean patient age was 63.72 years [standard deviation (SD) 18.92]. The patients did not suffer from any systemic or eye disease affecting the anterior and posterior segments of the eye, and their refractive error (spherical and astigmatic) did not exceed ± 3.0 dioptres.

Results:  The value of the CCT was 541.55 (SD 34.97) µm with the OcuScan RxP, and 547.46 (SD 35.70) µm with the AL‐2000 device (P < 0.001). With respect to the ACD and AL, significantly lower values were obtained with the AL‐2000 instrument (P < 0.001). The ACD was 2.92 (SD 0.48) mm with the AL‐2000 and 3.07 (SD 0.47) mm with the OcuScan RxP device. The AL was 22.67 (SD 0.84) mm with the AL‐2000 and 22.81 (SD 0.87) mm with the OcuScan RxP instrument. However, a positive and significant correlation could be demonstrated between the devices (r = 0.88 CCT, r = 0.86 ACD and r = 0.91 AL; P < 0.001).

Conclusion:  The instruments are reliable in clinical use; however, statistically significant differences were found between the devices. During patient follow‐up, the devices cannot simply be used interchangeably.
New emphasis in the treatment of dental trauma: avulsion and luxation
Authors: Lin Shaul , Zuckerman Offer , Fuss Zvi , Ashkenazi Malka
Published: July 2007

Abstract –  There are several protocols for the successful management of dental trauma emergencies. However, these existing protocols are inconsistent regarding several issues. As the Israeli dental community and patients have specific characteristics, a modified and adaptable protocol was required. This new protocol contains simple and straightforward clinical guidelines, arranged in table format, according to the nature of the trauma. The present study shows the protocol for luxation and avulsion injuries, with new recommendations for the treatment of luxated closed‐apex teeth, the preferred at‐site treatment and storage medium for avulsed teeth, and the conditioning of the root surface in these cases. To emphasize and explain the modification of this new protocol, research‐based information has been incorporated.
Brazilian dentists’ knowledge regarding immediate treatment of traumatic dental injuries
Authors: De França Rossana Índia , Traebert Jefferson , De Lacerda Josimari Telino
Published: July 2007

Abstract –  The objective of this study was to assess the knowledge of dentists working in the city of Tubarão, southern Brazil, about the immediate treatment of traumatic dental injuries. A cross‐sectional study was carried out involving all dentists who were working in the city in 2004 (n = 108). Data were collected through self‐applied questionnaires with questions about sex, time elapsed since graduation, whether the dentists had attended postgraduate courses and also four questions about traumatic dental injuries in which the dentists selected the best answer. The response rate was 86.1%. For the two questions related to dental avulsion, 36.6% and 16.1% of professionals respectively, chose the correct answer according to the literature. For the question related to coronal fracture, 75.3% chose the correct answer. For the questions related to an incident without dental avulsion or fracture, 73.1% chose the correct answer. Time elapsed since graduation was the only variable statistically associated with the correct answer for the question related to coronal fracture. A significantly greater number of professionals with ≤10 years of experience chose the correct answer when compared with professionals with >10 years experience (P < 0.001). It can be concluded that the great majority of professionals would not intervene according to the literature in the cases of avulsion. Less time elapsed since graduation was statistically associated with the correct answer in the coronal fracture case.
Structure determination and biochemical studies on Bacillus stearothermophilus E53Q serine hydroxymethyltransferase and its complexes provide insights on function and enzyme memory
Authors: Rajaram V. , Bhavani B. S. , Kaul Purnima , Prakash V. , Appaji Rao N. , Savithri H. S. , Murthy M. R. N.
Published: July 2007

