bluuebunny/crossref_metadata_2025 huggingface dataset:
Does foraging efficiency vary with colony size in the fairy martin Petrochelidon ariel?
Authors: Santema Peter , Griffith Simon C. , Langmore Naomi E. , Komdeur Jan , Magrath Michael J. L.
Published: December 2008

Colonial breeding occurs in a wide range of taxa, however the advantages promoting its evolution and maintenance remain poorly understood. In many avian species, breeding colonies vary by several orders of magnitude and one approach to investigating the evolution of coloniality has been to examine how potential costs and benefits vary with colony size. Several hypotheses predict that foraging efficiency may improve with colony size, through benefits associated with social foraging and information exchange. However, it is argued that competition for limited food resources will also increase with colony size, potentially reducing foraging success. Here we use a number of measures (brood feeding rates, chick condition and survival, and adult condition) to estimate foraging efficiency in the fairy martin Petrochelidon ariel, across a range of colony sizes in a single season (17 colonies, size range 28–139 pairs). Brood provisioning rates were collected from multiple colonies simultaneously using an electronic monitoring system, controlling for temporal variation in environmental conditions. Provisioning rate was correlated with nestling condition, though we found no clear relationship between provisioning rate and colony size for either male or female parents. However, chicks were generally in worse condition and broods more likely to fail or experience partial loss in larger colonies. Moreover, the average condition of adults declined with colony size. Overall, these findings suggest that foraging efficiency declines with colony size in fairy martins, supporting the increased competition hypothesis. However, other factors, such as an increased ectoparasitise load in large colonies or change in the composition of phenotypes with colony size may have also contributed to these patterns.
Histopathologic evidence of the nondermatophytic mould Scopulariopsis brevicaulis masking the presence of dermatophytes in a toenail infection
Authors: Stefanato Catherine M. , Verdolini Roberto
Published: December 2008

Nondermatophytic toenail infection with Scopulariopsis brevicaulis is rare, but may occur often in association with dermatophytes. We report a case of an 84‐year‐old man who presented with onychomycosis of the big toenail. Histopathologic examination of the avulsed nail showed evidence of S.brevicaulis coinfection with a dermatophyte, despite negative mycology results for the latter. Our case underscores the importance of histopathologic examination of nail specimens as an additional invaluable tool in the diagnosis of onychomycosis, as it may unmask false‐negative mycology findings.
High intracellular content of cyclin‐dependent kinase inhibitor p27Kip1 in early‐ and intermediate stage B‐cell chronic lymphocytic leukemia lymphocytes predicts rapid progression of the disease
Authors: Wolowiec Dariusz , Wojtowicz Marcin , Ciszak Lidia , Kosmaczewska Agata , Frydecka Irena , Potoczek Stanislaw , Urbaniak‐Kujda Donata , Kapelko‐Slowik Katarzyna , Kuliczkowski Kazimierz
Published: December 2008

Previous studies showed that peripheral blood lymphocytes of B‐cell chronic lymphocytic leukemia (B‐CLL) displayed a high intracellular level of cell cycle inhibitory protein p27Kip1. It has been suggested that its’ high expression may confer them survival advantage and lead to unfavorable prognosis, but the prognostic significance of p27Kip1 expression for previously untreated, non‐advanced stage B‐CLL was not established. We studied a relationship between the intracellular level of p27Kip1 of lymphocytes of early‐ and intermediate stage B‐CLL patients and their spontaneous apoptosis in vitro, as well as prognostic significance of p27Kip1 in B‐CLL lymphocytes for the risk of disease progression. Intracellular p27Kip1 content of peripheral blood lymphocytes obtained from 48 previously untreated 0–II Rai stage B‐CLL patients was determined by flow cytometry. The viability and apoptosis of those lymphocytes after 72‐h culture were also assessed. During the follow‐up period (6–71 months, median 59.5), we recorded the time elapsed to the doubling of lymphocyte count, progression to a higher Rai stage and the appearance of indications for cytostatic treatment. The p27Kip1 expression was neither correlated with initial lymphocyte count, CD38 expression, cell viability nor spontaneous apoptosis ratio after 72‐h culture. Higher p27Kip1 level was related to the probability of earlier occurrence of each of three above‐mentioned events. We did not find a prognostic significance of in vitro cell viability nor apoptosis as to the risk of disease progression. Our results indicate that elevated intracellular p27Kip1 level in leukemic lymphocytes of early‐ and intermediate stage B‐CLL patients contributes to rapid progression of the disease.
Haploinsufficiency of glutamine synthetase increases susceptibility to experimental febrile seizures
Authors: Van Gassen K. L. I. , Van Der Hel W. S. , Hakvoort T. B. M. , Lamers W. H. , De Graan P. N. E.
Published: December 2008

