bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictive model for chloride penetration through concrete
Authors: Khitab A. , Lorente S. , Ollivier J. P.
Published: October 2005

This work documents a numerical model, the objective of which is to predict the chloride penetration through saturated concrete. The model solves the Nernst–Planck/current law equations and accounts for the chloride interactions with the solid phase. In addition to boundary conditions, it requires a set of five experimental characteristics available from a single sample of material namely: density; porosity; pore solution composition; effective chloride diffusion coefficient; and chloride binding isotherm. The input data do not evolve with time; the exceptions are the ionic diffusivities, which are time dependent. The method used to obtain the input data is outlined. Particular attention is paid to the metrology of the unsteady state migration test, which makes it possible for the chloride diffusion coefficient to be measured. The manner in which the chloride binding isotherm is reached is emphasised. Finally, the method is validated by comparing the numerical simulations with experimental results made on a CEM-I-based concrete.
Stress–strain behaviour of high-strength concrete at elevated temperatures
Authors: Fu Y. F. , Wong Y. L. , Poon C. S. , Tang C. A.
Published: October 2005

In this paper, the results of a series of experiments are presented to show the temperature-dependent stress–strain relationship of high-strength concrete (HSC) when exposed to elevated temperatures. The effects of mineral additions and test conditions on the stress–strain behaviour are discussed. The result shows that addition of fly ash (FA) was effective in improving the residual properties (compressive strength and elastic modulus) of concrete. All the concrete mixes had higher residual mechanical properties in the stressed tests than in the unstressed tests. In the stressed test condition, all the concrete mixes retained elastic modulus values close to the original unheated values.
30-year creep and shrinkage of concrete
Authors: Brooks J. J.
Published: October 2005

Experimental results of creep, shrinkage, swelling, modulus of elasticity and strength of 18 types of concrete after 30 years are presented. While the compressive strength of dry-stored concrete was greater than that of wet-stored concrete, the modulus of elasticity behaved in the opposite way, suggesting that some of the water within the concrete is capable of withstanding significant load. Shrinkage ranged from 280 to 1460 × 10−6 and swelling varied from 25 to 35% of shrinkage. The accuracy of five current design methods of estimating 30-year deformation is compared. Most methods fail to recognise the influence of strength of concrete and type of aggregate on creep coefficient, which ranged from 1·2 to 9·2.
Describing the stress–crack-opening relationship using a three-exponential model
Authors: Lee M. K. , Barr B.
Published: October 2005

The paper reports on a proposed simple mathematical function to describe the strain–softening behaviour observed in uniaxial tensile tests on a wide range of concretes. Two mathematical functions—a linear-double-e and a three-e model—are proposed which are able to describe such curves via one continuous function and thus have the advantage of being mathematically efficient. The proposed functions have been compared with actual uniaxial tensile test results on both plain and steel-fibre-reinforced concrete. Both qualitative and quantitative results show that the three-e model can accurately describe the strain–softening curves for a wide range of concrete strengths. In addition, a systematic procedure is reported whereby model parameters are determined objectively.
Modification of a Crop‐Specific Drought Index for Simulating Corn Yield in Wet Years
Authors: Hubbard Kenneth G. , Wu Hong
Published: October 2005

Drought occurs when there is a deficit in soil water supply to the plant. Severe drought limits crop yield by causing the plant's water use to be limited compared with a well‐watered crop. Too much water (flooded soils) also causes stress to the plant whose roots are in saturated soil for long periods. Both situations lead to crop water stress, ultimately resulting in reduced crop yield. Since flood and drought can occur intermittently in cropping, an effective yield predictor should contain both flood and drought stress components for better representation of the range of natural conditions the plant might encounter during its growth period. This paper details the modification of the Crop‐Specific Drought Index (CSDI) model by introducing a soil saturation factor, resulting in a Crop‐Specific Stress Index (CSSI) model. The study was conducted in eastern Nebraska and southeastern Minnesota. The coefficients used in the CSSI model were estimated by a jackknifing procedure based on 1971–2002 climate data, nonirrigated yield data of corn (Zea mays L.), and soil information retrieved from the STATSGO database in the crop districts. Results show that all indicators of agreement between the estimated and actual yields show improvement of the new CSSI model over the old CSDI model in all districts. Results also show that the CSSI model outperforms the CSDI model in years characterized by soil saturation. For instance, the CSDI for 1993 overestimates the relative yield in northeastern Nebraska by about 28% while the CSSI underestimates the 1993 yield by 3%.
Determination of a Multivariate Indicator of Nitrogen Imbalance (MINI) in Potato Using Reflectance and Fluorescence Spectroscopy
Authors: Bélanger M-C. , Viau A. A. , Samson G. , Chamberland M.
Published: October 2005

In this study, we evaluated the potential of reflectance and fluorescence for the detection of the Compositional Nutrient Diagnosis (CND) N index (IN). The CND reflects nutrient deficiencies as well as nutrient interactions, contrary to conventional methods of nutrient stress detection. Potato plants (Solanum tuberosum L. cv. Superior) were grown in a greenhouse, and three different nutrient deficiencies (K, Mg, and N) were induced at three levels and compared with a control receiving a complete nutrient solution. Nitrogen deficiency induced a significant biomass reduction compared with control plants whereas no significant effect was observed for K or Mg treatments. Foliar analyses were realized to compute the CND_r2 using the CND. The ANOVA conducted on CND_r2 and IN showed significant differences only between N‐deficient and control plants. Using a canonical discriminant analysis over reflectance and fluorescence indices, it was possible to correctly classify 96.6% of potato plants in its corresponding IN class. A new Multivariate Indicator of Nitrogen Imbalance (MINI) was developed using the canonical variable computed from reflectance and fluorescence indices. The MINI can detect almost 70% of the N‐deficient plants and more than 90% of the N‐sufficient plants. This indicator allows a rapid data acquisition and handling and provides deficiency detection within the time‐window for plant response to recovery fertilization.
Influence of Sowing Date on Emergence Characteristics of Maize Seed Coated with a Temperature‐Activated Polymer
Authors: Gesch Russ W. , Archer David W.
Published: October 2005

