bluuebunny/crossref_metadata_2025 huggingface dataset:
Geno3D: automatic comparative molecular modelling of protein
Authors: Combet Christophe , Jambon Martin , Deléage Gilbert , Geourjon Christophe
Published: July 2002

Geno3D (http://geno3d-pbil.ibcp.fr) is an automatic web server for protein molecular modelling. Starting with a query protein sequence, the server performs the homology modelling in six successive steps: (i) identify homologous proteins with known 3D structures by using PSI-BLAST; (ii) provide the user all potential templates through a very convenient user interface for target selection; (iii) perform the alignment of both query and subject sequences; (iv) extract geometrical restraints (dihedral angles and distances) for corresponding atoms between the query and the template; (v) perform the 3D construction of the protein by using a distance geometry approach and (vi) finally send the results by e-mail to the user.

Availability: Free to academic users http://geno3d-pbil.ibcp.fr

Contact: c.geourjon@ibcp.fr

* To whom correspondence should be addressed.
Caenorhabditis elegans has a single pathway to target matrix proteins to peroxisomes
Authors: Motley Alison M , Hettema Ewald H , Ketting Rene , Plasterk Ronald , Tabak Henk F
Published: July 2002

All eukaryotes so far studied, including animals, plants, yeasts and trypanosomes, have two pathways to target proteins to peroxisomes. These two pathways are specific for the two types of peroxisome targeting signal (PTS) present on peroxisomal matrix proteins. Remarkably, the complete genome sequence of Caenorhabditis elegans lacks the genes encoding proteins specific for the PTS2 targeting pathway. Here we show, by expression of green fluorescent protein (GFP) reporters for both pathways, that the PTS2 pathway is indeed absent in C. elegans. Lack of this pathway in man causes severe disease due to mislocalization of PTS2‐containing proteins. This raises the question as to how C. elegans has accommodated the absence of the PTS2 pathway. We found by in silico analysis that C. elegans orthologues of PTS2‐containing proteins have acquired a PTS1. We propose that switching of targeting signals has allowed the PTS2 pathway to be lost in the phylogenetic lineage leading to C. elegans.
RNA degradation buffers asymmetries of transcription in Arabidopsis mitochondria
Authors: Giegé Philippe , Hoffmann Michaela , Binder Stefan , Brennicke Axel
Published: July 2002

To understand better the relative contributions of transcriptional and post‐transcriptional processes towards the regulation of gene expression in plant mitochondria, we compared the steady state levels of RNAs with the respective transcriptional activities. All of the protein and rRNA coding genes of the Arabidopsis mitochondrial genome and several orfs were analyzed by run‐on and northern experiments. rRNAs constitute the bulk of the steady state RNA in Arabidopsis mitochondria, but are (different from maize mitochondria) not equally prominent among the run‐on transcripts. Their relatively low rate of active transcription is apparently compensated by their high stability. Run‐on transcription values differ significantly between genes coding for different subunits of the same protein complex. The steady state RNA levels are considerably more homogeneous, indicating that high variations of transcription rates are counterbalanced by post‐transcriptional processes. The relative amounts of the steady state transcripts for the different subunits in a given protein complex reflect the relative stoichiometries of the protein subunits much more closely than the respective transcriptional activities. Post‐transcriptional RNA processing and stability thus contribute significantly to the regulation of gene expression in Arabidopsis mitochondria.
Rapid caspase‐3 activation during apoptosis revealed using fluorescence‐resonance energy transfer
Authors: Tyas Lorraine , Brophy Victoria A , Pope Andrew , Rivett A Jennifer , Tavaré Jeremy M
Published: July 2002

Caspase‐3 is a crucial component of the apoptotic machinery in many cell types. Here, we report the timescale of caspase‐3 activation in single living cells undergoing apoptosis. This was achieved by measuring the extent of fluorescence resonance energy transfer within a recombinant substrate containing cyan fluorescent protein (CFP) linked by a short peptide possessing the caspase‐3 cleavage sequence, DEVD, to yellow fluorescent protein (YFP; i.e. CFP–DEVD–YFP). We demonstrate that, once initiated, the activation of caspase‐3 is a very rapid process, taking 5 min or less to reach completion. Furthermore, this process occurs almost simultaneously with a depolarization of the mitochondrial membrane potential. These events occur just prior to the characteristic morphological changes associated with apoptosis. Our results clearly demonstrate that, once initiated, the commitment of cells to apoptosis is a remarkably rapid event when visualized at the single cell level.
Flexibility in the “Age of Fordism”: Technology and Production in the
International Automobile Industry
Authors: Zeitlin Jonathan
Published: July 2002