Glutamine synthetase (GS) is a pivotal glial enzyme in the glutamate–glutamine cycle. GS is important in maintaining low extracellular glutamate concentrations and is downregulated in the hippocampus of temporal lobe epilepsy patients with mesial–temporal sclerosis, an epilepsy syndrome that is frequently associated with early life febrile seizures (FS). Human congenital loss of GS activity has been shown to result in brain malformations, seizures and death within days after birth. Recently, we showed that GS knockout mice die during embryonic development and that haploinsufficient GS mice have no obvious abnormalities or behavioral seizures. In the present study, we investigated whether reduced expression/activity of GS in haploinsufficient GS mice increased the susceptibility to experimentally induced FS. FS were elicited by warm‐air‐induced hyperthermia in 14‐day‐old mice and resulted in seizures in most animals. FS susceptibility was measured as latencies to four behavioral FS characteristics. Our phenotypic data show that haploinsufficient mice are more susceptible to experimentally induced FS (P < 0.005) than littermate controls. Haploinsufficient animals did not differ from controls in hippocampal amino acid content, structure (Nissl and calbindin), glial properties (
glial fibrillary acidic protein and vimentin) or expression of other components of the glutamate–glutamine cycle (excitatory amino acid transporter‐2 and vesicular glutamate transporter‐1). Thus, we identified GS as a FS susceptibility gene. GS activity‐disrupting mutations have been described in the human population, but heterozygote mutations were not clearly associated with seizures or epilepsy. Our results indicate that individuals with reduced GS activity may have reduced FS seizure thresholds. Genetic association studies will be required to test this hypothesis.
Genetic complexity of absence seizures in substrains of C3H mice
Authors: Tokuda S. , Beyer B. J. , Frankel W. N.
Published: December 2008

Absence epilepsy is a common form of idiopathic generalized epilepsy whose etiology is poorly understood because of genetic and phenotypic heterogeneity. The inbred mouse strain C3H/He exhibits spontaneous absence seizures characterized by spike and wave discharges (SWD) on the electroencephalogram concomitant with behavioral arrest. Previous studies using the C3H/HeJ (HeJ) substrain identified a mutation in the Gria4 gene as a major susceptibility locus. In the present study, we found that two closely related substrains C3H/HeOuJ (OuJ) and C3H/HeSnJ, which have a similar SWD incidence as HeJ, do not contain the Gria4 mutation. Further analysis of backcross mice segregating OuJ and C57BL/6J alleles shows that, unlike the HeJ substrain, OuJ does not have a major locus for SWD but has suggestive loci at best that would explain only a fraction of the phenotypic variance. These results illustrate how the genetic etiology of a common neurological disorder can differ between substrains with similar phenotypes. We infer that all C3H strains are sensitized to SWD and that additional mutations affecting SWD arose or were fixed independently in the years since the substrains diverged.
Habitual micronutrient intake during and after pregnancy in Caucasian Londoners
Authors: Derbyshire E. , Davies G.J. , Costarelli V. , Dettmar P.W.
Published: December 2008

Micronutrient status is of fundamental importance both upon conception and throughout pregnancy. There is an abundance of literature investigating nutrient intakes during individual trimesters of pregnancy but few studies have investigated baseline intakes of nutrients throughout gestation as a continuum. The current investigation set out to measure habitual micronutrient intakes at weeks 13, 25, 35 of pregnancy and 6 weeks postpartum using a prospective background information questionnaire, 4–7‐day weighed food diary and postnatal questionnaire. Seventy‐two primiparous, Caucasian Londoners were recruited at the study start with 42 completing the first, second, third trimester and postpartum study stages respectively. Study findings indicated that sodium intakes were significantly higher than UK guidelines throughout and after pregnancy (P < 0.001). Intakes of folate, iron, vitamin D, potassium, iodine and selenium were lower than UK recommendations during and after pregnancy, but to varying levels of statistical significance (P < 0.05). Only 23–38% of women met UK recommendations for folate (300 µg day−1) through dietary sources. Similarly, only a small percentage of women met dietary guidelines for iron (19–28%). The findings from the current study indicate that public health interventions may be required to help expectant mothers achieve an optimal diet, particularly after birth when dietary recommendations increase for some micronutrients.
Relationship between socio‐demographic and anthropometric variables and number of erupted primary teeth in suburban Nigerian children
Authors: Oziegbe Elizabeth Obhioneh , Adekoya‐Sofowora Comfort , Folayan Morenike Oluwatoyin , Esan Temitope Ayodeji , Owotade Foluso John
Published: December 2008

The socio‐demographic and anthropometric variables could influence the number of teeth present in the child's mouth. To determine the effect of anthropometric and socio‐demographic variables on the number of erupted primary teeth, a cross‐sectional study was performed involving 1013 children aged between 4 and 36 months who attended the immunization clinics in Ile‐Ife, Nigeria. Statistical analyses were performed using stata. The analyses included frequencies, cross‐tabulations, chi squared test and t‐test. The number of erupted teeth was modelled as the dependent variable in a multiple regression (Binomial) model, and the socio‐demographic (age, gender and socio‐economic status) and anthropometric variables, such as weight and height at presentation, as predictor variables. Statistical significance was inferred at P < 0.05. The age and height at presentation had significant association with the number of erupted teeth in this study population (P < 0.001). Also children from high socio‐economic class in relation to low socio‐economic class had significant larger number of erupted teeth in this study population (P < 0.001). The age and height of the child at presentation were significantly related to the number of erupted teeth. Also children from high socio‐economic class had significant lager number of erupted teeth compared with children from low socio‐economic class.
Parental distress around supplementing breastfed babies using nasogastric tubes on the post‐natal ward: a theme from an ethnographic study
Authors: Taylor Alison M. , Cloherty Michele , Alexander Jo , Holloway Immy , Galvin Kathleen , Inch Sally
Published: December 2008

