bluuebunny/crossref_metadata_2025 huggingface dataset:
Heritability and genetic constraints of life-history trait evolution in preindustrial humans
Authors: Pettay Jenni E. , Kruuk Loeske E. B. , Jokela Jukka , Lummaa Virpi
Published: February 2005

An increasing number of studies have documented phenotypic selection on life-history traits in human populations, but less is known of the heritability and genetic constraints that mediate the response to selection on life-history traits in humans. We collected pedigree data for four generations of preindustrial (1745–1900) Finns who lived in premodern fertility and mortality conditions, and by using a restricted maximum-likelihood animal-model framework, we estimated the heritability of and genetic correlations between a suite of life-history traits and two alternative measures of fitness. First, we demonstrate high heritability of key life-history traits (fecundity, interbirth interval, age at last reproduction, and adult longevity) and measures of fitness (individual λ and lifetime reproductive success) for females but not for males. This sex difference may have arisen because most of the measured traits are under physiological control of the female, such that a male's fitness in monogamous societies may depend mainly on the reproductive quality of his spouse. We found strong positive genetic correlations between female age at first reproduction and longevity, and between interbirth intervals and longevity, suggesting reduced life spans in females who either started to breed relatively early or who then bred frequently. Our results suggest that key female life-history traits in this premodern human population had high heritability and may have responded to natural selection. However genetic constraints between longevity and reproductive life-history traits may have constrained the evolution of life history and facilitated the maintenance of additive genetic variance in key life-history traits.
The induction of matrix metalloproteinase and cytokine expression in synovial fibroblasts stimulated with immune cell microparticles
Authors: Distler Jörg H. W. , Jüngel Astrid , Huber Lars C. , Seemayer Christian A. , Reich Charles F. , Gay Renate E. , Michel Beat A. , Fontana Adriano , Gay Steffen , Pisetsky David S. , Distler Oliver
Published: February 2005

Rheumatoid arthritis is a chronic inflammatory disease characterized by destruction of cartilage and bone that is mediated by synovial fibroblasts. To determine the mechanisms by which these cells are activated to produce matrix metalloproteinases (MMPs), the effects of microparticles were investigated. Microparticles are small membrane-bound vesicles whose release from immune cells is increased during activation and apoptosis. Because microparticles occur abundantly in the synovial fluid in rheumatoid arthritis, they could represent novel stimulatory agents. Microparticles derived from T cells and monocytes strongly induced the synthesis of MMP-1, MMP-3, MMP-9, and MMP-13 in fibroblasts. The induction was time-dependent, with effects primarily observed after 36 h; under these conditions, MMP-2, MMP-14, and tissue inhibitor of MMP-1 (TIMP-1), TIMP-2, and TIMP-3 were not induced. Microparticles also increased the synthesis of inflammatory mediators including IL-6, IL-8, monocyte chemoattractant protein 1 (MCP-1), and MCP-2. In Iκ-B-transfected synovial fibroblasts, MMPs were less inducible by microparticles compared with wild-type fibroblasts. Blocking of TNFα and IL-1β with antibodies against TNFα and with IL-1 receptor antagonist did not abrogate stimulation by microparticles. These data provide evidence for a novel mechanism by which vesicles derived from activated or apoptotic immune cells can promote the destructive activity of synovial fibroblasts in rheumatoid arthritis.
Accrediting Prior Learning
Authors: Hamill John , Sutherland John
Published: February 2005

Research was undertaken in 1992 to evaluate the success of the “Portfolio
Exercise” on which entry into the suite of post‐graduate programmes in
personnel management at Leeds Business School was based. Describes the
suite of personnel programmes available within the School, identifying
where the portfolio exercise was used to allow non‐standard entry. Goes
on to describe the research methods used in the inquiry and concludes
with a report on the non‐standard entrants′ perceptions of the portfolio
exercise.
The international management of change: a problem‐based
learning/case study approach
Authors: Cockerill Steve , Stewart Gerry , Hamilton Les , Douglas John , Gold Jeff
Published: February 2005

Reports on the development of a module concerning the
international management of change by a multidisciplined team at
Leeds Metropolitan University. The aim of the module is to enable
students to combine problem‐based learning within an action research
methodology using a case study to highlight the nature and processes
of change within international business organizations. Explains the
underlying rationale and describes the phases of learning,
incorporating qualitative data from the evaluations of pilots in the
UK and France.
Enhancing supply chain operations through effective classification of warranty returns
Authors: Gary Teng S. , Ho S. Michael , Shumar Debra
Published: February 2005

Purpose

To show that handling warranty returns is essential in a supply chain for product/process improvement and that the major step in resolving warranty return problems is to correctly classify the returned parts and identify the problem(s).