Is manufacturing flexibility a purely contemporary phenomenon, an
outgrowth of computer-controlled technologies, volatile markets, and
sophisticated consumers that did not exist in a previous age of Fordist mass
production? Or did mass manufacturers in earlier periods face comparable
problems of combining high productivity, low costs, rapid product
innovation, and frequent adjustments to shifting demand? And if so, what
technological and organizational solutions did they develop in response? Did
the flexible manufacturing practices made famous by Japanese firms in the
1970s and 1980s such as just-in-time logistics, collaborative supplier
relations, joint product development, quick tooling changes, and mixed-model
assembly represent a sharp break with the canonical principles of Western
mass production? Or were these innovations anticipated—and even to some
extent inspired—by earlier experiments with manufacturing flexibility
pioneered by American and European firms during the heyday of mass
production itself ? Focusing on the archetypal mass production industry at
the height of the Fordist era between the 1920s and the 1970s, the papers in
this special issue of Enterprise & Society
offer new and surprising answers to these questions.
Innovative Enterprise and Historical Transformation
Authors: Lazonick William
Published: July 2002

The social conditions that affect innovation change over time and vary across productive activities. Hence theoretical analysis of the innovative enterprise must be integrated with historical study through the use of what I call ahistorical-transformation methodology—a methodology that stands in sharp contrast to, but can nonetheless be complemented by, the constrained-optimization methodology favored by conventional economists. In surveying some major attempts to analyze the role of the business enterprise in generating superior economic performance in the advanced economies, including the works of Oliver Williamson, Alfred Chandler, Edith Penrose, and resource-based theorists, I explain what a historical-transformation methodology is and why such a methodology is needed for understanding how and under what conditions business enterprises can in fact be innovative enterprises.
The Sino-Japanese War and the Formation of the State Enterprise System in China: A Case Study of the Dadukou Iron and Steel Works, 1938–1945
Authors: Bian Morris L.
Published: July 2002

This article examines the formation of China's state enterprise system, using the case of the Dadukou Iron and Steel Works (DISW). I argue that the basic institutional arrangement of the DISW, and by extension other state-owned enterprises, consisted of a bureaucratic governance structure, distinctive management and incentive mechanisms, and the provision of social services and welfare. This arrangement took shape during the Sino-Japanese War, with the sustained systemic crisis and the nature and character of the institutional endowments leading to the formation of China's state enterprise system. In considering implications for understanding institutional change, I suggest that crisis shapes radical institutional change and that both path dependence and path independence characterize such change.
Bactericidal properties of moxifloxacin and post-antibiotic effect
Authors: Boswell F. J. , Andrews J. M. , Wise R. , Dalhoff A.
Published: July 2002

The time–kill kinetics and post-antibiotic effect (PAE) of moxifloxacin were studied for strains of Streptococcus pneumoniae,Streptococcus pyogenes,Haemophilus influenzae,Staphylococcus aureus and Escherichia coli. Moxifloxacin had a bactericidal effect against all strains tested, with the least rapid bactericidal effect being against S. pyogenes and the most rapid effect against S. aureus and E. coli. The PAE of moxifloxacin was similar to that of other fluoroquinolones and increased with increasing concentration. No association was found between the bactericidal effect of moxifloxacin and the duration of PAE. Gram-positive and Gram-negative organisms were also exposed to concentrations of moxifloxacin, sparfloxacin and amoxycillin that simulated the drug concentrations obtained in human serum after standard oral dosing schedules. Simulation of moxifloxacin concentrations in human serum reduced viable counts more effectively and more rapidly than shown in time–kill experiments; in contrast, sparfloxacin and amoxycillin were less effective than when constant concentrations of these antibacterials were used.
A Seemingly Unrelated Regression Model for Analyzing Multiparty Elections
Authors: Jackson John E.
Published: July 2002

This paper develops an estimator for models of election returns in multiparty elections. It shares the same functional formas the Katz—King estimator but is computationally simpler, can be used with any number of parties, and is based on more conventional distributional assumptions. Small sample properties of the estimator are derived, which makes it particularly useful in many of the applications where there are a relatively small number of voting districts. The distributional assumptions are contained in two elements. The first treats the observed votes as the outcomes resulting from sampling the voters in each district. The second stochastic element arises from the usual treatment of the stochastic term in a regression model, namely, the inability of the included variables and the linear form to match the underlying process perfectly. The model is then used to analyze the 1993 Polish parliamentary elections. The results from this analysis are used to develop Monte Carlo experiments comparing several different yet feasible estimators. The conclusion is that a number of accessible estimators, including the standard seemingly unrelated regression model and the Beck-Katz model with panel-corrected standard errors, are all good choices.
Na+/H+ exchanger‐dependent intracellular alkalinization is an early event in malignant transformation and plays an essential role in the development of subsequent transformation‐associated phenotypes
Authors: Reshkin Stephan J. , Bellizzi Antonia , Caldeira Sandra , Albarani Valentina , Malanchi Ilaria , Poignee Manuela , Alunni‐Fabbroni Marianna , Casavola Valeria , Tommasino Massimo
Published: July 2002