There is abundant evidence of the benefits of breastfeeding. In the UK, supplementation in hospital has consistently been shown to be associated with shortened duration of breastfeeding. This paper reports on a subset of the data from an ethnographic study that explored the expectations, beliefs and experiences of mothers and health professionals concerning supplementation, using a variety of methods, of breastfed babies in an English maternity unit in 2002. This paper aims to describe the expectations, beliefs and experiences of mothers and health professionals concerning supplementation by nasogastric (NG) tube on the post‐natal ward. Participant observation was carried out on day and night shifts and at weekends over 9 months. Mothers, midwives, neonatal nurses, health care assistants and senior paediatricians were interviewed. Categories and themes were generated. The researchers' constructs of ‘the essential method’, when the tube was the method needed for medical reasons, and ‘the chosen method’, when other methods of oral feeding should have been possible, emerged. The latter included time pressures and the avoidance of any form of oral activity that might perhaps make return to the breast more difficult. The data concerning the use of NG tubes for supplementation yielded the specific theme of parental distress. In the absence of evidence that supplementation by NG tube on the post‐natal ward is associated with greater breastfeeding success than other methods, the use of the tube to avoid any form of ‘oral confusion’ should be discontinued. Its use primarily to save time should not be considered acceptable.
Effect of parity on phalangeal bone mineral density in post‐menopausal Sri Lankan women: a community based cross‐sectional study
Authors: Lekamwasam Sarath , Wijayaratne Lalith , Rodrigo Mahinda , Hewage Udul
Published: December 2008

There is paucity of studies related to parity and bone mineral density in South Asian countries. We recruited 713 healthy, community dwelling post‐menopausal women from seven provinces in Sri Lanka for this survey. The number of pregnancies, including miscarriages beyond 20 weeks of gestation, was recorded. Women with diseases and those who have taken drugs that can affect bone mineral density (BMD) were excluded (n = 15). Phalangeal BMD and bone mineral content (BMC) were measured using AccuDEXA in 713 women. Mean (SE) BMD of nulliparous women (n = 32), women with one to two pregnancies (n = 284), three to four pregnancies (n = 290) and more than four pregnancies (n = 107) were 0.437(0.014), 0.454(0.005), 0.455(0.005) and 0.417(0.006) g/cm2, respectively (P < 0.001). Corresponding mean (SE) BMCs were 1.30(0.063), 1.41(0.021), 1.43(0.022) and 1.32(0.033) g, respectively (P < 0.001). Women with more than four pregnancies were older and lighter when compared with other groups. When results were adjusted for current age and current weight, differences in mean BMD and BMC between groups became non‐significant. BMD of nulliparous women remained low in all analyses. We report a significant difference in unadjusted phalangeal BMD in women categorized according to their parity. Women with one to four pregnancies had the highest phalangeal BMD and BMC, while multi‐parous (more than four pregnancies) and nulliparous women had lower values. However, in an adjusted analysis, the differences in BMD and BMC were partially explained by the differences of age and body weight between the groups and the unique effect of parity was difficult to determine. Women with lower BMD may have a higher risk of future fractures.
Effects of Pravastatin on the Function of Dendritic Cells in Patients with Coronary Heart Disease
Authors: Li Xiang , Liu Cheng , Cui Jian , Dong Min , Peng Cheng‐Hai , Li Qing‐Song , Cheng Jia‐Li , Jiang Shu‐Lin , Tian Ye
Published: December 2008

Abstract:  The aim of the study was to investigate the functional profile of dendritic cells in patients with coronary heart disease and the effects of pravastatin on this. Forty‐eight patients with coronary heart disease were divided into three groups: 16 treated with pravastatin 10 mg/day, 16 treated with pravastatin 20 mg/day and 16 not treated with pravastatin. Dendritic cells from 48 patients with coronary heart disease (before and 4 weeks after the treatment) and 16 healthy individuals were derived from peripheral blood. CD86 of dendritic cells was assessed by flow cytometry. Immunostimulatory capacity of dendritic cells was measured by mixed lymphocyte reaction. The levels of cytokines in the medium of mixed lymphocyte reaction were analysed. Blood lipids and high‐sensitivity C‐reactive protein were measured. Compared to normal group, more CD86+ dendritic cells were expressed in coronary heart disease and greater immunostimulatory capacity of dendritic cells in coronary heart disease was demonstrated. T lymphocytes in coronary heart disease in mixed lymphocyte reaction secreted higher levels of pro‐inflammation cytokines and lower levels of anti‐inflammation cytokines. CD86 expression significantly correlated with C‐reactive protein, but did not correlate with low‐density lipoprotein cholesterol. Both dosages of pravastatin markedly inhibited the function of dendritic cells and lowered C‐reactive protein, which is independent of plasma cholesterol lowering. The anti‐inflammatory effect of pravastatin showed no obvious difference between the two dosage groups. In conclusion, dendritic cells were activated in coronary heart disease and dendritic cell‐mediated immune mechanisms may be involved in the pathogenesis of coronary heart disease. Pravastatin can inhibit dendritic cell activation, which is independent of plasma cholesterol lowering. Pravastatin in different doses showed no apparent differences in the inhibition of dendritic cell functions.
SMND‐309, a Novel Derivate of Salvianolic Acid B, Attenuates Apoptosis and Ameliorates Mitochondrial Energy Metabolism in Rat Cortical Neurons
Authors: Tian Jingwei , Li Guisheng , Zhang Shumin , Gao Yubai , Jiang Wanglin , Fu Fenghua , Liu Zhifeng
Published: December 2008

