bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential Role of Dissolved Organic Carbon in Phosphorus Transport in Forested Soils
Authors: Donald Richard G. , Anderson Darwin W. , Stewart John W. B.
Published: July 2010

Soils of the northern boreal forest have undergone significant pedogenic losses of P. This study was undertaken to examine the hypothesis that the leaching of dissolved organic carbon (DOC) is a mechanism for P removal from forested soils. The sorption of DOC and DOC fractions by soil horizons from the shoulder, backslope, and footslope soils of a catenary sequence was examined. Variation in DOC sorption among the soil horizons, and between positions in the catena, was related to differences in the clay content (r = 0.71) and citrate‐dithionate‐extractable Fe, Al, and Mn (r = 0.66). The hydrophobic acid and the hydrophilic acid fractions were the most abundant in the soil solution (72% of the total DOC) and accounted for most of the sorption of DOC in the Bt and C horizons (isotherm distribution coefficient Kd = 27.1 × 10−4 to 337 × 10−4 m3 kg−1). The hydrophobic neutral fraction (14% of the DOC) was not sorbed by any of the soil horizons (average Kd = 20.0 × 10−4 m3 kg−1). The hydrophobic neutral fraction (14% of the DOC) was not sorbed by any of the soil horizons (average Kd = 20.0 × 10−4 m3 kg−1). The hydrophobic neutral fraction had a molar C/P ratio of 2800, compared with 21 000 and 35 600 for the hydrophobic acid and hydrophilic acid fractions, respectively. Phosphorus in the hydrophobic neutral fraction constituted 64% of the P measured in these three fractions. The high P content and low sorption of the hydrophobic neutral fraction suggests that the leaching of the hydrophobic neutral fraction may be a possible mechanism for the redistribution and loss of P in these soils.
Soil Parameters Related to Crop Growth Variability in Western Niger, West Africa
Authors: Manu A. , Wilding L. P. , Hossner L. R. , Pfordresher A. A. , Geiger S. C.
Published: July 2010

A study was carried out to determine soil morphological and chemical properties that influence short‐range variability in the growth of millet [Pennisetum glaucum (L.) R. Br.] in western Niger. Paired productive and adjacent nonproductive sites within millet fields were evaluated along transects in three soil‐geomorphic regions. Transects totaled >300 km in length. Mean depth to subsoil of productive sites ranged from 17.06 cm in the sand valley transect to 19.98 cm in the Dallol Bosso transect. These were different from the topsoil depths of the adjacent nonproductive sites within the respective transects, which ranged from 7.8 to 12.9 cm. Productive sites were located in microtopographic “high” positions relative to nonproductive sites. The mean relief differential between productive and nonproductive sites was 6.13 cm. Vesicular crusts 2 to 5 cm thick and exposed Bt horizon crusts (2.5YR 4/6) were mostly associated with nonproductive sites. The acidity parameters were highly intercorrelated in all transects. Mean pH of soils associated with productive growth of millet ranged from 5.8 to 6.3, compared with 5.4 to 6.0 in the nonproductive areas. Mean exchangeable acidity in the nonproductive sites ranged from 0.2 to 0.36 cmolc kg‐1, about three times higher than the mean in the productive areas. Bray‐1 P levels to a depth of 30 cm did not differ between paired sites in any of the transects. Microtopography was the most important factor influencing millet growth variability in western Niger because it directly influenced the factors related to crust formation and determined the depth to acidic, Al‐rich, P‐deficient subsoil that impeded millet growth and development.
Nitrate pollution in groundwater in two selected areas from Cameroon and Chad in the Lake Chad basin
Authors: Ngatcha Benjamin Ngounou , Daira Djoret
Published: July 2010

The shallow aquifer in the Lake Chad basin is highly vulnerable to pollution. Analysis carried out on 316 wells and boreholes have showed a tendency towards an increase of nitrate values, exceeding 50 mg l−1. Nitrate concentrations ranged between about 1 and 300 mg l−1. Large variation in concentration was observed in wells and boreholes that are only short distances apart. High concentrations of nitrate in wells, especially in a recharge area along the sand dunes, or via infiltration from river banks, irrigation channels, and infiltration of urban wastewater into groundwater from septic tanks, pose a serious problem for drinking water supply. In Cameroon and Chad, the results of the investigation indicate a variation of nitrate concentration in groundwater between the two areas. The primary origin of this pollution is agricultural proliferation activities that are developed and stressed by socio-economic needs outside the urban area, and by urban expansion within the area served by a decrepit network of urban area sewers. Substancial differences in values of nitrate concentrations were observed in groundwater from adjacent wells and boreholes, indicating local rather than regional contamination.
The authorship of Plantae rariores agro Dunelmensi indigenae
Authors: DAVIS P. S. , GRAHAM G. G.
Published: July 2010

Stephen Robson (1741–1779) and his nephew Edward Robson (1763–1813) were both Quaker botanists who lived in Darlington, County Durham. Stephen is best known for his British Flora published in 1777, and Edward had a considerable reputation as a particularly competent botanist. Some confusion seems to exist regarding the authorship of a rare plant list for Durham, Plantae rariores agro Dunelmensi indigenae, attributed to Stephen Robson in most recent bibliographical literature. This paper re-examines the evidence for the authorship of this list and suggests that although Stephen Robson produced a short list of local plants the longer and more critical list, Plantae rariores … was compiled by his more knowledgeable nephew Edward.
Hermann Schlegel's investigation of the Maastricht mosasaurs
Authors: MULDER E. W. A. , THEUNISSEN B.
Published: July 2010

