bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential modulation of myosin heavy chain phenotype in an inactive extensor and flexor muscle of adult rats
Authors: Zhong H. , Roy R. R. , Woo J. , Kim J. A. , Edgerton V. R.
Published: November 2006

The effects of chronic neuromuscular inactivity on the phenotype and size of muscle fibres in a fast ankle extensor (medial gastrocnemius, MG) and a fast ankle flexor (tibialis anterior, TA) muscle of the rat hindlimb were determined. Inactivity was produced by spinal cord isolation (SI), i.e. complete spinal cord transections at a mid‐thoracic and high sacral level and bilateral deafferentation between the transection sites. After 90 days of SI, the MG and TA muscle weights were 53 and 45% lower than in age‐matched controls. Overall mean fibre sizes in the deep (close to the bone) and superficial (away from the bone) regions were ∼60 and 65% smaller in the MG and ∼40 and 50% smaller in the TA of SI than control rats, respectively. The myosin heavy chain (MHC) composition shifted towards the faster isoforms after SI: the MG showed an increase in both types IIx (20%) and IIb (23%), whereas the TA showed a marked increase in type IIx (94%) and a decrease in type IIb (18%) MHC. Both muscles in SI rats showed no type IIa and only one MG muscle had ∼5% type I MHC. These results show that prolonged inactivity has a stronger effect on a fast extensor compared with a fast flexor in the rat hindlimb. The larger decrease in mass and fibre size in the MG than the TA most probably reflects the larger impact of chronic inactivity on the normally more highly recruited extensor than flexor muscle. The primary shift to type IIb MHC in the MG and type IIx MHC in the TA indicate a different default mode for an inactive extensor vs. flexor muscle, and may reflect differing activity‐independent neural influences, i.e. neurotrophic factors, on muscle fibre phenotype in extensors vs. flexors.
Monoclonal antibodies that target pathological assemblies of Aβ
Authors: Lambert Mary P. , Velasco Pauline T. , Chang Lei , Viola Kirsten L. , Fernandez Sara , Lacor Pascale N. , Khuon Daliya , Gong Yuesong , Bigio Eileen H. , Shaw Pamela , De Felice Fernanda G. , Krafft Grant A. , Klein William L.
Published: November 2006

Amyloid beta (Aβ) immunotherapy for Alzheimer's disease has shown initial success in mouse models of Alzheimer's disease and in human patients. However, because of meningoencephalitis in clinical trials of active vaccination, approaches using therapeutic antibodies may be preferred. As a novel antigen to generate monoclonal antibodies, the current study has used Aβ oligomers (amyloid β‐derived diffusible ligands, ADDLs), pathological assemblies known to accumulate in Alzheimer's disease brain. Clones were selected for the ability to discriminate Alzheimer's disease from control brains in extracts and tissue sections. These antibodies recognized Aβ oligomers and fibrils but not the physiologically prevalent Aβ monomer. Discrimination derived from an epitope found in assemblies of Aβ1–28 and ADDLs but not in other sequences, including Aβ1–40. Immunoneutralization experiments showed that toxicity and attachment of ADDLs to synapses in culture could be prevented. ADDL‐induced reactive oxygen species (ROS) generation was also inhibited, establishing this response to be oligomer‐dependent. Inhibition occurred whether ADDLs were prepared in vitro or obtained from Alzheimer's disease brain. As conformationally sensitive monoclonal antibodies that selectively immunoneutralize binding and function of pathological Aβ assemblies, these antibodies provide tools by which pathological Aβ assemblies from Alzheimer's disease brain might be isolated and evaluated, as well as offering a valuable prototype for new antibodies useful for Alzheimer's disease therapeutics.
Down‐regulation of dopamine transporter by iron chelationin vitrois mediated by altered trafficking, not synthesis
Authors: Wiesinger Jason A. , Buwen James P. , Cifelli Christopher J. , Unger Erica L. , Jones Byron C. , Beard John L.
Published: November 2006

Neurological development and functioning of dopamine (DA) neurotransmission is adversely affected by iron deficiency in early life. Iron‐deficient rats demonstrate significant elevations in extracellular DA and a reduction in dopamine transporter (DAT) densities in the caudate putamen and nucleus accumbens. To explore possible mechanisms by which cellular iron concentrations control DAT functioning, endogenous DAT‐expressing PC12 cells were used to determine the effect of iron chelation on DAT protein and mRNA expression patterns. In addition, we used human DAT (hDAT)‐transfected Neuro2a (N2A) cells to examine DAT degradation and trafficking patterns. A 50 µmtreatment for 24 h with the iron chelator, desferrioxamine (DFO), significantly decreased dopamine uptake in a dose‐dependent manner, with no apparent change inKm, in both PC12 and N2A cells. Reduced DA uptake was accompanied by concentration‐ and time‐dependent reductions in total DAT protein levels in both cell lines. Exposure to increasing concentrations of DFO did not significantly alter DAT mRNA in either PC12 or N2A cells. However, DAT degradation rates increased three–fivefold in both cell types exposed to 50 µmDFO for 24 h. Biotinylation studies in N2A cells indicate a more dramatic loss of DAT in the membrane fraction, while OptiPrep fractionation experiments revealed an increase in lysosomal DAT with iron chelation. Inhibition of protein kinase C activation with staurosporin prevented the effect of iron chelation on DAT function, suggesting thatin vitroiron chelation affects DAT primarily through the effects on trafficking rather than on synthesis.
Adriamycin‐mediated nitration of manganese superoxide dismutase in the central nervous system: insight into the mechanism of chemobrain
Authors: Tangpong Jitbanjong , Cole Marsha P. , Sultana Rukhsana , Estus Steven , Vore Mary , St. Clair William , Ratanachaiyavong Suvina , St. Clair Daret K. , Butterfield D. Allan
Published: November 2006

