bluuebunny/crossref_metadata_2025 huggingface dataset:
High-performance, hysteresis-free carbon nanotube field-effect transistors via directed assembly
Authors: McGill Stephen A. , Rao Saleem G. , Manandhar Pradeep , Xiong Peng , Hong Seunghun
Published: October 2006

High-performance, single-wall carbon nanotube field-effect transistors (SWCNT-FETs) are fabricated using directed assembly and mass-produced carbon nanotubes (CNTs). These FETs exhibit operating characteristics comparable to state-of-the-art devices, and the process provides a route to large-scale functional CNT circuit assembly that circumvents problems inherent in processes relying on chemical vapor deposition. Furthermore, the integration of hydrophobic self-assembled monolayers in the device structure eliminates the primary source of gating hysteresis in SWCNT-FETs; this leads to hysteresis-free FET operation while exposing unmodified nanotube surfaces to ambient air.
Developing and Evaluating Small-Area Indicators of the Neighbourhood Social Environment
Authors: Twigg Liz , Barnard Steve , Mohan John , Jones Kelvyn
Published: October 2006

We describe a method of producing small-area estimates of characteristics of the neighbourhood social environment, such as participation in associational life. The method may be characterised as ‘modelling nationally, and predicting locally’ because the initial models are estimated using multilevel data derived from national datasets, calibrated to allow for within-region as well as between-region variation. These models produce coefficients which can then be applied to socioeconomic data at the local scale. As an example we outline a model of the determinants of volunteering. This indicates significant variation between places in the relationship between individual and area characteristics which influence the probability of volunteering. Then we proceed to show how this can be used to generate predictions of the variations between places in a number of aspects of the social environment. The estimates we produce are validated against survey data from other surveys, and a satisfactory degree of correlation is obtained, giving us confidence in the estimates we have produced.
Performing Regions: Territorial Development and Cultural Politics in a Europe of the Regions
Authors: Donaldson Andrew
Published: October 2006

In this paper I examine the politics of regional development in the European Union from the perspective of language and identity. The idea that regions are performed through forms of knowledge and political practice is advanced and explored through an engagement with development as a discourse. Within the European Union regional-development discourse is inextricably tied into the cultural political rhetoric of the ‘Europe of the Regions' concept. Local actors can utilise the discourse of development as a political resource. To illustrate this process the concept of cultural literacy is developed and explored through a case study of cultural and political activism related to the European Union Objective 1 programme in Cornwall in the South West of England. Cultural literacy refers to knowledge that aids in the assimilation of further knowledge (about a specific culture) through the creation and comprehension of tailored communications; such knowledge is inherently political and can act as a central constituent of a social identity. The discourse of European regional development itself can also be coopted into new cultural literacies towards specific political goals. In this way regional development discourses can become part of the performance of regions.
Theorizing with GIS: A Tool for Critical Geographies?
Authors: Pavlovskaya Marianna
Published: October 2006

In this paper I explore the potential of using geographical information systems (GIS) in qualitative research by disentangling the seemingly rigid association of the field of geographic information science with quantitative geography. I examine the opposition between quantitative and qualitative methods as an extension of different epistemologies and not as indicative of their innate incompatibility, and reposition GIS within these methods seen as a continuum. I show that the always-assumed alignment of GIS with quantitative research has never been complete and the many openings in GIS enable qualitative research. I also discuss how critical geographers can engage with and transform GIS as well as enhance their explanations and social theory in general by representing spatially complex social processes and relationships.
Prospects for Qualitative GIS at the Intersection of Youth Development and Participatory Urban Planning
Authors: Dennis Samuel F
Published: October 2006

In this paper I report on a participatory planning project undertaken in a community engaged in a ten-year revitalization effort. Working with several youth-serving organizations, a community planning project was conducted in which local youth collected qualitative data about their neighborhood through a variety of techniques (photography, drawings, narratives). The project took place against the backdrop of an emerging neighborhood indicators geographical information system (GIS) aimed at tracking the impact of the revitalization effort. Although techniques for collecting and using qualitative data have matured during several decades of use in the field of participatory planning and development, their effective incorporation into GIS remains elusive. Although few technical barriers remain, the absence of stakeholder participation and the lack of community capacity to implement a community-based GIS are important obstacles to a fully realized qualitative GIS. Drawing on the youth-development literature, I demonstrate in this case study the potential of qualitative GIS for engaging young people in participatory planning, while also highlighting the continuing challenge to its implementation.
Exploring the engine of anthropogenic iron cycles
Authors: Müller Daniel B. , Wang Tao , Duval Benjamin , Graedel T. E.
Published: October 2006

