bluuebunny/crossref_metadata_2025 huggingface dataset:
Sequential megafaunal collapse in the North Pacific Ocean: An ongoing legacy of industrial whaling?
Authors: Springer A. M. , Estes J. A. , van Vliet G. B. , Williams T. M. , Doak D. F. , Danner E. M. , Forney K. A. , Pfister B.
Published: October 2003

Populations of seals, sea lions, and sea otters have sequentially collapsed over large areas of the northern North Pacific Ocean and southern Bering Sea during the last several decades. A bottom-up nutritional limitation mechanism induced by physical oceanographic change or competition with fisheries was long thought to be largely responsible for these declines. The current weight of evidence is more consistent with top-down forcing. Increased predation by killer whales probably drove the sea otter collapse and may have been responsible for the earlier pinniped declines as well. We propose that decimation of the great whales by post-World War II industrial whaling caused the great whales' foremost natural predators, killer whales, to begin feeding more intensively on the smaller marine mammals, thus “fishing-down” this element of the marine food web. The timing of these events, information on the abundance, diet, and foraging behavior of both predators and prey, and feasibility analyses based on demographic and energetic modeling are all consistent with this hypothesis.
Chromatin assembly factor 1 is essential and couples chromatin assembly to DNA replication
in vivo
Authors: Hoek Maarten , Stillman Bruce
Published: October 2003

De novo
chromatin assembly maintains histone density on the daughter strands in the wake of the replication fork. The heterotrimer chromatin assembly factor 1 (CAF-1) couples DNA replication to histone deposition
in vitro
, but is not essential for yeast cell proliferation. Depletion of CAF-1 in human cell lines demonstrated that CAF-1 was required for efficient progression through S-phase. Cells lacking CAF-1 accumulated in early and mid S-phase and replicated DNA slowly. The checkpoint kinase Chk1, but not Chk2, was phosphorylated in response to CAF-1 depletion, consistent with a DNA replication defect. CAF-1-depleted cell extracts completely lacked DNA replication-coupled chromatin assembly activity, suggesting that CAF-1 is required for efficient S-phase progression in human cells. These results indicate that, in contrast to yeast, human CAF-1 is necessary for coupling chromatin assembly with DNA replication.
Functional map of human cytomegalovirus AD169 defined by global mutational analysis
Authors: Yu Dong , Silva Maria C. , Shenk Thomas
Published: October 2003

Human cytomegalovirus has a complex double-stranded DNA genome of ≈240,000 bp that contains ≈150 ORFs likely to encode proteins, most of whose functions are not well understood. We have used an infectious bacterial artificial chromosome to introduce 413 defined insertion and substitution mutations into the human cytomegalovirus AD169 genome by random and site-directed transposon mutagenesis. Mutations were produced in all unique ORFs with a high probability of encoding proteins for which mutants have not been previously documented and in many previously characterized ORFs. The growth of selected mutants was assayed in cultured human fibroblasts, and we now recognize 41 essential, 88 nonessential, and 27 augmenting ORFs. Most essential and augmenting genes are located in the central region, and nonessential genes generally cluster near the ends of the viral genome.
Induction of pulmonary hypertension by an angiopoietin 1/TIE2/serotonin pathway
Authors: Sullivan Christopher C. , Du Lingling , Chu Danny , Cho Augustine J. , Kido Masakuni , Wolf Paul L. , Jamieson Stuart W. , Thistlethwaite Patricia A.
Published: October 2003

Smooth muscle cell proliferation around small pulmonary vessels is essential to the pathogenesis of pulmonary hypertension. Here we describe a molecular mechanism and animal model for this vascular pathology. Rodents engineered to express angiopoietin 1 (Ang-1) constitutively in the lung develop severe pulmonary hypertension. These animals manifest diffuse medial thickening in small pulmonary vessels, resulting from smooth muscle cell hyperplasia. This pathology is common to all forms of human pulmonary hypertension. We demonstrate that Ang-1 stimulates pulmonary arteriolar endothelial cells through a TIE2 (receptor with tyrosine kinase activity containing IgG-like loops and epidermal growth factor homology domains) pathway to produce and secrete serotonin (5-hydroxytryptamine), a potent smooth muscle mitogen, and find that high levels of serotonin are present both in human and rodent pulmonary hypertensive lung tissue. These results suggest that pulmonary hypertensive vasculopathy occurs through an Ang-1/TIE2/serotonin paracrine pathway and imply that these signaling molecules may be targets for strategies to treat this disease.
Self-organized queuing and scale-free behavior in real escape panic
Authors: Saloma Caesar , Perez Gay Jane , Tapang Giovanni , Lim May , Palmes-Saloma Cynthia
Published: October 2003

