bluuebunny/crossref_metadata_2025_split huggingface dataset:
Individualized drug and dose: The clinical pharmacologist's calling or curse?
Authors: Begg EJ 
Published: December 2005

SUMMARY1. The role of the clinical pharmacologist is to promote the rational, safe and effective use of medicines. This revolves around the notion of variability, between and within patients and between and within drugs, in terms of both pharmacokinetics and pharmacodynamics. Ideal therapeutics involves tailoring the drug and its dosing to the individual patient, taking into account this variability.2. In the 25 years of my membership of the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists, three themes have dominated my research: (i) drugs and breast feeding; (ii) aminoglycoside dosing; and (iii) pharmacogenetics. In all these, the research has been orientated towards identifying factors involved in variability and working towards dose individualization based on the understanding of these factors.3. Our model for predicting drug concentrations in milk has assisted not only in estimating the safety of drug ingestion via breast milk, but also in the understanding of the processes involved in drug transfer.4. The aminoglycoside studies have assisted in the understanding of the basis behind extended interval dosing, leading to a model for dose prediction that is widely used, especially in Australasia.5. Pharmacogenetics is a field widely acclaimed as having a huge future in terms of individualization of drug therapy. Our early studies in this area lend only cautious support to this optimism.
G‐Protein‐coupled receptor–protein interactions: Basis for new concepts on receptor structure and function
Authors: Tilakaratne Nanda , Sexton Patrick M 
Published: December 2005

SUMMARY1. G‐Protein‐coupled receptors (GPCRs) constitute a large family of cell surface proteins. Their primary function is to transmit extracellular stimuli to intracellular signals. It is estimated that the human genome contains more than 1000 genes that code for proteins of the GPCR structure. These receptors also comprise the most important class of therapeutic drug targets.2. The mechanism of GPCR signalling was initially envisioned as involving coupling to the heterotrimeric G‐proteins only. However, recent developments in the field suggest that such a simplistic model cannot be sustained any longer. The emerging view is that a wide range of accessory proteins are involved in the regulation of every aspect of GPCR activity.3. G‐Protein‐coupled receptor‐interacting proteins are implicated in the regulation of several aspects of GPCR biology, including receptor targeting to the respective sites of action, receptor anchoring, signalling and receptor desensitization. In some cases (e.g. receptor activity modifying proteins), they may contribute to the receptor structure and form a part of the ligand‐binding domain.4. These findings have contributed to new concepts of cellular organization in which modular protein–protein interactions provide a network through which signalling pathways are assembled and controlled.
Why girls say ‘holded’ more than boys
Authors: Hartshorne Joshua K. , Ullman Michael T. 
Published: December 2005

Abstract Women are better than men at verbal memory tasks, such as remembering word lists. These tasks depend on declarative memory. The declarative/procedural model of language, which posits that the lexicon of stored words is part of declarative memory, while grammatical composition of complex forms depends on procedural memory, predicts a female superiority in aspects of lexical memory. Other neurocognitive models of language have not made this prediction. Here we examine the prediction in past‐tense over‐regularizations (e.g. holded) produced by children. We expected that girls would remember irregular past‐tense forms (held) better than boys, and thus would over‐regularize less. To our surprise, girls over‐regularized far more than boys. We investigated potential explanations for this sex difference. Analyses showed that in girls but not boys, over‐regularization rates correlated with measures of the number of similar‐sounding regulars (folded, molded). This sex difference in phonological neighborhood effects is taken to suggest that girls tend to produce over‐regularizations in associative lexical memory, generalizing over stored neighboring regulars, while boys are more likely to depend upon rule‐governed affixation (hold+‐ed). The finding is consistent with the hypothesis that, likely due to their superior lexical abilities, females tend to retrieve from memory complex forms (walked) that men generally compose with the grammatical system (walk+‐ed). The results suggest that sex may be an important factor in the acquisition and computation of language.
Toddler subtraction with large sets: further evidence for an analog‐magnitude representation of number
Authors: Slaughter Virginia , Kamppi Dorian , Paynter Jessica 
Published: December 2005