Abstract:  SMND‐309, a novel compound (2E)‐2‐{6‐[(E)‐2‐carboxyvinyl]‐2,3‐dihydroxyphenyl}‐3‐(3,4‐dihydroxyphenyl) acrylic acid, is a new derivate of salvianolic acid B. The present study elucidates the effects of SMND‐309 on the cultured rat cortical neuron damage induced by oxygen‐glucose deprivation. The results show that SMND‐309 treatment obviously attenuates apoptosis and ameliorates mitochondrial energy metabolism in rat cortical neurons by increasing cell survival rate, mitochondrial antioxidant enzyme activities, mitochondrial respiratory enzymes activities, mitochondrial respiratory control ratio and the adenosine triphosphate content, and by decreasing mitochondrial malondialdehyde content, lactate dehydrogenase release, intracellular Ca2+ level and caspase‐3 activity in a concentration‐dependent manner. Moreover, SMND‐309 exhibits significantly higher potency as compared to salvianolic acid B. These findings indicate that SMND‐309 has a protective potential against cerebral ischaemic injury and its protective effects may be due to the suppression of intracellular Ca2+ elevation and caspase‐3 activity, and improvement of mitochondrial energy metabolism and antioxidant property.
Pharmacogenetic Studies of Paclitaxel in the Treatment of Ovarian Cancer
Authors: Gréen Henrik , Söderkvist Peter , Rosenberg Per , Mirghani Rajaa A. , Rymark Per , Lundqvist Elisabeth Åvall , Peterson Curt
Published: December 2008

Abstract: The purpose of this study was to evaluate the role of sequence variants in the CYP2C8, ABCB1 and CYP3A4 genes and the CYP3A4 phenotype for the pharmacokinetics and toxicity of paclitaxel in ovarian cancer patients. Thirty‐eight patients were treated with paclitaxel and carboplatin. The genotypes of CYP2C8*1B, *1C, *2, *3, *4, *5, *6, *7, *8 and P404A, ABCB1 G2677T/A and C3435T, as well as CYP3A4*1B, were determined by pyrosequencing. Phenotyping of CYP3A4 was performedin vivowith quinine as a probe. The patients were monitored for toxicity and 23 patients underwent a more extensive neurotoxicity evaluation. Patients heterozygous for G/A in position 2677 in ABCB1 had a significantly higher clearance of paclitaxel than most other ABCB1 variants. A lower clearance of paclitaxel was found for patients heterozygous for CYP2C8*3 when stratified according to the ABCB1 G2677T/A genotype. In addition, the CYP3A4 enzyme activityin vivoaffected which metabolic pathway was dominant in each patient, but not the total clearance of paclitaxel. The exposure to paclitaxel correlated to the degree of neurotoxicity. Our findings suggest that interindividual variability in paclitaxel pharmacokinetics might be predicted by ABCB1 and CYP2C8 genotypes and provide useful information for individualized chemotherapy.
Field mapping of chemical composition of forage using hyperspectral imaging in a grass meadow
Authors: Suzuki Yumiko , Tanaka Katsuyuki , Kato Wataru , Okamoto Hiroshi , Kataoka Takashi , Shimada Hiroshi , Sugiura Toshihiro , Shima Eikichi
Published: December 2008

Spatial information on the quantity and quality of forage is important for practicing precision agriculture in grasslands. The objective of this research was to generate a field map of the concentrations of total digestible nutrients (TDN) and crude protein (CP) of forage in an orchardgrass‐dominated meadow field (0.6 ha) using a hyperspectral imaging sensor. The sensor was mounted on the roof of a vehicle in order to scan the whole meadow field. Calibration models to estimate the concentrations of the chemical components were developed using a dataset consisting of observed concentrations and spectral data acquired from the hyperspectral images. The models were developed by multiple linear regression analysis with stepwise variable selection, and were evaluated by cross‐validation and evaluation index (EI) methods. The cross‐validation for the calibration model using 10 explanatory variables resulted in R2 values of 0.74 and 0.76 for TDN and CP, respectively. Standard error of prediction (SEP) was, respectively, 4.51 and 1.04. Bias was close to 0 for both TDN and CP. The EI values ranged 28.1–29.4, showing rank C. These results show that the calibration models are practical for estimating the concentrations of TDN and CP. Finally, field maps of the concentrations of TDN and CP were generated by applying the calibration models to field‐scale image data. The maps were able to identify the variations in the concentrations of TDN and CP throughout the field. In conclusion, this system is a useful technique for obtaining maps of forage chemical composition for site‐specific field management.
Relationship between liveweight change of cattle and forage supply in a young tree plantation in southern Kyushu, Japan
Authors: Hirata Masahiko , Hasegawa Nobumi , Takahashi Tomotsugu , Chowdappa Rekha , Ogura Shin‐ichiro , Nogami Kangoro , Sonoda Tatsunobu
Published: December 2008