Stocks of products in use are the pivotal engines that drive anthropogenic metal cycles: They support the lives of people by providing services to them; they are sources for future secondary resources (scrap); and demand for in-use stocks generates demand for metals. Despite their great importance and their impacts on other parts of the metal cycles and the environment, the study of in-use stocks has heretofore been widely neglected. Here we investigate anthropogenic and geogenic iron stocks in the United States (U.S.) by analyzing the iron cycle over the period 1900–2004. Our results show the following. (
i
) Over the last century, the U.S. iron stock in use increased to 3,200 Tg (million metric tons), which is the same order of magnitude as the remaining U.S. iron stock in identified ores. On a global scale, anthropogenic iron stocks are less significant compared with natural ores, but their relative importance is increasing. (
ii
) With a perfect recycling system, the U.S. could substitute scrap utilization for domestic mining. (
iii
) The per-capita in-use iron stock reached saturation at 11–12 metric tons in ≈1980. This last finding, if applicable to other economies as well, could allow a significant improvement of long-term forecasting of steel demand and scrap availability in emerging market economies and therefore has major implications for resource sustainability, recycling technology, and industrial and governmental policy.
The gene responsible for borate cross-linking of pectin Rhamnogalacturonan-II is required for plant reproductive tissue development and fertilization
Authors: Iwai Hiroaki , Hokura Akiko , Oishi Masahiro , Chida Hiroshi , Ishii Tadashi , Sakai Shingo , Satoh Shinobu
Published: October 2006

Deficiencies in boron, a microelement that is essential for the growth and development of higher plants, often cause problems in reproductive growth. Rhamnogalacturonan-II (RG-II) in cell wall pectin acts as the sole receptor for boron in plant cells, forming a borate cross-linked RG-II dimer (dRG-II-B), but the physiological functions of dRG-II-B remain unknown. We have previously shown that the pectin glucuronyltransferase 1 gene
NpGUT1
, which is involved in the biosynthesis of RG-II sugar chains, is essential for the formation of the RG-II-B complex, resulting in tight intercellular attachment in meristematic tissues. Because
NpGUT1
expression was found to be abundant in reproductive organs in addition to meristematic tissues, we analyzed the expression and functions of
NpGUT1
in more detail in tobacco reproductive tissues. Specific
NpGUT1
expression was detected in the tapetum of flower buds and in the pollen, pollen tube tips, and transmitting tissue of the pistils of flowers. Dexamethasone-induced expression of the
NpGUT1
antisense gene in flower buds resulted in the formation of sterile flowers with aberrant development of pollen and transmitting tissue. Pollen tubes could not pass through pistils with aborted transmitting tissue, and expression of an
NpGUT1
antisense gene in germinating pollen inhibited pollen tube elongation, accompanied by the absence of pectin RG-II and boron in the pollen tube tip. These results indicate that expression of
NpGUT1
is required for the development and functions of male and female tissues.
PGC-1α protects skeletal muscle from atrophy by suppressing FoxO3 action and atrophy-specific gene transcription
Authors: Sandri Marco , Lin Jiandie , Handschin Christoph , Yang Wenli , Arany Zoltan P. , Lecker Stewart H. , Goldberg Alfred L. , Spiegelman Bruce M.
Published: October 2006

Maintaining muscle size and fiber composition requires contractile activity. Increased activity stimulates expression of the transcriptional coactivator PGC-1α (peroxisome proliferator-activated receptor γ coactivator 1α), which promotes fiber-type switching from glycolytic toward more oxidative fibers. In response to disuse or denervation, but also in fasting and many systemic diseases, muscles undergo marked atrophy through a common set of transcriptional changes. FoxO family transcription factors play a critical role in this loss of cell protein, and when activated, FoxO3 causes expression of the atrophy-related ubiquitin ligases atrogin-1 and MuRF-1 and profound loss of muscle mass. To understand how exercise might retard muscle atrophy, we investigated the possible interplay between PGC-1α and the FoxO family in regulation of muscle size. Rodent muscles showed a large decrease in PGC-1α mRNA during atrophy induced by denervation as well as by cancer cachexia, diabetes, and renal failure. Furthermore, in transgenic mice overexpressing PGC-1α, denervation and fasting caused a much smaller decrease in muscle fiber diameter and a smaller induction of atrogin-1 and MuRF-1 than in control mice. Increased expression of PGC-1α also increased mRNA for several genes involved in energy metabolism whose expression decreases during atrophy. Transfection of PGC-1α into adult fibers reduced the capacity of FoxO3 to cause fiber atrophy and to bind to and transcribe from the atrogin-1 promoter. Thus, the high levels of PGC-1α in dark and exercising muscles can explain their resistance to atrophy, and the rapid fall in PGC-1α during atrophy should enhance the FoxO-dependent loss of muscle mass.
Functional reconstitution and characterization of
Pyrococcus furiosus
RNase P
Authors: Tsai Hsin-Yue , Pulukkunat Dileep K. , Woznick Walter K. , Gopalan Venkat
Published: October 2006

RNase P, which catalyzes the magnesium-dependent 5′-end maturation of tRNAs in all three domains of life, is composed of one essential RNA and a varying number of protein subunits depending on the source: at least one in bacteria, four in archaea, and nine in eukarya. To address why multiple protein subunits are needed for archaeal/eukaryal RNase P catalysis, in contrast to their bacterial relative,
in vitro
reconstitution of these holoenzymes is a prerequisite. Using recombinant subunits, we have reconstituted
in vitro
the RNase P holoenzyme from the thermophilic archaeon
Pyroccocus furiosus
(
Pfu
) and furthered our understanding regarding its functional organization and assembly pathway(s). Whereas
Pfu
RNase P RNA (RPR) alone is capable of multiple turnover, addition of all four RNase P protein (Rpp) subunits to
Pfu
RPR results in a 25-fold increase in its
k
cat
and a 170-fold decrease in
K
m
. In fact, even in the presence of only one of two specific pairs of Rpps, the RPR displays activity at lower substrate and magnesium concentrations. Moreover, a pared-down, mini-
Pfu
RNase P was identified with an RPR deletion mutant. Results from our kinetic and footprinting studies on
Pfu
RNase P, together with insights from recent structures of bacterial RPRs, provide a framework for appreciating the role of multiple Rpps in archaeal RNase P.
Modelling the biomechanical properties of DNA using computer simulation
Authors: Harris Sarah Anne
Published: October 2006