Adriamycin (ADR), a potent anti‐tumor agent, produces reactive oxygen species (ROS) in cardiac tissue. Treatment with ADR is dose‐limited by cardiotoxicity. However, the effect of ADR in the other tissues, including the brain, is unclear because ADR does not pass the blood–brain barrier. Some cancer patients receiving ADR treatment develop a transient memory loss, inability to handle complex tasks etc., often referred to by patients as chemobrain. We previously demonstrated that ADR causes CNS toxicity, in part, via systemic release of cytokines and subsequent generation of reactive oxygen and nitrogen species (RONS) in the brain. Here, we demonstrate that treatment with ADR led to an increased circulating level of tumor necrosis factor‐alpha in wild‐type mice and in mice deficient in the inducible form of nitric oxide (iNOSKO). However, the decline in mitochondrial respiration and mitochondrial protein nitration after ADR treatment was observed only in wild‐type mice, not in the iNOSKO mice. Importantly, the activity of a major mitochondrial antioxidant enzyme, manganese superoxide dismutase (MnSOD), was reduced and the protein was nitrated. Together, these results suggest that NO is an important mediator, coupling the effect of ADR with cytokine production and subsequent activation of iNOS expression. We also identified the mitochondrion as an important target of ADR‐induced NO‐mediated CNS injury.
Agmatine transport into spinal nerve terminals is modulated by polyamine analogs
Authors: Goracke‐Postle Cory J. , Overland Aaron C. , Stone Laura S. , Fairbanks Carolyn A.
Published: November 2006

Agmatine (decarboxylated arginine) is an endogenous amine found in the CNS that antagonizes NMDA receptors and inhibits nitric oxide synthase. Intrathecally administered agmatine inhibits hyperalgesia evoked by inflammation, nerve injury and intrathecally administered NMDA. These actions suggest an antiglutamatergic neuromodulatory role for agmatine in the spinal cord. Such a function would require a mechanism of regulated clearance of agmatine such as neuronal or glial uptake. Consistent with this concept, radiolabeled agmatine has been shown to accumulate in synaptosomes, but the mechanism of this transport has not been fully characterized. The present study describes an agmatine uptake system in spinal synaptosomes that appears driven by a polyamine transporter. [3H]Agmatine uptake was Ca2+, energy and temperature dependent. [3H]Agmatine transport was not moderated byl‐arginine,l‐glutamate, glycine, GABA, norepinephrine or serotonin. In contrast, [3H]agmatine uptake was concentration dependently inhibited by unlabeled putrescine and by unlabeled spermidine (at significantly higher concentrations). Similarly, [3H]putrescine uptake was inhibited in a concentration‐dependent manner by unlabeled agmatine and spermidine. The polyamine analogs paraquat and methylglyoxal bis (guanylhydrazone) inhibited, whereas the polyamine transport enhancer difluoromethylornithine increased, [3H]agmatine transport. Taken together, these results suggest that agmatine transport into spinal synaptosomes may be governed by a polyamine transport mechanism.
Emerging concepts: novel integration of in vivo approaches to localize the function of nicotinic receptors
Authors: Maskos Uwe
Published: November 2006

Nicotinic acetylcholine receptors (nAChRs) are important targets of the neuromodulator acetylcholine (ACh) and the drug nicotine. The role of their different subunits has been analysed for a decade by the creation of knock‐out (KO) mice using homologous recombination. This technique shows that a given subunit is necessary for a given function. However, for ubiquitously expressed genes, it cannot demonstrate the localization for a given subunit in which its expression is sufficient, especially for behavioural phenotypes. Sufficient in this context means that the brain region requiring the expression of the gene product has been localized. Novel strategies have therefore been developed to re‐express, region specifically, nAChR subunits on a KO background using lentiviral vectors. Localized regeneration of fully functional high‐affinity nAChRs in defined brain regions has proven that these receptors are sufficient to restore a variety of functions: nicotine‐induced dopamine release, nicotine self‐administration in mice, dopamine neuron firing patterns, and exploratory and locomotor behaviours in a sequential locomotor task testing executive function were thus defined as depending exclusively on the ‘knock‐back’ of β2*‐nAChRs into the ventral tegmental area. These analyses highlight the important role of endogenous cholinergic regulation of a variety of functions. The novel integrated use of restricted re‐expressed nAChR subunits with in vivo electrophysiology and automated quantitative behavioural analysis enables the further analysis of defined neuronal circuits in nicotine addiction and higher cognitive function.
Changes in the serotonergic system in the main olfactory bulb of rats unilaterally deprived from birth to adulthood
Authors: Gómez C. , Briñón J. G. , Orio L. , Colado M. I. , Lawrence A. J. , Zhou F. C. , Vidal M. , Barbado M. V. , Alonso J. R.
Published: November 2006