Design/methodology/approach

Demonstrates two classification processes that separate available warranty returned parts into correct categories.

Findings

The result of these two processes provides pertinent parties in the supply chain more accurate warranty failure information, so the companies involved can precisely pin‐point the source of the failure cause in the products and improve the product's design and manufacturing. Meanwhile, it also resolves potential conflicts in a supply chain and assigns responsibility to the right party to cover incurred warranty repair cost. Its applications can enhance quality and reliability management in a supply chain and streamline the reverse logistics operations in the chain.

Originality/value

This paper offers companies an effective procedure in reducing wrongly classified warranty returns and makes root cause analysis of warranty returns more efficient.
Energy consideration of the T(x) model of hysteresis
Authors: Takacs Jeno
Published: February 2005

Purpose

The paper sets out to develop the T(x) model, based on well known principles and using the free energy of the ferromagnetic binary system as a starting point.

Design/methodology/approach

With the inclusion of the coercive and the intermolecular forces the model fully describes the hysteretic process for both major and minor loops, with exchange field between adjacent magnetic moments.

Findings

The paper formulates the dependence of the hysteretic system's normalised free energy on parameters such as the temperature, coercivity, other magnetic and materials properties of the ferromagnetic medium.

Research limitations/implications

Experimental verification will still be needed as to the accuracy of the model and the applicability to the various magnetic materials.

Practical implications

The paper provides an easy mathematical and visual method to present the energy state and its variation of the magnetic materials during magnetisation, including non‐saturation conditions. It has a great value to people engaged in theoretical research in magnetism.

Originality/value

So far free energy calculations were only possible for major hysteresis loops. The T(x) model, as presented here, is applicable to the calculation of the free energy flow of any symmetrical minor loops as well.
The Canadian National Site Licensing Project and the logic model
Authors: Hoffman Ellen
Published: February 2005

Purpose

To determine whether Canada's university research capacity could be increased in quantity, breadth and depth of published scholarly information available to academic researchers, especially through the use of e‐journals and cooperatively negotiated pricing and licensing of them.

Design/methodology/approach

Evaluates the three‐year demonstration project funded by the Canada Foundation for Innovation known as the Canadian National Site Licensing Project (CNSLP). This project used surveys and a logical model method, which integrates inputs, activities, outputs, outcomes and impacts into an account of how a program is fulfilling its objectives.

Findings

Demonstrates that CNSLP has successfully found a new model for negotiating and licensing electronic information to expand information available to researchers. It also identified that over 80 percent of respondents surveyed believe that e‐journal access has had a significant impact on their ability to conduct research.

Originality/value

Both illustrates a model to provide greater access to e‐journals and shows that greater access to electronic information increases use of peripheral literature.
Experiences gained from the First Internet Disaster Conference
Authors: Keller A.Z. , Coles E.L. , Heal R.
Published: February 2005

Discusses the background of the First Internet Disaster Conference. Debates the advantages and disadvantages of Internet conferencing, and covers the lessons learnt and experiences gained from this conference.
Innovation projects in Israeli incubators
Authors: Kahane Bernard , Raz Tzvi
Published: February 2005

Purpose

Based on an Israeli innovation incubators program, aims to describe a procedure to define relevant categories in order to reduce the complexity of representing the population of projects supported by an innovation program in a meaningful way.

Design/methodology/approach

Provides a concise description of the Israeli innovation incubators program and presents the characteristics of the data available. Introduces the analysis methodology and describes in detail its application to the specific data set and the classification scheme that it induces. Discusses the information that can be obtained based on this classification, and outlines some policy implications. Concludes with remarks regarding possible applications and extensions of the methodology.