Liveweight change (LWC) of cattle grazing a young Chamaecyparis obtusa (an evergreen conifer) plantation in southwestern Japan was investigated in relation to forage supply and diet selection by animals. While the animals ate 29–53 species or species groups (mean = 42; six herbaceous species or groups, 12 lianas, 23 shrubs and trees, one fern group) during a morning feeding bout, most bites (71–97%, mean = 85) were taken from 10 species or species groups, with Miscanthus sinensis as the most selected plant (27–74%, mean = 55). Reflecting this and the low defoliation‐tolerance of the grass, live leaf mass of M. sinensis decreased drastically with time under grazing. Daily LWC of animals increased with increasing live leaf mass of M. sinensis to 45 kg dry matter (DM) ha−1, and thereafter increased with increasing percentage bite count of three non‐herbaceous species, Ficus erecta (tree), Broussonetia kaempferi (liana) and Mallotus japonicus (tree), with F. erecta being the most contributing species. The results highlight the importance of grasses (mainly M. sinensis) as the basal (major) diet and the importance of some non‐herbaceous species (mainly F. erecta, B. kaempferi and M. japonicus) as the quality supplement in cattle foraging in the forest environment. The results also show that adjusting stocking rates to maintain live leaf mass of M. sinensis closely above the critical level (45 kg DM ha−1) is a criterion in the management of this forest grazing system, in terms of meeting the requirements of forest manager (effective control of herbaceous and woody weeds) and livestock producer (satisfactory level of animal performance).
Characterization of a Lolium multiflorum accessory chromosome
Authors: Kindiger Bryan
Published: December 2008

The meiotic behavior and the male and female transmission rates of a Lolium multiflorum accessory chromosome were investigated. Typically, accessory chromosomes display an accumulative behavior termed non‐disjunction that allows them to increase their numbers in a population. Root‐tip counts, utilizing individuals with known numbers of accessory chromosomes were evaluated to determine male and female transmission rates and cytogenetic examinations of microspores and developing pollen grains were performed at the metaphase and anaphase stages where such accumulative non‐disjunction events occur. Results of the investigation identified that the accessory chromosome of this Lolium cv. did not exhibit a strong accumulation mechanism and were relatively normal during meiosis and pollen mitosis. Accessory chromosome transmission through the egg was normal without accumulation and frequent non‐disjunction events did not occur during the microspore or pollen development stages. The pattern of chromosome movement was more similar to that of the A‐chromosome set than that observed for the characterized accessory chromosome of Festuca pratensis. Because the Lolium accessory chromosome meiotic and pollen mitotic behavior are relatively normal with a low rate of accumulation, such a chromosome may serve as a mini‐chromosome carrier platform for directed biolistic‐mediated gene transformation or the generation of accessory chromosome‐Lolium and accessory chromosome‐Festuca translocations.
Ethylene Response Factor TERF1 Enhances Glucose Sensitivity in Tobacco through Activating the Expression of Sugar‐related Genes
Authors: Li Ang , Zhang Zhijin , Wang Xue‐Chen , Huang Rongfeng
Published: December 2008

Ethylene response factor (ERF) proteins are important plant‐specific transcription factors. Increasing evidence shows that ERF proteins regulate plant pathogen resistance, abiotic stress response and plant development through interaction with different stress responsive pathways. Previously, we revealed that overexpression of TERF1 in tobacco activates a cluster gene expression through interacting with GCC box and dehydration responsive element (DRE), resulting in enhanced sensitivity to abscisic acid (ABA) and tolerance to drought, and dark green leaves of mature plants, indicating that TERF1 participates in the integration of ethylene and osmotic responses. Here we further report that overexpression of TERF1 confers sugar response in tobacco. Analysis of the novel isolated tomato TERF1 promoter provides information indicating that there are many cis‐acting elements, including sugar responsive elements (SURE) and W box, suggesting that TERF1 might be sugar inducible. This prediction is confirmed by results of reverse transcription‐polymerase chain reaction amplification, indicating that transcripts of TERF1 are accumulated in tomato seedlings after application of glucose. Further investigation indicates that the expression of TERF1 in tobacco enhances sensitivity to glucose during seed germination, root and seedling development, showing a decrease of the fresh weight and root elongation under glucose treatment. Detailed investigations provide evidence that TERF1 interacts with the sugar responsive cis‐acting element SURE and activates the expression of sugar response genes, establishing the transcriptional regulation of TERF1 in sugar response. Therefore, our results deepen our understanding of the glucose response mediated by the ERF protein TERF1 in tobacco.
Application of a Discrete‐Continuum Model to Karst Aquifers in North China
Authors: Wu Qiang , Zhou Wanfang , Pan Guoying , Ye Siyuan
Published: December 2008

A generalized discrete‐continuum model is developed to simulate ground water flow in the karst aquifers of North China. The model is a hybrid numerical flow model, which takes into account both quick conduit flow and diffusive fissure flow. The conduit flow is represented by a discrete network model, and the fissure flow is modeled by a continuum approach. The developed model strongly emphasizes the function of the conduits in the flow fields. They control the general drainage pattern, as demonstrated in the simulation of a complex karst aquifer in North China. The model reproduces reasonably well the flow field in response to an unanticipated discharge of ground water from the karst aquifer into an underground mine based on the aquifer parameters that are manually calibrated from a multiple‐well pumping test. Sensitivity of the model to the aquifer parameters was evaluated in the context of the case study.
Brealey, Myers, and Allen on Valuation, Capital Structure, and Agency Issues*
Authors: Brealey Richard A. , Myers Stewart C. , Allen Franklin
Published: December 2008

In these “extracts” from the world's best‐selling graduate textbook, the authors offer a number of suggestions for practitioners, including:

When valuing a company or an investment project, managers should start whenever possible with the asset's market price as the best initial estimate and then make adjustments that reflect their own private information. One obvious example of this process is when companies are evaluating possible acquisitions.