Serine hydroxymethyltransferase (SHMT) belongs to the α‐family of pyridoxal 5′‐phosphate‐dependent enzymes and catalyzes the reversible conversion of l‐Ser and tetrahydrofolate to Gly and 5,10‐methylene tetrahydrofolate. 5,10‐Methylene tetrahydrofolate serves as a source of one‐carbon fragment in many biological processes. SHMT also catalyzes the tetrahydrofolate‐independent conversion of l‐allo‐Thr to Gly and acetaldehyde. The crystal structure of Bacillus stearothermophilus SHMT (bsSHMT) suggested that E53 interacts with the substrate, l‐Ser and tetrahydrofolate. To elucidate the role of E53, it was mutated to Q and structural and biochemical studies were carried out with the mutant enzyme. The internal aldimine structure of E53QbsSHMT was similar to that of the wild‐type enzyme, except for significant changes at Q53, Y60 and Y61. The carboxyl of Gly and side chain of l‐Ser were in two conformations in the respective external aldimine structures. The mutant enzyme was completely inactive for tetrahydrofolate‐dependent cleavage of l‐Ser, whereas there was a 1.5‐fold increase in the rate of tetrahydrofolate‐independent reaction with l‐allo‐Thr. The results obtained from these studies suggest that E53 plays an essential role in tetrahydrofolate/5‐formyl tetrahydrofolate binding and in the proper positioning of Cβ of l‐Ser for direct attack by N5 of tetrahydrofolate. Most interestingly, the structure of the complex obtained by cocrystallization of E53QbsSHMT with Gly and 5‐formyl tetrahydrofolate revealed the gem‐diamine form of pyridoxal 5′‐phosphate bound to Gly and active site Lys. However, density for 5‐formyl tetrahydrofolate was not observed. Gly carboxylate was in a single conformation, whereas pyridoxal 5′‐phosphate had two distinct conformations. The differences between the structures of this complex and Gly external aldimine suggest that the changes induced by initial binding of 5‐formyl tetrahydrofolate are retained even though 5‐formyl tetrahydrofolate is absent in the final structure. Spectral studies carried out with this mutant enzyme also suggest that 5‐formyl tetrahydrofolate binds to the E53QbsSHMT‐Gly complex forming a quinonoid intermediate and falls off within 4 h of dialysis, leaving behind the mutant enzyme in the gem‐diamine form. This is the first report to provide direct evidence for enzyme memory based on the crystal structure of enzyme complexes.
Understanding the binding properties of an unusual metal‐binding protein − a study of bacterial frataxin
Authors: Pastore Chiara , Franzese Marisa , Sica Filomena , Temussi Pierandrea , Pastore Annalisa
Published: July 2007

Deficiency of the small mitochondrial protein frataxin causes Friedreich's ataxia, a severe neurodegenerative pathology. Frataxin, which has been highly conserved throughout evolution, is thought to be involved in, among other processes, Fe–S cluster formation. Independent evidence shows that it binds iron directly, although with very distinct features and low affinity. Here, we have carried out an extensive study of the binding properties of CyaY, the bacterial ortholog of frataxin, to different divalent and trivalent cations, using NMR and X‐ray crystallography. We demonstrate that the protein has low cation specificity and contains multiple binding sites able to chelate divalent and trivalent metals with low affinity. Binding does not involve cavities or pockets, but exposed glutamates and aspartates, which are residues that are unusual for iron chelation when not assisted by histidines and/or cysteines. We have related how such an ability to bind cations on a relatively large area through an electrostatic mechanism could be a valuable asset for protein function.
Effects of Thresholding Techniques on μCT-Based Finite Element Models of Trabecular Bone
Authors: Kim Chi Hyun , Zhang Henry , Mikhail George , Stechow Dietrich von , Müller Ralph , Kim Han Sung , Guo X. Edward
Published: July 2007

Microimaging based finite element analysis is widely used to predict the mechanical properties of trabecular bone. The choice of thresholding technique, a necessary step in converting grayscale images to finite element models, can significantly influence the predicted bone volume fraction and mechanical properties. Therefore, we investigated the effects of thresholding techniques on microcomputed tomography (micro-CT) based finite element models of trabecular bone. Three types of thresholding techniques were applied to 16-bit micro-CT images of trabecular bone to create three different models per specimen. Bone volume fractions and apparent moduli were predicted and compared to experimental results. In addition, trabecular tissue mechanical parameters and morphological parameters were compared among different models. Our findings suggest that predictions of apparent mechanical properties and structural properties agree well with experimental measurements regardless of the choice of thresholding methods or the format of micro-CT images.
Fracture Toughness and Fatigue Crack Propagation Rate of Short Fiber Reinforced Epoxy Composites for Analogue Cortical Bone
Authors: Chong Alexander C. M. , Miller Forrest , Buxton McKee , Friis Elizabeth A.
Published: July 2007