Abstract Two experiments were conducted to test the hypothesis that toddlers have access to an analog‐magnitude number representation that supports numerical reasoning about relatively large numbers. Three‐year‐olds were presented with subtraction problems in which initial set size and proportions subtracted were systematically varied. Two sets of cookies were presented and then covered. The experimenter visibly subtracted cookies from the hidden sets, and the children were asked to choose which of the resulting sets had more. In Experiment 1, performance was above chance when high proportions of objects (3 versus 6) were subtracted from large sets (of 9) and for the subset of older participants (older than 3 years, 5 months; n= 15), performance was also above chance when high proportions (10 versus 20) were subtracted from the very large sets (of 30). In Experiment 2, which was conducted exclusively with older 3‐year‐olds and incorporated an important methodological control, the pattern of results for the subtraction tasks was replicated. In both experiments, success on the tasks was not related to counting ability. The results of these experiments support the hypothesis that young children have access to an analog‐magnitude system for representing large approximate quantities, as performance on these subtraction tasks showed a Weber's Law signature, and was independent of conventional number knowledge.
Young children make scale errors when playing with dolls
Authors: Ware Elizabeth A. , Uttal David H. , Wetter Emily K. , DeLoache Judy S. 
Published: December 2005

Abstract Prior research (

DeLoache, Uttal & Rosengren, 2004

) has documented that 18‐ to 30‐month‐olds occasionally make scale errors: they attempt to fit their bodies into or onto miniature objects (e.g. a chair) that are far too small for them. The current study explores whether scale errors are limited to actions that directly involve the child's body. We investigated whether children would also make scale errors with a doll and objects that were much too small for the doll (e.g. a chair, a bed). Many participants did try to fit the doll into or onto the miniature objects. Thus, the previously documented phenomenon of scale errors extends to situations in which the relevant size difference is between two objects. This finding supports the view that scale errors occur when visual information about object size fails to influence the decision to act on an object. The results are discussed in terms of the use of visual information for the planning and control of actions.
How fantasy benefits young children's understanding of pretense
Authors: Sobel David M. 
Published: December 2005

AbstractSobel and Lillard (2001) demonstrated that 4‐year‐olds’ understanding of the role that the mind plays in pretending improved when children were asked questions in a fantasy context. The present study investigated whether this fantasy effect was motivated by children recognizing that fantasy contains violations of real‐world causal structure. In Experiment 1, 4‐year‐olds were shown a fantasy character engaged in ordinary actions or actions that violated causal knowledge. Children were more likely to say that a troll doll who was acting like but ignorant of the character was not pretending to be that character when read the violation story. Experiment 2 suggested that this difference was not caused by a greater interest in the violation story. Experiment 3 demonstrated a similar difference for characters engaged in social and functional violations that were possible in the real world. These data are consistent with the hypothesis that preschoolers use actions and appearance more than mental states to make judgments about pretense, but that those judgments can be influenced by the context in which the questions are presented.
Germs and angels: the role of testimony in young children's ontology
Authors: Harris Paul L. , Pasquini Elisabeth S. , Duke Suzanne , Asscher Jessica J. , Pons Francisco 
Published: December 2005

AbstractIn three experiments, children's reliance on other people's testimony as compared to their own, first‐hand experience was assessed in the domain of ontology. Children ranging from 4 to 8 years were asked to judge whether five different types of entity exist: real entities (e.g. cats, trees) whose existence is evident to everyone; scientific entities (e.g. germs, oxygen) that are normally invisible but whose existence is generally presupposed in everyday discourse; endorsed beings (e.g. the Tooth Fairy, Santa Claus) whose existence is typically endorsed in discourse with young children; equivocal beings (e.g. monsters, witches) whose existence is not typically endorsed in discourse with young children; and impossible entities (e.g. flying pigs, barking cats) that nobody believes in. Children make a broad dichotomy between entities and beings that they claim to exist (real entities; scientific entities; and endorsed beings) and those whose existence they deny (equivocal beings and impossible entities). They also make a more fine‐grained distinction among the invisible entities that they claim to exist. Thus, they assert the existence of scientific entities such as germs with more confidence than that of endorsed beings such as Santa Claus. The findings confirm that children's ontological claims extend beyond their first‐hand encounters with instances of a given category. Children readily believe in entities that they cannot see for themselves but have been told about. Their confidence in the existence of those entities appears to vary with the pattern of testimony that they receive.
Socrates in the Platonic Dialogues
Authors: Osborne Catherine 
Published: December 2005