SUMMARY

In 1852, Hermann Schlegel (1804–1884), as a correspondent of the ’Committee for the Geological Map and Description of the Netherlands’, was charged with the description of the fossil reptiles Mosasaurus and Allopleuron (Testudinata). However, as a consequence of the premature dissolution of the Geological Committee in 1855, Schlegel never completed his task. He only published a preliminary note on his investigations, which is extensively discussed in this paper. Schlegel turns out to have been the first to prove, by means of anatomical arguments, that Mosasaurus had flipper–like limbs. Furthermore, several recently discovered drawings shed new light on Schlegel's claim that some of the fossils of Mosasaurus in the famous Camper collection had been falsified.
Fractional‐order iterative learning control for fractional‐order linear systems
Authors: Li Yan , Chen YangQuan , Ahn Hyo‐Sung
Published: July 2010

In this paper, we discuss in time domain the convergence of the iterative process for fractional‐order systems. Fractional order iterative learning updating schemes are considered. For the linear time invariant (LTI) system case, the convergence conditions of the fractional‐order and integer‐order iterative learning schemes are proved to be equivalent for D=0. It has been proved by theory and verified by MATLAB/SIMULINK that the tracking speed is the fastest when the system and iterative learning scheme have the same fractional order.

Copyright © 2010 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society
Impact of antibody aggregation on a flowthrough anion‐exchange membrane process
Authors: Lajmi Ajay R. , Nochumson Samuel , Berges Aym
Published: July 2010

The impact of typical anion‐exchange flowthrough conditions on the IgG mass loading of an anion‐exchange membrane scale‐down unit (Mustang® Q coin) was investigated. High performance size‐exclusion chromatography and multiangle laser light scattering results suggested the presence of a small fraction of IgG aggregates with average radius >100 nm under anion‐exchange flowthrough conditions. The small filtration area presented by the 0.35 mL membrane volume Mustang® Q coin limited the membrane throughput due to fouling from the aggregates at higher antibody loading. Data in this report indicated that a 0.2 μm hybrid polyethersulfone and polyvinylidene fluoride membrane in‐line prefilter with a minimum filtration area of 20 sq cm alleviated the Mustang® Q coin fouling. The combined cake filtration and intermediate blocking model was proposed as the most likely membrane pore blocking mechanism. Increasing the filtration area in the in‐line prefilter resulted in higher IgG mass throughput. Thus, using an appropriately sized in‐line prefilter could provide more robust antibody throughput performance on scale‐down membrane anion‐exchange units. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010
Ampicillin Synthesis Using a Two‐Enzyme Cascade with Both α‐Amino Ester Hydrolase and Penicillin G Acylase
Authors: Blum Janna K. , Deaguero Andria L. , Perez Carolina V. , Bommarius Andreas S.
Published: July 2010

The current enzymatic production of semisynthetic β‐lactam antibiotics requires isolation and purification of the intermediate 6‐aminopenicillanic acid which adds cost and complexity to the manufacturing process. In this work, we took advantage of the unique substrate specificity of α‐amino ester hydrolases to perform a purely aqueous one‐pot production of ampicillin from penicillin G and D‐phenylglycine methyl ester, catalyzed by α‐amino ester hydrolase and penicillin G acylase. The synthesis was performed in both a one‐pot, one‐step synthesis resulting in a maximum conversion of 39 %, and a one‐pot, two‐step process resulting in a maximum conversion of 47 %. The two‐enzyme cascade reported in this paper is a promising alternative to the current enzymatic two‐step, two‐pot manufacturing process for semisynthetic β‐lactam antibiotics which requires intermittent isolation of 6‐aminopenicillanic acid.
On the importance of anchoring and the consequences of its impairment in dyslexia
Authors: Banai Karen , Ahissar Merav
Published: July 2010

One of the main impediments of individuals with reading difficulties and individuals with language difficulties is poor working memory. Typically measured using verbal stimuli, working memory deficits have often been considered as one aspect of the phonological difficulty putatively underlying dyslexia. Over the years it has been shown that a broad range of auditory discrimination abilities are also mildly impaired. Here we present evidence that a domain general, rather than a phonology specific, deficits in the ability to implicitly use contextual information, which we term anchoring, can account for both types of deficits. We propose that anchoring ability, which reflects a basic biological mechanism for replacing effortful mechanisms of explicit working memory with automatic mechanisms of implicit memory, and consequently boost performance in both perceptual and cognitive tasks, is a crucial factor in our ability to be expert users of oral and written language. Copyright © 2010 John Wiley & Sons, Ltd.
Influence of groundwater spring discharge on small‐scale spatial variation of an alpine stream ecosystem
Authors: Roy James W. , Zaitlin Beryl , Hayashi Masaki , Watson Sue B.
Published: July 2010

