bluuebunny/crossref_metadata_2025_split huggingface dataset:
Software that assists learning within a complex abstract domain: the use of constraint and consequentiality as learning mechanisms
Authors: Aczel James , Fung Pat , Bornat Richard , Oliver Martin , O'Shea Tim , Sufrin Bernard 
Published: November 2003

AbstractThis paper describes a research project into undergraduates’ use of a software tool to learn symbolic logic—a complex abstract domain that has been shown to be intimidating for students. The software allows the students to manipulate proofs in certain ways and then calculates the consequences of their actions. A research method has been developed that allowed students’ use of this tool to be modelled, and this model was then used to identify, refine and create visual cues that provide support for students’ reasoning. The focus of this paper is the role of the software as an artefact to aid students’ visualisation of reasoning processes rather than the logic itself. The main mechanisms by which this visualisation is supported are the imposition of constraints on the actions available and the demonstration to students of the consequences of their actions. The study shows that the software encouraged experimentation with different routes to a proof, and constituted a challenge to fixated reasoning.
The development, design and delivery of a retail simulation
Authors: Stubbs Mark , Pal John 
Published: November 2003

Abstract theRetailGame.com is a web‐based package of e‐learning materials designed to support students on retailing courses. It uses the focal point of a ‘store opening’ to draw attention to key operational variables. The web‐based package allows students to explore the impacts of variable combinations in a risk‐free environment. This paper outlines the rationale for developing this new package; explains the design principles underlying its construction; and describes the delivery and assessment mechanisms in which it has been embedded. The case history of the project is reviewed, and actor‐network theory is used to characterise the alignment of requisite time and expertise as a feat of engineering, facilitated by top‐down support but dependent upon the creative manoeuvrings of the bottom‐up enthusiast.
Population structure of the Southeast Asian river catfish Mystus nemurus
Authors: Usmani S. , Tan S. G. , Siraj S. S. , Yusoff K. 
Published: November 2003

SummaryA total of 143 microsatellites were isolated from Mystus nemurus using a 5′ anchored polymerase chain reaction technique or the random amplified hybridization microsatellite method, the first set of microsatellite markers developed for the Southeast Asian river catfish. Twenty polymorphic microsatellite loci were used as markers for population characterization of M. nemurus from six different geographical locations in Malaysia (Perak, Kedah, Johor, UPM, Sarawak and Terengganu). The number of alleles per locus ranged from 2 to 11 with 6.3 as the average number of alleles per locus. Characterization of the populations showed relatively high levels of genetic variation compared with previous studies using allozyme markers. The highest genetic similarity was found between Perak and Kedah, while the highest genetic distance was found between Terengganu and Kedah. The majority of clustering was in accordance with geographical locations and the histories of the populations. Microsatellite analysis indicated that the Sarawak population might be genetically closer to the Peninsular Malaysian populations than has been previously shown by other molecular marker studies.
Stop codon recognition and interactions with peptide release factor RF3 of truncated and chimeric RF1 and RF2 from Escherichia coli
Authors: Mora Liliana , Zavialov Andrei , Ehrenberg Måns , Buckingham Richard H. 
Published: November 2003

SummaryRelease factors RF1 and RF2 recognize stop codons present at the A‐site of the ribosome and activate hydrolysis of peptidyl‐tRNA to release the peptide chain. Interactions with RF3, a ribosome‐dependent GTPase, then initiate a series of reactions that accelerate the dissociation of RF1 or RF2 and their recycling between ribosomes. Two regions of Escherichia coli RF1 and RF2 were identified previously as involved in stop codon recognition and peptidyl‐tRNA hydrolysis. We show here that removing the N‐terminal domain of RF1 or RF2 or exchanging this domain between the two factors does not affect RF specificity but has different effects on the activity of RF1 and RF2: truncated RF1 remains highly active and able to support rapid cell growth, whereas cells with truncated RF2 grow only poorly. Transplanting a loop of 13 amino acid residues from RF2 to RF1 switches the stop codon specificity. The interaction of the truncated factors with RF3 on the ribosome is defective: they fail to stimulate guanine nucleotide exchange on RF3, recycling is not stimulated by RF3, and nucleotide‐free RF3 fails to stabilize the binding of RF1 or RF2 to the ribosome. However, the N‐terminal domain seems not to be required for the expulsion of RF1 or RF2 by RF3:GTP.
The distribution of RNA polymerase in Escherichia coli is dynamic and sensitive to environmental cues
Authors: Cabrera Julio E. , Jin Ding J. 
Published: November 2003