Cold, wet soils, coupled with a short growing season, create a narrow window of optimum time for planting corn (Zea mays L.) in the northern Corn Belt. Temperature‐activated polymer (TAP) coatings designed to inhibit planted seed from imbibing water until adequate soil temperatures are reached to promote germination and emergence may offer potential for planting corn exceptionally early. A study from 2000 to 2002 was conducted in west central Minnesota on a Barnes soil (Calcic Hapludoll) to determine the potential for earlier‐than‐average planting of TAP‐coated corn seed. The objective was to compare emergence characteristics of coated and uncoated hybrid corn planted early and at a near‐average planting date. Seed planted 29 Mar. 2000 and 24 Apr. 2002 remained in the soil for as long as 26 to 32 d before emerging. In these instances, stands from TAP‐coated seed, which ranged from 60 to 90% of seed planted, were generally greater than those of uncoated seed, which ranged from 49 to 68%. Stand establishment and time required to obtain 50% and from 10 to 90% emergence for most early planted coating × hybrid seed combinations were similar to uncoated seed planted at near‐average planting dates of 1, 14, and 16 May in 2000, 2001, and 2002, respectively. When both coated and uncoated seed were sown at an average planting date, stand establishment was similar, but emergence for coated seed was generally delayed. Results of this study indicate that TAP coatings protected seeds from injury caused by extended exposure to cold soils, and therefore, might be a useful management tool for early corn planting.
Seeding Rates for Stale Seedbed Rice Production in the Midsouthern United States
Authors: Bond Jason A. , Walker Timothy W. , Bollich Patrick K. , Koger Clifford H. , Gerard Patrick
Published: October 2005

The establishment of an adequate and uniform rice (Oryza sativa L.) stand is critical to achieve high grain yields. The literature is extensive for older cultivars planted in conventional tillage and/or water‐seeded systems; however, there are no published data for current cultivars grown in stale seedbed systems. Six of the cultivars most commonly grown in the Midsouth rice production area of the USA were drill seeded at densities of 108, 215, 323, 430, and 538 seeds m−2 into a stale seedbed at Crowley, LA, from 2002 to 2004, and in Clarksdale, MS, in 2003 and 2004. Established plant densities responded linearly to seeding rate for all cultivars except Cocodrie, which responded quadratically. Rough rice yields were not affected by seeding rate for Cheniere, but followed a quadratic relationship for the cultivars CL161, Cocodrie, and Priscilla. A location × seeding rate interaction was detected for yield of Wells. Seeding rate did not affect rough rice yields for Wells in Mississippi, while in Louisiana, yields responded quadratically. Francis rough rice yields increased linearly with increased seeding rates. Optimal rough rice grain yields can be achieved in Mississippi and Louisiana with a seeding rate of 323 seeds m−2 for cultivars that are currently grown across the Midsouth rice‐producing area in the USA. Furthermore, depending on the cultivar, when plant densities are uniform and range from 50 to 70 plants m−2, the resulting rice grain yields may offset the cost of terminating the stand and replanting.
Freezing Point Temperatures of Corn Seed Structures during Seed Development
Authors: Woltz James M. , Egli Dennis B. , TeKrony Dennis M.
Published: October 2005

Seed in hybrid corn (Zea mays L.) production can be exposed to freezing temperatures before harvest, which may reduce quality. This study examined changes in freezing point temperature (FPT) in seed, embryo, and endosperm tissue from ears of three F1 hybrids and one F2 hybrid harvested at various stages of development and exposed to temperatures of −6 or −11°C. Seed FPT decreased in a curvilinear manner from −0.5°C for immature seed (>500 g kg−1 seed moisture concentrations, SMC) to below −4°C when freezing was last detectable in mature seed (SMC ≈ 300 g kg−1). There were no differences in FPT when seeds were frozen at −6 or −11°C or at different rates (rapid vs. gradual) of temperature change. Seeds froze at the same FPT across all hybrids and years, except for one F1 hybrid in 1999. As seeds matured (SMC < 400 g kg−1), the embryo tissue had higher moisture levels than the endosperm, which resulted in the embryo freezing at warmer temperatures (−4.5°C) than the endosperm (−9.2°C). Immature seeds can freeze at temperatures ranging from −1.0 to −2.0°C (typical of the first freeze of autumn); however, if seed has reached or exceeded physiological maturity (SMC 360 g kg−1), it is unlikely that injury will occur.
Influence of Nitrogen Fertilization on Multi‐Cut Forage Sorghum–Sudangrass Yield and Nitrogen Use
Authors: Beyaert Ronald P. , Roy Robert C.
Published: October 2005