In this study we investigate the mechanism of intracellular pH change and its role in malignant transformation using the E7 oncogene of human papillomavirus type 16 (HPV16). Infecting NIH3T3 cells with recombinant retroviruses expressing the HPV16 E7 or a transformation deficient mutant we show that alkalinization is transformation specific. In NIH3T3 cells in which transformation can be turned on and followed by induction of the HPV16 E7 oncogene expression, we demonstrate that cytoplasmic alkalinization is an early event and was driven by stimulation of Na+/H+ exchanger activity via an increase in the affinity of the intracellular NHE‐1 proton regulatory site. Annulment of the E7‐induced cytoplasmic alkalinization by specific inhibition of the NHE‐1, acidification of culture medium, or clamping the pHi to nontransformed levels prevented the development of later transformed phenotypes such as increased growth rate, serum‐independent growth, anchorage‐independent growth, and glycolytic metabolism. These findings were verified in human keratinocytes (HPKIA), the natural host of HPV. Results from both NIH3T3 and HPKIA cells show that alkalinization acts on pathways that are independent of the E2F‐mediated transcriptional activation of cell cycle regulator genes. Moreover, we show that the transformationdependent increase in proliferation is independent of the concomitant stimulation of glycolysis. Finally, treatment of nude mice with the specific inhibitor of NHE‐1, DMA, delayed the development of HPV16‐keratinocyte tumors. Our data confirm that activation of the NHE‐1 and resulting cellular alkalinization is a key mechanism in oncogenic transformation and is necessary for the development and maintenance of the transformed phenotype.—Reshkin, S. J., Bellizzi, A., Caldeira, S., Albarani, V., Malanchi, I., Poignee, M., Alunni‐Fabbroni, M., Casavola, V., Tommasino, M. Na+/H+ exchanger‐dependent intracellular alkalinization is an early event in malignant transformation and plays an essential role in the development of subsequent transformation‐associated phenotypes.
Sexual selection and natural selection in bird speciation
Authors: Price Trevor
Published: July 2002

The role of sexual selection in speciation is investigated, addressing two main issues. First, how do sexually selected traits become species recognition traits? Theory and empirical evidence suggest that female preferences often do not evolve as a correlated response to evolution of male traits. This implies that, contrary to runaway (Fisherian) models of sexual selection, premating isolation will not arise as an automatic side effect of divergence between populations in sexually selected traits. I evaluate premating isolating mechanisms in one group, the birds. In this group premating isolation is often a consequence of sexual imprinting, whereby young birds learn features of their parents and use these features in mate choice. Song, morphology and plumage are known recognition cues. I conclude that perhaps the main role for sexual selection in speciation is in generating differences between populations in traits. Sexual imprinting then leads to these traits being used as species recognition mechanisms. The second issue addressed in this paper is the role of sexual selection in adaptive radiation, again concentrating on birds. Ecological differences between species include large differences in size, which may in themselves be sufficient for species recognition, and differences in habitat, which seem to evolve frequently and at all stages of an adaptive radiation. Differences in habitat often cause song and plumage patterns to evolve as a result of sexual selection for efficient communication. Therefore sexual selection is likely to have an important role in generating premating isolating mechanisms throughout an adaptive radiation. It is also possible that sexual selection, by creating more allopatric species, creates more opportunity for ecological divergence to occur. The limited available evidence does not support this idea. A role for sexual selection in accelerating ecological diversification has yet to be demonstrated.
Tissue architecture: the ultimate regulator of epithelial function?
Authors: Hagios Carmen , Lochter André , Bissell Mina J.
Published: July 2002

The architecture of a tissue is defined by the nature and the integrity of its cellular and extracellular compartments, and is based on proper adhesive cell–cell and cell–extracellular matrix interactions. Cadherins and integrins are major adhesion–mediators that assemble epithelial cells together laterally and attach them basally to a subepithelial basement membrane, respectively. Because cell adhesion complexes are linked to the cytoskeleton and to the cellular signalling pathways, they represent checkpoints for regulation of cell shape and gene expression and thus are instructive for cell behaviour and function. This organization allows a reciprocal flow of mechanical and biochemical information between the cell and its microenvironment, and necessitates that cells actively maintain a state of homeostasis within a given tissue context. The loss of the ability of tumour cells to establish correct adhesive interactions with their microenvironment results in disruption of tissue architecture with often fatal consequences for the host organism. This review discusses the role of cell adhesion in the maintenance of tissue structure and analyses how tissue structure regulates epithelial function.
The effects of host heterogeneity on pathogen population structure
Authors: Gupta Sunetra , Galvani Alison
Published: July 2002

We have shown that among pathogens, populations may self–organize into strains with non–overlapping repertoires of antigenic variants as a consequence of strong immune selection operating on polymorphic antigens. Recently, we have also demonstrated that over a wide range of intermediate levels of immune selection, pathogens may still be structured into discrete strains, but different sets of non–overlapping pathogen types will replace each other in a cyclical or chaotic manner. These models assume that the ranking of antigens in terms of the strength of the induced immune response is the same for every host. However, host immune responses may be restricted by the genotype of the individual. To explore this issue, a mathematical model was constructed under the assumption that a proportion of the host population responds principally to a variable antigen while the remainder of the population responds principally to a conserved antigen. The results of this analysis indicate that discrete strain structure (DSS) will be maintained even with a high frequency of hosts that do not respond in a variant–specific manner. Furthermore, the range of the immune selection pressure over which DSS prevails is increased (and the region of cyclical or chaotic behaviour reduced) by the inclusion of hosts that respond in a cross–reactive rather than a variant–specific manner.
Control of metaphase–anaphase progression by proteolysis: cyclosome function regulated by the protein kinase A pathway, ubiquitination and localization
Authors: Yanagida M. , Yamashita Y. M. , Tatebe H. , Ishii K. , Kumada K. , Nakaseko Y.
Published: July 2002