Findings

Finds that the classification induced by the iterative category exclusion (ICE) procedure can serve as the basis for more sophisticated analysis using statistical tools such as regression analysis. Once the relevant categorization is obtained, it becomes easier to collect meaningful data about incubator performance for analysis at various levels of aggregation. The ICE procedure has the advantage that it does not give a priori preference to any category or to any relationship between categories, and does not require a priori identification of the categories that are to be kept and those that are to be deleted. Further, it does not need to classify categories under headings such as “scientific and technological” on the one side, and “sector applications” on the other. Both are seen as equal from the beginning to the end and thus avoid any bias in the process. The subjectivity inherent in the selection process is reduced, perhaps even eliminated. The same values provided the basis for the identification and quantification of overlap and proximities between the final categories, throwing some light on their mutual dependencies and interactions and leading to a level of representation from which strategic assessment and thinking can start.

Originality/value

The core principle of ICE is to eliminate categories that do not convey sufficient information to justify the additional complexity. This principle is universal and can be applied to a wide variety of situations that suffer from too much data and not enough information.
Simulating reality: the role of the case incident in higher education
Authors: Wright Phillip
Published: February 2005

Reports the results of a study on how undergraduates in one BBA programme perceived the use of case incidents and illustrates different methodologies for using case incidents in higher education. Argues that they are a powerful, easily utilized methodology which could embrace a variety of disciplines, but even in business only a third of the teaching profession uses them regularly.
Fiscal Policy with Agents Differing in Altruism and Ability
Authors: Michel Philippe , Pestieau Pierre
Published: February 2005

This paper explores the effects of a menu of intergenerational fiscal policies (public debt financed by taxes, PAYG social security system, inheritance taxation) in an overlapping‐generations model with perfect altruism. It generalizes Barro's model by introducing intragenerational heterogeneity; in other words, households differ in productivity and altruism. Within such a model, wealth is held entirely in the steady state by those families with the highest degree of altruism. Under plausible assumptions, both public debt and social security are neutral à la Ricardo, while inequality increases. Also, estate taxation can be Pareto‐worsening even though it fosters income equality.
Histochemical localisation of a galactose‐containing glycoconjugate expressed by sensory neurones innervating different peripheral tissues in the rat
Authors: Thornton Peter D. J. , Gerke Michelle B. , Plenderleith Mark B.
Published: February 2005

Abstract  The plant lectin Bandeiraea simplicifolia I‐isolectin B4 (BSI‐B4) identifies a galactose‐containing, membrane‐associated glycoconjugate expressed by a discrete subpopulation of unmyelinated primary sensory neurones in the rat. We have previously suggested that BSI‐B4 selectively binds to primary sensory neurones that innervate the skin. However, in that study, the tracer diamidino yellow was applied to the cut ends of peripheral nerves to identify neurones innervating particular target tissues. In this study, we have avoided axotomy by retrogradely labelling primary sensory neurones from peripheral tissues using the carbocyanine dye 1,1′‐dioctadecyl‐3,3,3′,3′‐tetramethylindocarbacyanine perchlorate (DiI). DiI was injected into the plantar skin, gastrocnemius muscle, and pyloric region of the stomach in rats. Corresponding ganglia were sectioned, incubated in BSI‐B4 conjugated to fluorescein isothiocyanate, and examined with a fluorescence microscope. DiI‐labelled cells were identified by red fluorescence within the cytoplasm, whereas cells binding BSI‐B4 displayed green fluorescence associated with the plasma membrane and Golgi apparatus. Quantitative analysis revealed that 36.2% of cutaneous neurones, 7.6% of muscle neurones, and 6.8% of visceral neurones expressed the BSI‐B4‐binding site, indicating that a small but significant proportion of small‐diameter primary sensory neurones innervating muscle and viscera also express BSI‐B4‐binding sites.
Nitric oxide emission from tobacco leaves and cell suspensions: rate limiting factors and evidence for the involvement of mitochondrial electron transport
Authors: Planchet Elisabeth , Jagadis Gupta Kapuganti , Sonoda Masatoshi , Kaiser Werner M.
Published: February 2005