The influence of groundwater discharge on aquatic ecosystems of alpine streams at the patch to reach‐scale (1–100 m) has received little attention to date. In this study, small‐scale variation was evaluated for an alpine stream in the Canadian Rockies receiving groundwater on one side from a large spring. The evaluation was based on measures of (1) spatial changes in the physico‐chemical properties that are commonly used to classify stream types for ecological purposes and (2) variation in periphyton (predominantly diatom and macroalgal) communities. Stream water and algae were sampled along longitudinal and lateral transects of the stream. The results showed that groundwater discharge increased stream flow, electrical conductivity, pH, nitrate concentrations, and turbidity, and lowered temperature. This caused variation in stream physico‐chemical properties along the stream reach and laterally across the mixing area. The influence of the groundwater discharge was reflected in a change in the stream's ecological classification from nivo‐krenal (i.e. snowmelt–groundwater mix) to krenal (i.e. groundwater dominated). The discharge of groundwater to the stream was also associated with changes in the algal community both downstream (reach‐scale) and across the mixing area (sub‐reach‐scale), as indicated by differences in relative abundance of dominant diatom taxa and macroalgae, including a proliferation of the chrysophycean alga Hydrurus. Groundwater‐affected areas also showed reduced species richness, but increased biomass. These findings have implications for the sampling of benthic algal communities in alpine settings and their use as indicators of climate and land‐use changes. Copyright © 2010 John Wiley & Sons, Ltd.
Impact of hemochromatosis gene (HFE) mutations on epithelial ovarian cancer risk and prognosis
Authors: Gannon Philippe O. , Medelci Sanae , Le Page Cécile , Beaulieu Martin , Provencher Diane M. , Mes‐Masson Anne‐Marie , Santos Manuela M.
Published: July 2010

Cancer cells require large amounts of micronutrients, particularly iron, for their rapid growth and frequent divisions. Cellular iron uptake is regulated by the transferrin receptor and the hemochromatosis protein (HFE) system. Two frequent mutations in the HFE gene, H63D and C282Y, are associated with hemochromatosis type I, an inherited iron overload disease and, possibly, with cancer. In this study, we evaluated the frequency of the H63D and C282Y mutations in a cohort of 677 consecutive cases of woman with gynecological pathologies. Cases included 80 women with tumor‐free pathologies normal ovary (NOV), 124 with benign ovarian tumors (BOV), 96 with epithelial ovarian cancer (EOC) tumors of low malignant potential (LPM), 264 with invasive tumors of the ovary (TOV) and 113 with endometrial cancer. We found that the C282Y allele frequency in EOC patients was higher than that in the control NOV group (5.8% vs. 1.3%, p < 0.001) and was associated with an increased risk of ovarian cancer (OR = 4.88; 95% CI 1.15‐20.61; p = 0.018). The effect of the two HFE mutations on patient survival was also analyzed. Kaplan‐Meier analyses did not find any significant association between the H63D allele and patient survival. However, EOC patients with at least one C282Y allele had a decreased overall survival compared to those with no C282Y allele (p = 0.001). These results indicate that the C282Y mutation may increase the risk of developing ovarian cancer and may be further associated with poor outcomes.
Silencing of the SEC62 gene inhibits migratory and invasive potential of various tumor cells
Authors: Greiner Markus , Kreutzer Birgit , Jung Volker , Grobholz Rainer , Hasenfus Andrea , Stöhr Robert Franz , Tornillo Luigi , Dudek Johanna , Stöckle Michael , Unteregger Gerhard , Kamradt Jörn , Wullich Bernd , Zimmermann Richard
Published: July 2010

Sec62 is part of the protein translocation apparatus in the membrane of the endoplasmic reticulum (ER). In yeast, Sec62 participates in the post‐translational translocation of proteins into the ER, but its function in mammals remains elusive. Previously we described the amplification and over‐expression of the SEC62 gene in prostate cancer cell lines and the protein has been described as a potential target gene in prostate cancer. In the current study we show that in the tumor tissue of prostate cancer patients Sec62 protein levels are elevated compared with tumor‐free tissue derived from the same patients or from prostates of control group patients and that the higher Sec62 protein content correlates with an increasing de‐differentiation of the cells. Therefore, up‐regulation of Sec62 protein content indeed is a phenomenon associated with prostate cancer progression. Analysis of a multi‐tissue tumor array showed that in addition to prostate cancer, overproduction of Sec62 is observed in various other tumors, most significantly in tumors of the lung and the thyroid. To examine the tumor‐related functions of Sec62, we silenced the SEC62 gene in the prostate cancer cell‐line PC3 as well as in a set of other tumor cell‐lines with two different siRNAs. In general, after silencing of SEC62 the cell migration and the invasive potential of the cells was blocked or at least dramatically reduced while cell viability was hardly affected. Thus, the SEC62 gene may indeed be considered as a target gene in the therapy of various tumors.
Inducible expression of stem cell associated intermediate filament nestin reveals an important role in glioblastoma carcinogenesis
Authors: Lu Wen Jing , Lan Feng , He Qihua , Lee Andrew , Tang Chad Z. , Dong Lin , Lan Baojin , Ma Xiaowen , Wu Joseph C. , Shen Li
Published: July 2010