Ubiquitin–mediated proteolysis is fundamental to cell cycle progression. In the fission yeastSchizosaccharomyces pombe, a mitotic cyclin (Cdc13), a key cell cycle regulator, is degraded for exiting mitosis, while Cut2 has to be destroyed for the onset of sister chromatid separation in anaphase. Ubiquitination of these proteins requires the special destruction box (DB) sequences locating in their N–termini and the large, 20S complex called the anaphase–promoting complex or cyclosome. Here we show that cyclosome function during metaphase–anaphase progression is regulated by the protein kinase A (PKA) inactivation pathway, ubiquitination of the cyclosome subunit, and cellular localization of the target substrates. Evidence is provided that the cyclosome plays pleiotropic roles in the cell cycle: mutations in the subunit genes show a common anaphase defect, but subunit–specific phenotypes such as in G1/S or G2/M transition, septation and cytokinesis, stress response and heavy metal sensitivity, are additionally produced, suggesting that different subunits take distinct parts of complex cyclosome functions. Inactivation of PKA is important for the activation of the cyclosome for promoting anaphase, perhaps through dephosphorylation of the subunits such as Cut9 (Apc6). Cut4 (Apc1), the largest subunit, plays an essential role in the assembly and functional regulation of the cyclosome in response to cell cycle arrest and stresses. Cut4 is highly modified, probably by ubiquitination, when it is not assembled into the 20S cyclosome. Sds23 is implicated in DB–mediated ubiquitination possibly through regulating de–ubiquitination, while Cut8 is necessary for efficient proteolysis of Cdc13 and Cut2 coupled with cytokinesis. Unexpectedly, the timing of proteolysis is dependent on cellular localization of the substrate. Cdc13 enriched along the spindle disappears first, followed by decay of the nuclear signal, whereas Cut2 in the nucleus disappears first, followed by decline in the spindle signal during metaphase–anaphase progression.
Therapeutic strategies in multiple sclerosis. I. Immunotherapy
Authors: Hohlfeldf Reinhard
Published: July 2002

This review first addresses several general aspects of the immunotherapy of multiple sclerosis. Next, two approved immunomodulatory treatments, interferon–β and copolymer–1 (glatiramer acetate), are reviewed in more detail. Finally, other immunosuppressive therapies and experimental strategies are briefly discussed.
Ascorbate biosynthesis and function in photoprotection
Authors: Smirnoff Nicholas
Published: July 2002

Ascorbate (vitamin C) can reach very high concentrations in chloroplasts (20–300 mM).The pool size in leaves and chloroplasts increases during acclimation to high light intensity and the highest concentrations recorded are in high alpine plants. Multiple functions for ascorbate in photosynthesis have been proposed, including scavenging of active oxygen species generated by oxygen photoreduction and photorespiration, regeneration of α–tocopherol from α–tocopheryl radicals, cofactor for violaxanthin de–epoxidase and donation of electrons to photosystem II. Hydrogen peroxide scavenging is catalysed by ascorbate peroxidase (Mehler peroxidase reaction) and the subsequent regeneration of ascorbate by reductant derived from photosystem I allows electron flow in addition to that used for CO2assimilation. Ascorbate is synthesized from guanosine diphosphate–mannoseviaL–galactose and L–galactono–1,4–lactone. The last step, catalysed by L–galactono–1,4–lactone dehydrogenase, is located on the inner mitochondrial membrane and uses cytochromecas electron acceptor. L–galactono–1,4–lactone oxidation to ascorbate by intact leaves is faster in high–light acclimated leaves and is also enhanced by high light, suggesting that this step contributes to the control of pool size by light. Ascorbate–deficientArabidopsis thaliana vtcmutants are hypersensitive to a number of oxidative stresses including ozone and ultraviolet B radiation. Further investigation of these mutants shows that they have reduced zeaxanthin–dependent non–photochemical quenching, confirming that ascorbate is the cofactor for violaxanthin de–epoxidase and that availability of thylakoid lumen ascorbate could limit this reaction. The vtc mutants are also more sensitive to photooxidation imposed by combined high light and salt treatments.
Illustrating cerebral function: the iconography of arrows
Authors: Schott G. D.
Published: July 2002

For over a century the arrow has appeared in illustrations of cerebral function, yet the implications of using such symbols have not been previously considered. This review seeks to outline the nature, evolution, applications and limitations of this deceptively simple graphic device when it is used to picture functions of the brain. The arrow is found to have been used in several different ways: as a means of endowing anatomical structures with functional properties; as a method of displaying neural function either in free–standing form or in a structural or spatial framework; as a device for correlating functional data with underlying brain topography; and as a technique for linking functions of the brain with the world outside and with various philosophical concepts. For many of these uses the essential feature of the arrow is its directional characteristic. In contrast to the line, it is direction that enables the arrow to display information about time, which in turn can be exploited to depict functional rather than structural data. However, the use of the arrow is fraught with difficulties. It is often unclear whether an arrow has been used to illustrate fact, hypothesis, impression or possibility, or merely to provide a decorative flourish. Furthermore, the powerful symbolic nature of the arrow can so easily confer a spurious validity on the conjectural. Increasingly now there are insuperable difficulties when attempting to illustrate complex mechanisms of brain function. In the iconography of cerebral function, therefore, arrows with all their ambiguities may in certain circumstances become superseded by more non–representational symbols such as the abstract devices of the computational neuroscientist.
Intrafamilial conflict and parental investment: a synthesis
Authors: Parker G. A. , Royle N. J. , Hartley I. R.
Published: July 2002