Duplex DNA must remain stable when not in use to protect the genetic material. However, the two strands must be separated whenever genes are copied or expressed to expose the coding strand for synthesis of complementary RNA or DNA bases. Therefore, the double stranded structure must be relatively easy to take apart when required. These conflicting biological requirements have important implications for the mechanical properties of duplex DNA. Considerable insight into the forces required to denature DNA has been provided by nanomanipulation experiments, which measure the mechanical properties of single molecules in the laboratory. This paper describes recent computer simulation methods that have been developed to mimic nanomanipulation experiments and which, quite literally, ‘destruction test’ duplex DNA
in silico
. The method is verified by comparison with single molecule stretching experiments that measure the force required to unbind the two DNA strands. The model is then extended to investigate the thermodynamics of DNA bending and twisting. This is of biological importance as the DNA must be very tightly packaged to fit within the nucleus, and is therefore usually found in a highly twisted or
supercoiled
state (in bacteria) or wrapped tightly around histone proteins into a densely compacted structure (in animals). In particular, these simulations highlight the importance of thermal fluctuations and entropy in determining the biomechanical properties of DNA. This has implications for the action of DNA processing molecular motors, and also for nanotechnology. Biological machines are able to manipulate single molecules reliably on an energy scale comparable to that of thermal noise. The hope is that understanding the statistical mechanisms that a cell uses to achieve this will be invaluable for the future design of ‘nanoengines’ engineered to perform new technological functions at the nanoscale.
Locating mammalian transcription factor binding sites: A survey of computational and experimental techniques
Authors: Elnitski Laura , Jin Victor X. , Farnham Peggy J. , Jones Steven J.M.
Published: October 2006

Fields such as genomics and systems biology are built on the synergism between computational and experimental techniques. This type of synergism is especially important in accomplishing goals like identifying all functional transcription factor binding sites in vertebrate genomes. Precise detection of these elements is a prerequisite to deciphering the complex regulatory networks that direct tissue specific and lineage specific patterns of gene expression. This review summarizes approaches for in silico, in vitro, and in vivo identification of transcription factor binding sites. A variety of techniques useful for localized- and high-throughput analyses are discussed here, with emphasis on aspects of data generation and verification.
Whole-genome comparison of Leu3 binding in vitro and in vivo reveals the importance of nucleosome occupancy in target site selection
Authors: Liu Xiao , Lee Cheol-Koo , Granek Joshua A. , Clarke Neil D. , Lieb Jason D.
Published: October 2006

Sequence motifs that are potentially recognized by DNA-binding proteins occur far more often in genomic DNA than do observed in vivo protein–DNA interactions. To determine how chromatin influences the utilization of particular DNA-binding sites, we compared the in vivo genome-wide binding location of the yeast transcription factor Leu3 to the binding location observed on the same genomic DNA in the absence of any protein cofactors. We found that the DNA-sequence motif recognized by Leu3 in vitro and in vivo was functionally indistinguishable, but Leu3 bound different genomic locations under the two conditions. Accounting for nucleosome occupancy in addition to DNA-sequence motifs significantly improved the prediction of protein–DNA interactions in vivo, but not the prediction of sites bound by purified Leu3 in vitro. Use of histone modification data does not further improve binding predictions, presumably because their effect is already manifest in the global histone distribution. Measurements of nucleosome occupancy in strains that differ in Leu3 genotype show that low nucleosome occupancy at loci bound by Leu3 is not a consequence of Leu3 binding. These results permit quantitation of the epigenetic influence that chromatin exerts on DNA binding-site selection, and provide evidence for an instructive, functionally important role for nucleosome occupancy in determining patterns of regulatory factor targeting genome-wide.
Measuring average alcohol consumption: the impact of including binge drinks in quantity–frequency calculations
Authors: Stahre Mandy , Naimi Timothy , Brewer Robert , Holt James
Published: October 2006

Aims  Average daily alcohol consumption is usually calculated based on self‐reports of the quantity (number of drinks consumed per drinking‐day) and frequency (number of drinking‐days) of alcohol consumption within a given time period. However, this method may underestimate average daily alcohol consumption (and in turn, the prevalence of heavy drinking), because studies demonstrate that respondents do not typically include binge drinking occasions in estimates of their ‘usual’ or ‘average’ daily alcohol consumption.

Design  We used the Behavioral Risk Factor Surveillance System (BRFSS), an annual random‐digit telephone survey of US adults aged 18 years or older, to estimate average daily alcohol consumption using standard quantity–frequency questions, and then recalculated this measure by including self‐reports of binge drinking. The proportion of respondents who met a standard, sex‐specific definition of heavy drinking based on average daily alcohol consumption was then assessed nationally and for each state.