The intermediate filament nestin is transiently expressed in neural stem/progenitor cells during the development of central nervous system. Recently, increasing evidence has shown that upregulation of nestin is related to malignancy of several cancers, especially glioblastoma. However, the function of nestin in carcinogenesis remains unclear. In this study, we investigated the role of nestin in glioblastoma carcinogenesis by comparing subclones of rat C6 glioblastoma cells that were either high or low for nestin expression. We found that while nestin expression did not influence the in vitro proliferation of glioblastoma cells, subclones characterized by high levels of nestin formed tumors in vivo at significantly faster rates than subclones with low expression. Importantly, C6 subclones that expressed nestin at low levels in vitro were also found to give rise to tumors highly positive for the protein, suggesting that induction of nestin plays an important role in glioblastoma carcinogenesis. Derivation of nestin positive tumors from nestin negative human U87 glioblastoma cells in immunodeficient mice further confirmed that a switch to positive expression of nestin is fundamental to the course of glioblastoma development. Blocking the expression of nestin in glioblastoma tumors via intratumor injection of shRNA significantly slowed tumor growth and volume. These results demonstrated that nestin plays a crucial role in development of glioblastoma and may potentially be targeted for treatment of the disease.
One‐step synthesis of 2‐amino‐5‐(4,5‐diphenylpyrimidin‐2‐ylamino)pentanoic acid from isoflavones and arginine
Authors: Zhang Zun‐Ting , Han Wen‐Yong , Qiu Li
Published: July 2010

magnified image

A simple and straightforward methodology toward the synthesis of novel 2‐amino‐5‐(4,5‐diphenylpyrimidin‐2‐ylamino)pentanoic acid has been developed by one‐step reaction of isoflavones with arginine. A series of 14 new compounds was reported. All of them were characterized by FTIR, NMR, and elemental analysis. A variety of substrates can participate in the process with good yields and high purities making this methodology suitable for library synthesis in drug discovery. J. Heterocyclic Chem., (2010).
Ensemble forecast post‐processing over Belgium: comparison of deterministic‐like and ensemble regression methods
Authors: Vannitsem Stéphane , Hagedorn Renate
Published: July 2010

A comparison of the benefits of post‐processing ECMWF ensemble forecasts based on a deterministic‐like and a regression technique is performed for Belgium. The former is a Linear Model Output Statistics technique (EVMOS) recently developed to allow provision of an appropriate ensemble variability at all lead times, and the latter is the Non‐homogeneous Gaussian Regression, NGR. The training of the post‐processing techniques is based on the reforecast dataset of ECMWF which covers a period from 1991 to 2007. The EVMOS approach is mainly providing a correction of the systematic error and does not enhance substantially the variance of the ensemble. The application of the NGR method provides an ensemble which encompasses the observations, unlike the EVMOS scheme. However, by taking into account the observational error, the analysis suggests that the ensemble based on the EVMOS post‐processing scheme is also found to be consistent. This apparent contradiction is clarified and it turns out that both schemes are valuable depending on the specific purpose, the evaluation of the uncertainty of large scale flows or the downscaling of the temperature uncertainty at the level of the local observations. Copyright © 2010 Royal Meteorological Society
Intracellular and extracellular T1 and T2 relaxivities of magneto‐optical nanoparticles at experimental high fields
Authors: Klug Gert , Kampf Thomas , Bloemer Steffen , Bremicker Johannes , Ziener Christian H. , Heymer Andrea , Gbureck Uwe , Rommel Eberhard , Nöth Ulrich , Schenk Wolfdieter A. , Jakob Peter M. , Bauer Wolfgang R.
Published: July 2010

This study reports the T1 and T2 relaxation rates of rhodamine‐labeled anionic magnetic nanoparticles determined at 7, 11.7, and 17.6 T both in solution and after cellular internalization. Therefore cells were incubated with rhodamine‐labeled anionic magnetic nanoparticles and were prepared at decreasing concentrations. Additionally, rhodamine‐labeled anionic magnetic nanoparticles in solution were used for extracellular measurements. T1 and T2 were determined at 7, 11.7, and 17.6 T. T1 times were determined with an inversion‐recovery snapshot‐flash sequence. T2 times were obtained from a multispin‐echo sequence. Inductively coupled plasma‐mass spectrometry was used to determine the iron content in all samples, and r1 and r2 were subsequently calculated. The results were then compared with cells labeled with AMI‐25 and VSOP C‐200. In solution, the r1 and r2 of rhodamine‐labeled anionic magnetic nanoparticles were 4.78/379 (7 T), 3.28/389 (11.7 T), and 2.00/354 (17.6 T). In cells, the r1 and r2 were 0.21/56 (7 T), 0.19/37 (11.7 T), and 0.1/23 (17.6 T). This corresponded to an 11‐ to 23‐fold decrease in r1 and an 8‐ to 15‐fold decrease in r2. A decrease in r1 was observed for AMI‐25 and VSOP C‐200. AMI‐25 and VSOP exhibited a 2‐ to 8‐fold decrease in r2. In conclusion, cellular internalization of iron oxide nanoparticles strongly decreased their T1 and T2 potency. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
Modeling magnitude and phase neuronal current MRI signal dependence on echo time
Authors: Luo Qingfei , Gao Jia‐Hong
Published: July 2010