Forage sorghum–sudangrass [Sorghum bicolor (L.) Moench] is a relatively new crop to eastern Canada and the effects of additions of fertilizer N on yield, N accumulation, and N use efficiency are not available for this region. In 1998, 1999, and 2000 the response of forage sorghum–sudangrass to additions of fertilizer N rates (0, 50, 100, 150, 200, and 250 kg N ha−1) either applied as a single sidedress application or split into two sidedress applications was evaluated on a Fox loamy sand (Psammentic Hapludalf). Although timing of N application had little effect on DM production, splitting the N application into two equal applications may be of benefit by enhancing the NUE and ANR of individual cuts. Maximum yield was estimated at 5.95 Mg ha−1 at an N rate of 125 kg N ha−1 and the most economic rates of N ranged from 83 to 107 kg N ha−1 dependent on the cost of N fertilizer and value of hay. Nitrogen concentration increased linearly with increasing N application and the maximum N accumulation was 161 kg N ha−1 at an N rate of 196 kg N ha−1. Total N use efficiency and apparent N recovery decreased with increasing N rates ranging from 36 to 11 kg DM kg−1 and 90 to 24%, respectively. Optimum yield and N efficiency occurred when 100 kg N ha−1 was applied as a split application. Producers in southern Ontario require N fertilizer additions to optimize sorghum–sudangrass yields but need to avoid overfertilization with N to maximize N use efficiency and apparent N recovery.
Corn Stalk Nitrate Concentration Profile
Authors: Wilhelm W. W. , Varvel G. E. , Schepers J. S.
Published: October 2005

The end‐of‐season stalk nitrate test provides a method of assessing the N available to the corn (Zea mays L.) crop during the latter part of the season. This study was conducted to determine how stalk nitrate test results and interpretations are affected by sample composition. Stalks were collected from three field sites and separated into phytomers (node plus internode above), which were subdivided into three or five segments after length was measured. Nitrate‐N concentration of phytomers decreased linearly from the soil to the ear. Within a phytomer, segments also decreased acropetally (from base to apex). Node tissue NO3–N concentration did not differ from that of the internode segment immediately above the node. Weighted means were used to compute NO3–N concentration of stalk samples collected 5 cm higher (from 20 to 40 cm above the soil) or lower (from 10 to 30 cm above the soil) on the stalk than in the original method (from 15 to 35 cm above the soil). Although the three samples (10–30, 15–35, and 20–40 cm) differed in NO3–N concentration, the difference was only about 15% compared with the 25% difference in sampling position (±5 cm of 20‐cm sample length). The phytomer nearest the soil had 35 to 40% greater NO3–N concentrations than the section of stalk 15 to 35 cm above the soil. Critical values delineating yield‐limiting, adequate, and excessive N availability should be modified if stalk sections other than the standard 15 to 35 cm section are used. However, the qualitative nature of the stalk nitrate test and the range of NO3–N concentrations observed with reasonable corn cultural practices (1000×) make this test quite robust and precise definition of sample composition and critical values less necessary.
Quality Issues of Group Work and Leadership Emergence in E-Learning: Case Study
Authors: Fisher M. , Tucker D. , Silverberg D.
Published: October 2005

This case study investigates the participant structure of leadership in online course environments and helps instructors design and facilitate high-quality lessons. Researchers used course experiences that were authentic, collaborative, and computer-based to collect student data: assignments, discussion transcripts, and interviews. Analysis of the data reveals the issues, strategies, and implications that arose in the context of group projects; these findings are especially applicable to real-world work situations.
Using Anchored Instruction to Evaluate Mathematical Growth and Understanding
Authors: Kurz Terri L. , Batarelo Ivana
Published: October 2005

Anchored instruction is designed to present problems in a meaningful context to allow for investigations into real life environments. The Jasper Project was created to allow students to investigate mathematical dilemmas using anchored instruction techniques. This study uses case study methods to examine the perceptions that preservice teachers have toward the use of anchored instruction after having the opportunity to investigate and evaluate a Jasper predicament as a group. The guiding research questions were: 1) Through exploration and evaluation, are preservice teachers able to determine significance of using anchored instruction with their future students? And if they see significance, 2) How do preservice teachers envision student learning and mathematical growth using anchored instruction? Four individual cases were evaluated, specifically examining the features of anchored instruction each preservice teacher described. The preservice teachers were optimistic about the utilization of anchored instruction and described features that support student learning and growth.
Characterization versus Narration: Drama's Role in Multimedia Instructional Software
Authors: Cates Ward Mitchell , Bishop M. J. , Hung Woei
Published: October 2005

As part of an ongoing research program, the authors investigated the use of single-voiced narration and multi-voiced characterizations/monologues in a formative evaluation study of an instructional lesson on information processing. That lesson employed a design based on the use of content-related metaphors and a metaphorical graphical user interface. The results suggest that single-voiced narration is at least as effective as multi-voiced characterizations/monologues, and may in some ways be superior. Analysis of the findings is linked to Laurel's dramatic model with proposed enhancements to the lesson's design to increase its conformance to that model.
The Effect of Flexible Learning Delivery Format on Online Learners' Learning, Application, and Instructional Perception
Authors: Lim Doo H. , Morris Michael Lane
Published: October 2005

Instructional condition has been an important area of study to improve learner satisfaction and learning outcomes within public and private organizations. Among various types of learning methods satisfying the online learner's learning styles, this study examined the effect of flexible learning delivery format on learning and application of learning made by a group of Human Resource Development (HRD) undergraduate students. Quantitative data analysis results revealed a flexible learning delivery format did not influence online learners' perceived learning. From a qualitative data analysis, however, various reasons why online learners' attained high or low degree of perceived learning and application of learning were analyzed and categorized. Discussions about instructional conditions and strategies to enhance learning and the application of learning for online curriculum are included.
Worth of Electronic Portfolios to Education Majors: A “Two by Four” Perspective
Authors: Sherry Annette C. , Bartlett Andrea
Published: October 2005