Findings  Compared to standard quantity–frequency methods, including binge drinks in calculations of average daily alcohol consumption increased the relative prevalence of heavy drinking among all adults by 19% to 42% (depending on the method used to estimate the number of drinks per binge). Among binge drinkers, the overall prevalence of heavy drinking increased 53% relative to standard quantity–frequency methods. As a result, half of women binge drinkers and half of binge drinkers aged 55 or older met criteria for heavy drinking.

Conclusions  Including binge drinks (especially the application of age‐ and sex‐specific estimates of binge drinks) in the calculation of average daily alcohol consumption can improve the accuracy of prevalence estimates for heavy drinking among US adults, and should be considered to increase the usefulness of this measure for alcohol surveillance.
Effects of low‐dose continuous combined hormone replacement therapy on glucose homeostasis and markers of cardiovascular risk in women with type 2 diabetes
Authors: Kernohan A. F. B. , Sattar N. , Hilditch T. , Cleland S. J. , Small M. , Lumsden M. A. , Connell J. M. C. , Petrie J. R.
Published: October 2006

Background  Low‐dose hormone replacement therapy (HRT) has attracted interest for the treatment of postmenopausal symptoms in diabetes because of concerns about increased risk of coronary heart disease (CHD) and stroke with conventional HRT containing conjugated equine oestrogens (CEEs) and medroxyprogesterone acetate (MPA).

Objectives  We assessed the effects on glucose homeostasis and cardiovascular risk factors of continuous oral 17β oestradiol (1 mg) and norethisterone (0·5 mg) in postmenopausal women with type 2 diabetes.

Design  Double‐blind, randomized placebo‐controlled trial.

Assessments  Hyperinsulinaemic isoglycaemic clamp and cardiovascular risk factors were assessed before and after 3 months of treatment.

Results  Twenty‐eight women completed the study. HRT decreased fasting glucose compared with placebo [−9·4% with HRT vs.+2·3% for placebo, 95% confidence interval (CI) −23·2 to −0·3] and total cholesterol (−13·7 vs.+1·0%, 95% CI −22·4 to −3·1%) No significant effect was seen on metabolic clearance rate of glucose, glycated haemoglobin (HbA1c), triglycerides, high density lipoprotein (HDL)‐cholesterol or C‐reactive protein (CRP).

Conclusions  In women with type 2 diabetes, low‐dose HRT decreased fasting glucose and total cholesterol without detectable adverse effects on glucose clearance, triglycerides and CRP as reported with conventional HRT.
Estimation of the day‐specific probabilities of conception: current state of the knowledge and the relevance for epidemiological research
Authors: Lynch Courtney D. , Jackson Leila W. , Buck Louis Germaine M.
Published: October 2006

Conception, as defined by the fertilisation of an ovum by a sperm, marks the beginning of human development. Currently, a biomarker of conception is not available; as conception occurs shortly after ovulation, the latter can be used as a proxy for the time of conception. In the absence of serial ultrasound examinations, ovulation cannot be readily visualised leaving researchers to rely on proxy measures of ovulation that are subject to error. The most commonly used proxy measures include: charting basal body temperature, monitoring cervical mucus, and measuring urinary metabolites of oestradiol and luteinising hormone.

Establishing the timing of the ovulation and the fertile window has practical utility in that it will assist couples in appropriately timing intercourse to achieve or avoid pregnancy. Identifying the likely day of conception is clinically relevant because it has the potential to facilitate more accurate pregnancy dating, thereby reducing the iatrogenic risks associated with uncertain gestation. Using data from prospective studies of couples attempting to conceive, several researchers have developed models for estimating the day‐specific probabilities of conception. Elucidating these will allow researchers to more accurately estimate the day of conception, thus spawning research initiatives that will expand our current limited knowledge about the effect of exposures at critical periconceptional windows. While basal body temperature charting and cervical mucus monitoring have been used with success in field‐based studies for many years, recent advances in science and technology have made it possible for women to get instant feedback regarding their daily fertility status by monitoring urinary metabolites of reproductive hormones in the privacy of their own homes. Not only are innovations such as luteinising hormone test kits and digital fertility monitors likely to increase study compliance and participation rates, they provide valuable prospective data that can be used in epidemiological research. Although we have made great strides in estimating the timing and length of the fertile window, more work is needed to elucidate the day‐specific probabilities of conception using proxy measures of ovulation that are inherently subject to error. Modelling approaches that incorporate the use of multiple markers of ovulation offer great promise to fill these important data gaps.
Anti‐tumour necrosis factor‐α activity in Ixodes ricinus saliva
Authors: KONÍK P. , SLAVÍKOVÁ V. , SALÁT J. , ŘEZNÍČKOVÁ J. , DVOROŽŇÁKOVÁ E. , KOPECKÝ J.
Published: October 2006