SummaryDespite extensive genetic, biochemical and structural studies on Escherichia coli RNA polymerase (RNAP), little is known about its location and distribution in response to environmental changes. To visualize the RNAP by fluorescence microscopy in E. coli under different physiological conditions, we constructed a functional rpoC–gfp gene fusion on the chromosome. We show that, although RNAP is located in the nucleoid and at its periphery, the distribution of RNAP is dynamic and dramatically influenced by cell growth conditions, nutrient starvation and overall transcription activity inside the cell. Moreover, mutational analysis suggests that the stable RNA synthesis plays an important role in nucleoid condensation.
An Arabidopsis thaliana gene for methylsalicylate biosynthesis, identified by a biochemical genomics approach, has a role in defense
Authors: Chen Feng , D'Auria John C. , Tholl Dorothea , Ross Jeannine R. , Gershenzon Jonathan , Noel Joseph P. , Pichersky Eran 
Published: November 2003

SummaryEmission of methylsalicylate (MeSA), and occasionally of methylbenzoate (MeBA), from Arabidopsis thaliana leaves was detected following the application of some forms of both biotic and abiotic stresses to the plant. Maximal emission of MeSA was observed following alamethicin treatment of leaves. A gene (AtBSMT1) encoding a protein with both benzoic acid (BA) and salicylic acid (SA) carboxyl methyltransferase activities was identified using a biochemical genomics approach. Its ortholog (AlBSMT1) in A. lyrata, a close relative of A. thaliana, was also isolated. The AtBSMT1 protein utilizes SA more efficiently than BA, whereas AlBSMT1 catalyzes the methylation of SA less effectively than that of BA. The AtBSMT1 and AlBSMT1 genes showed expression in leaves under normal growth conditions and were more highly expressed in the flowers. In A. thaliana leaves, the expression of AtBSMT1 was induced by alamethicin, Plutella xylostella herbivory, uprooting, physical wounding, and methyl jasmonate. SA was not an effective inducer. Using a β‐glucuronidase (GUS) reporter approach, the promoter activity of AtBSMT1 was localized to the sepals of flowers, and also to leaf trichomes and hydathodes. Upon thrip damage to leaves, AtBSMT1 promoter activity was induced specifically around the lesions.
FIRST YEAR OF PRACTICE VISITS FOR THE RURAL DEPRESSION ANXIETY RESEARCH AND TREATMENT GENERAL PRACTICE PROGRAM
Authors: Judd Fiona , Cockram Alex , Davis Julian , Fahey Anne , Hodgins Gene , Jackson Henry , Scopelliti Joe 
Published: November 2003

ABSTRACTObjective: To describe the first 12 months activities of a key component of a General Practice Psychiatry program– the GP practice visit.Design: Questionnaire to evaluate effects on participating general practitioners practice.Setting: Rural group general practices.Subjects: Thirty‐two general practitioners in the Loddon Campaspe Southern Mallee region in Victoria.Interventions: Practice visits involved a combination of each of three key activities: primary consultation, secondary consultation and/or case discussion and formal teaching.Results: General practitioners reported a variety of changes in their practice as a result of the visits.Conclusion: Practice visits appear to be a useful means of influencing GP's practice. Further work is required to determine whether such changes are accompanied by demonstrable benefits in patient outcome.
What Use is a Policy Cycle? Plenty, if the Aim is Clear
Authors: Bridgman Peter , Davis Glyn 
Published: November 2003

What use is a policy cycle? Plenty, if the aim is to help public servants make sense of the policy task. Setting out a sequence of steps to turn ideas into Cabinet recommendations can provide structure in the otherwise dizzying world of policy‐making. It would be a mistake, though, to see a policy cycle as other than a first step, a guide amid complexity. To read the policy cycle as rationalism revived is to misjudge both form and intent.Debate is a wonderful thing, and we are pleased the policy cycle described in The Australian Policy Handbook (Bridgman and Davis 2000) has stimulated a response. Although we believe a critique in the June issue of the Australian Journal of Public Administration (Everett 2003) is misguided, it invites reflection on the purpose ‐ and limitations ‐ of a policy cycle approach.
Automatic design of gene-specific sequence tags for genome-wide functional studies
Authors: Thareau Vincent , Déhais Patrice , Serizet Carine , Hilson Pierre , Rouzé Pierre , Aubourg Sébastien 
Published: November 2003