Two groups of education majors—23 undergraduates and 14 educational technology graduate students—provided perspectives about their electronic portfolios. Two investigators independently directed them, evaluating the process from students' perspectives, including holistic evaluations by departmental faculty. Survey data were framed within Kirkpatrick's Levels of Evaluation with worth expressed on four levels as attitudes, learning, planned job usage, and potential organization impact. Despite different technological capabilities and limited similarities in implementing the process, both groups primarily viewed electronic portfolios as worthwhile overall, being largely positive on three levels. Systemizing the process is suggested. Technological ability, overall, was not a major factor.
Experimental study of gas mixing in a spout‐fluid bed
Authors: Zhong Wenqi , Xiao Rui , Zhang Mingyao
Published: October 2005

Gas mixing in a spout‐fluid bed with a cross section of 0.3 × 0.03 m and height of 2 m was investigated by simultaneously injecting two different tracer gases. One was injected into the spouting gas flow and the other was injected into the fluidizing gas flow. Steady‐state tracer gas measurements were carried out to obtained radial tracer gas concentrations at various bed elevations. Effects of two important operating parameters—spouting gas velocity and fluidizing gas flow rate—on the gas mixing were discussed with flow patterns recorded by a high‐resolution digital CCD camera. The results show that increasing spouting gas velocity and fluidizing gas flow rate can both promote the gas mixing in spout‐fluid beds. Increasing fluidizing gas flow rate is the more effective way, given that a satisfactory mixing condition at a relatively low bed height can be obtained by increasing the fluidizing gas flow rate. For both cases, it is difficult to obtain a good mixing condition in the wall layers. Besides, the mechanism of gas mixing was preliminarily discussed. Results indicate that gas mixing in the spout‐fluid bed is caused by both convection and diffusion. Diffusion other than molecular diffusion should not be neglected, especially at high spouting gas velocity or fluidizing gas flow rate. © 2005 American Institute of Chemical Engineers AIChE J, 2006
Calcitonin gene–related peptide does not excite or sensitize meningeal nociceptors: Implications for the pathophysiology of migraine
Authors: Levy Dan , Burstein Rami , Strassman Andrew M.
Published: October 2005

Migraine is among the most common types of pain, but its mechanisms are poorly understood. A growing body of evidence points to a critical role of calcitonin gene–related peptide (CGRP) in the pathophysiology of migraine headache. During migraine, CGRP is thought to be released from peripheral endings of perivascular meningeal nociceptors primary and to promote vasodilatation. A current hypothesis suggests that peripheral CGRP and its related meningeal vasodilatation results in activation and sensitization, leading to the generation of migraine headache. However, direct evidence supporting this idea is lacking. Here, using electrophysiological, extracellular, single‐unit recording combined with laser–Doppler flowmetry measurements of dural blood flow (DBF), we examined whether CGRP and meningeal vasodilatation promote activation or sensitization of meningeal nociceptors. Changes in (DBF), ongoing discharge, and responsiveness to mechanical stimulation of the dura were studied after either topical administration or intravenous infusion of rat α‐CGRP in anesthetized rats. Both topical and systemic administration of CGRP caused a significant increase in dural blood flow; however, neither method of CGRP administration resulted in activation or sensitization of meningeal nociceptors. The results of this study suggest that CGRP effects in the meninges, including meningeal vasodilatation, are not sufficient to activate or sensitize meningeal nociceptors. Ann Neurol 2005;58:698–705
Overdiagnosis of multiple sclerosis and magnetic resonance imaging criteria
Authors: Nielsen Jessica M. , Korteweg Tijmen , Barkhof Frederik , Uitdehaag Bernard M. J. , Polman Chris H.
Published: October 2005

Retrospectively, we assessed the specificity of two proposed magnetic resonance imaging (MRI) criteria for multiple sclerosis (MS) in patients suspected to have MS but who ultimately receive another diagnosis. Brain MRIs of 28 patients mixed with 28 MRIs of MS patients from the same cohort of 377 consecutively referred patients were scored by a neuroradiologist masked to the final diagnosis. The criteria for dissemination in space incorporated in the McDonald International Panel showed good specificity (89%). However, the more sensitive criteria proposed by a Subcommittee of the American Academy of Neurology resulted in a lower specificity (29%), indicating an increased risk of a false‐positive diagnosis. Ann Neurol 2005;58:781–783
A common pattern of persistent gene activation in human neocortical epileptic foci
Authors: Rakhade Sanjay N. , Yao Bin , Ahmed Sharlin , Asano Eishi , Beaumont Thomas L. , Shah Aashit K. , Draghici Sorin , Krauss Raul , Chugani Harry T. , Sood Sandeep , Loeb Jeffrey A.
Published: October 2005