The serotonergic system plays a key role in the modulation of olfactory processing. The present study examined the plastic response of this centrifugal system after unilateral naris occlusion, analysing both serotonergic afferents and receptors in the main olfactory bulb. After 60 days of sensory deprivation, the serotonergic system exhibited adaptive changes. Olfactory deprivation caused a general increase in the number of fibres immunopositive for serotonin but not of those immunopositive for the serotonin transporter. HPLC data revealed an increase in serotonin levels but not in those of its major metabolite, 5‐hydroxyindole acetic acid, resulting in a decrease in the 5‐hydroxyindole acetic acid/serotonin ratio. These changes were observed not only in the deprived but also in the contralateral olfactory bulb. Double serotonin–tyrosine hydroxylase immunolabelling revealed that the glomerular regions of the deprived olfactory bulb with a high serotonergic fibre density showed a strong reduction in tyrosine hydroxylase. Finally, the serotonin2A receptor distribution density and the number of juxtaglomerular cells immunopositive for serotonin2A receptor remained unaltered after olfactory deprivation. Environmental stimulation modulated the serotonergic afferents to the olfactory bulb. Our results indicate the presence of a bilateral accumulation of serotonin in the serotonergic axon network, with no changes in serotonin2A receptor density after unilateral olfactory deprivation.
Induction of haem oxygenase‐1 causes cortical non‐haem iron increase in experimental pneumococcal meningitis: evidence that concomitant ferritin up‐regulation prevents iron‐induced oxidative damage
Authors: Ren Hao , Leib Stephen L. , Ferriero Donna M. , Täuber Martin G. , Christen Stephan
Published: November 2006

Desferrioxamine inhibits cortical necrosis in neonatal rats with experimental pneumococcal meningitis, suggesting that iron‐induced oxidative damage might be responsible for neuronal damage. We therefore examined the spatial and temporal profile of changes in cortical iron and iron homeostatic proteins during pneumococcal meningitis. Infection was associated with a steady and global increase of non‐haem iron in the cortex, particularly in neuronal cell bodies of layer II and V, and in capillary endothelial cells. The non‐haem iron increase was associated with induction of haem oxygenase (HO)‐1 in neurones, microglia and capillary endothelial cells, whereas HO‐2 levels remained unchanged, suggesting that the non‐haem iron increase might be the result of HO‐1‐mediated haem degradation. Indeed, treatment with the haem oxygenase inhibitor tin protoporphyrin (which completely blocked the accumulation of bilirubin detected in HO‐1‐positive cells) completely prevented the infection‐associated non‐haem iron increase. The same cells also displayed markedly increased ferritin staining, the increase of which occurred independently of HO activity. At the same time, no increase in DNA/RNA oxidation was observed in infected animals (as assessed by in situ detection of 8‐hydroxy[deoxy]guanosine), strongly suggesting that ferritin up‐regulation protected the brain from iron‐induced oxidative damage. Thus, although pneumococcal meningitis leads to an increase of cortical non‐haem iron, protective mechanisms up‐regulated in parallel prevent iron‐induced oxidative damage. Cortical damage does not appear to be a direct consequence of increased iron, therefore.
Multiple sclerosis: a battle between destruction and repair
Authors: McQualter Jonathan L. , Bernard Claude C. A.
Published: November 2006

Multiple sclerosis (MS) is a chronic neurodegenerative disease of the CNS in which an unrelenting attack from the innate and adaptive arms of the immune system results in extensive demyelination, loss of oligodendrocytes and axonal degeneration. This review summarizes advances in the understanding of the cellular and molecular pathways involved in neurodegeneration following autoimmune‐mediated inflammation in the CNS. The mechanisms underlying myelin and axonal destruction and the equally important interaction between degenerative and repair mechanisms are discussed. Recent studies have revealed that the failure of CNS regeneration may be in part a result of the presence of myelin‐associated growth inhibitory molecules in MS lesions. Successful therapeutic intervention in MS is likely to require suppression of the inflammatory response, in concert with blockade of growth inhibitory molecules and possibly the mobilization or transplantation of stem cells for regeneration.
Acyl peptide hydrolase, a serine proteinase isolated from conditioned medium of neuroblastoma cells, degrades the amyloid‐β peptide
Authors: Yamin Rina , Bagchi Sandipan , Hildebrant Rick , Scaloni Andrea , Widom Russell L. , Abraham Carmela R.
Published: November 2006