Tumour necrosis factor‐α (TNF‐α) is one of the most prominent inflammatory mediators playing a central role in starting off the inflammatory reactions of the innate immune system. We identified a TNF‐α‐inhibitory activity in the saliva and salivary gland extract (SGE) from partially fed Ixodes ricinus ticks. Using mouse and human TNF‐α specific ELISA, we showed that tick saliva or SGE markedly reduced the level of detectable cytokine. Both saliva and SGE inhibited the cytotoxic effect of TNF‐α in a bioassay. Elimination of the TNF‐α‐inhibitory activity in SGE by trypsin digestion demonstrated that the anti‐TNF‐α factor is a protein. Fast protein liquid chromatography fractionation of SGE showed one peak of TNF‐α‐inhibitory activity corresponding to a protein with estimated molecular mass 23 kDa. The likely mechanism of the inhibitory effect is a direct binding of the cytokine. The TNF‐α‐inhibitory molecule seems to play an important role in the anti‐inflammatory effect of tick saliva at the tick feeding site, providing a gateway to the host for tick‐borne pathogens.
The Arabidopsis MAP kinase kinase MKK1 participates in defence responses to the bacterial elicitor flagellin
Authors: Mészáros Tamás , Helfer Anne , Hatzimasoura Elizabeth , Magyar Zoltán , Serazetdinova Liliya , Rios Gabino , Bardóczy Viola , Teige Markus , Koncz Csaba , Peck Scott , Bögre László
Published: October 2006

Plants sense pathogens through both pathogen‐associated molecular patterns and recognition of race‐specific virulence factors, which induce basal defence or an accelerated defence (often manifest in the form of local cell death), respectively. A mitogen‐activated protein kinase (MAPK) module in Arabidopsis was previously proposed to signal from perception of the bacterial elicitor flagellin to the activation of basal defence‐related genes. Here, we present evidence for a parallel MAPK‐signalling pathway involved in the response to flg22, a peptide corresponding to the most conserved domain of flagellin. The endogenous Arabidopsis MAP kinase kinase MKK1 is activated in cells treated with flg22, phosphorylates the MAPK MPK4 in vitro, and activates it in vivo in protoplasts. In mkk1 mutant plants, the activation by flg22 of MPK4 and two other flg22‐induced MAPKs (MPK3 and MPK6) is impaired. In the mkk1 mutant, a battery of both flg22‐induced and flg22‐repressed genes show altered expression, indicating that MKK1 negatively regulates the activity of flagellin‐responsive genes. Intriguingly, in contrast to the mpk4 mutant, mkk1 shows no morphological anomalies and is compromised in resistance to both virulent and avirulent Pseudomonas syringae strains. Thus, the MKK1 signalling pathway modulates the expression of genes responding to elicitors and plays an important role in pathogen defence.
Haematological and biochemical indices in young African children: in search of reference intervals
Authors: Quintó Llorenç , Aponte John J. , Sacarlal Jahit , Espasa Mateu , Aide Pedro , Mandomando Inacio , Guinovart Caterina , Macete Eusebio , Navia Margarita M. , Thompson Ricardo , Menéndez Clara , Alonso Pedro L.
Published: October 2006

Introduction  The reference intervals of haematological and biochemical indices currently used in Africa are derived from data collected from populations living in industrialized countries. Few studies have been performed in Africa questioning the validity of these values when applied to local African populations.

Objective  To provide reference intervals of haematological [haemoglobin (Hb), white blood cells (WBC), haematocrit (Htc) and platelets] and biochemical indices (ALT, creatinine and bilirubin) for children aged 1–4 from a rural area of southern Mozambique.

Methods  Reference intervals were developed using the 2.5 and 97.5 centiles. Partition tests were performed to evaluate age and gender differences. Quantile regression models were estimated for those variables in which age partition was recommended. Deviances from linearity in the estimated models were evaluated using fractional polynomials of first or second degree. Agreement to classify normality, using the estimated reference intervals or values in use in a western paediatric hospital, was made using the kappa statistic.

Results  Reference intervals for Hb, WBC, Htc, platelets, ALT and creatinine show significant differences by age. Gender differences were observed for creatinine values, while for bilirubin there were no significant differences for age or gender. Estimated Hb and Htc reference intervals in African children were lower than the accepted western ones, while ALT values were higher in the former. Agreement between normal classification, using the estimated intervals or the western values, was from slight to fair.

Conclusions  Reference intervals of haematological and biochemical indices based on results from western individuals of the same age are not in agreement with the estimated values for African children. These observed values should not be used as a rule to define normality, but are the ones usually found in this population where anaemia, malaria and high mortality rates are also common.
Species Recognition Influences Female Mate Preferences in the Common European Grasshopper (Chorthippus biguttulus Linnaeus, 1758)
Authors: Safi Kamran , Heinzle Jakob , Reinhold Klaus
Published: October 2006

Species recognition and intraspecific mating preferences constitute two basic aspects of animal communication. Both can be considered as variations in response to signals and it has been suggested that they represent a continuum. Selection on species recognition could therefore influence intraspecific mating preferences. We show that females of the common European grasshopper Chorthippus biguttulus prefer conspecific male signals that can be distinguished more reliably from sympatrically occurring heterospecific signals. This suggests that in C. biguttulus, sexual selection might be influenced by pleiotropic effects from species recognition. The results show how the heterospecific signal environment could have determined why and in which direction specific traits become sexually selected.
Facing the challenges of e‐learning initiatives in African universities
Authors: Gunga Samson O. , Ricketts Ian W.
Published: October 2006