We outline and develop current theory on how inherent genetic conflicts of interest between the various family members can affect the flow of parental investment from parents to offspring, and discuss the problems for empirical testing that this generates. The parental investment pattern realized in nature reflects the simultaneous resolution of all the conflicts between the family players. This depends on the genetic mechanism, the mating system and reproductive constraints, on whether extra demand by progeny affects current or future sibs, and particularly on the behavioural mechanisms underlying demand (begging or solicitation) and supply (provision of parental investment by parents). The direction of deviation from the optimal parental investment for the parent(s) depends on the slope of what we term the ‘effect of supply on demand’, the mechanism that determines how changes in food supply affect begging levels. If increasing food increases begging (positive slope), less parental investment is supplied than the parental optimum and if increasing food decreases begging (negative slope), more parental investment is supplied. The magnitude of deviation depends on both the ‘effect of supply on demand’ and on the ‘effect of demand on supply’ (the mechanism determining how changes in begging affect food supply, which always has a positive slope). We conclude that it will often be impossible to deduce the extent of underlying conflict by establishing the amount of parental investment given relative to the ideal optimum for the parent. Some possible directions for future research are discussed.
Peripheral clocks and their role in circadian timing: insights from insects
Authors: Giebultowicz Jadwiga M.
Published: July 2002

Impressive advances have been made recently in our understanding of the molecular basis of the cell–autonomous circadian feedback loop; however, much less is known about the overall organization of the circadian systems. How many clocks tick in a multicellular animal, such as an insect, and what are their roles and the relationships between them? Most attempts to locate clock–containing tissues were based on the analysis of behavioural rhythms and identified brain–located timing centres in a variety of animals. Characterization of several essential clock genes and analysis of their expression patterns revealed that molecular components of the clock are active not only in the brain, but also in many peripheral organs ofDrosophilaand other insects as well as in vertebrates. Subsequent experiments have shown that isolated peripheral organs can maintain self–sustained and light sensitive cycling of clock genesin vitro. This, together with earlier demonstrations that physiological output rhythms persist in isolated organs and tissues, provide strong evidence for the existence of functionally autonomous local circadian clocks in insects and other animals. Circadian systems in complex animals may include many peripheral clocks with tissue–specific functions and a varying degree of autonomy, which seems to be correlated with their sensitivity to external entraining signals.
The
Neurospora
circadian clock: simple or complex?
Authors: Bell-Pedersen Deborah , Crosthwaite Susan K. , Lakin-Thomas Patricia L. , Martha Merrow , Okland Merete
Published: July 2002

The fungus
Neurospora crassa
is being used by a number of research groups as a model organism to investigate circadian (daily) rhythmicity. In this review we concentrate on recent work relating to the complexity of the circadian system in this organism. We discuss: the advantages of
Neurospora
as a model system for clock studies; the
frequency
(
frq
),
white collar–1
and
white collar–2
genes and their roles in rhythmicity; the phenomenon of rhythmicity in null
frq
mutants and its implications for clock mechanisms; the study of output pathways using clock–controlled genes; other rhythms in fungi; mathematical modelling of the
Neurospora
circadian system; and the application of new technologies to the study of
Neurospora
rhythmicity. We conclude that there may be many gene products involved in the clock mechanism, there may be multiple interacting oscillators comprising the clock mechanism, there may be feedback from output pathways onto the oscillator(s) and from the oscillator(s) onto input pathways, and there may be several independent clocks coexisting in one organism. Thus even a relatively simple lower eukaryote can be used to address questions about a complex, networked circadian system.
Circadian systems: different levels of complexity
Authors: Roenneberg Till , Merrow Martha
Published: July 2002

After approximately 50 years of circadian research, especially in selected circadian model systems (Drosophila, Neurospora, Gonyaulaxand, more recently, cyanobacteria and mammals), we appreciate the enormous complexity of the circadian programme in organisms and cells, as well as in physiological and molecular circuits. Many of our insights into this complexity stem from experimental reductionism that goes as far as testing the interaction of molecular clock components in heterologous systems orin vitro. The results of this enormous endeavour show circadian systems that involve several oscillators, multiple input pathways and feedback loops that contribute to specific circadian qualities but not necessarily to the generation of circadian rhythmicity. For a full appreciation of the circadian programme, the results from different levels of the system eventually have to be put into the context of the organism as a whole and its specific temporal environment. This review summarizes some of the complexities found at the level of organisms, cells and molecules, and highlights similar strategies that apparently solve similar problems at the different levels of the circadian system.
Evolution of Intron/Exon Structure of DEAD Helicase Family Genes in Arabidopsis, Caenorhabditis, and Drosophila
Authors: Boudet Nathalie , Aubourg Sébastien , Toffano-Nioche Claire , Kreis Martin , Lecharny Alain
Published: July 2002