When valuing a company or an asset, don't worry about risks that you can hedge separately. For example, foreign exchange risk can be hedged using forwards or futures, and there is no need to form an opinion on the future path of exchange rates.

A positive NPV for a project is credible only if the company has some special advantage that competitors cannot match. That requires an understanding of the sources of the competitive advantage and how long they are likely to last.

Although market inefficiencies may offer economic rents from “convergence trades,” as a general rule nonfinancial corporations gain nothing, on average, by speculating in financial markets.

Since corporate managers know more about their company than outside investors, investors are likely to infer from corporate decisions to issue equity that the firm is overvalued (otherwise, why not issue debt instead?). And issuing overpriced stock to invest in projects that offer below‐normal rates of return is a sure way to destroy value.

To make the most of their growth opportunities and create value for outside investors, most public companies require a co‐investment of insiders' human capital with outsiders' financial capital. Such co‐investment in turn implies a larger return to managers' and employees' human capital than that suggested by either the conventional prescription of shareholder value maximization (or even the financial economist's model of firm value maximization).
Can Companies Use Hedging Programs to Profit from the Market? Evidence from Gold Producers*
Authors: Adam Tim R. , Fernando Chitru S.
Published: December 2008

In this article, the authors summarize the findings of their recent study of the hedging activities of 92 North American gold mining companies during the period 1989‐1999. The aim of the study was to answer two questions: (1) Did such hedging activities increase corporate cash flows? (2) And if yes, were such increases the result of management's ability to anticipate price movements when adjusting their hedge ratios? Although the author's answer to the first question is “yes,” their answer to the second is “no.”

More specifically, the authors concluded that:

During the 1989‐1999 period, the gold derivatives market was characterized by a persistent positive risk premium— that is, a positive spread between the forward price and the realized future spot price—that caused short forward positions to generate positive cash flows. The gold mining companies that hedged their future gold production realized an average total cash flow gain of $11 million, or $24 per ounce of gold hedged, per year, as compared to average annual net income of only $3.5 million. Because of the positive risk premium, short derivatives positions did not generate significant losses even during those subperiods of the study when the gold price increased.

There was considerable volatility in corporate hedge ratios during the period of the study, which is consistent with managers incorporating market views into their hedging programs and attempting to time the market by hedging selectively. But after attempting to distinguish between derivatives activities designed to hedge and those designed to profit from a view, the authors conclude that corporate efforts to time the market through selective hedging were largely if not completely futile. In fact, the companies' adjustments of hedge ratios appeared to consistently lag instead of leading the market.
Development of Predictive 3D‐QSAR CoMFA and CoMSIA Models for β‐aminohydroxamic Acid‐Derived Tumor Necrosis Factor‐α Converting Enzyme Inhibitors
Authors: Murumkar Prashant R. , Gupta Shirshendu Das , Zambre Vishal P. , Giridhar Rajani , Yadav Mange Ram
Published: December 2008

A three‐dimensional quantitative structure–activity relationship study was performed on a series of β‐aminohydroxamic acid‐derived tumor necrosis factor‐α converting enzyme inhibitors employing comparative molecular field analysis and comparative molecular similarity indices analysis techniques to investigate the structural requirements for the inhibitors, and derive a predictive model that could be used for the design of novel tumor necrosis factor‐α converting enzyme inhibitors. log P was used as an additional descriptor in the comparative molecular field analysis analysis to study the effects of lipophilic parameters on activity. Inclusion of log P did not improve the models significantly. The statistically significant model was established with 45 molecules, which were validated by a test set of 11 compounds. Ligand molecular superimposition on the template structure was performed by the atom‐/shape‐based root mean square fit and database alignment methods. Docked conformer based alignment (V) yielded the best predictive comparative molecular field analysis model  = 0.673,  = 0.860, F‐value = 86.073, predictive r 2 = 0.642, with two components, standard error of prediction = 0.394 and standard error of estimates = 0.243 while the comparative molecular similarity indices analysis model yielded  = 0.635,  = 0.858, F‐value = 84.451, predictive r 2 = 0.441 with three components, standard error of prediction = 0.393 and standard error of estimates = 0.245. The contour maps obtained from three‐dimensional quantitative structure–activity relationship studies were appraised for activity trends for the molecules analyzed. The comparative molecular field analysis models exhibited good external predictivity as compared with that of comparative molecular similarity indices analysis models. The model generated through comparative molecular field analysis was validated with the IK‐682. The data generated from this study may guide our efforts in designing and predicting the tumor necrosis factor‐α converting enzyme inhibitory activity of novel molecules.
Peptide Nanoparticles as Novel Immunogens: Design and Analysis of a Prototypic Severe Acute Respiratory Syndrome Vaccine
Authors: Pimentel Tais A. P. F. , Yan Zhe , Jeffers Scott A. , Holmes Kathryn V. , Hodges Robert S. , Burkhard Peter
Published: December 2008