Quantitative data on nitric oxide (NO) production by plants, and knowledge of participating reactions and rate limiting factors are still rare. We quantified NO emission from tobacco (Nicotiana tabacum) wild‐type leaves, from nitrate reductase (NR)‐ or nitrite reductase (NiR)‐deficient leaves, from WT‐ or from NR‐deficient cell suspensions and from mitochondria purified from leaves or cells, by following NO emission through chemiluminescence detection. In all systems, NO emission was exclusively due to the reduction of nitrite to NO, and the nitrite concentration was an important rate limiting factor. Using inhibitors and purified mitochondria, mitochondrial electron transport was identified as a major source for reduction of nitrite to NO, in addition to NR. NiR and xanthine dehydrogenase appeared to be not involved. At equal respiratory activity, mitochondria from suspension cells had a much higher capacity to produce NO than leaf mitochondria. NO emission in vivo by NiR‐mutant leaves (which was not nitrite limited) was proportional to photosynthesis (high in light +CO2, low in light −CO2, or in the dark). With most systems including mitochondrial preparations, NO emission was low in air (and darkness for leaves), but high under anoxia (nitrogen). In contrast, NO emission by purified NR was not much different in air and nitrogen. The low aerobic NO emission of darkened leaves and cell suspensions was not due to low cytosolic NADH, and appeared only partly affected by oxygen‐dependent NO scavenging. The relative contribution of NR and mitochondria to nitrite‐dependent NO production is estimated.
Acute treatment with TNF-α attenuates insulin-stimulated protein synthesis in cultures of C2C12myotubes through a MEK1-sensitive mechanism
Authors: Williamson David L. , Kimball Scot R. , Jefferson Leonard S.
Published: February 2005

Insulin and TNF-α exert opposing effects on skeletal muscle protein synthesis that are mediated in part by the rapamycin-sensitive mammalian target of rapamycin (mTOR) pathway and the PD-98059-sensitive, extracellular signal-regulated kinase (ERK)1/2 pathway. The present study examined the separate and combined effects of insulin (INS), TNF, PD-98059, or dnMEK1 adenovirus on the translational control of protein synthesis in C2C12myotubes. Cultures were treated with INS, TNF, PD-98059, dnMEK1, or a combination of INS + TNF with PD-98059 or dnMEK1. INS stimulated protein synthesis, enhanced eIF4E·eIF4G association, and eIF4G phosphorylation and repressed eIF4E·4E-BP1 association vs. control. INS also promoted phosphorylation of ERK1/2, S6K1, and 4E-BP1 and dephosphorylation of eIF4E. TNF alone did not have an effect on protein synthesis (vs. control), eIF4E·eIF4G association, or the phosphorylation of eIF4G, S6K1, or 4E-BP1, although it transiently increased ERK1/2 and eIF4E phosphorylation. When myotubes were treated with TNF + INS, the cytokine blocked the insulin-induced stimulation of protein synthesis. This appeared to be due to an attenuation of insulin-stimulated eIF4E·eIF4G association, because other stimulatory effects of INS, e.g., phosphorylation of ERK1/2, 4E-BP1, S6K1, eIF4G, and eIF4E and eIF4E·4E-BP1 association, were unaffected. Finally, treatment of myotubes with PD-98059 or dnMEK1 adenovirus before TNF + INS addition resulted in a derepression of protein synthesis and the association of eIF4G with eIF4E. These findings suggest that TNF abrogates insulin-induced stimulation of protein synthesis in myotubes through a decrease in eIF4F complex assembly independently of S6K1 and 4E-BP1 signaling and dependently on a MEK1-sensitive signaling pathway.
Homogeneous Ice Nucleation in Subtropical and Tropical Convection and Its Influence on Cirrus Anvil Microphysics
Authors: Heymsfield Andrew J. , Miloshevich Larry M. , Schmitt Carl , Bansemer Aaron , Twohy Cynthia , Poellot Michael R. , Fridlind Ann , Gerber Hermann
Published: February 2005

This study uses a unique set of microphysical measurements obtained in a vigorous, convective updraft core at temperatures between −33° and −36°C, together with a microphysical model, to investigate the role of homogeneous ice nucleation in deep tropical convection and how it influences the microphysical properties of the associated cirrus anvils. The core and anvil formed along a sea-breeze front during the Cirrus Regional Study of Tropical Anvils and Cirrus Layers–Florida Area Cirrus Experiment (CRYSTAL–FACE).

The updraft core contained two distinct regions as traversed horizontally: the upwind portion of the core contained droplets of diameter 10–20 μm in concentrations of around 100 cm−3 with updraft speeds of 5–10 m s−1; the downwind portion of the core was glaciated with high concentrations of small ice particles and stronger updrafts of 10–20 m s−1. Throughout the core, rimed particles up to 0.6-cm diameter were observed. The anvil contained high concentrations of both small particles and large aggregates.