The DEAD box RNA helicase (RH) proteins are homologs involved in diverse cellular functions in all of the organisms from prokaryotes to eukaryotes. Nevertheless, there is a lack of conservation in the splicing pattern in the 53 Arabidopsis thaliana (AtRHs), the 32 Caenorhabditis elegans (CeRHs) and the 29 Drosophila melanogaster (DmRHs) genes. Of the 153 different observed intron positions, 4 are conserved between AtRHs,CeRHs, and DmRHs, and one position is also found inRHs from yeast and human. Of the 27 different AtRHstructures with introns, 20 have at least one predicted ancient intron in the regions coding for the catalytic domain. In all of the organisms examined, we found at least one gene with most of its intron predicted to be ancient. In A. thaliana, the large diversity inRH structures suggests that duplications of the ancestralRH were followed by a high number of intron deletions and additions. The very high bias toward phase 0 introns is in favor of intron addition, preferentially in phase 0. Results from this comparative study of the same gene family in a plant and in two animals are discussed in terms of the general mechanisms of gene family evolution.
Accounting for Human Polymorphisms Predicted to Affect Protein Function
Authors: Ng Pauline C. , Henikoff Steven
Published: July 2002

A major interest in human genetics is to determine whether a nonsynonymous single-base nucleotide polymorphism (nsSNP) in a gene affects its protein product and, consequently, impacts the carrier's health. We used the SIFT (Sorting Intolerant From Tolerant) program to predict that 25% of 3084 nsSNPs from dbSNP, a public SNP database, would affect protein function. Some of the nsSNPs predicted to affect function were variants known to be associated with disease. Others were artifacts of SNP discovery. Two reports have indicated that there are thousands of damaging nsSNPs in an individual's human genome; we find the number is likely to be much lower.
Interaction between Amount and Pattern of Training in the Induction of Intermediate- and Long-Term Memory for Sensitization in Aplysia
Authors: Sutton Michael A. , Ide Jasmine , Masters Sarah E. , Carew Thomas J.
Published: July 2002

In Aplysia, three distinct phases of memory for sensitization can be dissociated based on their temporal and molecular features. A single training trial induces short-term memory (STM, lasting <30 min), whereas five trials delivered at 15-min intervals induces both intermediate-term memory (ITM, lasting >90 min) and long-term memory (LTM, lasting >24 h). Here, we explore the interaction of amount and pattern of training in establishing ITM and LTM by examining memory for sensitization after differentnumbers of trials (each trial = one tail shock) and differentpatterns of training (massed vs. spaced). Under spaced training patterns, two trials produced STM exclusively, whereas four or five trials each produced both ITM and LTM. Three spaced trials failed to induce LTM but did produce an early decaying form of ITM (E-ITM) that was significantly shorter and weaker in magnitude than the late-decaying ITM (L-ITM) observed after four to five trials. In addition, E-ITM was induced after three trials with both massed and spaced patterns of training. However, L-ITM and LTM after four to five trials require spaced training: Four or five massed trials failed to induce LTM and produced only E-ITM. Collectively, our results indicate that in addition to three identified phases of memory for sensitization—STM, ITM, and LTM—a unique temporal profile of memory, E-ITM, is revealed by varying either the amount or pattern of training.
EstB from Burkholderia gladioli: A novel esterase with a β‐lactamase fold reveals steric factors to discriminate between esterolytic and β‐lactam cleaving activity
Authors: Wagner Ulrike G. , Petersen Evamaria I. , Schwab Helmut , Kratky Christoph
Published: July 2002

Esterases form a diverse class of enzymes of largely unknown physiological role. Because many drugs and pesticides carry ester functions, the hydrolysis of such compounds forms at least one potential biological function. Carboxylesterases catalyze the hydrolysis of short chain aliphatic and aromatic carboxylic ester compounds. Esterases, d‐alanyl‐d‐alanine‐peptidases (DD‐peptidases) and β‐lactamases can be grouped into two distinct classes of hydrolases with different folds and topologically unrelated catalytic residues, the one class comprising of esterases, the other one of β‐lactamases and DD‐peptidases. The chemical reactivities of esters and β‐lactams towards hydrolysis are quite similar, which raises the question of which factors prevent esterases from displaying β‐lactamase activity and vice versa. Here we describe the crystal structure of EstB, an esterase isolated from Burkholderia gladioli. It shows the protein to belong to a novel class of esterases with homology to Penicillin binding proteins, notably DD‐peptidase and class C β‐lactamases. Site‐directed mutagenesis and the crystal structure of the complex with diisopropyl‐fluorophosphate suggest Ser75 within the “β‐lactamase” Ser‐x‐x‐Lys motif to act as catalytic nucleophile. Despite its structural homology to β‐lactamases, EstB shows no β‐lactamase activity. Although the nature and arrangement of active‐site residues is very similar between EstB and homologous β‐lactamases, there are considerable differences in the shape of the active site tunnel. Modeling studies suggest steric factors to account for the enzyme's selectivity for ester hydrolysis versus β‐lactam cleavage.
Automated detection of lung nodules in CT scans: Preliminary results
Authors: Armato Samuel G. , Giger Maryellen L. , MacMahon Heber
Published: July 2002