Abstract
Motivation: The availability of complete genome sequences allows the identification of short DNA segments that are specific to each annotated gene. Such unique gene sequence tags (GSTs) replace advantageously cDNAs in microarray transcript profiling experiments. In particular, probes corresponding to individual members of multigene families can be chosen carefully to avoid cross-hybridization events.
Results: The Specific Primer and Amplicon Design Software (SPADS) was constructed to delineate the more divergent regions in each gene by comparing them with a completely annotated genome sequence and to select optimal primer pairs for the polymerase chain reaction amplification of one divergent region per gene. SPADS is a unique integrated tool to design specific GSTs from any public or private genome sequences and allows the user to fine-tune GST size and specificity. SPADS has been used to obtain probes for whole genome and family-wide transcript profiling, as well as inserts for gene-specific knock-out experiments.
Availability: The GENOPLANTE™ SPADS source code and web interface are available upon request. The online version is accessible via http://genoplante-info.infobiogen.fr/spads and via http://oberon.fvms.ugent.be:8080/SPADS/
Linking the growth inhibition response from the National Cancer Institute's anticancer screen to gene expression levels and other molecular target data
Authors: Wallqvist Anders , Rabow Alfred A. , Shoemaker Robert H. , Sausville Edward A. , Covell David G. 
Published: November 2003

Abstract
Motivation: Data mining tools are proposed to establish mechanistic connections between chemotypes and specific cellular functions. Drawing on a previous study that classified the cellular response patterns of growth inhibition measurements log( GI50) from the National Cancer Institute's (NCI's) anticancer screen, we have examined additional data for mRNA expression, sets of known molecular targets and mutational status against these same tumor cell lines to relate chemosensitivity more precisely to biochemical pathways.
Results: Our analysis finds that gene expression levels do not, in general, correlate with log(GI50) measurements, instead they reflect a generic toxic condition. Within the remaining set of non-generic conditions, examples were found where a correlation suggesting a biochemical basis for cellular cytotoxicity could be supported. These included reconfirmation of previously observed associations between mutant and wild-type status of p53, and chemosensitivity to alkylating agents, while extending these results to reveal associations with γ-induced expressions of MDM2, WAF1 and GADD45, signals that were not apparent in measurements of basal mRNA expression levels for any of these genes. Additional examinations revealed that mRNA expression levels directly correlated with paclitaxel chemosensitivity to mitosis, while also identifying additional chemotypes as P-glycoprotein substrates. Our analysis revealed well-known direct associations between p16 mutant status and chemotypes implicated in cell cycle control, and extended these results to include expression levels for three additional tyrosine kinase proteins (TEK, transgelin and hCdc4). Links were also found that suggested associations between chemosensitivity and the endocrine, paracrine ligand–receptor loops, via expression of the adrenergic receptor, calcium second messenger pathways via expression levels of carbonic anhydrase and cellular communication pathways via fibrillin.
BLAST++: BLASTing queries in batches
Authors: Wang Hao , Ooi Beng Chin , Tan Kian-Lee , Ong Twee-Hee , Zhou Lei 
Published: November 2003

Abstract
Summary: BLAST++ is a tool that is integrated with NCBI BLAST, allowing multiple, say K, queries to be searched against a database concurrently. The results obtained by BLAST++ are identical to that obtained by executing BLAST on each of the K queries, but BLAST++ completes the processing in a much shorter time.
Availability: http://xena1.ddns.comp.nus.edu.sg/~genesis/blast++
Supplementary information: http://xena1.ddns.comp.nus.edu.sg/~genesis/blast++
Reliability and Validity of a Simulation-based Acute Care Skills Assessment for Medical Students and Residents
Authors: Boulet John R. , Murray David , Kras Joe , Woodhouse Julie , McAllister John , Ziv Amitai 
Published: November 2003

Background
Medical students and residents are expected to be able to manage a variety of critical events after training, but many of these individuals have limited clinical experiences in the diagnosis and treatment of these conditions. Life-sized mannequins that model critical events can be used to evaluate the skills required to manage and treat acute medical conditions. The purpose of this study was to develop and test simulation exercises and associated scoring methods that could be used to evaluate the acute care skills of final-year medical students and first-year residents.