Severe acute respiratory syndrome (SARS) is an infectious disease caused by a novel coronavirus that cost nearly 800 lives. While there have been no recent outbreaks of the disease, the threat remains as SARS coronavirus (SARS‐CoV) like strains still exist in animal reservoirs. Therefore, the development of a vaccine against SARS is in grave need. Here, we have designed and produced a prototypic SARS vaccine: a self‐assembling polypeptide nanoparticle that repetitively displays a SARS B‐cell epitope from the C‐terminal heptad repeat of the virus’ spike protein. Biophysical analyses with circular dichroism, transmission electron microscopy and dynamic light scattering confirmed the computational design showing α‐helcial nanoparticles with sizes of about 25 nm. Immunization experiments with no adjuvants were performed with BALB/c mice. An investigation of the binding properties of the elicited antibodies showed that they were highly conformation specific for the coiled‐coil epitope because they specifically recognized the native trimeric conformation of C‐terminal heptad repeat region. Consequently, the antisera exhibited neutralization activity in an in vitro infection inhibition assay. We conclude that these peptide nanoparticles represent a promising platform for vaccine design, in particular for diseases that are characterized by neutralizing epitopes with coiled‐coil conformation such as SARS‐CoV or other enveloped viruses.
Combining Cluster Analysis, Feature Selection and Multiple Support Vector Machine Models for the Identification of Human Ether‐a‐go‐go Related Gene Channel Blocking Compounds
Authors: Nisius Britta , Göller Andreas H. , Bajorath Jürgen
Published: December 2008

Blockade of the human ether‐a‐go‐go related gene potassium channel is regarded as a major cause of drug toxicity and associated with severe cardiac side‐effects. A variety of in silico models have been reported to aid in the identification of compounds blocking the human ether‐a‐go‐go related gene channel. Herein, we present a classification approach for the detection of diverse human ether‐a‐go‐go related gene blockers that combines cluster analysis of training data, feature selection and support vector machine learning. Compound learning sets are first divided into clusters of similar molecules. For each cluster, independent support vector machine models are generated utilizing preselected MACCS structural keys as descriptors. These models are combined to predict human ether‐a‐go‐go related gene inhibition of our large compound data set with consistent experimental measurements (i.e. only patch clamp measurements on mammalian cell lines). Our combined support vector machine model achieves a prediction accuracy of 85% on this data set and performs better than alternative methods used for comparison. We also find that structural keys selected on the basis of statistical criteria are associated with molecular substructures implicated in human ether‐a‐go‐go related gene channel binding.
Conformational Dynamics of the Flexible Catalytic Loop in Mycobacterium tuberculosis 1‐Deoxy‐d‐xylulose 5‐Phosphate Reductoisomerase
Authors: Williams Sarah L. , Andrew McCammon J.
Published: December 2008

In mycobacteria, the biosynthesis of the precursors to the essential isoprenoids, isopentenyl diphosphate and dimethylallyl pyrophosphate is carried out by the methylerythritol phosphate pathway. This route of synthesis is absent in humans, who utilize the alternative mevalonate acid route, thus making the enzymes of the methylerythritol phosphate pathway of chemotherapeutic interest. One such identified target is the second enzyme of the pathway, 1‐deoxy‐d‐xylulose 5‐phosphate reductoisomerase. Only limited information is currently available concerning the catalytic mechanism and structural dynamics of this enzyme, and only recently has a crystal structure of Mycobacterium tuberculosis species of this enzyme been resolved including all factors required for binding. Here, the dynamics of the enzyme is studied in complex with NADPH, Mn2+, in the presence and absence of the fosmidomycin inhibitor using conventional molecular dynamics and an enhanced sampling technique, reversible digitally filtered molecular dynamics. The simulations reveal significant differences in the conformational dynamics of the vital catalytic loop between the inhibitor‐free and inhibitor‐bound enzyme complexes and highlight the contributions of conserved residues in this region. The substantial fluctuations observed suggest that 1‐deoxy‐D‐xylulose 5‐phosphate reductoisomerase may be a promising target for computer‐aided drug discovery through the relaxed complex method.
A Specific Pharmacophore Model of Aurora B Kinase Inhibitors and Virtual Screening Studies Based on it
Authors: Wang Hui‐Yuan , Li Lin‐Li , Cao Zhi‐Xing , Luo Shi‐Dong , Wei Yu‐Quan , Yang Sheng‐Yong
Published: December 2008

In this study, 3D‐pharmacophore models of Aurora B kinase inhibitors have been developed by using HipHop and HypoGen modules in Catalyst software package. The best pharmacophore model, Hypo1, which has the highest correlation coefficient (0.9911), consists of one hydrogen‐bond acceptor, one hydrogen‐bond donor, one hydrophobic aliphatic moiety and one ring aromatic feature. Hypo1 was validated by test set and cross‐validation methods. And the specificity of Hypo1 to Aurora B inhibitors was examined with the use of selective inhibitors against Aurora B and its paralogue Aurora A. The results clearly indicate that Hypo1 can differentiate selective inhibitors of Aurora B from those of Aurora A, and the ring aromatic feature likely plays some important roles for the specificity of Hypo1. Then Hypo1 was used as a 3D query to screen several databases including Specs, NCI, Maybridge and Chinese Nature Product Database (CNPD) for identifying new inhibitors of Aurora B. The hit compounds were subsequently subjected to filtering by Lipinski’s rule of five and docking studies to refine the retrieved hits, and some compounds selected from the top ranked hits have been suggested for further experimental assay studies.
In vivo functions of the prolyl‐4‐hydroxylase domain oxygen sensors: direct route to the treatment of anaemia and the protection of ischaemic tissues
Authors: Katschinski D. M.
Published: December 2008