Considerable evidence indicates that the amyloid‐β (Aβ) peptide, a proteolytic fragment of the amyloid precursor protein, is the pathogenic agent in Alzheimer's disease (AD). A number of proteases have been reported as capable of degrading Aβ, among them: neprilysin, insulin‐degrading enzyme, endothelin‐converting enzyme‐1 and ‐2, angiotensin‐converting enzyme and plasmin. These proteases, originating from a variety of cell types, degrade Aβ of various conformational states and in different cellular locations. We report here the isolation of a serine protease from serum‐free conditioned medium of human neuroblastoma cells. Tandem mass spectrometry (MS/MS)‐based sequencing of the isolated protein identified acyl peptide hydrolase (APH; EC3.4.19.1) as the active peptidase. APH is one of four members of the prolyl oligopeptidase family of serine proteases expressed in a variety of cells and tissues, including erythrocytes, liver and brain, but its precise biological activity is unknown. Here, we describe the identification of APH as an Aβ‐degrading enzyme, and we show that the degradation of Aβ by APH isolated from transfected cells is inhibited by APH‐specific inhibitors, as well as by synthetic Aβ peptide. In addition, we cloned APH from human brain and from neuroblastoma cells. Most importantly, our results indicate that APH expression in AD brain is lower than in age‐matched controls.
Body size, rarity, and phylogenetic community structure: insights from diving beetle assemblages of Alberta
Authors: Vamosi Jana C. , Vamosi Steven M.
Published: November 2006

Although it is implicit that interactions between species depend on their traits, studies on the probability of finding related species in a community are in their infancy. Community composition and species richness of predaceous diving beetles (Dytiscidae: Coleoptera) have been used as indicators of freshwater ecosystem function yet no incorporation of phylogenetic relationships of coexisting dytiscids has been attempted to date. Improved knowledge of phylogenetic relationships and phylogenetic community structure analysis methods may provide additional insight into the relationships between community composition and species richness, thus impacting our interpretation of aquatic indicator species metrics. Here, we use museum records of dytiscid beetles in 53 lakes of Alberta, Canada to: (1) compile a supertree of dytiscid beetles that live in the province, (2) examine whether coexisting dytiscids tend to be more or less related than expected by chance, and (3) examine whether phylogenetic structuring depends on species richness or mean size of coexisting species. We find that, although the majority of dytiscid assemblages exhibited phylogenetic clustering, the extent to which this occurred depended on the mean size of dytiscids. We discuss the potential mechanisms and implications of the observed patterns in phylogenetic clustering, along with data that would further improve our understanding of community dynamics in dytiscid beetles.
Threats to Avifauna on Oceanic Islands
Authors: TREVINO HEATHER S. , SKIBIEL AMY L. , KARELS TIM J. , DOBSON F. STEPHEN
Published: November 2006

Abstract: Results of the study byBlackburn et al. (2004a)of avifauna on oceanic islands suggest that distance from the mainland and time since European colonization have major influences on species extinctions and that island area is a significant but secondary contributing factor. After augmenting the data of the study on geographical properties for some of the islands they examined, we used a causal analysis approach with structural equation modeling to reexamine their conclusions. In our model geographical properties of islands, such as island area and isolation, were considered constraints on biological factors, such as the number of introduced mammalian predators and existing number of avifauna, that can directly or indirectly influence extinction. Of the variables we tested, island area had the greatest total influence on the threat of extinction due to its direct and indirect effects on the size of island avifauna. Larger islands had both a greater number of threatened bird species and more avifauna, increasing the number of species that could become threatened with extinction. Island isolation also had a significant, positive, and direct effect on threats to island avifauna because islands farther from the mainland had fewer current extant avifauna. Time since European colonization had a significant negative, but relatively weaker, influence on threats compared with the traditional biogeographic factors of island area and distance to the mainland. We also tested the hypothesis that the amount of threat is proportionally lower on islands that have had more extinctions (i.e., there is a “filter effect”). Because the proportion of bird extinctions potentially explained only 2.3% of the variation in the proportion of threatened species on islands, our results did not support this hypothesis. Causal modeling provided a powerful tool for examining threat of extinction patterns of known and hypothesized pathways of influence.
Demographic Side Effects of Selective Hunting in Ungulates and Carnivores
Authors: MILNER JOS M. , NILSEN ERLEND B. , ANDREASSEN HARRY P.
Published: November 2006