Methods
The authors developed and tested 10 simulated acute care situations that clinical faculty at a major medical school expects graduating physicians to be able to recognize and treat at the conclusion of training. Forty medical students and residents participated in the evaluation of the exercises. Four faculty members scored the students/residents.

Results
The reliability of the simulation scores was moderate and was most strongly influenced by the choice and number of simulated encounters. The validity of the simulation scores was supported through comparisons of students'/residents' performances in relation to their clinical backgrounds and experience.

Conclusion
Acute care skills can be validly and reliably measured using a simulation technology. However, multiple simulated encounters, covering a broad domain, are needed to effectively and accurately estimate student/resident abilities in acute care settings.
Tissue Factor and Platelet Glycoprotein Ib-α Alleles Are Associated with Age at First Coronary Bypass Operation
Authors: Donahue Brian S. , Byrne Daniel W. , Gailani David , George Alfred L. 
Published: November 2003

Background
Age is a known risk factor for postoperative complications, but the genetic factors that account for variability in age at presentation for surgery have not been characterized. Because thrombosis is a critical process in the development of coronary syndromes, the authors hypothesized that patients bearing the -1208 insertion allele of tissue factor (TF) and longer glycoprotein Ib-alpha (GpIbalpha) variants may come to surgical attention sooner and undergo coronary artery bypass grafting (CABG) at a younger age. The authors tested this hypothesis in a cardiac surgery population.

Methods
The impact of the number of TF -1208 insertion alleles and the number of GpIbalpha repeats on age at first CABG were tested in 424 elective coronary bypass patients. Multivariate regression included traditional risk factors of sex, hypertension, diabetes, hyperlipidemia, and smoking. The authors also tested the hypothesis that these alleles are correlated with age at first noncoronary cardiac surgery in a group of 143 patients undergoing noncoronary cardiac operations.

Result
Both the number of TF -1208 insertion alleles and total number of GpIbalpha repeats were associated with younger age at first CABG in a univariate analysis. In multivariate regression in which traditional risk factors were included, the number of TF -1208 insertion alleles and the total number of GpIbalpha repeats were independent contributors toward age at first CABG. Neither polymorphism had a significant impact on age at first noncoronary cardiac surgery.

Conclusions
Genetic variants in TF and GpIbalpha are associated with younger age at first CABG, indicating that the younger and older first-time CABG populations are different on the genetic level. How these genetic differences may account for age-associated differences in perioperative risk will be the subject of future investigations.
Acid-induced Lung Injury
Authors: Madjdpour Lilly , Kneller Sita , Booy Christa , Pasch Thomas , Schimmer Ralph C. , Beck-Schimmer Beatrice 
Published: November 2003

Background
Aspiration of acidic gastric contents leads to acute lung injury and is still one of the most common clinical events associated with acute lung injury. This study was performed to assess acid-induced lung inflammation in vitro and in vivo with respect to the time pattern of activated transcription factor nuclear factor-kappaB (NF-kappaB) and proinflammatory molecules.

Methods
L2 cells (alveolar epithelial cells) were exposed for various periods to a medium with a pH of 6. In the in vivo model, 1 ml/kg of 0.1 n acidic solution was instilled into the lungs of rats. NF-kappaB binding activity and expression pattern of inflammatory mediators were determined. Blocking studies were performed with the NF-kappaB inhibitor pyrrolidine dithiocarbamate.

Results
In vitro NF-kappaB binding activity showed a biphasic expression pattern with a first peak at 1 h and a second one at 6-8 h. In acid-injured rat lungs, NF-kappaB binding activity was confirmed in a biphasic manner with a first increase at 0.5-2 h (608 +/- 93% and 500 +/- 15%, respectively, P < 0.05) and a second peak at 8 h (697 +/- 35% increase, P < 0.005). Whole lung mRNA for macrophage inflammatory protein-1beta and macrophage inflammatory protein-2 showed a similar expression pattern, which could explain the biphasic neutrophil recruitment. Intratracheal pyrrolidine dithiocarbamate attenuated lung injury as evidenced by a reduction of neutrophil accumulation and expression of inflammatory mediators.