We have developed a fully automated computerized method for the detection of lung nodules in helical computed tomography (CT) scans of the thorax. This method is based on two‐dimensional and three‐dimensional analyses of the image data acquired during diagnostic CT scans. Lung segmentation proceeds on a section‐by‐section basis to construct a segmented lung volume within which further analysis is performed. Multiple gray‐level thresholds are applied to the segmented lung volume to create a series of thresholded lung volumes. An 18‐point connectivity scheme is used to identify contiguous three‐dimensional structures within each thresholded lung volume, and those structures that satisfy a volume criterion are selected as initial lung nodule candidates. Morphological and gray‐level features are computed for each nodule candidate. After a rule‐based approach is applied to greatly reduce the number of nodule candidates that corresponds to non‐nodules, the features of remaining candidates are merged through linear discriminant analysis. The automated method was applied to a database of 43 diagnostic thoracic CT scans. Receiver operating characteristic (ROC) analysis was used to evaluate the ability of the classifier to differentiate nodule candidates that correspond to actual nodules from false‐positive candidates. The area under the ROC curve for this categorization task attained a value of 0.90 during leave‐one‐out‐by‐case evaluation. The automated method yielded an overall nodule detection sensitivity of 70% with an average of 1.5 false‐positive detections per section when applied to the complete 43‐case database. A corresponding nodule detection sensitivity of 89% with an average of 1.3 false‐positive detections per section was achieved with a subset of 20 cases that contained only one or two nodules per case.
Electron contamination in 8 and 18 MV photon beams
Authors: Zhu Timothy C. , Palta Jatinder R.
Published: July 2002

The contribution from contaminant electrons in the buildup region of a photon beam must be separated when calculating the dose using a photon convolution kernel. Their contribution can be extrapolated from fractional depth dose (FDD) data using the fractional depth kerma (or the “equilibrium dose”) derived from measured quantities such as beam attenuation with depth, phantom scatter factor as a function of field size and depth, and inverse‐square law for the incident photon beam. Good agreement is observed between the extrapolated and the EGS4 Monte Carlo simulated, primary dose‐to‐kerma ratios in the surface region for the photon beams, excluding electron contamination. The FDD was measured using a Scanditronix photon diode and was normalized to a reference depth far beyond maximum range of contaminant electrons. An analysis for the 8 and 18 MV photon beams from a Varian 2100CD indicates that at a source‐to‐surface distance (SSD) of 100 cm, the maximum electron contaminant dose (relative to its maximum FDD) varies from 1% to 33% for 8 MV and 2% to 44% for 18 MV, for square collimator settings ranging from 5 to 40 cm (defined at 100 cm from the source). This value at a depth of maximum dose (2 cm for 8 MV and 3.5 cm for 18 MV) can reach 1% for 8 MV and 2.3% for 18 MV. This contaminant electron dose is almost independent of SSD for 8 MV and starts to fall off for 18 MV at SSDs larger than 120 cm. Compared with the open beam, the contaminant electron dose increases when a solid tray is used, and the magnitude of increase increases with field size, reaching 19% and 16% for a field for 8 and 18 MV photons, respectively. The contaminant electron dose increases slightly for a blocked beam compared with an open beam of the same field size if a tray is used in both cases. The contaminant electron dose for the wedged field is less than that for an open field. However, the reduction is less significant at larger collimator settings and may increase slightly for 8 MV photons.
The linear no‐threshold debate: Where do we go from here?
Authors: Mossman Kenneth L.
Published: July 2002

For the past several years, the LNT (linear no‐threshold) theory has come under attack within the scientific community. Analysis of a number of epidemiological studies of the Japanese survivors of the atomic bombings and workers exposed to low level radiation suggest that the LNT philosophy is overly conservative, and low‐level radiation may be less dangerous than commonly believed. Proponents of current standards argue that risk conservatism is justified because low level risks remain uncertain and it is prudent public health policy; LNT opponents maintain that regulatory compliance costs are excessive, and there is now substantial scientific information arguing against the LNT model. Regulators use the LNT theory in the standards setting process to predict numbers of cancers due to exposure to low level radiation because direct observations of radiation‐induced cancers in populations exposed to low level radiation are difficult. The LNT model is simplistic and provides a conservative estimate of risk. Abandoning the LNT philosophy and relaxing regulations would have enormous economic implications. However, alternative models to predict risk at low dose are as difficult to justify as the LNT model. Perhaps exposure limits should be based on model‐independent approaches. There is no requirement that exposure limits be based on any predictive model. It is prudent to base exposure limits on what is known directly about health effects of radiation exposure of human populations.
Functional magnetic resonance imaging aided radiation treatment planning
Authors: Liu Wen‐Ching , Schulder Michael , Narra Venkat , Kalnin Andrew J. , Cathcart Charles , Jacobs Alexander , Lange Gudrun , Holodny Andrei I.
Published: July 2002