Third-generation mechanical analogue bone models and synthetic analogue cortical bone materials manufactured by Pacific Research Laboratories, Inc. (PRL) are popular tools for use in mechanical testing of various orthopedic implants and biomaterials. A major issue with these models is that the current third-generation epoxy–short fiberglass based composite used as the cortical bone substitute is prone to crack formation and failure in fatigue or repeated quasistatic loading of the model. The purpose of the present study was to compare the tensile and fracture mechanics properties of the current baseline (established PRL “third-generation” E-glass–fiber–epoxy) composite analogue for cortical bone to a new composite material formulation proposed for use as an enhanced fourth-generation cortical bone analogue material. Standard tensile, plane strain fracture toughness, and fatigue crack propagation rate tests were performed on both the third- and fourth-generation composite material formulations using standard ASTM test techniques. Injection molding techniques were used to create random fiber orientation in all test specimens. Standard dog-bone style tensile specimens were tested to obtain ultimate tensile strength and stiffness. Compact tension fracture toughness specimens were utilized to determine plane strain fracture toughness values. Reduced thickness compact tension specimens were also used to determine fatigue crack propagation rate behavior for the two material groups. Literature values for the same parameters for human cortical bone were compared to results from the third- and fourth-generation cortical analogue bone materials. Tensile properties of the fourth-generation material were closer to that of average human cortical bone than the third-generation material. Fracture toughness was significantly increased by 48% in the fourth-generation composite as compared to the third-generation analogue bone. The threshold stress intensity to propagate the crack was much higher for the fourth-generation material than for the third-generation composite. Even at the higher stress intensity threshold, the fatigue crack propagation rate was significantly decreased in the fourth-generation composite compared to the third-generation composite. These results indicate that the bone analogue models made from the fourth-generation analogue cortical bone material may exhibit better performance in fracture and longer fatigue lives than similar models made of third-generation analogue cortical bone material. Further fatigue testing of the new composite material in clinically relevant use of bone models is still required for verification of these results. Biomechanical test models using the superior fourth-generation cortical analogue material are currently in development.
Osmotic Loading of Spherical Gels: A Biomimetic Study of Hindered Transport in the Cell Protoplasm
Authors: Albro Michael B. , Chahine Nadeen O. , Caligaris Matteo , Wei Victoria I. , Likhitpanichkul Morakot , Ng Kenneth W. , Hung Clark T. , Ateshian Gerard A.
Published: July 2007

Osmotic loading of cells has been used to investigate their physicochemical properties as well as their biosynthetic activities. The classical Kedem–Katchalsky framework for analyzing cell response to osmotic loading, which models the cell as a fluid-filled membrane, does not generally account for the possibility of partial volume recovery in response to loading with a permeating osmolyte, as observed in some experiments. The cell may be more accurately represented as a hydrated gel surrounded by a semi-permeable membrane, with the gel and membrane potentially exhibiting different properties. To help assess whether this more elaborate model of the cell is justified, this study investigates the response of spherical gels to osmotic loading, both from experiments and theory. The spherical gel is described using the framework of mixture theory. In the experimental component of the study alginate is used as the model gel, and is osmotically loaded with dextran solutions of various concentrations and molecular weight, to verify the predictions from the theoretical analysis. Results show that the mixture framework can accurately predict the transient and equilibrium response of alginate gels to osmotic loading with dextran solutions. It is found that the partition coefficient of dextran in alginate regulates the equilibrium volume response and can explain partial volume recovery based on passive transport mechanisms. The validation of this theoretical framework facilitates future investigations of the role of the protoplasm in the response of cells to osmotic loading.