Abstract: Selective harvesting regimes are often implemented because age and sex classes contribute differently to population dynamics and hunters show preferences associated with body size and trophy value. We reviewed the literature on how such cropping regimes affect the demography of the remaining population (here termeddemographic side effects). First, we examined the implications of removing a large proportion of a specific age or sex class. Such harvesting strategies often bias the population sex ratio toward females and reduce the mean age of males, which may consequently delay birth dates, reduce birth synchrony, delay body mass development, and alter offspring sex ratios. Second, we reviewed the side effects associated with the selective removal of relatively few specific individuals, often large trophy males. Such selective harvesting can destabilize social structures and the dominance hierarchy and may cause loss of social knowledge, sexually selected infanticide, habitat changes among reproductive females, and changes in offspring sex ratio. A common feature of many of the reported mechanisms is that they ultimately depress recruitment and in some extreme cases even cause total reproductive collapse. These effects could act additively and destabilize the dynamics of populations, thus having a stronger effect on population growth rate than first anticipated. Although more experimental than observational studies reported demographic side effects, we argue that this may reflect the quite subtle mechanisms involved, which are unlikely to be detected in observational studies without rigorous monitoring regimes. We call for more detailed studies of hunted populations with marked individuals that address how the expression of these effects varies across mating systems, habitats, and with population density. Theoretical models investigating how strongly these effects influence population growth rates are also required.
Scale‐Dependent Effects of Habitat Fragmentation on Hawthorn Pollination, Frugivory, and Seed Predation
Authors: GARCÍA DANIEL , CHACOFF NATACHA P.
Published: November 2006

Abstract:  Habitat fragmentation is a major cause of functional disruption in plant‐animal interactions. The net effect on plant regeneration is, however, controversial because a given landscape change can simultaneously hamper mutualism and attenuate antagonism. Furthermore, fragmentation effects may emerge at different spatial scales, depending on the size of the foraging range of the different interacting animals. We studied pollination by insects, frugivory by birds acting as seed dispersers, and postdispersal seed predation by rodents in 60 individual hawthorn (Crataegus monogyna Jacq.) trees in relation to structural fragmentation in the surrounding habitat. We evaluated fragmentation at three spatial scales by measuring the percentage of forest cover in three concentric areas around each tree of, respectively, 10‐m, 20‐ to 50‐m, and 50‐ to 100‐m radius. The number of developing pollen tubes per flower style and fruit set decreased in proportion to the decrease of forest cover. Similarly, the magnitude of frugivory in focal trees was negatively affected by habitat loss. In contrast, seed predation was higher under plants in highly fragmented contexts. The effect of fragmentation was additive in terms of reducing the potential of plant regeneration. Moreover, the functional scale of response to habitat loss differed among interactions. Fragmentation effects on pollination emerged at the largest scale, whereas seed predation was mostly affected at the intermediate scale. In contrast to expectations from the larger foraging range of birds, fragmentation effects on frugivory mainly operated at the finest scale, favored by the ability of birds to cope hierarchically with spatial heterogeneity at different scales. Given that two opposing demographic forces (frugivory and seed predation) would be potentially affected by fine‐scale features, we propose structural scale as the primary spatial dimension of fragmentation effects on the process of plant regeneration.
Risk Analysis in Developing Countries1
Authors: Pe Benito Claudio Corazon
Published: November 2006

SUMMARY AND CONCLUSIONS

In summary, risk analysis is not yet well practiced in developing countries, although there are numerous, diverse environmental and other risk‐related issues and concerns that need attention. A few initiatives have been taken, but, so far, they have created only relatively small impact in a few areas. Many risk issues may not be addressed, partly as a result of lack of resources and inadequate knowledge by policy makers.

Risk analysis is an essential tool for the planning and implementation of development projects. To enhance its use, however, risk analysis approaches and methods must be adapted to developing countries, and this requires research. Unfortunately, funds for research, in general, are hard to find. There are other problems in the implementation of risk analysis. Trained professionals on risk analysis are few. Existing institutions that are tasked with resolving environmental and other risk issues are overburdened. Risk‐related data are sorely lacking. Resources are very limited for addressing numerous natural and technological hazards.

In most developing countries, political and economic stability is still threatened by both internal and external forces, hence, that is what receives priority attention. Activities like risk analysis, which generally lead to long‐term results and benefits, do not get enough interest. In addition, there is still little public awareness of risks even among those who have passed the stage of survival; thus, there is little public concern about them.

We cannot afford this lack of concern for long. In the Philippines, the government was the first to recognize after our peaceful revolution in 1986 that “the environmental issues can add fuel to the insurgency; they can also hamper efforts towards national recovery”.(4) To this point, I have added that risk management (including risk assessment and risk communication), like attainment of peace and freedom, is a social imperative because risk issues affect our health, safety, and both our physical and economic well‐being.(7) Many of such issues in developing countries have not only local, but also global origin and impacts. They thus deserve the interest of each of us.
One‐Hit Models of Carcinogenesis: Conservative or Not?
Authors: Bailar John C. , Crouch Edmund A. C. , Shaikh Rashid , Spiegelman Donna
Published: November 2006