Epilepsy is a disease of recurrent seizures that can develop after a wide range of brain insults. Although surgical resection of focal regions of seizure onset can result in clinical improvement, the molecular mechanisms that produce and maintain focal hyperexcitability are not understood. Here, we demonstrate a regional, persistent induction of a common group of genes in human epileptic neocortex in 17 patients with neocortical epilepsy, regardless of the underlying pathology. This relatively small group of common genes, identified using complementary DNA microarrays and confirmed with quantitative reverse transcription polymerase chain reaction and immunostaining, include the immediate early gene transcription factors EGR‐1, EGR‐2, and c‐fos, with roles in learning and memory, and signaling genes such as the dual‐specificity kinase/phosphatase MKP‐3. Maximal expression of these genes was observed in neurons in neocortical layers II through IV. These neurons also showed persistent cyclic adenosine monophosphate response element binding protein (CREB) activation and nuclear translocation of EGR‐2 and c‐fos proteins. In two patients, local interictal epileptiform discharge frequencies correlated precisely with the expression of these genes, suggesting that these genes either are directly modulated by the degree of epileptic activity or help sustain ongoing epileptic activity. The identification of a common set of genes and the persistent activation of CREB signaling in human epileptic foci provide a clinically relevant set of biological markers with potential importance for developing future diagnostic and therapeutic options in human epilepsy. Ann Neurol 2005;58;736–747
Resolution of EBV+ CNS lymphoma with appearance of CSF EBV‐specific T cells
Authors: de Beukelaar Janet W. , van Arkel Cornelis , van den Bent Martin J. , van 't Veer Mars B. , van Doornum Gerard J. , Cornelissen Jan J. , Sillevis Smitt Peter A. , Gratama Jan W.
Published: October 2005

Current knowledge of Epstein–Barr virus (EBV)–specific T‐cell responses in the cerebrospinal fluid (CSF) of patients with EBV‐related lymphoproliferative disease (EBV‐LPD) in the central nervous system (CNS) is very limited. Here, we present two recipients of hematopoietic stem cell transplants with EBV‐LPD in the CNS. EBV‐specific CD8+ T lymphocytes were detected in CSF and peripheral blood using major histocompatibility complex (MHC) class I multimers loaded with EBV‐derived peptides. The appearance of EBV‐specific CD8+ T cells in CSF and blood correlated with neurological improvement and disappearance of EBV‐LPD. These observations suggest a role for EBV‐specific CD8+ T cells in the control of EBV‐LPD in the CNS. Ann Neurol 2005;58:788–792
Developing and implementing future stroke therapies: The potential of telemedicine
Authors: Fisher Marc
Published: October 2005

Stroke is a major public health concern with few positive phase III clinical trials and a shortage of stroke care expertise. Drug development likely can be enhanced by adapting new outcome measures and following guidelines generated by consensus groups. To enhance rates of drug implementation and to improve stroke care, some states are requiring that acute care hospitals obtain primary stroke center certification, and this mandate necessitates that smaller hospitals join larger ones in stroke care networks. Cutting‐edge technology in the form of telemedicine is being implemented in stroke care networks to combat the lack of stroke care expertise by extending the availability of physician stroke expertise. The telemedicine network can be used to transmit real‐time data from stroke care–certified community hospitals (spokes) to a tertiary center (hub). Telemedicine can be used to educate physicians in spoke hospitals about new stroke treatments. The advent and development of telemedicine has the potential to ensure that patients with stroke have a greater opportunity to receive the full range of therapeutic options currently available and those that will become available in the future. The implementation of future drug therapies through telemedicine‐organized stroke networks will likely substantially influence the future of acute stroke therapy. Ann Neurol 2005;58:666–671
DJ‐1 mutations and parkinsonism‐dementia‐amyotrophic lateral sclerosis complex
Authors: Annesi Grazia , Savettieri Giovanni , Pugliese Pierfrancesco , D'Amelio Marco , Tarantino Patrizia , Ragonese Paolo , La Bella Vincenzo , Piccoli Tommaso , Civitelli Donatella , Annesi Ferdinanda , Fierro Brigida , Piccoli Federico , Arabia Gennarina , Caracciolo Manuela , Cirò Candiano Innocenza Claudia , Quattrone Aldo
Published: October 2005

DJ‐1 gene mutations have been found to cause early‐onset Parkinson's disease. We report a family from southern Italy with three brothers affected by early‐onset parkinsonism, dementia, and amyotrophic lateral sclerosis. Molecular analysis of the DJ‐1 gene in two living patients showed a novel homozygous mutation in exon 7 (E163K) and a new homozygous mutation (g.168_185dup) in the promoter region of the gene. Both mutations cosegregated with the disease and were detected in a heterozygous state in the patients' mother and their healthy siblings. Our findings expand the spectrum of clinical presentations associated with mutations in DJ‐1 gene. Ann Neurol 2005;58:803–807
Phenotypic heterogeneity within a new family with the MAPT p301s mutation
Authors: Yasuda Minoru , Nakamura Yoshitsugu , Kawamata Toshio , Kaneyuki Hiroshi , Maeda Kiyoshi , Komure Osamu
Published: October 2005

Mutations in the gene encoding the microtubule‐associated protein tau (MAPT) cause frontotemporal dementia and parkinsonism linked to chromosome 17. Clinical variability is seen not only among families with different mutations, but also among family members with the same mutation. We investigated a newly identified familial frontotemporal dementia and parkinsonism family. The disease was of early onset and was inherited as an autosomal dominant trait. Clinically, parkinsonism was the prominent and often early feature, and it preceded dementia. Three autopsied cases shared involvement predominantly in the frontal and temporal lobes and also in the subcortical nuclei, including substantia nigra, globus pallidus, and subthalamic nucleus, that microscopically consisted of neuronal loss, microvacuolation, and astrocytic fibrosis. Immunohistochemistry demonstrated neuropil threads, ballooned cells, and glial fibrillary tangles. Sequencing analysis of the MAPT gene showed an alteration in one allele, resulting in a P301S substitution. These findings suggest that the MAPT P301S mutation can cause pathologically subcortical‐predominant, neuropil thread‐rich, tau‐containing lesions, which could result in consistent parkinsonism. Our study confirms the notion that the phenotype observed in affected individuals from P301S MAPT mutation families is heterogeneous and is broader than the phenotypes seen to date in affected family members carrying other MAPT mutations. Ann Neurol 2005
The role of the ND5 gene in LHON: Characterization of a new, heteroplasmic LHON mutation
Authors: Mayorov Vladimir , Biousse Valerie , Newman Nancy J. , Brown Michael D.
Published: October 2005