Numerical investigations of escape panic of confined pedestrians have revealed interesting dynamical features such as pedestrian arch formation around an exit, disruptive interference, self-organized queuing, and scale-free behavior. However, these predictions have remained unverified because escape panic experiments with real systems are difficult to perform. For mice escaping out of a water pool, we found that for a critical sampling rate the escape behavior exhibits the predicted features even at short observation times. The mice escaped via an exit in bursts of different sizes that obey exponential and (truncated) power-law distributions depending on exit width. Oversampling or undersampling the mouse escape rate prevents the observation of the predicted features. Real systems are normally subject to unavoidable constraints arising from occupancy rate, pedestrian exhaustion, and nonrigidity of pedestrian bodies. The effect of these constraints on the dynamics of real escape panic is also studied.
Position-specific trapping of topoisomerase II by benzo[
a
]pyrene diol epoxide adducts: Implications for interactions with intercalating anticancer agents
Authors: Khan Qasim A. , Kohlhagen Glenda , Marshall Richard , Austin Caroline A. , Kalena Govind P. , Kroth Heiko , Sayer Jane M. , Jerina Donald M. , Pommier Yves
Published: October 2003

DNA topoisomerase II (Top2) is the target of some of the most effective anticancer DNA intercalators. To determine the effect of intercalating ligands at defined positions relative to a known DNA cleavage site for human Top2α, we synthesized oligodeoxynucleotides containing single trans-opened benzo[
a
]pyrene 7,8-diol 9,10-epoxide (DE) deoxyadenosine (dA) adducts of known absolute configuration, placed at specific positions in a duplex sequence containing staggered Top2 cleavage sites on both strands. Because the orientations of the intercalated hydrocarbon are known from NMR solution structures of duplex oligonucleotides containing these dA adducts, a detailed analysis of the relationship between the position of intercalation and trapping of Top2 is possible. Our findings demonstrate that (
i
) Top2 cleavage complexes are trapped by intercalation of the hydrocarbon at either of the staggered cleavage sites or immediately adjacent to the base pairs flanking the cleavage sites within the stagger; (
ii
) both concerted and nonconcerted cleavage by both subunits of a Top2 homodimer were detected depending on the position of the benzo[
a
]pyrene DE dA adduct; and (
iii
) intercalation immediately outside of the staggered Top2 cleavage site, and to a lesser extent in the middle of the stagger, prevents Top2 from cleaving DNA at this site, consistent with the effect of some intercalators as suppressors of Top2-mediated DNA cleavage. These results identify specific binding sites for intercalators that result in trapping of Top2. Such poisoning of Top2 by bulky polycyclic aromatic hydrocarbon DE adducts constitutes a potential mechanism for their carcinogenic activity.
Disruption ofPPT2in mice causes an unusual lysosomal storage disorder with neurovisceral features
Authors: Gupta Praveena , Soyombo Abigail A. , Shelton John M. , Wilkofsky Ian G. , Wisniewski Krystyna E. , Richardson James A. , Hofmann Sandra L.
Published: October 2003

The palmitoyl protein thioesterase-2 (PPT2) gene encodes a lysosomal thioesterase homologous to PPT1, which is the enzyme defective in the human disorder called infantile neuronal ceroid lipofuscinosis. In this article, we report that PPT2 deficiency in mice causes an unusual form of neuronal ceroid lipofuscinosis with striking visceral manifestations. All PPT2-deficient mice displayed a neurodegenerative phenotype with spasticity and ataxia by 15 mo. The bone marrow was infiltrated by brightly autofluorescent macrophages and multinucleated giant cells, but interestingly, the macrophages did not have the typical appearance of foam cells commonly associated with other lysosomal storage diseases. Marked splenomegaly caused by extramedullary hematopoiesis was observed. The pancreas was grossly orange to brown as a result of massive storage of lipofuscin pigments in the exocrine (but not islet) cells. Electron microscopy showed that the storage material consisted of multilamellar membrane profiles (“zebra bodies”). In summary, PPT2 deficiency in mice manifests as a neurodegenerative disorder with visceral features. Although PPT2 deficiency has not been described in humans, manifestations would be predicted to include neurodegeneration with bone marrow histiocytosis, visceromegaly, brown pancreas, and linkage to chromosome 6p21.3 in affected families.
Rapid PCR amplification of minimal enediyne polyketide synthase cassettes leads to a predictive familial classification model
Authors: Liu Wen , Ahlert Joachim , Gao Qunjie , Wendt-Pienkowski Evelyn , Shen Ben , Thorson Jon S.
Published: October 2003

A universal PCR method for the rapid amplification of minimal enediyne polyketide synthase (PKS) genes and the application of this methodology to clone remaining prototypical genes from producers of structurally determined enediynes in both family types are presented. A phylogenetic analysis of the new pool of bona fide enediyne PKS genes, consisting of three from 9-membered producers (neocarzinostatin, C1027, and maduropeptin) and three from 10-membered producers (calicheamicin, dynemicin, and esperamicin), reveals a clear genotypic distinction between the two structural families from which to form a predictive model. The results from this study support the postulation that the minimal enediyne PKS helps define the structural divergence of the enediyne core and provides the key tools for generating enediyne hybrid genes/molecular scaffolds; by using the model, a classification is also provided for the unknown enediyne PKS genes previously identified via genome scanning.
Topological analysis of a plant vacuolar Na
+
/H
+
antiporter reveals a luminal C terminus that regulates antiporter cation selectivity
Authors: Yamaguchi Toshio , Apse Maris P. , Shi Huazhong , Blumwald Eduardo
Published: October 2003