To enhance sensitivity in measuring neuronal current MRI (ncMRI) signal using T2*‐weighted sequences, appropriate selection of echo time (TE) is vital for optimizing data acquisition strategy. The purpose of this study is to establish the contrast‐to‐noise ratio of neuronal current MRI signal dependence on TE and determine the optimum TE (TEopt) in achieving its highest detection power. The TEopt in human brain and tissue preparation at 1.5, 3, and 7 T are estimated with different voxel sizes. Our results show that TEopt values are different between magnitude and phase images, and TEopt is larger in magnitude than phase imaging. This suggests that a dual‐echo data acquisition strategy would provide the best efficiency in detecting magnitude and phase neuronal current MRI signals simultaneously. Our results also indicated that the detection sensitivity will be stronger at lower magnetic fields for human brain, whereas the sensitivity will be enhanced/reduced as field strength increases for phase/magnitude imaging on tissue preparation. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
The in vivo influence of white matter fiber orientation towards B0 on T2* in the human brain
Authors: Bender B. , Klose U.
Published: July 2010

It is well known that, at higher field strength, T2*‐weighted images show an extensive heterogeneity in white matter fiber bundles. The basis of this phenomenon is still under discussion, as many factors, such as iron concentration, myelination and tissue microstructure, could influence relaxation times. Furthermore, fiber direction in relation to the main magnetic field seems to influence T2* relaxation times. In this study, diffusion tensor imaging and T2* measurements were combined in seven subjects with the head in a normal and tilted position. It was shown that fiber orientation has a strong influence on T2* in the human brain, with the average T2* value changing from 49 ms for a perpendicular orientation to B0 to 57 ms for a parallel orientation to B0. Nevertheless, T2* times showed a wide variety of values at any orientation towards B0. Copyright © 2010 John Wiley & Sons, Ltd.
Dynamics and fate of USPIO in the central nervous system in experimental autoimmune encephalomyelitis
Authors: Oude Engberink Raoul D. , Blezer Erwin L.A. , Dijkstra Christine D. , van der Pol Susanne M.A. , van der Toorn Annette , de Vries Helga E.
Published: July 2010

Signal loss observed in the brain by MRI following the administration of ultrasmall superparamagnetic particles of iron oxide (USPIO) has been correlated with immune cell activity in inflammatory areas during multiple sclerosis. Uptake of USPIO by circulating monocytes and their migration towards inflammatory areas have been considered as the most important mechanism for USPIO uptake by the brain parenchyma. However, the involvement of a damaged blood–brain barrier is also debated as a possible mechanism for cerebral USPIO uptake. Compared with these uptake‐associated issues, little is known about the clearance of USPIO from the brain. The acute uptake and chronic clearance of USPIO in the brain were therefore studied with MRI in an animal model of multiple sclerosis. Lewis Hannover rats with acute experimental autoimmune encephalomyelitis received a single intravenous injection of USPIO (300 µmol Fe/kg), and repetitive MRI of the brain and cervical lymph nodes, a possible drainage pathway, was performed. USPIO were detected in the brain within 1 h after injection independent of the severity of experimental autoimmune encephalomyelitis, and histological analysis revealed extracellular iron clusters colocalising with a leaky blood–brain barrier. Loss of signal was not present 72 h after USPIO injection, irrespective of the disease state. MR images of cervical lymph nodes showed USPIO accumulation at 24 h after administration, which stabilised at 72 h. Histological analyses revealed that USPIO accumulated in infiltrated macrophages in the medulla and subcapsular sinus. The current study demonstrates that USPIO enter the central nervous system directly after administration, pointing to the involvement of a damaged blood–brain barrier in the appearance of USPIO‐associated MR abnormalities. Furthermore, a possible role of the cervical lymph nodes as a drainage pathway of USPIO is suggested. These data shed new light on the use of USPIO in neuroinflammatory diseases, identifying USPIO as a marker for both cellular infiltration and blood–brain barrier damage. Copyright © 2010 John Wiley & Sons, Ltd.
Selected control events and reporting odds ratio in signal detection methodology
Authors: Ooba Nobuhiro , Kubota Kiyoshi
Published: July 2010

Purpose

To know whether the reporting odds ratio (ROR) using “control events” can detect signals hidden behind striking reports on one or more particular events.

Methods

We used data of 956 drug use investigations (DUIs) conducted between 1970 and 1998 in Japan and domestic spontaneous reports (SRs) between 1998 and 2008. The event terms in DUIs were converted to the preferred terms in Medical Dictionary for Regulatory Activities (MedDRA). We calculated the incidence proportion for various events and selected 20 “control events” with a relatively constant incidence proportion across DUIs and also reported regularly to the spontaneous reporting system. A “signal” was generated for the drug‐event combination when the lower limit of 95% confidence interval of the ROR exceeded 1. We also compared the ROR in SRs with the RR in DUIs.

Results

The “control events” accounted for 18.2% of all reports. The ROR using “control events” may detect some hidden signals for a drug with the proportion of “control events” lower than the average. The median of the ratios of the ROR using “control events” to RR was around the unity indicating that “control events” roughly represented the exposure distribution though the range of the ratios was so diverse that the individual ROR might not be regarded as the estimate of RR.