This paper explores the possibility of bringing e‐learning to African universities through collaborative networks of public–private partnerships. It is envisaged that this approach will solve the dual problem of infrastructural barriers and weak ICT policies. As technology is used more in education, the teachers’ roles are increasingly integrated with those of support staff, administrators and technical staff. The needs of e‐learning environments suggest the viability of multistakeholder networks to share expertise and resolve issues related to training needs. The paper concludes that collaboration networks that include e‐learning sponsors, policy makers, telecommunication network service providers and educators are required to solve the problems of online education in Africa.
The Role of Investment, Financing and Dividend Decisions in Explaining Corporate Ownership Structure: Empirical Evidence from Spain
Authors: Pindado Julio , De La Torre Chabela
Published: October 2006

This paper analyses the determinants of ownership structure by focusing on the role played by investment, financing and dividend decisions. The use of the Generalised Method of Moments allows us to provide new evidence on this important corporate governance topic, since it controls for the endogeneity problem. Our most relevant findings show that: i) increases in debt lead insiders to limit the risk they bear by reducing their holdings; ii) monitoring by large outside owners substitutes for the disciplinary role of debt; and iii) both inside and outside owners are encouraged to increase their stakes in the firm in view of higher dividends. Our results hold after controlling for equity issues and share repurchases.
The Effect of Family Control on Firm Value and Performance: Evidence from Continental Europe
Authors: Barontini Roberto , Caprio Lorenzo
Published: October 2006

We investigate the relation between ownership structure and firm performance in Continental Europe, using data from 675 publicly traded corporations in 11 countries. Although family‐controlled corporations exhibit larger separation between control and cash‐flow rights, our results do not support the hypothesis that family control hampers firm performance. Valuation and operating performance are significantly higher in founder‐controlled corporations and in corporations controlled by descendants who sit on the board as non‐executive directors. When a descendant takes the position of CEO, family‐controlled companies are not statistically distinguishable from non‐family firms in terms of valuation and performance.
The Impact of Corporate Governance on Closed‐end Funds
Authors: Gemmill Gordon , Thomas Dylan C.
Published: October 2006

This study uses a large sample of UK‐listed closed‐end funds to examine whether governance has an impact on two indicators of fund performance: the level of fund‐management fees and the discount at which a fund trades. Fees are under the control of the directors, and we find that they are inversely related to fund returns, even after allowing for differences across investment sectors. Fees are, on average, higher if a fund has a large board, few directors from outside the fund‐family, many directors from within the fund‐family, and low ownership by the management company. Discounts for funds are wider if the management company or any blockholder has a significant long‐term stake, suggesting that investors are wary of entrenched management. The results suggest that boards are frequently compromised in their duty to shareholders by their dependence on fund‐management companies.
Bringing High Technology to Market: Successful Strategies Employed in the Worldwide Software Industry
Authors: Easingwood Chris , Moxey Steven , Capleton Henry
Published: October 2006

The launch stage can be critical for many new products, but particularly so for technology‐intensive ones. This study examines this key stage in a high‐tech sector: the worldwide computer software industry. Using a research instrument developed across a number of high‐tech sectors, but adapted to the targeted sector, it describes a worldwide telephone‐based survey of 300 organizations, resulting in 190 interviews, a response rate of 63%. It shows that five distinct and interpretable strategies are employed: (1) alliance strategy involves forming early strategic alliances as well as tactical alliances at the execution stage together with the development of unique distribution channels; (2) targeted low risk attempts to reduce the risk of adoption among identified segments by producing versions of the product specifically customized to the segments; (3) low‐price original equipment manufacturer (OEM) is the only price‐driven strategy and combines low price with channel building to OEMs who are looking for attractive price‐to‐performance ratios; (4) broadly based market preparation is an early‐stage strategy that concentrates on educating the market vis‐à‐vis the technology and developing channels; and (5) niche‐based technological superiority uses a technologically superior product to dominate a niche and corresponds closely to the chasm‐crossing strategy expounded by Moore and others. Regarding superior product performance, successful software companies first of all engage in a broadly based preparation of the market but switch to a targeted strategy at the following stages of positioning and execution, built around superior technological performance and reduced risk. A somewhat different mix of strategies is adopted when the objective is superior market development, namely opening up new markets, reaching new customers, and developing new product platforms. Again the mix includes broadly based market preparation, this time along with alliances. This strategy is very much about working with partners. The broadly based market preparation strategy is key for both objectives, is long term in nature, and avoids narrowly defined niches. It seems that starting broad based and narrowing down, perhaps to a niche, only at a later stage when this is clearly the appropriate thing to do, pays dividends.
Innovation that Fits by Michael Lord, Donald DeBethizy, and Jeffrey Wager
Authors: Kingston George
Published: October 2006

Although accidental, the last three of the reviews in this set follow a theme: They all address high levels of uncertainty and change in projects, which is what one encounters when developing a highly innovative product where the market, customer usage patterns, and the technology are being explored as the product is being developed. First, Roman Pichler reviews a book on agile estimating and planning, which describes agile software development methods applicable to planning and estimating nonsoftware products subject to high rates of change. Next, I review one on managing risk in high‐uncertainty projects. Finally, Carla Kuesten reviews a set of case studies from modern China where change and uncertainty abound.