We conducted an analysis of the topology of AtNHX1, an
Arabidopsis thaliana
vacuolar Na
+
/H
+
antiporter. Several hydrophilic regions of the antiporter were tagged with a hemagglutinin epitope, and protease protection assays were conducted to determine the membrane topology of the antiporter by using yeast as a heterologous expression system. The overall structure of AtNHX1 is distinct from the human Na
+
/H
+
antiporter NHE1 or any known Na
+
/H
+
antiporter. It is comprised of nine transmembrane domains and a hydrophilic C-terminal domain. Three hydrophobic regions do not appear to span the tonoplast membrane, yet appear to be membrane associated. Our results also indicate that, whereas the N terminus of AtNHX1 is facing the cytosol, almost the entire C-terminal hydrophilic region resides in the vacuolar lumen. Deletion of the hydrophilic C terminus resulted in a dramatic increase in the relative rate of Na
+
/H
+
transport. The ratio of Na
+
/K
+
transport was twice that of the unmodified AtNHX1. This altered ratio resulted from a relatively small decrease in K
+
/H
+
transport with a large increase in Na
+
/H
+
transport. The vacuolar localization of the C terminus of the AtNHX1, taken together with the regulation of the antiporter selectivity by its C terminus, demonstrates the existence of luminal vacuolar regulatory mechanisms of the antiporter activity.
Multiple shifts in the representation of a motor sequence during the acquisition of skilled performance
Authors: Korman Maria , Raz Naftali , Flash Tamar , Karni Avi
Published: October 2003

When do learning-related changes in performance occur? Here we show that the knowledge of a sequence of movements evolves through several distinctive phases that depend on two critical factors: the amount of practice as well as the passage of time. Our results show the following. (
i
) Within a given session, large performance gains constituted a signature for motor novelty. Such gains occurred only for newly introduced conditions irrespective of the absolute level of performance. (
ii
) A single training session resulted in both immediate but also time-dependent, latent learning hours after the termination of practice. Time in sleep determined the time of expression of these delayed gains. Moreover, the delayed gains were sequence-specific, indicating a qualitative change in the representation of the task within 24 h posttraining. (
iii
) Prolonged training resulted in additional between-session gains that, unlike the effects of a single training session, were confined to the trained hand. Thus, the effects of multisession training were qualitatively different than the immediate and time-dependent effects of a single session. Altogether, our results indicate multiple time-dependent shifts in the representation of motor experience during the acquisition of skilled performance.
A strabismus susceptibility locus on chromosome 7p
Authors: Parikh Vaishali , Shugart Yin Yao , Doheny Kimberly F. , Zhang Jie , Li Lan , Williams John , Hayden David , Craig Brian , Capo Hilda , Chamblee Denise , Chen Cathy , Collins Mary , Dankner Stuart , Fiergang Dean , Guyton David , Hunter David , Hutcheon Marcia , Keys Marshall , Morrison Nancy , Munoz Michelle , Parks Marshall , Plotsky David , Protzko Eugene , Repka Michael X. , Sarubbi Maria , Schnall Bruce , Siatkowski R. Michael , Traboulsi Elias , Waeltermann Joanne , Nathans Jeremy
Published: October 2003

Strabismus has been known to have a significant genetic component, but the mode of inheritance and the identity of the relevant genes have been enigmatic. This paper reports linkage analysis of nonsyndromic strabismus. The principal results of this study are: (i) the demonstrated feasibility of identifying and recruiting large families in which multiple members have (or had) strabismus; (ii) the linkage in one large family of a presumptive strabismus susceptibility locus to 7p22.1 with a multipoint logarithm of odds score of 4.51 under a model of recessive inheritance; and (iii) the failure to observe significant linkage to 7p in six other multiplex families, consistent with genetic heterogeneity among families. These findings suggest that it will be possible to localize and ultimately identify strabismus susceptibility genes by linkage analysis and mutation screening of candidate genes.
Activation domain–mediator interactions promote transcription preinitiation complex assembly on promoter DNA
Authors: Cantin Greg T. , Stevens Jennitte L. , Berk Arnold J.
Published: October 2003