Conclusions

The use of the ROR with “control events” may give an adjunctive to the traditional signal detection methods to find a signal hidden behind some major events. Copyright © 2010 John Wiley & Sons, Ltd.
25 Years of Stakeholder Theory in Project Management Literature (1984-2009)
Authors: Littau Paul , Jujagiri Nirmala Jyothi , Adlbrecht Gerald
Published: July 2010

After 25 years from its inception by Freeman in 1984, the stakeholder approach enjoys support from a growing community of researchers and practitioners. In this article, we try to outline this development by carrying out a meta-analysis within the leading project management journals. We found that stakeholder theory is predominantly fed by articles from Anglo-American countries and applied in the construction and IT sectors. The understanding of the stakeholder notion is moved towards a more complex view. Articles from different project management areas indicate the key role of stakeholders in projects.
Steps in reductive activation of the disulfide‐generating enzyme Ero1p
Authors: Heldman Nimrod , Vonshak Ohad , Sevier Carolyn S. , Vitu Elvira , Mehlman Tevie , Fass Deborah
Published: July 2010

Ero1p is the primary catalyst of disulfide bond formation in the yeast endoplasmic reticulum (ER). Ero1p contains a pair of essential disulfide bonds that participate directly in the electron transfer pathway from substrate thiol groups to oxygen. Remarkably, elimination of certain other Ero1p disulfides by mutation enhances enzyme activity. In particular, the C150A/C295A Ero1p mutant exhibits increased thiol oxidation in vitro and in vivo and interferes with redox homeostasis in yeast cells by hyperoxidizing the ER. Inhibitory disulfides of Ero1p are thus important for enzyme regulation. To visualize the differences between de‐regulated and wild‐type Ero1p, we determined the crystal structure of Ero1p C150A/C295A. The structure revealed local changes compared to the wild‐type enzyme around the sites of mutation, but no conformational transitions within 25 Å of the active site were observed. To determine how the C150C295 disulfide nonetheless participates in redox regulation of Ero1p, we analyzed using mass spectrometry the changes in Ero1p disulfide connectivity as a function of time after encounter with reducing substrates. We found that the C150C295 disulfide sets a physiologically appropriate threshold for enzyme activation by guarding a key neighboring disulfide from reduction. This study illustrates the diverse and interconnected roles that disulfides can play in redox regulation of protein activity.
The influence of involvement on the endowment effect: The moveable value function
Authors: Saqib Najam U. , Frohlich Norman , Bruning Edward
Published: July 2010

The endowment effect is based on the loss aversion built into Prospect Theory's asymmetric value function. This paper posits that the level of consumer involvement with a decision is a moderator of the endowment effect. It is proposed that high involvement increases the slope differential between the loss and gain regions of the value function, enhancing loss aversion. The research further posits that higher involvement is accompanied by higher arousal and cognitive processing which produces stronger negativity in thoughts. The argument for these effects is discussed in the context of evolutionary theory. We conclude that consumers are more loss averse in high versus low involvement conditions.
Coordination of frontline defense mechanisms under severe oxidative stress
Authors: Kaur Amardeep , Van Phu T , Busch Courtney R , Robinson Courtney K , Pan Min , Pang Wyming Lee , Reiss David J , DiRuggiero Jocelyne , Baliga Nitin S
Published: July 2010

Complexity of cellular response to oxidative stress (OS) stems from its wide‐ranging damage to nucleic acids, proteins, carbohydrates, and lipids. We have constructed a systems model of OS response (OSR) for Halobacterium salinarum NRC‐1 in an attempt to understand the architecture of its regulatory network that coordinates this complex response. This has revealed a multi‐tiered OS‐management program to transcriptionally coordinate three peroxidase/catalase enzymes, two superoxide dismutases, production of rhodopsins, carotenoids and gas vesicles, metal trafficking, and various other aspects of metabolism. Through experimental validation of interactions within the OSR regulatory network, we show that despite their inability to directly sense reactive oxygen species, general transcription factors have an important function in coordinating this response. Remarkably, a significant fraction of this OSR was accurately recapitulated by a model that was earlier constructed from cellular responses to diverse environmental perturbations—this constitutes the general stress response component. Notwithstanding this observation, comparison of the two models has identified the coordination of frontline defense and repair systems by regulatory mechanisms that are triggered uniquely by severe OS and not by other environmental stressors, including sub‐inhibitory levels of redox‐active metals, extreme changes in oxygen tension, and a sub‐lethal dose of γ rays.
Dissecting Ent3p: the ENTH domain binds different SNAREs via distinct amino acid residues while the C-terminus is sufficient for retrograde transport from endosomes
Authors: Zimmermann Jana , Chidambaram Subbulakshmi , Fischer von Mollard Gabriele
Published: July 2010

The ENTH (epsin N-terminal homology) domain protein Ent3p and the ANTH [AP (adaptor protein)-180 N-terminal homology] domain protein Ent5p serve as partially redundant adaptors in vesicle budding from the TGN (trans-Golgi network) in Saccharomyces cerevisiae. They interact with phosphoinositides, clathrin, adaptor proteins and cargo such as chitin synthase Chs3p and SNAREs (soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptors). In the present study, we show that ent3Δent5Δ cells displayed defects in cell separation and bud site selection. Ent3p and Ent5p were also involved in retrograde transport from early endosomes to the TGN because GFP (green fluorescent protein)–Snc1p shifted from a plasma membrane to an intracellular localization in ent3Δent5Δ cells. The C-terminal part of Ent3p was sufficient to restore retrograde transport from early endosomes to the TGN in ent3Δent5Δ cells. In contrast, the ENTH domain and the C-terminus were required for transport from the TGN to late endosomes, demonstrating that both functions are distinct. The ENTH domain of Ent3p is known to bind the N-terminal domains of the SNAREs Vti1p, Pep12p and Syn8p, which are required for fusion with late endosomes. The interaction surface between the Ent3p-related mammalian epsinR and vti1b is known. In the present paper, we show that Vti1p bound to the homologous surface patch of Ent3p. Pep12p and Syn8p interacted with the same surface area of Ent3p. However, different amino acid residues in Ent3p were crucial for the interaction with these SNAREs in two-hybrid assays. This provides the necessary flexibility to bind three SNAREs with little sequence homology but maintains the specificity of the interaction.
Cell cycle events mediate lactacystin‐induced apoptotic death of neuronal PC12 cells
Authors: Zhang Zhentao , Xu Yan , Qin Kairong , Wang Tao , Cao Xuebing
Published: July 2010