Functional MRI (magnetic resonance imaging) allows one to noninvasively identify various eloquent cortices in the brain. The integration of cortical activation information into radiosurgical treatment planning may provide an alternative to prevent or minimize radiation damage to eloquent cortex. A novel approach of directly integrating the fMRI (functional magnetic resonance imaging) brain map into treatment planning is proposed. Three brain tumor patients have been studied using this method with motor and/or visual paradigms. Brain activation was demonstrated in eloquent cortex at the precentral gyrus (motor area) and medial occipital lobe (visual area). The activation maps were transferred to a treatment planning workstation, (XKnife), and 3D (three‐dimensional) activation maps were generated and co‐registered to a 3D CT (computed tomography) anatomical data set, which provided the calibration localizer, for treatment planning. Radiosurgery was designed based on both functional and structural information by the medical team consisting of a radiation oncologist, a neurosurgeon and a physicist. The average maximum dose for the tumor was 2113 cGy. The average maximum dose for tissue surrounding the tumor was 1600 cGy. The average dose with fMRI information to the eloquent cortex was 163.4 cGy over three patients, while without fMRI information it was 240.5 cGy. The average percentage dose reduction over three patients is 32%. The results suggest that using this method can reduce the dose to the eloquent cortex. This approach provides the physician with additional information for treatment planning and may spare the patient unnecessary radiation exposure to adjacent eloquent cortices.
Resource Letter TLC-1: Teaching light and color
Authors: Rossing Thomas D. , Chiaverina Christopher J.
Published: July 2002

This Resource Letter provides a guide to resources for teaching light and color on the basic level, both in high school and college. We have included textbooks, reference books, articles, videos, laboratory and demonstration experiments, sources of materials, and websites. The letters E, I, and A identify material written primarily on the elementary, intermediate, and advanced levels.
Emil Wiechert (1861–1928): Esteemed seismologist, forgotten physicist
Authors: Mulligan Joseph F.
Published: July 2002

Emil Wiechert was well known during his lifetime as Professor of Geophysics at the Georg-August-Universität in Göttingen and Director of the Geophysical Institute there. He made many significant contributions to geophysics and seismology, and is highly respected by present-day geophysicists for his research and organizational contributions to the development of geophysics and seismology as major scientific disciplines. On the other hand, his contributions to fundamental physics—cathode rays, the discovery of the electron, the Liénard–Wiechert potentials, his electron theory—are unknown to many physicists today. This article presents Wiechert’s life, achievements in physics, and relationship to well-known physicists like Arnold Sommerfeld, Hendrik Lorentz, and Woldemar Voigt, to enable contemporary physicists to know better Wiechert’s important contributions to pure physics, and to appreciate more fully his role in the history of physics.
Inexpensive optical tweezers for undergraduate laboratories
Authors: Smith Stephen P. , Bhalotra Sameer R. , Brody Anne L. , Brown Benjamin L. , Boyda Edward K. , Prentiss Mara
Published: July 2002

Single beam gradient force optical traps, or tweezers, are a powerful tool for a wide variety of experiments in physics, chemistry, and biology. We describe how to build an optical tweezer with a total cost of ≈$6500 using only commercially available optics and mounts. We also suggest measurements that could be made using the apparatus.
Category restructuring during second-language speech acquisition
Authors: MacKay Ian R. A. , Flege James Emil , Piske Thorsten , Schirru Carlo
Published: July 2002

This study examined the production of English /b/ and the perception of short-lag English /b d g/ tokens by four groups of bilinguals who differed according to their age of arrival (AOA) in Canada from Italy and amount of self-reported native language (L1) use. A clear difference emerged between early bilinguals (mean AOA=8 years) and late bilinguals (mean AOA=20 years). The late bilinguals showed a stronger L1 influence than the early bilinguals did on both the production and perception of English stops. In experiment 2, the late bilinguals produced a larger percentage of prevoiced English /b/ tokens than early bilinguals and native English (NE) speakers did. In experiment 3, the late bilinguals misidentified short-lag English /b d g/ tokens as /p t k/ more often than the early bilinguals and NE speakers did. Experiment 4 revealed that the frequencies with which the bilinguals prevoiced /b d g/ in Italian and English were correlated. The observed differences between the early and late bilinguals were attributed to differences in the quantity and quality of English phonetic input they had received, not to a greater likelihood by the early than late bilinguals to establish new phonetic categories for English /b d g/.
Saturation of thermoacoustic mixture separation
Authors: Geller D. A. , Swift G. W.
Published: July 2002

The theory for thermoacoustic mixture separation is extended to include the effects of a nonzero concentration gradient. New data are presented, which are in excellent agreement with this theory. The maximum concentration gradient which may be achieved in a binary mixture of gases through this separation process is intrinsically limited by the fractional pressure amplitude, by the tidal displacement, and by the size of the thermal diffusion ratio. Ordinary diffusion further detracts from the attainable final concentration gradient and can become the dominant remixing process as the cross section of the duct is increased. Rayleigh streaming also works against thermoacoustic separation, and an estimate of the molar flux from streaming is given.