The interaction of activators with mediator has been proposed to stimulate the assembly of RNA polymerase II (Pol II) preinitiation complexes, but there have been few tests of this model. The finding that the major adenovirus E1A and mitogen-activated protein kinase-phosphorylated Elk1 activation domains bind to Sur2 uniquely among the metazoan mediator subunits and the development of transcriptionally active nuclear extracts from WT and
sur2
–/–
embryonic stem cells, reported here, allowed a direct test of the model. We found that whereas VP16, E1A, and phosphorylated Elk1 activation domains each stimulate binding of mediator, Pol II, and general transcription factors to promoter DNA in extracts from WT cells, only VP16 stimulated their binding in extracts from
sur2
–/–
cells. This stimulation of mediator, Pol II, and general transcription factor binding to promoter DNA correlated with transcriptional activation by these activators in WT and mutant extracts. Because the mutant mediator was active in reactions with the VP16 activation domain, the lack of activity in response to the E1A and Elk1 activation domains was not due to loss of a generalized mediator function, but rather the inability of the mutant mediator to be bound by E1A and Elk1. These results directly demonstrate that the interaction of activation domains with mediator stimulates preinitiation complex assembly on promoter DNA.
Facile synthesis of site-specifically acetylated and methylated histone proteins: Reagents for evaluation of the histone code hypothesis
Authors: He Shu , Bauman David , Davis Jamaine S. , Loyola Alejandra , Nishioka Kenichi , Gronlund Jennifer L. , Reinberg Danny , Meng Fanyu , Kelleher Neil , McCafferty Dewey G.
Published: October 2003

The functional capacity of genetically encoded histone proteins can be powerfully expanded by posttranslational modification. A growing body of biochemical and genetic evidence clearly links the unique combinatorial patterning of side chain acetylation, methylation, and phosphorylation mainly within the highly conserved N termini of histones H2A, H2B, H3, and H4 with the regulation of gene expression and chromatin assembly and remodeling, in effect constituting a “histone code” for epigenetic signaling. Deconvoluting this code has proved challenging given the inherent posttranslational heterogeneity of histone proteins isolated from biological sources. Here we describe the application of native chemical ligation to the preparation of full-length histone proteins containing site-specific acetylation and methylation modifications. Peptide thioesters corresponding to histone N termini were prepared by solid phase peptide synthesis using an acid labile Boc/HF assembly strategy, then subsequently ligated to recombinantly produced histone C-terminal globular domains containing an engineered N-terminal cysteine residue. The ligation site is then rendered traceless by hydrogenolytic desulfurization, generating a native histone protein sequence. Synthetic histones generated by this method are fully functional, as evidenced by their self-assembly into a higher order H3/H4 heterotetramer, their deposition into nucleosomes by human ISWI-containing (
I
mitation of
Swi
tch) factor RSF (
R
emodeling and
S
pacing
F
actor), and by enzymatic modification by human Sirt1 deacetylase and G9a methyltransferase. Site-specifically modified histone proteins generated by this method will prove invaluable as novel reagents for the evaluation of the histone code hypothesis and analysis of epigenetic signaling mechanisms.
Modular organization of directionally tuned cells in the motor cortex: Is there a short-range order?
Authors: Amirikian Bagrat , Georgopoulos Apostolos P.
Published: October 2003

We investigated the presence of short-range order (<600 μm) in the directional properties of neurons in the motor cortex of the monkey. For that purpose, we developed a quantitative method for the detection of functional cortical modules and used it to examine such potential modules formed by directionally tuned cells. In the functional domain, we labeled each cell by its preferred direction (PD) vector in 3D movement space; in the spatial domain, we used the position of the tip of the recording microelectrode as the cell's coordinate. The images produced by this method represented two orthogonal dimensions in the cortex; one was parallel (“horizontal”) and the other perpendicular (“vertical”) to the cortical layers. The distribution of directionally tuned cells in these dimensions was nonuniform and highly structured. Specifically, cells with similar PDs tended to segregate into vertically oriented minicolumns 50–100 μm wide and at least 500 μm high. Such minicolumns aggregated across the horizontal dimension in a secondary structure of higher order. In this structure, minicolumns with similar PDs were ≈200 μm apart and were interleaved with minicolumns representing nearly orthogonal PDs; in addition, nonoverlapping columns representing nearly opposite PDs were ≈350 μm apart.
Patterning of the cardiac outflow region in
Drosophila
Authors: Zikova Martina , Da Ponte Jean-Philippe , Dastugue Bernard , Jagla Krzysztof
Published: October 2003

Specification of bilateral cardiac primordia and formation of the linear heart tube are highly conserved from
Drosophila
to humans. However, subsequent heart morphogenesis involving nonmesodermal neural crest cells was thought to be specific for vertebrates. Here, we provide evidence that a group of nonmesodermal cells that we have named heart-anchoring cells (HANCs) contribute to heart morphogenesis in
Drosophila
. We show that the homeobox genes
ladybird
(
lb
) known to be involved in diversification of cardiac precursors are expressed in HANCs and required for their specification. Interestingly, the HANCs selectively contact the anterior cardiac cells, which express
lb
as well. Direct interaction between HANCs and cardiac cells is assisted by a pair of cardiac outflow muscles (COMs), each of which selectively attaches to both the
lb
-expressing cardiac cells and HANCs. COM muscles seem to ensure ventral bending of the heart tip and together with HANCs determine the spatial positioning of the cardiac outflow region. Experimentally depleted cardiac
lb
expression leads to the disruption of the contact between the tip of the heart and either the COM muscles or the HANC cells, indicating a pivotal morphogenetic role for the
lb
expression within the heart.
Mechanism and energetics of green fluorescent protein chromophore synthesis revealed by trapped intermediate structures
Authors: Barondeau David P. , Putnam Christopher D. , Kassmann Carey J. , Tainer John A. , Getzoff Elizabeth D.
Published: October 2003