AbstractIf Socrates is portrayed holding one view in one of Plato's dialogues and a different view in another, should we be puzzled? If (as I suggest) Plato's Socrates is neither the historical Socrates, nor a device for delivering Platonic doctrine, but a tool for the dialectical investigation of a philosophical problem, then we should expect a new Socrates, with relevant commitments, to be devised for each setting. Such a dialectical device – the tailor‐made Socrates – fits with what we know of other contributions to the genre of the Sokratikos Logos, to which Plato was neither the first nor the only contributor.
The Unity of Language and Logic in Wittgenstein's Tractatus
Authors: Cheung Leo K. C. 
Published: December 2005

AbstractThe purpose of this paper is to offer an interpretation of the Tractatus’ proof of the unity of logic and language. The kernel of the proof is the thesis that the sole logical constant is the general propositional form. I argue that the Grundgedanke, the existence of the sole fundamental operation N and the analyticity thesis, together with the fact that the operation NN can always be seen as having no specific formal difference between its result and its base, imply that NN is intrinsic to every elementary proposition. I also argue that the picture theory of proposition is an account of the generation of propositions via naming, and that its crucial idea is that naming is the instantiation of the form of a name, which consists in arbitrarily picking out an object as the meaning of the name from those objects sorted out by the form of the name. It follows that the existential quantifier, that is, NN, is intrinsic to naming (and therefore to every elementary proposition). It is then proven that the sole logical constant is the general propositional form. This, together with the truth‐functionality of logical necessity, implies that logic and language are unified via a general rule – logical syntax.
Spillovers from Foreign Firms through Worker Mobility: An Empirical Investigation*
Authors: Görg Holger , Strobl Eric 
Published: December 2005

AbstractWhile there is a large empirical literature on productivity spillovers from multinationals, this literature treats the channels through which these spillover effects work as a black box. The new approach in this paper is to investigate whether spillovers occur via worker mobility. We use data on whether or not the owner of a domestic firm has previous experience in a multinational, and relate this information to firm‐level productivity. Our results suggest that firms which are run by owners who worked for multinationals in the same industry immediately prior to opening up their own firm are more productive than other domestic firms.
Moore's Law and the Semiconductor Industry: A Vintage Model*
Authors: Aizcorbe Ana , Kortum Samuel 
Published: December 2005

AbstractIn this paper we develop a vintage model to gain a better understanding of the semiconductor industry and its role in recent U.S. productivity gains. Unlike previous work, in our model the observed price declines of individual chips are driven by the introduction of better vintages rather than by learning economies. Dominated chips, nonetheless, continue to be produced, for a time, due to sunk investments in chip‐specific production equipment. The model lends partial support to Jorgenson's hypothesis that an exogenous increase in Moore's Law could have generated the more rapid price declines, and faster productivity growth, seen after 1995.
Information Technology and the World Economy*
Authors: Jorgenson Dale W. , Vu Khuong 
Published: December 2005

AbstractThis paper addresses the impact of investment in information technology (IT) on the recent resurgence of world economic growth. We describe the growth of the world economy, seven regions and 14 major economies during the period 1989–2003. We allocate the growth of world output between input growth and productivity and find, surprisingly, that input growth greatly predominates! The contributions of IT investment have increased in all regions, but especially in industrialized economies and Developing Asia. Differences in per capita output are explained by differences in per capita input, rather than by variations in productivity.
Panel‐data Estimates of the Production Function and the Revenue Function: What Difference Does It Make?*
Authors: Mairesse Jacques , Jaumandreu Jordi 
Published: December 2005