Conclusions
These data suggest that NF-kappaB binding activity plays a key role in molecular and cellular events in acid-induced lung injury.
Development of Neuropathic Pain in the Rat Spared Nerve Injury Model Is Not Prevented by a Peripheral Nerve Block
Authors: Suter Marc R. , Papaloïzos Michael , Berde Charles B. , Woolf Clifford J. , Gilliard Nicolas , Spahn Donat R. , Decosterd Isabelle 
Published: November 2003

Background
The mechanisms responsible for initiation of persistent neuropathic pain after peripheral nerve injury are unclear. One hypothesis is that injury discharge and early ectopic discharges in injured nerves produce activity-dependent irreversible changes in the central nervous system. The aim of this study was to determine whether blockade of peripheral discharge by blocking nerve conduction before and 1 week after nerve injury could prevent the development and persistence of neuropathic pain-like behavior in the spared nerve injury model.

Methods
Bupivacaine-loaded biodegradable microspheres embedded in fibrin glue were placed in a silicone tube around the sciatic nerve to produce a conduction block. After sensory-motor testing of block efficacy, a spared nerve injury procedure was performed. Development of neuropathic pain behavior was assessed for 4 weeks by withdrawal responses to stimulation (i.e., von Frey filaments, acetone, pinprick, radiant heat) in bupivacaine microspheres-treated animals (n = 12) and in controls (n = 11).

Results
Bupivacaine microspheres treatment produced conduction blockade with a complete lack of sensory responsiveness in the sural territory for 6 to 10 days. Once the block wore off, the degree of hypersensitivity to stimuli was similar in both groups.

Conclusions
Peripheral long-term nerve blockade has no detectable effect on the development of allodynia or hyperalgesia in the spared nerve injury model. It is unlikely that injury discharge at the time of nerve damage or the early onset of ectopic discharges arising from the injury site contributes significantly to the persistence of stimulus-evoked neuropathic pain in this model.
Antinociceptive Effect of Morphine, but not μ Opioid Receptor Number, Is Attenuated in the Spinal Cord of Diabetic Rats
Authors: Chen Shao-Rui , Pan Hui-Lin 
Published: November 2003

Background
The mechanisms of decreased analgesic potency of mu opioids in diabetic neuropathic pain are not fully known. The authors recently found that G protein activation stimulated by the mu opioid agonist is significantly reduced in the spinal cord dorsal horn in diabetes. In the current study, they determined potential changes in the number and binding affinity of mu opioid receptors in the spinal cord in diabetic rats.

Methods
Rats were rendered diabetic with an intraperitoneal injection of streptozotocin. The nociceptive withdrawal threshold was measured before and after intrathecal injection of morphine by applying a noxious pressure stimulus to the hind paw. The mu opioid receptor was determined with immunocytochemistry labeling and a specific mu opioid receptor radioligand, [3H]-(D-Ala2,N-Me-Phe4,Gly-ol5)-enkephalin ([3H]-DAMGO), in the dorsal spinal cord obtained from age-matched normal and diabetic rats 4 weeks after streptozotocin treatment.

Results
The antinociceptive effect of intrathecal morphine (2-10 microg) was significantly reduced in diabetic rats, with an ED50 about twofold higher than that in normal rats. However, both the dissociation constant (3.99 +/- 0.22 vs. 4.01 +/- 0.23 nm) and the maximal specific binding (352.78 +/- 37.26 vs. 346.88 +/- 35.23 fmol/mg protein) of [3H]-DAMGO spinal membrane bindings were not significantly different between normal and diabetic rats. The mu opioid receptor immunoreactivity in the spinal cord dorsal horn also was similar in normal and diabetic rats.

Conclusions
The reduced analgesic effect of intrathecal morphine in diabetes is probably due to impairment of mu opioid receptor-G protein coupling rather than reduction in mu opioid receptor number in the spinal cord dorsal horn.