Green fluorescent protein has revolutionized cell labeling and molecular tagging, yet the driving force and mechanism for its spontaneous fluorophore synthesis are not established. Here we discover mutations that substantially slow the rate but not the yield of this posttranslational modification, determine structures of the trapped precyclization intermediate and oxidized postcyclization states, and identify unanticipated features critical to chromophore maturation. The protein architecture contains a dramatic ≈80° bend in the central helix, which focuses distortions at G67 to promote ring formation from amino acids S65, Y66, and G67. Significantly, these distortions eliminate potential helical hydrogen bonds that would otherwise have to be broken at an energetic cost during peptide cyclization and force the G67 nitrogen and S65 carbonyl oxygen atoms within van der Waals contact in preparation for covalent bond formation. Further, we determine that under aerobic, but not anaerobic, conditions the Gly-Gly-Gly chromophore sequence cyclizes and incorporates an oxygen atom. These results lead directly to a conjugation-trapping mechanism, in which a thermodynamically unfavorable cyclization reaction is coupled to an electronic conjugation trapping step, to drive chromophore maturation. Moreover, we propose primarily electrostatic roles for the R96 and E222 side chains in chromophore formation and suggest that the T62 carbonyl oxygen is the base that initiates the dehydration reaction. Our molecular mechanism provides the basis for understanding and eventually controlling chromophore creation.
Philosophical Papers
Authors: Austin J. L.
Published: October 2003

This text collects all Austin’s published articles plus a new one, ch. 13, hitherto unpublished. The analysis of the ordinary language to clarify philosophical questions is the common element of the 13 papers. Chapters 2 and 4 discuss the nature of knowledge, focusing on ‘performative utterances’. The doctrine of ‘speech acts’, i.e. a statement may be the pragmatic use of language, is discussed in Chs 6 and 10. Chapters 8, 9, and 12 reflect on the problems the language encounters in discussing actions and consider the cases of excuses, accusations, and freedom. The ‘correspondence theory’, i.e. a statement is truth when it corresponds to a fact, is presented in Chs 5 and 6. Finally, Chs 1 and 3 study how a word may have different but related senses considering Aristotle’s view. Chapters 11 and 13 illustrate the meaning of ‘pretending’ and a Plato’s text respectively.
Aγαθόν and Eὐδαιμονία In the Ethics of Aristotle
Authors: Austin J. L. , Urmson J. O. , Warnock G. J.
Published: October 2003

‘Agathon and Eudaimonia in the Ethics of Aristotle’ is a response to an article on the meaning of Agathon in the Ethics of Aristotle, published by H. A. Pritchard in 1935. In this paper, Pritchard argued that Aristotle regarded Agathon to mean ‘conducive to our happiness’ and, consequently, that he maintained that every deliberate action stems, ultimately, from the desire to become happy. Austin finds fault with this view: first, Agathon in Aristotle does not have a single meaning, and a fortiori not the one Pritchard suggested; secondly, if one had to summarise the meaning of ‘being agathon’ in one phrase, then ‘being desired’ cannot fulfil this function, for there are other objects of desire besides τό άγαθόν (the good).
Other Minds
Authors: Austin J. L. , Urmson J. O. , Warnock G. J.
Published: October 2003

Austin takes on the problem of other minds, of how to respond to the question ‘how do you know?’, if this question is raised with regard to the thoughts, feelings, sensations, minds of other creatures. This problem has traditionally been understood as the problem of justifying our belief in the existence of other minds. Austin argues that believing in other persons, in authority and testimony, is an essential part of the act of communicating, and as such is an irreducible part of our experience. While we can state certain advantages of communicative performances, there is no justification for our doing them as such.
Pretending
Authors: Austin J. L. , Urmson J. O. , Warnock G. J.
Published: October 2003

Addresses Bedford’s attack on appeals to introspection in the identification of emotions, which lead him to raise the question of how to draw the line between genuine and pretended anger. Austin demonstrates, through a close examination of the speech acts of ‘pretending’ and ‘really being’, that none of the supposed conditional relations (e.g. not really being  pretending; really being  not pretending etc.) between these two notions actually holds. The essay further introduces Austin’s distinction between ‘pretending to do’ and ‘pretending to be’ and emphasises the complex and diverse forms speech acts involving ‘pretending’ can take.,
Measuring the quality of life in European Union
Authors: Yoruk Baris K. , Zaim Osman
Published: October 2003

This paper is aimed at measuring and comparing the quality of life in European Union (EU) and Turkey as an important candidate country on the process of integrating with the EU. Rather than using per capita income as a classical measure, this study uses social indicators of development as a measure of well‐being. Instead of using human development index (HDI) – an index commonly referred as “deprivation index” – we adopt the indices that are developed in Zaim, Fare and Grosskopf. The “achievement index” measures the success of a country in the provision of standard of life. On the other hand “improvement index” is used to measure the improvement of the country over time in terms of its life quality. The stated results suggest that Turkey should improve its quality of life on the way of integrating with the EU.
Modeling access to health care within a community
Authors: Zayas‐Cabán Teresa
Published: October 2003