Dysfunction of the UPS (ubiquitin—proteasome system) has been implicated in dopaminergic neuronal death in PD (Parkinson's disease). Recent studies suggest that unregulated cell cycle events play a key role in neuronal death. In this study, the effects of UPS dysfunction on cell cycle events in neuronal differentiated PC12 cells were analysed using a specific inhibitor of proteasome, lactacystin. Lactacystin induced apoptosis, G2/M cell cycle arrest and sustained the phosphorylation of the pRB (retinoblastoma protein), the key molecular process of G1/S transition, in neuronal PC12 cells. Furthermore, inhibition of cell cycle progression protected against lactacystin‐induced cell apoptosis. Finally, we determined that lactacystin activated the ERK signalling pathway. Inhibition of ERK1/2 activation by MEK‐1 inhibitor PD98059 decreased cell cycle aberrant and prevented apoptosis induced by lactacystin. These results indicate that aberrant cell cycle events contribute to apoptotic death induced by UPS dysfunction.
Comment on “Ab initio molecular dynamics calculation of ion hydration free energies” [J. Chem. Phys. 130, 204507 (2009)]
Authors: Chen Edward S. , Chen Edward C. M.
Published: July 2010

We suggest that the authors compare their theoretical Gibbs free energies −ΔGhyd (kcal/mol) Li+, 128(1), 135; Cl−, 78(1), 70(2); and Ag+, 120(1) to recent absolute experimental values Li+, 128; Cl−, 74; and Ag+, 119 kcal/mol referenced to that for H+, 266(2) kcal/mol. We present bulk Gibbs hydration free energies and ionic radii for other ions from aqueous electron affinities, monohydration free energies, and diatomic halogen anion potential energy curves consistent with the Born dielectric constant, 3.4, for electrons and protons.
Ultrafast observation of shocked states in a precompressed material
Authors: Armstrong Michael R. , Crowhurst Jonathan C. , Bastea Sorin , Zaug Joseph M.
Published: July 2010

We apply ultrafast single shot interferometry to determine the pressure and density of argon shocked from up to 7.8 GPa static initial pressure in a diamond anvil cell. This method enables the observation of thermodynamic states distinct from those observed in either single shock or isothermal compression experiments. In particular, this method enables access to high density, relatively low temperature states of light materials, such as isentropically compressed states of giant planets. Further, since excitation by a shock wave is intrinsically ultrafast and this method has picoseconds time resolution, it has the potential to observe the collective dynamics of materials undergoing shock induced phase transitions and chemistry on ultrafast time scales. We also present a straightforward method for interpreting ultrafast shock wave data which determines the index of refraction at the shock front, and the particle and shock velocities for shock waves in transparent materials. Based on these methods, we observe shocked thermodynamic states between the room temperature isotherm of argon and the shock adiabat of cryogenic argon at final shock pressures up to 28 GPa.
Functional diversity of microbial decomposers facilitates plant coexistence in a plant–microbe–soil feedback model
Authors: Miki Takeshi , Ushio Masayuki , Fukui Shin , Kondoh Michio
Published: July 2010

Theory and empirical evidence suggest that plant–soil feedback (PSF) determines the structure of a plant community and nutrient cycling in terrestrial ecosystems. The plant community alters the nutrient pool size in soil by affecting litter decomposition processes, which in turn shapes the plant community, forming a PSF system. However, the role of microbial decomposers in PSF function is often overlooked, and it remains unclear whether decomposers reinforce or weaken litter-mediated plant control over nutrient cycling. Here, we present a theoretical model incorporating the functional diversity of both plants and microbial decomposers. Two fundamental microbial processes are included that control nutrient mineralization from plant litter: (
i
) assimilation of mineralized nutrient into the microbial biomass (microbial immobilization), and (
ii
) release of the microbial nutrients into the inorganic nutrient pool (net mineralization). With this model, we show that microbial diversity may act as a buffer that weakens plant control over the soil nutrient pool, reversing the sign of PSF from positive to negative and facilitating plant coexistence. This is explained by the decoupling of litter decomposability and nutrient pool size arising from a flexible change in the microbial community composition and decomposition processes in response to variations in plant litter decomposability. Our results suggest that the microbial community plays a central role in PSF function and the plant community structure. Furthermore, the results strongly imply that the plant-centered view of nutrient cycling should be changed to a plant–microbe–soil feedback system, by incorporating the community ecology of microbial decomposers and their functional diversity.
Isolation by crystallization of translational isomers of a bistable donor-acceptor [2]catenane
Authors: Wang Cheng , Olson Mark A. , Fang Lei , Benítez Diego , Tkatchouk Ekaterina , Basu Subhadeep , Basuray Ashish N. , Zhang Deqing , Zhu Daoben , Goddard William A. , Stoddart J. Fraser
Published: July 2010