Leber's hereditary optic neuropathy (LHON) causes central vision loss from bilateral optic neuropathy. Although 13 mitochondrial DNA (mtDNA) mutations are strongly associated with LHON, only three account for roughly 90% of cases and thus are found in multiple independent LHON families. The remaining LHON mutations are rare. Here, we describe the clinical and genetic characterization of a new LHON mtDNA mutation. The 12848T mutation alters a highly conserved amino acid in the ND5 complex I gene, is not found in controls, and is heteroplasmic. Despite ND5 being the largest of the mtDNA complex I genes, ND5 mutations are quite rare in LHON. Ann Neurol 2005;58:807–811
OPA1 R445H mutation in optic atrophy associated with sensorineural deafness
Authors: Amati‐Bonneau Patrizia , Guichet Agnès , Olichon Aurélien , Chevrollier Arnaud , Viala Frédérique , Miot Stéphanie , Ayuso Carmen , Odent Sylvie , Arrouet Catherine , Verny Christophe , Calmels Marie‐Noelle , Simard Gilles , Belenguer Pascale , Wang Jing , Puel Jean‐Luc , Hamel Christian , Malthièry Yves , Bonneau Dominique , Lenaers Guy , Reynier Pascal
Published: October 2005

The heterozygous R445H mutation in OPA1 was found in five patients with optic atrophy and deafness. Audiometry suggested that the sensorineural deafness resulted from auditory neuropathy. Skin fibroblasts showed hyperfragmentation of the mitochondrial network, decreased mitochondrial membrane potential, and adenosine triphosphate synthesis defect. In addition, OPA1 was found to be widely expressed in the sensory and neural cochlear cells of the guinea pig. Thus, optic atrophy and deafness may be related to energy defects due to a fragmented mitochondrial network. Ann Neurol 2005
Multiple sclerosis in twins from continental Italy and Sardinia: A nationwide study
Authors: Ristori Giovanni , Cannoni Stefania , Stazi Maria Antonietta , Vanacore Nicola , Cotichini Rodolfo , Alfò Marco , Pugliatti Maura , Sotgiu Stefano , Solaro Claudio , Bomprezzi Roberto , Di Giovanni Simone , Figà Talamanca Lorenzo , Nisticò Lorenza , Fagnani Corrado , Neale Michael C. , Cascino Isabella , Giorgi Gabriele , Battaglia Mario A. , Buttinelli Carla , Tosi Roberto , Salvetti Marco ,   Italian Study Group on Multiple Sclerosis in Twins
Published: October 2005

Knowledge about the balance between heritable and nonheritable risk in multiple sclerosis (MS) is based on twin studies in high‐prevalence areas. In a study that avoided ascertainment limitations and directly compared continental Italy (medium‐prevalence) and Sardinia (high‐prevalence), we ascertained 216 pairs from 34,549 patients. This gives a twinning rate of 0.62% among MS patients, significantly less than that of the general population. In continental Italy, probandwise concordance was 14.5% (95% confidence interval, 5.1–23.8) for monozygotic and 4.0% (95% confidence interval, 0.8–7.1) for dizygotic twins. Results in Sardinia resemble those in northern populations but in limited numbers. Monozygotic concordance was 22.2% (95% confidence interval, 0–49.3) probandwise, but no concordant dizygotic pairs were identified. A questionnaire on 80 items possibly related to disease cause was administered to 70 twin pairs, 135 sporadic patients, and 135 healthy volunteers. Variables positively (7) or negatively (2) associated with predisposition and concordance in twins largely overlapped and were mainly linked to infection. If compared with previous studies, our data demonstrate that penetrance in twins appears to correlate with MS prevalence. They highlight the relevance of nonheritable variables in Mediterranean areas. The apparent underrepresentation of MS among Italian twins draws attention to protective factors, shared by twins, that may influence susceptibility. Ann Neurol 2005
Status epilepticus in mice deficient for succinate semialdehyde dehydrogenase: GABAAreceptor–mediated mechanisms
Authors: Wu Ying , Buzzi Andrea , Frantseva Marina , Velazquez Jose Perez L. , Cortez Miguel , Liu Chunche , Shen Liqing , Gibson K. Michael , Snead O. Carter
Published: October 2005