Health disparities have been a growing concern in the USA. Differences in access to healthcare play a role in these health disparities. This article presents a model that illustrates access to healthcare in two rural Midwestern communities. The simulation model developed helps determine if people in these communities have equal access to health care and if physician’s insurance coverage practices prevent certain people from accessing care. From the simulation, it can be determined which characteristics may lead to the disparities in access to health care. Using the results of such a simulation model, the community may then begin to take action in order to ensure equal access to health care for all people within the community and help reduce health disparities.
The marketing strategies analysis for the umbilical cord blood banking service
Authors: Yang Muhsi , Kuo Tsai‐Chi Robert , Murphy Jones Roseanne
Published: October 2003

Recently, researchers have explored the medical applications of umbilical cord blood (UCB) to treat certain types of cancer and other disorders. UCB is a hematopoietic tissue that contains a motherlode of cells, and creates the blood cells that carry oxygen, fight infections, and form clots at the sites of injuries. The use of UCB involves fewer ethical and legal problems than other stem cell technology. UCB banking not only involves the creation of a UCB storage bank, but is also a serial process that includes collecting UCB, extracting stem cells from UCB, storing these stem cells in liquid nitrogen at –385°F, and defrosting them if required by their owner. UCB banking service is thus a form of biological insurance, where the reward is an increased chance of good health rather than monetary compensation. Many people have begun to consider the need for public and private UCB banks to preserve cord blood donations. The main purpose of this research is to develop the UCB consumers’ behavior based on the consumer buying behavior model. It clarifies the opinions of Taiwan people about UCB banking, identifies the main factors motivating people to store UCB, and provides the marketing strategies for the UCB banking service.
Implications of complexity and chaos theories for organizations that learn
Authors: Smith Peter A.C.
Published: October 2003

In 1996 Hubert Saint‐Onge and Smith published an article (“The evolutionary organization: avoiding a Titanic fate”, in The Learning Organization, Vol. 3 No. 4), based on their experience at the Canadian Imperial Bank of Commerce (CIBC). It was established at CIBC that change could be successfully facilitated through blended application of theory such as system dynamics, and the then emerging notions of “chaos and complexity”. The resulting enterprise was termed an evolutionary organization (EVO), and CIBC has continued since to re‐invent itself with great success. Although the all‐embracing nature of chaos and complexity was understood, in retrospect the impact of non‐rational people‐factors, e.g. emotion, trust, openness, spirituality were underestimated. Introduces the six papers included in this special issue, which illustrate how much more sophisticated chaos and complexity have become in the decade since Hubert Saint‐Onge and Smith first began to apply the notions at CIBC. However, although the papers in this issue present some evidence of managerial “take‐up” of chaos and complexity, whether “take‐off” will ever ensue is questionable. It is proposed that, just as in the 1990s, if there is one thing that more than any other stands in the way of exploration and adoption of these ideas, it is management mindsets.
Third possibility leaders: the invisible edge women have in complex organizations
Authors: Regine Birute , Lewin Roger
Published: October 2003

Complexity science may be described as a feminine science because it demands holistic thinking, something that women are generally better at than men. A total of 50 women leaders in the USA, Canada, Australia, and the UK were interviewed, women who displayed what is called “third possibility leadership”, that is they were able to hold masculine and feminine values and behaviors in dynamic balance. Finds that they displayed characteristics in common: they were “paradoxical”, they gathered people together, they were “wholistic” thinkers, and they displayed well‐developed “relational intelligence”. Although they were effective leaders, their style of leadership was often invisible, and even demeaned, for socio‐cultural reasons.
Approaches to studying and perceptions of academic quality in electronically delivered courses
Authors: Richardson John T. E. , Price Linda
Published: October 2003

The Course Experience Questionnaire (CEQ) and a short form of the Approaches to Studying Inventory (ASI) were administered to students who were taking electronically delivered courses in computer science. The constituent structure of the CEQ was preserved in this distinctive context, and a second‐order factor analysis confirmed its role as an index of perceived academic quality. The students' scores on the individual scales of the CEQ and the ASI shared nearly two‐thirds of their variance. In short, approaches to studying in electronically delivered courses are strongly associated with students' perceptions of the academic quality of those courses.
Speaking versus typing: a case‐study of the effects of using voice‐recognition software on academic correspondence
Authors: Hartley James , Sotto Eric , Pennebaker James
Published: October 2003

This paper contributes to the discussion about the effects of new technology on writing by assessing whether or not an experienced writer's style of writing changes when a new technology is introduced. 14 typed word‐processed letters from ES to JH were compared with 14 dictated word‐processed letters from ES after he had changed to using a voice‐recognition system (Dragon Naturally Speaking). The results showed that, although there were large differences between the methods and experience of writing with the two technologies, there were no significant differences between the average letter lengths, numbers of paragraphs written and number of sentences used in each group of letters. Nor were there any significant differences in terms of readability, or typographical and grammatical errors. However, the dictated letters did have significantly shorter sentences, significantly fewer particularly long sentences (ie, those containing more than 50 words), and used the first‐person pronoun more frequently. The overall results thus indicate that using the voice‐recognition software had only marginal effects upon the written products, despite the fact that it had a strong effect on ES's experience of the writing process.
Fodor on Inscrutability
Authors: Wakefield Jerome C.
Published: October 2003