One‐hit formulas are widely believed to be “conservative” when used to analyze carcinogenesis bioassays, in the sense that they will rarely underestimate risks of cancer at low exposures. Such formulas are generally applied to the lifetime incidence of cancer at a specific site, with risks estimated from animal data at zero dose (control), and two or more additional doses that are appreciable fractions of a maximum tolerated dose. No empirical study has demonstrated that the one‐hit formula is conservative in the sense described. The Carcinogenesis Bioassay Database System contains data on 1212 separate bioassays of 308 chemical substances tested at exactly three evaluable doses. These provided sufficient data to examine 8432 specific combinations of cancer site with sex, species, and chemical. For each of these we fitted a one‐hit formula to the zero and maximum dose data points, then examined the relation of the fitted curve to the incidence rate observed at the mid‐dose, with and without adjustment for intercurrent mortality.Both underestimates and overestimates of risk at mid‐dose occurred substantially more often than expected by chance. We cannot tell whether such underestimates would occur at lower doses, but offer six biological reasons why underestimates might be expected. In a high percentage of animal bioassays, the one‐hit formula is not conservative when applied in the usual way to animal data. It remains possible that the one‐hit formula may indeed be conservative at sufficiently low doses (below the observational range), but the usual procedure, applied to the usual dose range, can be nonconservative in estimating the slope of the formula at such low doses. Risk assessments for regulation of carcinogens should incorporate some measure of additional uncertainty.
Linking Indoor Air and Pharmacokinetic Models to Assess Tetrachloroethylene Risk
Authors: Bogen Kenneth T. , McKone Thomas E.
Published: November 2006

Physiologically based pharmacokinetic (PBPK) models describing the uptake, metabolism, and excretion of xenobiotic compounds are now proposed for use in regulatory health‐risk assessments. In this study we investigate the extent of PCE metabolism arising from domestic respiratory exposure to tetrachloroethylene (PCE) from ground water, as predicted using a PBPK model. Indoor exposure patterns we use as input to the PBPK model are realistic ones generated from a three‐compartment model describing volatilization of PCE from domestic water into household air. Values we use for the metabolic parameters of the PBPK model are estimated from data on urinary metabolites in workers exposed to PCE. It is shown that for respiratory PCE exposure due to typical levels of PCE in ground water, use of time‐weighted average air concentrations with a steady‐state PBPK model yields estimates of total metabolized PCE similar to those obtained using completely dynamic modeling, despite considerable uncertainty in key exposure‐ and metabolic‐model parameters. These findings suggest that, for PCE, risk estimation taking pharmacokinetics into account may be accomplished using a simple analytic approach.
The U.S. Nuclear Regulatory Commission Safety Goal Policy: A Critical Review
Authors: Bier Vicki M.
Published: November 2006

The most recent U.S. Nuclear Regulatory Commission (NRC) statement of safety goal policy is a significant advance over previous versions. However, some areas of the policy are still in need of refinement, and the resolution of several key questions was deferred pending further review. To clarify some of these issues, this paper presents a critical review of the NRC safety goal policy to date.
Risk Assessment Criteria for Radioactive Waste Disposal
Authors: Corbett James O.
Published: November 2006

The assessment of radioactive waste disposal options in terms of the annual risk to the critical group can lead to ambiguities, which arise largely in defining what is meant by the critical group. Radically different risk estimates can be obtained, depending on whether statistical averaging is carried out before or after the critical group is located in the time dimension. The merits of two different approaches are discussed through simple thought experiments and mathematical models. A criterion based on lifetime risk to the critical group is suggested, which could be used to supplement the currently accepted annual risk Emits. The risks from both stochastic and nonstochastic radiation effects are taken into account.
Quantitative Risk Assessments as Evidence in Civil Litigation
Authors: Walker Vern R.
Published: November 2006

Those who prepare quantitative risk assessments do not always appreciate that those assessments might be used as evidence in civil litigation. This paper suggests that litigation attorneys, judges, and juries be regarded as audiences to whom the information in the risk assessment must be communicated. The way that a risk assessment is prepared can affect significantly whether litigation is brought at all, the resolution of evidentiary motions involving the risk assessment, as well as the ultimate outcome of the litigation. This paper discusses certain procedural and evidentiary aspects of the civil litigation process in the hope that a better understanding of that process might lead to the preparation of risk assessments that are more adequately understood by juries, judges, and litigants.
Expert Scientific Judgment and Cancer Risk Assessment: A Pilot Study of Pharmacokinetic Data
Authors: Hawkins Neil C. , Graham John D.
Published: November 2006

When high‐dose tumor data are extrapolated to low doses, it is typically assumed that the dose of a carcinogen delivered to target cells is proportional to the dose administered to test animals, even at exposure levels below the experimental range. Since pharmacokinetic data are becoming available that in some cases question the validity of this assumption, risk assessors must decide whether to maintain the standard assumption. A pilot study of formaldehyde is reported that was undertaken to demonstrate how expert scientific judgment can help guide a controversial risk assessment where pharmacokinetic data are considered inconclusive. Eight experts on pharmacokinetic data were selected by a formal procedure, and each was interviewed personally using a structured interview protocol. The results suggest that expert scientific opinion is polarized in this case, a situation that risk assessors can respond to with a range of risk characterizations considered biologically plausible by the experts. Convergence of expert opinion is likely in this case if several specific research strategies are executed in a competent fashion. Elicitation of expert scientific judgment is a promising vehicle for evaluating the quality of pharmacokinetic data, expressing uncertainty in risk assessment, and fashioning a research agenda that offers possible forging of scientific consensus.
Patterns of Development in Spanish L2 Pragmatic Acquisition: An Analysis of Novice Learners' Production of Directives
Authors: PEARSON LYNN
Published: November 2006