The prolyl‐4‐hydroxylase domain (PHD) 1–3 enzymes have been identified based on their ability to regulate the stability of hypoxia‐inducible factor α subunits and thus to modify hypoxia‐inducible gene expression. Transgenic mouse models provided insights into the isoform‐specific functions of these oxygen sensors with physiological implications for angiogenesis, erythropoiesis/oxygen transport, cardiovascular function, metabolism and tissue homeostasis. This knowledge is important for the ongoing development of small molecule PHD inhibitors that are currently tested in preclinical and clinical trials for the treatment of anaemia and for cytoprotection. This review aims at summarizing the insights obtained from key mouse knock‐out models as well as first experiences in the therapeutic application of PHD inhibitors.
Fishery‐induced selection on an Alpine whitefish: quantifying genetic and environmental effects on individual growth rate
Authors: Nusslé Sébastien , Bornand Christophe N. , Wedekind Claus
Published: December 2008

Size‐selective fishing, environmental changes and reproductive strategies are expected to affect life‐history traits such as the individual growth rate. The relative contribution of these factors is not clear, particularly whether size‐selective fishing can have a substantial impact on the genetics and hence on the evolution of individual growth rates in wild populations. We analysed a 25‐year monitoring survey of an isolated population of the Alpine whitefish Coregonus palaea. We determined the selection differentials on growth rate, the actual change of growth rate over time and indicators of reproductive strategies that may potentially change over time. The selection differential can be reliably estimated in our study population because almost all the fish are harvested within their first years of life, i.e. few fish escape fishing mortality. We found a marked decline in average adult growth rate over the 25 years and a significant selection differential for adult growth, but no evidence for any linear change in reproductive strategies over time. Assuming that the heritability of growth in this whitefish corresponds to what was found in other salmonids, about a third of the observed decline in growth rate would be linked to fishery‐induced evolution. Size‐selective fishing seems to affect substantially the genetics of individual growth in our study population.
Movement rates of woodland invertebrates: a systematic review of empirical evidence
Authors: BROUWERS NIELS C. , NEWTON ADRIAN C.
Published: December 2008

Abstract. 

A systematic review was conducted to gather empirical evidence on movement rates of invertebrates associated with woodland.

Eight scientific literature databases were systematically searched for relevant studies on invertebrates associated with woodland habitat.

Twenty‐five studies were identified that met the search selection criteria, which provided estimates of movement rate for 30 invertebrate species associated with woodland habitat. These 30 species represented insect species only, including 17 carabid (ground) beetle, eight butterfly, two bark beetle, two ant, and one moth species. From 2000 to 2008, only six studies were identified, indicating a current lack of dispersal‐related studies for woodland invertebrates.

A meta‐analysis of studies on ground‐dwelling species indicated that carabid beetle species that were strongly associated with woodland habitat were found to move more slowly than more generalist species (median: 2.1 m day−1 vs. 11.0 m day−1). Furthermore, for carabid beetles it was found that body size was positively correlated with movement rate.

The lack of field measurements of movement and dispersal ability for all but a tiny minority of woodland invertebrates indicates a substantial knowledge gap that should be addressed by future research, which might usefully test whether the patterns identified for carabid beetles are generally applicable.
A preliminary case–control study on nutritional status, body composition, and glycemic control of Greek children and adolescents with type 1 diabetes
Authors: GALLI‐TSINOPOULOU Assimina , GRAMMATIKOPOULOU Maria Georgiou , STYLIANOU Charilaos , KOKKA Paraskevi , EMMANOUILIDOU Elefteria
Published: December 2008

Background:  Because scientific data on the diet of diabetic Greek youngsters are scarce, diabetic experts use findings from international studies. However, because of diet variations between countries, this may result in problems in diabetes control. The aim of the present pilot study was to assess body composition, nutritional status, and diabetes control in Greek youngsters with type 1 diabetes mellitus (T1DM).

Methods:  Twenty‐four children and adolescents with diabetes, aged 4–16 years, and the same number of age‐ and sex‐matched controls participated in the study. Anthropometry included stature, weight, and body fat determined by bioelectrical impedance analysis. Body mass index (BMI), fat mass index (FMI), fat‐free mass index (FFMI), and z‐scores were calculated. Diabetes control was evaluated through glycosylated hemoglobin (HbA1c) and dietary intake was recorded for 3 days.

Results:  The FFMI, BMI z‐score and weight‐for‐age z‐score were lower in controls compared with diabetic youngsters (P ≤ 0.001, P ≤ 0.02, and P ≤ 0.01, respectively). Three diabetic participants were overweight (12.5%) and two controls were underweight (8.3%). The energy and nutrient intake was similar between the two groups, and all participants consumed a diet high in fats and proteins at the expense of carbohydrates. Dietary fat was highly correlated with BMI in both groups. The consumption of vitamin D was inadequate in the diabetic participants, but they had a higher intake of antioxidant vitamins, vitamin B6, and folate compared with the control group.

Conclusions:  In conclusion, youngsters with T1DM failed to adhere to the macronutrient recommendations for diabetes, but dietary patterns were similar in both the diabetic and control groups. The control of diabetes was not associated with any nutrient or anthropometric variable.