Interestingly, these reviewers follow their own advice, applying a major tool for operating in uncertain situations: iteration. Pichler's review went through eight versions before it was final, and Kuesten topped him at nine.

Books reviewed in this issue:

Innovation that Fits

Agile Estimating and Planning

Managing the Unknown: A New Approach to Managing High Uncertainty and Risk in Projects

Made in China: What Western Managers Can Learn from Trailblazing Chinese Entrepreneurs
Intracellular Trafficking of RNA in Neurons
Authors: Sossin Wayne S. , DesGroseillers Luc
Published: October 2006

The transport of messenger RNAs (mRNAs) in neurons serves many purposes. During development, trafficking of mRNAs to both axonal and dendritic growth cones regulates neuronal growth. After synapse formation, mRNAs continue to be transported to dendrites both as a mechanism for the localization of proteins to specific compartments and as a substrate for local translational regulation of synaptic plasticity. Finally, activity‐dependent mRNAs are transported quickly to dendrites after transcription. Determining how mRNAs are transported and specifically translated in these different paradigms is a major unanswered question. Addressing this question is also complicated by the presence of many other RNA processing and storage centers that may not be involved in transport but share components with the transport structures. In the present review, we will discuss several recent studies addressing mechanisms of mRNA transport in neurons, as well as proteomic characterization of mRNA transporting structures in neurons. We define two types of RNA transport structures in neurons, transport particles and RNA granules and distinguish them by the presence or absence of ribosomes. We will present a number of different molecular models for how mRNAs are repressed during transport, and how these may affect the regulation of local translation in neurons.
A time‐dependent effect of PDGF‐BB on adhesion and growth of cultured fibroblasts to root surfaces
Authors: Belal MH , Watanabe H , Ichinose S , Ishikawa I
Published: October 2006

Objective:  Platelet‐derived growth factor (PDGF‐BB) is suggested to be a potent stimulator and a strong mitogenic agent for human periodontal ligament cells (PDL). This study aimed at assessing the effectiveness of PDGF‐BB application on periodontally diseased root surfaces through attachment and growth of fibroblast cells.

Materials and methods:  Fifteen periodontally involved and five healthy teeth were selected, prepared from proximal surfaces and distributed into four groups (10 specimens per group): I: healthy; II: untreated diseased; III: scaling and root planning (SRP); and IV: SRP and PDGF‐BB. Each group had three subdivisions (three specimens per group) which were incubated at three different time periods. The remaining specimen for each group was used to examine surface topography. Fibroblasts were pooled on root specimens and incubated. Results were evaluated by using scanning electron microscopy. Repeated cell counting was done within a representative standard area.

Results:  The best results regarding PDL cell shape and density were obtained at day 3 in all experimental groups, except the diseased group. Although SRP samples showed slightly higher results in numbers of attached fibroblasts than diseased samples, they demonstrated a similar negative effect denoting incompatible root surfaces for fibroblast attachment. SRP plus PDGF‐BB and healthy samples showed a comparable positive effect, suggesting a good root surface biocompatibility. Inter‐group differences showed no significant differences on day 1, but statistically significant differences were found on both day 3 and day 7 incubation periods favoring groups I and IV over groups II and III.

Conclusions:  Platelet‐derived growth factor showed a positive effect on adhesion and growth of cultured fibroblasts to periodontally diseased surfaces. Thus, PDGF‐BB may have a promising role in clinical periodontics.
Gingival crevicular fluid matrix metalloproteinase‐13 levels and molecular forms in various types of periodontal diseases
Authors: İlgenli T , Vardar‐Sengul S , Gürkan A , Sorsa T , Stackelberg S , Köse T , Atilla G
Published: October 2006

Background:  The purpose of this study was to evaluate the levels, molecular forms and activation degree of matrix metalloproteinase‐13 (MMP‐13) in the gingival crevicular fluid (GCF) of patients with periodontal diseases and to correlate these findings with periodontal clinical parameters.

Methods:  Sixty one subjects participated in this study as healthy (n = 18), gingivitis (n = 17), aggressive periodontitis (AgP; n = 15) and chronic periodontitis (CP; n = 11) groups. Clinical measurements and GCF samples were obtained from each subject. The molecular forms of MMP‐13 in GCF samples were analyzed by Western immunoblotting method. Differences among the groups were assessed using non‐parametric statistical analysis.

Results:  In the CP group, levels of 29–30 kDa fragment of MMP‐13, total MMP‐13, and activated form of MMP‐13 were significantly higher than in the healthy, gingivitis and AgP groups. GCF levels of all molecular forms of MMP‐13 in AgP group were similar to those of healthy and gingivitis groups. Total and activated MMP‐13 levels were positively correlated with all clinical parameters. 29–30 kDa fragment levels of MMP‐13 were also positively correlated with papillary bleeding index and plaque index.