This article investigates from an acquisitional approach the development of pragmatic competence by novice learners of second language (L2) Spanish. Specifically, it examines the acquisition of various strategies (e.g., head acts, use of softeners, formality marking, and hearer‐oriented directives) to realize Spanish directives. A quantitative and qualitative analysis of the data detected patterns in the learners' directive production. The analysis considered factors such as instruction, L2 grammatical competence, and the influence of the first language (L1) to illustrate the patterns of development of L2 pragmatics at lower proficiency levels. The results show (a) verb forms with increased morphological complexity replaced lower level directive strategies, possibly as a result of the expansion of L2 grammatical competence; (b) pragmatic competence seems to precede grammatical competence; and (c) the L1 pragmatic system appears to play a role in interpreting and processing new L2 data for use in production.
Speaking Foreign Languages in the United States: Correlates, Trends, and Possible Consequences
Authors: ROBINSON JOHN P. , RIVERS WILLIAM P. , BRECHT RICHARD D.
Published: November 2006

With President George W. Bush's unprecedented call in January 2006 to expand the foreign language capacity of the United States, it has become clear that languages other than English (LOE) are of great interest to public policy in the United States. Yet the language capacity of the United States remains poorly documented. The 2000 General Social Survey (GSS) included new questions concerning the languages spoken by 1,398 respondents. Although about one quarter (26%) of respondents to this GSS sample claimed they could speak another language, only 10% overall said they could speak it very well. Those respondents who speak a foreign language were typically aged 25–44, graduate school educated, self‐identified as being of a race other than White, and living in large metropolitan cities and on the coasts. Spanish (50%), French (15%), and German (9%) were the most common languages spoken by the survey respondents. Whereas 67% of respondents who learned the language at home as a child said they could speak it very well, only 10% of those who learned it in school or elsewhere did speak it very well. As expected, LOE speakers gave significantly more responses revealing support of LOE and policies favorable to immigration, with LOE‐home speakers being more positive about these issues than LOE speakers who learned the language at school. These findings can help to inform national policy debates concerning how best to address the language needs of the United States.
On‐Task Versus Off‐Task Self‐Assessments Among Korean Elementary School Students Studying English
Authors: BUTLER YUKO GOTO , LEE JIYOON
Published: November 2006

This study examined the validity of Korean students' self‐assessments of their oral performance in English in a Foreign Language at the Elementary School (FLES) level. We examined the validity of 2 types of assessments: an off‐task self‐assessment and an on‐task self‐assessment. The off‐task assessment asked students to evaluate their overall performance in a general and somewhat decontextualized way. The on‐task self‐assessment asked students to self‐evaluate their performance immediately after they completed their English tasks. The results of the 2 types of self‐assessments were compared both with the students' general proficiency test scores and with their teachers' assessments based on classroom observation. The results indicate that if self‐assessments are administered in an on‐task format, students can self‐assess their oral performance more accurately than they can in an off‐task format. It was also found that the on‐task self‐assessment was generally less influenced by student attitude/personality factors than was the off‐task self‐assessment
Recasts in the Adult English L2 Classroom: Characteristics, Explicitness, and Effectiveness
Authors: LOEWEN SHAWN , PHILP JENEFER
Published: November 2006

A number of descriptive studies of language classrooms have identified recasts as a frequent form of feedback used by teachers following learners' nontarget‐like oral production. Some classroom‐based researchers (e.g., Lyster, 1998) have suggested that recasts are less effective than other forms of feedback because of the ambiguity of their potentially corrective purpose. The present study focused on both the provision and the effectiveness of recasts in 12 adult English second language classrooms throughout 17 hours of meaning‐based interaction. There were 12 teachers and 118 learners who participated, with class sizes ranging from 6 to 14 students. Comparisons involving the incidence of recasts, elicitation, and metalinguistic feedback, together with learner responses (e.g., successful uptake) following these types of feedback, revealed that recasts were widely used and, similar to other types of corrective feedback, were beneficial at least 50% of the time, as measured by posttests. The recasts differed according to characteristics that emphasized their corrective purpose. Logistic regression analysis revealed certain characteristics that were associated with successful uptake and with accuracy on posttests. Stress, declarative intonation, one change, and multiple feedback moves were predictive of successful uptake, whereas interrogative intonation, shortened length, and one change were predictive of the accuracy of the test scores. This study suggests that recasts vary in implicitness and that these differences may have an impact on their effectiveness, both in terms of learners' successful uptake and subsequent use. Moreover, the ambiguity of recasts is greatly reduced by the phrasal, prosodic, and discoursal cues that teachers provide. The effectiveness of recasts is likely to be affected by these cues and other factors, such as degree of difference between the recast and the nontarget‐like utterance.
Nondigestible Oligo‐ and Polysaccharides (Dietary Fiber): Their Physiology and Role in Human Health and Food
Authors: Tungland B.C. , Meyer D.
Published: November 2006