AbstractThe lack of individual firm information on output prices is a major problem in the econometrics of production. In particular, it may be expected to account for a significant share of the large discrepancies found between the cross‐sectional and time‐series estimates of capital and scale elasticities. However, taking advantage of two panel‐data samples for which we had such information, we find that estimating the revenue function (using a nominal output measure) or the production function proper (using a real output measure) makes very little difference for our results. The biases due to other sources of specification errors are probably more important.
Anterior cingulate activity correlates with blood pressure during stress
Authors: Gianaros Peter J. , Derbtshire Stuart W.G. , May J. Christopher , Siegle Greg J. , Gamalo Mark A. , Jennings J. Richard 
Published: December 2005

AbstractThe anterior cingulate cortex presumptively regulates blood pressure reactions to behavioral stressors. There is little evidence in humans, however, that stressor‐evoked changes in blood pressure correlate with concurrent changes in anterior cingulate activity. Using fMRI, we tested whether changes in mean arterial blood pressure correlate with ongoing changes in blood oxygen level dependent (BOLD) activation in 9 women and 11 men who completed a stressful Stroop color‐word interference task. Higher mean arterial pressure during the Stroop task correlated with greater BOLD activation in two regions of the cingulate cortex (perigenual and mid‐anterior) and in other networked brain regions, including the insula, thalamus, and periaqueductal gray. These results support the hypothesis that the anterior cingulate cortex regulates blood pressure reactions to behavioral stressors in humans.
Gliotoxin non‐selectively induces apoptosis in fibrotic and normal livers
Authors: Hagens Werner I. , Olinga Peter , Meijer Dirk K. F. , Groothuis Geny M. M. , Beljaars Leonie , Poelstra Klaas 
Published: December 2005

Abstract: Background: Liver fibrosis is the common response to chronic liver injury, ultimately leading to cirrhosis. Several lines of evidence indicate that inducing apoptosis of hepatic stellate cells (HSC) may lead to regression of liver fibrosis. Recently, it was shown that gliotoxin (GTX) induces apoptosis of HSC. However, the clinical use of GTX may be limited because of the lack of cell and tissue specificity, causing a high risk of potentially severe adverse effects. The aim of this study, therefore, was to study the effect of GTX on different cells of the liver.Methods: We used normal and fibrotic precision‐cut rat liver slices to study the effect of GTX on the various resident liver cell types. In these slices, the complex cell–cell interactions are preserved, which closely mimics the in vivo situation.Results: GTX exhibited a potent apoptosis‐inducing activity in these slices. Both immunohistochemical stainings and real‐time mRNA techniques showed that this apoptosis‐inducing effect was seen in HSC. However, Kupffer cells and liver endothelial cells were also affected by GTX, whereas hepatocytes were only mildly affected.Conclusions: This study indicates that the apoptosis‐inducing strategy to treat liver fibrosis has high potential, but it will be necessary to develop an HSC‐specific therapy to prevent adverse effects.
Myotilin is not the Causative Gene for Vocal Cord and Pharyngeal Weakness with Distal Myopathy (VCPDM)
Authors: Garvey Sean M. , Senderek Jan , Beckmann Jacques S. , Seboun Eric , Jackson Charles E. , Hauser Michael A. 
Published: December 2005

SummaryMyotilin (MYOT) is a promising candidate gene for Vocal Cord and Pharyngeal Weakness with Distal Myopathy (VCPDM, also known as MPD2). Located within the minimum VCPDM candidate interval, myotilin mutations also cause a similarly progressive and adult‐onset muscle disease. We examined myotilin in VCPDM patients by sequence analysis, RT‐PCR, Southern blotting, and western blotting. We detected no defects in the myotilin gene, transcript, or protein in VCPDM. We also report several useful SNPs and STRs for the analysis of myotilin in muscle diseases of suspected, yet unknown genetic origin. We conclude that MYOT mutations likely are not a cause of VCPDM.
The composition of polyunsaturated fatty acids in erythrocytes of lactating mothers and their infants
Authors: Jørgensen Marianne Hørby , Nielsen Pernille Kjær , Michaelsen Kim Fleischer , Lund Pia , Lauritzen Lotte 
Published: December 2005