Conclusion:  These results indicate that elevated GCF MMP‐13 levels may play an important role in the pathogenesis of CP. These data demonstrate, for the first time, pathologically activated and elevated MMP‐13 in GCF.
Bone marrow‐derived mesenchymal stem cells for regenerative medicine in craniofacial region
Authors: Miura M , Miura Y , Sonoyama W , Yamaza T , Gronthos S , Shi S
Published: October 2006

The craniofacial region contains many specified tissues including bone, cartilage, muscle, blood vessels and neurons. Defect or dysfunction of the craniofacial tissue after post‐cancer ablative surgery, trauma, congenital malformations and progressive deforming skeletal diseases has a huge influence on the patient's life. Therefore, functional reconstruction of damaged tissues is highly expected. Bone marrow‐derived mesenchymal stem cells (BMMSCs) are one of the most well characterized postnatal stem cell populations, and considered to be utilized for cell‐based clinical therapies. Here, the current understanding and the potential applications in craniofacial tissue regeneration of BMMSCs are reviewed, and the current limitations and drawbacks are also discussed.
Mutation and evolutionary analyses identify NR2E1‐candidate‐regulatory mutations in humans with severe cortical malformations
Authors: Kumar R. A. , Leach S. , Bonaguro R. , Chen J. , Yokom D. W. , Abrahams B. S. , Seaver L. , Schwartz C. E. , Dobyns W. , Brooks‐Wilson A. , Simpson E. M.
Published: October 2006

Nuclear receptor 2E1 (NR2E1) is expressed in human fetal and adult brains; however, its role in human brain–behavior development is unknown. Previously, we have corrected the cortical hypoplasia and behavioral abnormalities in Nr2e1−/− mice using a genomic clone spanning human NR2E1, which bolsters the hypothesis that NR2E1 may similarly play a role in human cortical and behavioral development. To test the hypothesis that humans with abnormal brain–behavior development may have null or hypomorphic NR2E1 mutations, we undertook the first candidate mutation screen of NR2E1 by sequencing its entire coding region, untranslated, splice site, proximal promoter and evolutionarily conserved non‐coding regions in 56 unrelated patients with cortical disorders, namely microcephaly. We then genotyped the candidate mutations in 325 unrelated control subjects and 15 relatives. We did not detect any coding region changes in NR2E1; however, we identified seven novel candidate regulatory mutations that were absent from control subjects. We used in silico tools to predict the effects of these candidate mutations on neural transcription factor binding sites (TFBS). Four candidate mutations were predicted to alter TFBS. To facilitate the present and future studies of NR2E1, we also elucidated its molecular evolution, genetic diversity, haplotype structure and linkage disequilibrium by sequencing an additional 94 unaffected humans representing Africa, the Americas, Asia, Europe, the Middle East and Oceania, as well as great apes and monkeys. We detected strong purifying selection, low genetic diversity, 21 novel polymorphisms and five common haplotypes at NR2E1. We conclude that protein‐coding changes in NR2E1 do not contribute to cortical and behavioral abnormalities in the patients examined here, but that regulatory mutations may play a role.
Structure and function of the 3‐carboxy‐cis,cis‐muconate lactonizing enzyme from the protocatechuate degradative pathway of Agrobacterium radiobacter S2
Authors: Halak Sad , Lehtiö Lari , Basta Tamara , Bürger Sibylle , Contzen Matthias , Stolz Andreas , Goldman Adrian
Published: October 2006

3‐carboxy‐cis,cis‐muconate lactonizing enzymes participate in the protocatechuate branch of the 3‐oxoadipate pathway of various aerobic bacteria. The gene encoding a 3‐carboxy‐cis,cis‐muconate lactonizing enzyme (pcaB1S2) was cloned from a gene cluster involved in protocatechuate degradation by Agrobacterium radiobacter strain S2. This gene encoded for a 3‐carboxy‐cis,cis‐muconate lactonizing enzyme of 353 amino acids − significantly smaller than all previously studied 3‐carboxy‐cis,cis‐muconate lactonizing enzymes. This enzyme, ArCMLE1, was produced in Escherichia coli and shown to convert not only 3‐carboxy‐cis,cis‐muconate but also 3‐sulfomuconate. ArCMLE1 was purified as a His‐tagged enzyme variant, and the basic catalytic constants for the conversion of 3‐carboxy‐cis,cis‐muconate and 3‐sulfomuconate were determined. In contrast, Agrobacterium tumefaciens 3‐carboxy‐cis,cis‐muconate lactonizing enzyme 1 could not, despite 87% sequence identity to ArCMLE1, use 3‐sulfomuconate as substrate. The crystal structure of ArCMLE1 was determined at 2.2 Å resolution. Consistent with the sequence, it showed that the C‐terminal domain, present in all other members of the fumarase II family, is missing in ArCMLE1. Nonetheless, both the tertiary and quaternary structures, and the structure of the active site, are similar to those of Pseudomonas putida 3‐carboxy‐cis,cis‐muconate lactonizing enzyme. One principal difference is that ArCMLE1 contains an Arg, as opposed to a Trp, in the active site. This indicates that activation of the carboxylic nucleophile by a hydrophobic environment is not required for lactonization, unlike earlier proposals [Yang J, Wang Y, Woolridge EM, Arora V, Petsko GA, Kozarich JW & Ringe D (2004) Biochemistry43, 10424–10434]. We identified citrate and isocitrate as noncompetitive inhibitors of ArCMLE1, and found a potential binding pocket for them on the enzyme outside the active site.