Nondigestible polysaccharides (NDP) and nondigestible oligosaccharides (NDO) occur naturally in many foods. The physicochemical and biological properties of these compounds, as they relate to dietary fiber, are associated with physiological actions in the small and large intestine, having important implications in human health. These properties include water dispersibility and solubility, viscosity effects, bulk, absorption and fermentability, and binding of other compounds. These features may lead to various physiological actions such as reducing cholesterol and attenuating blood glucose, maintaining gastrointestinal health, and positively affecting calcium bioavailability and immune function. Moreover, based on their physiochemical properties, many of the new oligosaccharides can help improve the organoleptic properties and nutritional value of foods.
Biofilm Formation and Control in Food Processing Facilities
Authors: Chmielewski R.A.N. , Frank J.F.
Published: November 2006

Microorganisms on wet surfaces have the ability to aggregate, grow into microcolonies, and produce biofilm. Growth of biofilms in food processing environments leads to increased opportunity for microbial contamination of the processed product. These biofilms may contain spoilage and pathogenic microorganisms. Microorganisms within biofilms are protected from sanitizers increasing the likelihood of survival and subsequent contamination of food. This increases the risk of reduced shelf life and disease transmission. Extracellular polymeric substances associated with biofilm that are not removed by cleaning provide attachment sites for microorganisms newly arrived to the cleaned system. Biofilm formation can also cause the impairment of heat transfer and corrosion to metal surfaces. Some of the methods used to control biofilm formation include mechanical and manual cleaning, chemical cleaning and sanitation, and application of hot water.
Food Process Engineering: The Last 25 Years and Challenges Ahead
Authors: Bruin S. , Jongen Th.R.G.
Published: November 2006

In the first part of this contribution, an overview is given of some of the main developments in food process engineering in the last 25 years of the 20th century. This overview is, of course, colored by the personal experience of the authors, but a sincere effort was made to maintain a general perspective. Topics that will be briefly discussed are: progress in understanding how to control food microstructure formation during processing, separation processes, conversion processes and stabilization processes, progress in flavor technology and understanding of flavor retention during processing and release. In the 2nd part, in our view, the most exiting future developments are briefly discussed. The major items here are: processing requirements for functional foods, integrated process design approaches, application of novel‘fields’in food processes,‘precision’processing, supply chain approaches to food manufacturing, and more.
Sporeformers as Human Probiotics: Bacillus, Sporolactobacillus, and Brevibacillus
Authors: Sanders M.E. , Morelli L. , Tompkins T.A.
Published: November 2006

The value of exogenously supplied live bacteria for the maintenance of health in humans has been recognized both scientifically in the published literature and commercially in the availability of probiotic products. Although many bacteria characterized as probiotics are strains of Lactobacillus or Bifidobacterium, sporeforming bacteria, primarily of the genus Bacillus and related genera, have also been studied and commercialized as probiotics. This article reviews the characterization, efficacy, and safety of sporeformers used as probiotics.
The Kosher and Halal Food Laws
Authors: Regenstein J.M. , Chaudry M.M. , Regenstein C.E.
Published: November 2006

Knowledge of the kosher and halal dietary laws is important to the Jewish and Muslim populations who observe these laws and to food companies that wish to market to these populations and to interested consumers who do not observe these laws. The kosher dietary laws determine which foods are “fit or proper” for Jews and deal predominantly with 3 issues: allowed animals, the prohibition of blood, and the prohibition of mixing milk and meat. These laws are derived from the Torah and the oral law received by Moses on Mount Sinai (Talmud). Additional laws cover other areas such as grape products, cheese, baking, cooking, tithing, and foods that may not be eaten during the Jewish festival of Passover. Halal laws are derived from the Quran and the Hadith, the traditions of the prophet Muhammad. As with Kosher laws, there are specific allowed animals and a prohibition of the consumption of blood. Additionally, alcohol is prohibited.
Nucleation and Expansion During Extrusion and Microwave Heating of Cereal Foods
Authors: Moraru C.I. , Kokini J.L.
Published: November 2006

Expansion of biopolymer matrices is the basis for the production of a wide variety of cereal foods. A limited number of manufacturing processes provide practical solutions for the development of an impressive variety of expanded products, just by changing process variables. It is therefore essential that the mechanisms involved in expansion are well known and controlled. This paper summarizes the knowledge of nucleation and expansion in extruded and microwaved products available to date. The effect of processing conditions and properties of the biopolymeric matrix on nucleation and expansion are discussed. Moisture content enables the glassy polymeric matrix to turn into rubbery state at process temperatures, which allows superheated steam bubbles to form at nuclei and then expand, expansion being governed by the biaxial extensional viscosity of the matrix. Nucleation and expansion theories are presented along with quantitative data that support them.