The template-directed synthesis of a bistable donor-acceptor [2]catenane wherein both translational isomers—one in which a tetrathiafulvalene unit in a mechanically interlocked crown ether occupies the cavity of a cyclobis(paraquat-
p
-phenylene) ring and the other in which a 1,5-dioxynaphthalene unit in the crown ether resides inside the cavity of the tetracationic cyclophane—exist in equilibrium in solution, has led to the isolation and separation by hand picking of single crystals colored red and green, respectively. These two crystalline co-conformations have been characterized separately at both the molecular and supramolecular levels, and also by dynamic NMR spectroscopy in solution where there is compelling evidence that the mechanically interlocked molecules are present as a complex mixture of translational, configurational, and conformational isomers wherein the isomerization is best described as being a highly dynamic and adaptable phenomenon.
Genome-wide histone acetylation data improve prediction of mammalian transcription factor binding sites
Authors: Ramsey Stephen A. , Knijnenburg Theo A. , Kennedy Kathleen A. , Zak Daniel E. , Gilchrist Mark , Gold Elizabeth S. , Johnson Carrie D. , Lampano Aaron E. , Litvak Vladimir , Navarro Garnet , Stolyar Tetyana , Aderem Alan , Shmulevich Ilya
Published: July 2010

Motivation: Histone acetylation (HAc) is associated with open chromatin, and HAc has been shown to facilitate transcription factor (TF) binding in mammalian cells. In the innate immune system context, epigenetic studies strongly implicate HAc in the transcriptional response of activated macrophages. We hypothesized that using data from large-scale sequencing of a HAc chromatin immunoprecipitation assay (ChIP-Seq) would improve the performance of computational prediction of binding locations of TFs mediating the response to a signaling event, namely, macrophage activation.

Results: We tested this hypothesis using a multi-evidence approach for predicting binding sites. As a training/test dataset, we used ChIP-Seq-derived TF binding site locations for five TFs in activated murine macrophages. Our model combined TF binding site motif scanning with evidence from sequence-based sources and from HAc ChIP-Seq data, using a weighted sum of thresholded scores. We find that using HAc data significantly improves the performance of motif-based TF binding site prediction. Furthermore, we find that within regions of high HAc, local minima of the HAc ChIP-Seq signal are particularly strongly correlated with TF binding locations. Our model, using motif scanning and HAc local minima, improves the sensitivity for TF binding site prediction by ∼50% over a model based on motif scanning alone, at a false positive rate cutoff of 0.01.

Availability: The data and software source code for model training and validation are freely available online at http://magnet.systemsbiology.net/hac.

Contact:  aderem@systemsbiology.org; ishmulevich@systemsbiology.org

Supplementary information:  Supplementary data are available at Bioinformatics online.
Understanding lactic acidosis in paracetamol (acetaminophen) poisoning
Authors: Shah Anoop D. , Wood David M. , Dargan Paul I.
Published: July 2010

Paracetamol (acetaminophen) is one of the most commonly taken drugs in overdose in many areas of the world, and the most common cause of acute liver failure in both the UK and USA. Paracetamol poisoning can result in lactic acidosis in two different scenarios. First, early in the course of poisoning and before the onset of hepatotoxicity in patients with massive ingestion; a lactic acidosis is usually associated with coma. Experimental evidence from studies in whole animals, perfused liver slices and cell cultures has shown that the toxic metabolite of paracetamol, N‐acetyl‐p‐benzo‐quinone imine, inhibits electron transfer in the mitochondrial respiratory chain and thus inhibits aerobic respiration. This occurs only at very high concentrations of paracetamol, and precedes cellular injury by several hours. The second scenario in which lactic acidosis can occur is later in the course of paracetamol poisoning as a consequence of established liver failure. In these patients lactate is elevated primarily because of reduced hepatic clearance, but in shocked patients there may also be a contribution of peripheral anaerobic respiration because of tissue hypoperfusion. In patients admitted to a liver unit with paracetamol hepatotoxicity, the post‐resuscitation arterial lactate concentration has been shown to be a strong predictor of mortality, and is included in the modified King's College criteria for consideration of liver transplantation. We would therefore recommend that post‐resuscitation lactate is measured in all patients with a severe paracetamol overdose resulting in either reduced conscious level or hepatic failure.
Interleukin‐9 as a T helper type 17 cytokine
Authors: Nowak Elizabeth C. , Noelle Randolph J.
Published: July 2010

The production of interleukin‐9 (IL‐9) by CD4 T cells has gathered renewed interest as the result of the observation that its expression is broader than originally thought. This includes the production of IL‐9 by a recently characterized subset of CD4 helper T (Th) cells that are termed Th9 as well as production by additional T‐cell subsets including Th17 cells. There is an incomplete understanding as to which IL‐9‐producing T‐cell subsets develop under physiological conditions. We describe the conditions used to generate IL‐9 in Th17 cells in vitro. We also summarize conditions where both IL‐9 and IL‐17 are found in vivo and propose that Th17 cells producing IL‐9 may co‐exist and interact with Th9 cells during conditions of autoimmunity, allergy and infection.