The epilepsy that occurs in SSADH deficiency has a seizure phenotype similar to that occurring in the SSADH−/−mouse. We examined the expression and function of the GABAAreceptor (GABAAR) in SSADH‐deficient mice. A selective decrease in binding of [35S]tert‐butylbicyclophosphorothionate was observed in SSADH−/−mice at postnatal day 7 that was progressive until the third postnatal week of life when, at the nadir of the decreased [35S]tert‐butylbicyclophosphorothionate binding, generalized convulsive seizures emerged that rapidly evolved into status epilepticus. We also observed a substantial downregulation of the β2subunit of GABAAR, a reduction in GABAA‐mediated inhibitory postsynaptic potentials, and augmented postsynaptic population spikes recorded from hippocampal slices. The SSADH−/−mouse model represents a powerful investigative tool for understanding the pathophysiology of the seizures associated with human SSADH deficiency. These data raise the possibility that progressive dysfunction of the GABAAR may be involved in the development of seizures in SSDAH‐deficient mice. Elucidation of the precise fundamental mechanisms of the perturbation of the GABAAR‐mediated function in SSADH−/−mice could lead to the development of novel treatment modalities designed to reduce the neurological morbidity in children with SSADH deficiency. Ann Neurol 2005
Shikimic acid production by a modified strain of E. coli (W3110.shik1) under phosphate‐limited and carbon‐limited conditions
Authors: Johansson Louise , Lindskog Anna , Silfversparre Gustav , Cimander Christian , Nielsen Kristian Fog , Lidén Gunnar
Published: October 2005

Shikimic acid is one of several industrially interesting chiral starting materials formed in the aromatic amino acid pathway of plants and microorganisms. In this study, the physiology of a shikimic acid producing strain of Escherichia coli (derived from W3110) deleted in aroL (shikimic acid kinase II gene), was compared to that of a corresponding control strain (W3110) under carbon‐ and phosphate‐limited conditions. For the shikimic acid producing strain (referred to as W3110.shik1), phosphate limitation resulted in a higher yield of shikimic acid (0.059 ± 0.012 vs. 0.024 ± 0.005 c‐mol/c‐mol) and a lower yield of by‐products from the shikimate pathway, when compared to carbon‐limited condition. The yield of the by‐product 3‐dehydroshikimic acid (DHS) decreased from 0.076 ± 0.028 to 0.022 ± 0.001 c‐mol/c‐mol. Several other by‐products were only detected under carbon‐limited conditions. The latter group included 3‐dehydroquinic acid (0.021 ± 0.021 c‐mol/c‐mol), quinic acid (0.012 ± 0.005 c‐mol/c‐mol), and gallic acid (0.002 ± 0.001 c‐mol/c‐mol). For both strains, more acetate was produced under phosphate than the carbon‐limited case. Considerable cell lysis was found for both strains but was higher for W3110.shik1, and increased for both strains under phosphate limitation. The advantages of the latter condition in terms of an increased shikimic acid yield was thus counteracted by an increased cell lysis, which may make downstream processing more difficult. © 2005 Wiley Periodicals, inc.
Effects of terpenoid precursor feeding on Catharanthus roseus hairy roots over‐expressing the alpha or the alpha and beta subunits of anthranilate synthase
Authors: Peebles Christie A.M. , Hong Seung‐Beom , Gibson Susan I. , Shanks Jacqueline V. , San Ka‐Yiu
Published: October 2005

Among the pharmacologically important terpenoid indole alkaloids produced by Catharanthus roseus are the anti‐cancer drugs vinblastine and vincristine. These two drugs are produced in small yields within the plant, which makes them expensive to produce commercially. Metabolic engineering has focused on increasing flux through this pathway by various means such as elicitation, precursor feeding, and introduction of genes encoding specific metabolic enzymes into the plant. Recently in our lab, a feedback‐resistant anthranilate synthase α subunit was over‐expressed in C. roseus hairy roots under the control of a glucocorticoid inducible promoter system. Upon induction we observed a large increase in the indole precursors, tryptophan, and tryptamine. The current work explores the effects of over‐expressing the anthranilate synthase α or α and β subunits in combination with feeding with the terpenoid precursors 1‐deoxy‐D‐xylulose, loganin, and secologanin. In feeding 1‐deoxy‐D‐xylulose to the hairy root line expressing the anthranilate synthase α subunit, we observed an increase of 125% in hörhammericine levels in the induced samples, while loganin feeding increased catharanthine by 45% in the induced samples. Loganin feeding to the hairy root line expressing anthranilate synthase α and β subunits increases catharanthine by 26%, ajmalicine by 84%, lochnericine by 119%, and tabersonine by 225% in the induced samples. These results suggest that the terpenoid precursors to the terpenoid indole alkaloids are important factors in terpenoid indole alkaloid production. © 2005 Wiley Periodicals, inc.
A new approach for modelling simultaneous storage and growth processes for activated sludge systems under aerobic conditions
Authors: Sin Gürkan , Guisasola Albert , De Pauw Dirk J. W. , Baeza Juan A. , Carrera Julián , Vanrolleghem Peter A.
Published: October 2005

By critically evaluating previous models, a new mechanistic model is developed to describe simultaneous storage and growth processes occurring in activated sludge systems under aerobic conditions. Identifiability was considered an important criterion during the model development since it among others helps to increase the realiability and applicability of models to full‐scale WWTPs. A second order model was proposed for description of the degradation of the storage products under famine conditions. The model is successfully calibrated by only using OUR data obtained from batch experiments. Calibrations were performed with biomass from full‐scale WWTPs in Belgium and Spain. Predictions of the calibrated model were successfully confirmed using off‐line PHB measurements, supporting the validity of the model. An iterative experimental design procedure was successfully applied and found to remarkably improve the parameter estimation accuracy for the growth on storage parameters K1 and K2, which used to have large confidence intervals when using standard experiments. The estimated biomass growth yield on substrate (0.58 mgCOD/mgCOD) is quite close to the theoretically expected range for heterotrophic growth. This became possible by properly accounting for the storage process. Moreover, the maximum growth rate was predicted in the range 0.7–1.3 per day. This range, albeit quite lower than the values reported for the growth‐based ASM models, is believed to be more realistic. Finally, the new model is expected to better and more mechanistically describe simultaneous storage and growth activities of activated sludge systems and as such could contribute to improved design, operation and control of those systems. © 2005 Wiley Periodicals, inc.
Cloning of deoxynucleoside monophosphate kinase genes and biosynthesis of deoxynucleoside diphosphates
Authors: Bao Jie , Ryu Dewey D.Y.
Published: October 2005