AbstractLong‐chain polyunsaturated fatty acids (LCPUFA) in breastmilk, specifically docosahexaenoic acid (DHA), are important for infant brain development. Accretion of DHA in the infant brain is dependent on DHA‐status, intake and metabolism. The aim of this study was to describe changes in maternal and infant erythrocyte (RBC) DHA‐status during the first four months of lactation. We examined 17 mothers and their term infants at 1, 2 and 4 months of age. Milk samples and RBC from the mothers and infants were obtained and analysed for fatty acid composition. Comparative analysis of the results showed that the content of DHA in maternal RBC‐phosphatidylcholine (PE) decreased over the four month period and this was not accompanied by a decrease in DHA in infant RBC‐PE (P = 0.005). The ratio of n‐6 PUFA to n‐3 PUFA increased over time in maternal RBC‐PE, but not in infant RBC‐PE (P < 0.001). The level of 22:5n‐6 and the ratio of LCPUFA to precursor PUFAs in infant RBC was higher than in maternal RBC phospholipids. (P = and P < 0.001 respectively). We found a decrease in the level of LCPUFA in milk, specifically AA. However, we did not observe a significant decrease in milk DHA, which may have been due to two outliers. These results indicate better DHA‐status and a higher n‐3/n‐6 PUFA in RBC of infants than in mothers. Whether these differences reflect preferential n‐3 PUFA transfer via breastmilk or differences in PUFA‐metabolism and utilization remains to be shown.
Segmental ulcerative vasculitis: a cutaneous manifestation of Takayasu's arteritis
Authors: Dourmishev Assen L , Serafimova Dimitrina K , Vassileva Snejina G , Dourmishev Lyubomir A , Schwartz Robert A 
Published: December 2005

AbstractA 16‐year‐old girl with pyoderma gangrenosum (PG)‐like skin lesions on the extremities, trunk and face developed Takayasu's arteritis (TA; pulseless disease). After 3 years under maintenance cyclosporin A therapy, the patient developed an ischaemic cerebral accident. Severe obstruction of both subclavian and left carotid arteries was found by Doppler sonography, angiography and computerised axial tomography. Evolution of this disease showed some characteristic findings: (a) PG‐like lesions as the first cutaneous manifestation of pulseless disease; (b) methotrexate and cyclosporin A giving good results for the cutaneous lesions, but apparently not exerting an influence on the evolution of TA and the fatal outcome. This morphologic pattern may reflect underlying TA or Wegener's arteritis, and should be termed segmental ulcerative vasculitis.
High glucose inhibits human epidermal keratinocyte proliferation for cellular studies on diabetes mellitus
Authors: Terashi Hiroto , Izumi Kenji , Deveci Mustafa , Rhodes Lenore M , Marcelo Cynthia L 
Published: December 2005

AbstractIn order to more clarify the delayed wound healing in diabetes mellitus, we cultured the human epidermal keratinocytes in both 6 mM (control group) and 12 mM glucose (high‐glucose group) of ‘complete’ MCDB 153 medium. Hyperglycaemia slowed the rate of their proliferation and inhibited their DNA synthesis and the production of total proteins. By 1 month after primary seeding in high‐glucose group, the cells ceased their proliferation, whereas the cells in control group grew for more than 40 days. Mean population doublings in high‐glucose group was 5·27 (vs. 7·25 in control, P = 0·001), and mean population doubling time during 1 month in high glucose group was 5·43 days (vs. 3·65 days in control, P = 0·02). They indicate that prolonged exposure to high glucose decreases the replicative life span of human epidermal keratinocytes in vitro. Furthermore, analysis of fatty acid contents in membrane phospholipids with thin‐layer and gas chromatography showed no difference between the cultured keratinocytes in both conditions. Immunocytochemical staining of glucose transporter 1 shows that 28·1% of cells in high‐glucose group were almost twice positive of those in control group (13·2%, P = 0·008). The mechanism of the ill effects of high glucose on epidermal keratinocytes is not so far clear, but it indicates the possibility of any direct effect of hyperglycaemia on glucose metabolism without changing lipid metabolism on cell membrane. The high‐glucose group presented in this report can be available as an in vitro valuable study model of skin epidermal condition on diabetes mellitus.