Abstract:  Jerry Fodor (1994) proposes a solution to Quine's inscrutability–of–reference problem for certain naturalized semantic theories, thereby defending such theories from charges that they cannot discriminate meanings finely enough. His proposal, combining elements of informational and inferential–role semantics, is to eliminate non–standard interpretations by testing predicate compatibility relations. I argue that Fodor's proposal, understood as primarily aimed at Mentalese, withstands Ray's (1997) and Gates's (1996) objections but nonetheless fails because of unwarranted assumptions about ontological homogeneity of target language predicates, and problems with Fodor's reliance on predicate conjunction to resolve ambiguity. Naturalized semantics thus remains without an answer to the inscrutability objection.
What is family friendly about the workplace in the home? The case of self‐employed parents and their children
Authors: Baines Susan , Gelder Ulrike
Published: October 2003

This article draws upon the narratives of self‐employed parents, their partners and children in order to examine the ‘family friendliness’ of making the home a site of paid work. While not fitting narrow definitions of ‘teleworker’ the subjects daily confronted the use of space in their homes, and access to technologies there.
A decline of linkage? Intra‐party participation in Norway, 1991–2000
Authors: Heidar Knut , Saglie Jo
Published: October 2003

Abstract. The decline in party membership in Western Europe is generally taken as an indicator of party transformation. This article looks beyond membership figures and asks whether membership decline should be interpreted to mean that the activities and motivation of the remaining members are changing. Hypotheses on changes in party activism and motivation for party membership are tested with data from the 1991 and 2000 Norwegian party member surveys. Rather than uncovering evidence of change, most analyses point to a remarkable level of stability. Active and passive members seem to have disappeared at about the same rate. The general diagnosis of party decline is neither improved nor aggravated, but the analysis casts doubt on propositions about the transformation of the grassroots organisation. The Internet is used by party office‐holders and the young, but the grassroots rarely use the new technology for political purposes. The character of the representative and participatory linkages provided by parties has, however, changed as a consequence of a shrinking party membership.
Time‐Driven Development of Software in Manufactured Goods
Authors: Rauscher Tomlinson G. , Smith Preston G.
Published: October 2003

Microprocessors are being incorporated into an increasingly wide range of products. However, many of the companies that manufacture such products are not effectively managing software development for these embedded systems. Despite the current focus on concurrent engineering and cross‐functional teams, software engineering is often poorly integrated with the rest of the product development effort. The result is usually a costly delay in the product's introduction to the market.

Tomlinson G. Rauscher and Preston G. Smith describe several practices that have proved helpful for accelerating the development of products that incorporate embedded software. Managerial and economic opportunities for accelerating development of hardware‐software systems involve planning for dramatic growth in products that include embedded software, cultivating in‐house software knowledge, recognizing the financial effects of project decisions, and measuring project progress. Improving time to market requires hiring and developing software engineering staff and managers with the requisite knowledge of the application, ensuring that they understand the techniques for specifying requirements and design, and providing them with clear guidelines for evaluating the trade‐offs between project duration, project cost, and product performance. Progress should be measured in terms of the number of components completed, rather than the number of lines of code that are written.

During the development process, emphasis should be placed on managing the scheduling links between hardware and software development, obtaining user feedback about the system as early as possible, and using a flexible, ongoing review process. Development groups should establish software requirements and design parameters before they start coding, and testing should commence early in the system design process. By creating a working prototype of the user interface, developers can obtain user feedback and thereby sharpen the design specification.

Effective, timely software development requires focusing greater energy and resources on development of the requirements specification. By expending this effort in the first phase of a project, the development team can minimize its use of the time‐consuming code‐and‐debug approach to software development. In addition to breaking down a complex system into understandable pieces, a modular design supports efforts to accelerate product development. With a modular design, work on various modules can be assigned concurrently to relatively independent teams. A modular design facilitates testing of the product as well as reuse of software that was developed and deployed in previous projects.
Contingent Product Design and Marketing Strategies Influencing New Product Success and Failure in U.S. and Japanese Electronics Firms
Authors: Souder Wm. E. , Song X. Michael
Published: October 2003

The commercial success or failure of a product doesn't rest solely on the whims of the marketplace. The myriad, often interdependent, strategic trade‐offs made throughout the product development process go a long way toward determining whether a product succeeds or fails. The key to success often rests in finding the right combination of product design and market choice decisions.