The genes encoding four deoxynucleoside monophosphate kinase (dNMP kinase) enzymes, including ADK1 for deoxyadenylate monophosphate kinase (AK), GUK1 for deoxyguanylate monophosphate kinase (GK), URA6 for deoxycytidylate monophosphate kinase (CK), and CDC8 for deoxythymidylate monophosphate kinase (TK), were isolated from the genome of Saccharomyces cerevisiae ATCC 2610 strain and cloned into E. coli strain BL21(DE3). Four recombinant plasmids, pET17b‐JB1 containing ADK1, pET17b‐JB2 containing GUK1, pET17b‐JB3 containing URA6, and pET17b‐JB4 containing CDC8, were constructed and transformed into E. coli strain for over‐expression of AK, GK, CK, and TK. The amino acid sequences of these enzymes were analyzed and a putative conserved peptide sequence for the ATP active site was proposed. The four deoxynucleoside diphosphates (dNDP) including deoxyadenosine diphosphate (dADP), deoxyguanosine diphosphate (dGDP), deoxycytidine diphosphate (dCDP), and deoxythymidine diphosphate (dTDP), were synthesized from the corresponding deoxynucleoside monophosphates (dNMP) using the purified AK, GK, CK, and TK, respectively. The effects of pH and magnesium ion concentration on the dNDP biosynthesis were found to be important. A kinetic model for the synthetic reactions of dNDP was developed based on the Bi–Bi random rapid equilibrium mechanism. The kinetic parameters including the maximum reaction velocity and Michaelis–Menten constants were experimentally determined. The study on dNDP biosynthesis reported in this article are important to the proposed bioprocess for production of deoxynucleoside triphosphates (dNTP) that are used as precursors for in vitro DNA synthesis. There is a significant advantage of using enzymatic biosyntheses of dNDP as compared to the chemical method that has been in commercial use. © 2005 Wiley Periodicals, inc.
The p53 pathway and human cancer
Authors: Soussi T
Published: October 2005

What we have learned since 1989
Meta-analysis of trials comparing ximelagatran with low molecular weight heparin for prevention of venous thromboembolism after major orthopaedic surgery
Authors: Cohen A T , Hirst C , Sherrill B , Holmes P , Fidan D
Published: October 2005

Background

Use of low molecular weight heparin (LMWH) is standard practice for preventing postoperative venous thromboembolism (VTE). Ximelagatran is a new direct thrombin inhibitor for this indication.

Methods

A systematic review was conducted to compare the efficacy and safety of LMWH with ximelagatran in orthopaedic surgery.

Results

Six eligible, well conducted clinical trials (10 051 patients) were identified. Overall, the risk of VTE (OR (odds ratio) 1·22 (95 per cent confidence interval (c.i.) 0·89 to 1·67)) and serious bleeding (OR 0·70 (95 per cent c.i. 0·42 to 1·18)) was not significantly different for LMWH compared with ximelagatran. Exploratory analyses to investigate statistical heterogeneity found that results varied by surgical subtype and treatment regimen. Compared with postoperative ximelagatran, LMWH had a significantly lower rate of VTE (OR 0·68 (95 per cent c.i. 0·56 to 0·82); P < 0·001), with no significant difference in bleeding rate (OR 1·09 (95 per cent c.i. 0·62 to 1·94); P = 0·76), in hip surgery, and no significant differences in knee surgery. When ximelagatran was started immediately before surgery, LMWH had a significantly higher rate of VTE in both hip (OR 1·87 (95 per cent c.i. 1·20 to 2·92); P = 0·006) and knee (OR 1·49 (95 per cent c.i. 1·14 to 1·93); P = 0·003) surgery, but less bleeding: hip OR 0·30 (95 per cent c.i. 0·17 to 0·53; P < 0·001); knee OR 0·71 (95 per cent c.i. 0·30 to 1·67; P = 0·43).

Conclusion

This review demonstrated no overall advantage for either LMWH or ximelagatran in thromboprophylaxis following orthopaedic surgery. Benefits in VTE prevention with ximelagatran were gained at the expense of an increased risk of serious bleeding.
Parathyroid carcinoma
Authors: Rawat N , Khetan N , Williams D W , Baxter J N
Published: October 2005

Background

Parathyroid carcinoma is a rare malignancy affecting 0·5–5 per cent of all patients with primary hyperparathyroidism. This article reviews the literature on the pathogenesis, pathology, clinical features, diagnosis and management of parathyroid carcinoma.

Methods

A Medline search was performed and all relevant English language articles published between 1970 and 2005 were retrieved. The search words included ‘parathyroid carcinoma’, ‘pathology’, ‘genetics’, ‘management’ and ‘radiotherapy’. Secondary references were obtained from key articles.

Results and conclusion

The exact aetiology of parathyroid carcinoma remains obscure. Recently, the HRPT2 gene has been implicated in its pathogenesis and may prove to be a genetic target in future. Surgical resection is the accepted ‘gold standard’. There is now a growing consensus on the use of adjuvant radiotherapy as it has been shown to provide a survival benefit.