Toward that end, William E. Souder and X. Michael Song examine the relationship between product success and several product design and market choice strategies. In particular, they explore the possibility that the correct strategy combination differs depending on a firm's perception of market uncertainty, which they measure in terms of the respondents' perceived familiarity with the market for a product, perceived understanding of customer needs, and perceived capability to translate those needs into product performance specifications. Recognizing that the correct combination of strategic choices may also depend on firm size, industry, and culture, the study focuses on small U.S. suppliers of electronics components. Fortune 500 producers of electronics final products, and Japanese producers of electronics final products.

For the small U.S. firms in the study, an emphasis on performance superiority, technical superiority, or radically new products provides a recipe for failure under low market uncertainty. Even under high market uncertainty, these characteristics do not equate to success for the small U.S. firms in this study. The findings suggest that these firms should focus on design compatibility with a purchaser's installed base. The responses from Fortune 500 firms and Japanese companies indicate that under low market uncertainty these larger organizations should consider emphasizing compatibility and avoiding radical designs. For markets that the larger firms perceive to be highly uncertain, the results suggest that these companies should emphasize performance superiority, technical superiority, and radical designs.

The findings related to market choice strategies also support the notion that the correct combination of strategic decisions depends on firm size, culture, and the perceived level of market uncertainty. However, the guidelines presented in this study should not be construed as hard‐and‐fast rules for formulating product strategy. Instead, the results presented here will be helpful for challenging assumptions and guiding actions, as one element in the effort to shape an effective product strategy.
Industrial New Product Launch Strategies and Product Development Performance
Authors: Hultink Erik Jan , Griffin Abbie , Hart Susan , Robben Henry S. J.
Published: October 2003

Just as reporters must answer a few fundamental questions in every story they write, decision‐makers in the new product development (NPD) process must address five key issues: what to launch, where to launch, when to launch, why to launch, and how to launch. These decisions involve significant commitments of time, money, and resources. They also go a long way toward determining the success or failure of any new product. Deeper insight into the tradeoffs these decisions involve may help to increase the likelihood of success for product launch efforts.

Erik Jan Hultink, Abbie Griffin, Susan Hart, and Henry Robben present the results of a study that examines the interplay between these product launch decisions and NPD performance. Noting that previous launch studies focus primarily on the tactical decisions (that is, how to launch) rather than on the strategic decisions (what, where, when, and why to launch), they explore not only which decisions are important to success, but also the associations between the two sets of decisions. Because the strategic launch decisions made early in the NPD process affect the tactical decisions made later in the process, their study emphasizes the importance of launch consistency—that is, the alignment of the strategic and tactical decisions made throughout the process. The survey respondents—managers from marketing, product development, or general management in U.K. firms—provided information about 221 industrial new products launched during the previous five years.

The responses identify associations between various sets of strategic and tactical decisions. That is, the responses suggest that the strategic decisions managers make regarding product innovativeness, market targeting, the number of competitors, and whether the product is marketing‐ or technology‐driven are associated with subsequent tactical decisions regarding branding, distribution expenditure and intensity, and pricing.

The study also suggests that different sets of launch decisions have differing effects on performance of industrial new products. In this study, the greatest success was enjoyed by a small group of respondents categorized as Niche Innovators. Their launch strategy involves a niche focus, targeting innovative products into markets with few competitors. Tactical decisions made by this group include exclusive distribution, a skimming pricing strategy, and a broad product assortment.
PDMA Research on New Product Development Practices: Updating Trends and Benchmarking Best Practices
Authors: Griffin Abbie
Published: October 2003

Product development professionals may have the feeling that yet another buzzword or magic bullet always lurks just around the corner. However, researchers have devoted considerable effort to helping practioners determine which tools, techniques, and methods really do offer a competitive edge. Starting 30 years ago, research efforts have aimed at understanding NPD practices and identifying those which are deemed “best practices.” During the past five years, pursuit of this goal has produced numerous privately available reports and two research efforts sponsored by the PDMA.

Abbie Griffin summarizes the results of research efforts undertaken during the past five years and presents findings from the most recent PDMA survey on NPD best practices. This survey, conducted slightly more than five years after PDMA's first best‐practices survey, updates trends in processes, organizations, and outcomes for NPD in the U.S., and determines which practices are more commonly associated with firms that are more successsful in developing new products. The survey has the following objectives: determining the current status of NPD practices and performance; understanding how product development has changed from five years ago; determining whether NPD practice and performance differ across industry segments; and, investigating process and product development tools that differentiate product development success.

The survey findings indicate that NPD processes continue to evolve and become more sophisticated. NPD changes continually on multiple fronts, and firms that fail to keep their NPD practices up to date will suffer an increasingly marked competitive disadvantage. Interestingly, although more than half of the respondents use a cross‐functional stage‐gate process for NPD, more than one‐third of all firms in the study still use no formal process for managing NPD.

The findings suggest that firms are not adequately handling the issue of team‐based rewards. Project‐completion dinners are for the most frequently used NPD reward; they are also the only reward used more by best‐practice firms than by the rest of the respondents. The best‐practice firms participating in the study do not use financial rewards for NPD. Compared to the other firms in the study, best‐practice firms use more multifunctional teams, are more likely to measure NPD processes and outcomes, and expect more from their NPD programs.