Thermodynamic analysis suggests that the air sampled in the updraft core was mixed with air from higher altitudes that descended along the upwind edge of the cloud in an evaporatively driven downdraft, introducing free-tropospheric cloud condensation nuclei into the updraft below the aircraft sampling height. Farther downwind in the glaciated portion of the core, the entrained air contained high concentrations of ice particles that inhibit droplet formation and homogeneous nucleation.

Calculations of droplet and ice particle growth and homogeneous ice nucleation are used to investigate the influence of large ice particles lofted in updrafts from lower levels in this and previously studied tropical ice clouds on the homogeneous nucleation process. The preexisting large ice particles act to suppress homogeneous nucleation through competition via diffusional and accretional growth, mainly when the updrafts are < 5 m s−1. In deep convective updrafts > 5–10 m s−1, the anvil is the depository for the small, radiatively important ice particles (homogeneously nucleated) and the large ice particles from below (heterogeneously or secondarily produced, or recycled).
Information Theory and Predictability for Low-Frequency Variability
Authors: Abramov Rafail , Majda Andrew , Kleeman Richard
Published: February 2005

A predictability framework, based on relative entropy, is applied here to low-frequency variability in a standard T21 barotropic model on the sphere with realistic orography. Two types of realistic climatology, corresponding to different heights in the troposphere, are used. The two dynamical regimes with different mixing properties, induced by the two types of climate, allow the testing of the predictability framework in a wide range of situations. The leading patterns of empirical orthogonal functions, projected onto physical space, mimic the large-scale teleconnections of observed flow, in particular the Arctic Oscillation, Pacific–North American pattern, and North Atlantic Oscillation. In the ensemble forecast experiments, relative entropy is utilized to measure the lack of information in three different situations: the lack of information in the climate relative to the forecast ensemble, the lack of information by using only the mean state and variance of the forecast ensemble, and information flow—the time propagation of the lack of information in the direct product of marginal probability densities relative to joint probability density in a forecast ensemble. A recently developed signal–dispersion–cross-term decomposition is utilized for climate-relative entropy to determine different physical sources of forecast information. It is established that though dispersion controls both the mean state and variability of relative entropy, the sum of signal and cross-term governs physical correlations between a forecast ensemble and EOF patterns. Information flow is found to be responsible for correlated switches in the EOF patterns within a forecast ensemble.
On the Generality of Event-Graph Models
Authors: Savage Eric L. , Schruben Lee W. , Yücesan Enver
Published: February 2005

Event graphs model the dynamics of a discrete-event simulation model. This paper demonstrates the modeling power of event graphs by presenting a model that simulates a Turing machine. Therefore, according to Church's thesis, event-graph models are able to model any system that can be implemented on a modern computer. Theoretical and practical implications of this assertion are also discussed.
Presenilin Attenuates Receptor-Mediated Signaling and Synaptic Function
Authors: Parent Angèle T. , Barnes Natalie Y. , Taniguchi Yoshihito , Thinakaran Gopal , Sisodia Sangram S.
Published: February 2005

Presenilin (PS) plays an essential role in intramembranous γ-secretase processing of amyloid precursor protein (APP) and several membrane-bound proteins. Here we report that selective accumulation of a membrane-tethered deleted in colorectal cancer (DCC) derivative (DCC-α) correlates with extensive neurite outgrowth in transfected neuroblastoma cells and axodendritic connectivity associated with increased spine density in cortical neurons derived fromPS1-/-embryos, as well as wild-type neurons treated with γ-secretase inhibitors. cAMP-dependent signaling was also increased in both the neuroblastoma and cortical neuron systems. As a physiological consequence of increases in axodendritic connectivity and in the magnitude of cAMP-dependent signaling, short- and long-term glutamatergic synaptic transmission was enhanced in PS-deficient neurons. Together, these results demonstrate for the first time that PS-mediated γ-secretase activity attenuates receptor-mediated intracellular signaling pathways that are critical in regulating glutamatergic synaptic transmission and memory processes.
Comparison of the Effects of Damage to the Perirhinal and Parahippocampal Cortex on Transverse Patterning and Location Memory in Rhesus Macaques
Authors: Alvarado Maria C. , Bachevalier Jocelyne
Published: February 2005

Monkeys with damage to the parahippocampal (TH/TF) or perirhinal (PRh) cortex were tested on two sets of the transverse patterning (TP) problem (A+/B-, B+/C-, C+/A- and D+/E-, E+/F-, F+/D-) and delayed nonmatching-to-location paradigm (DNML), with delays ranging from 10 to 600 s. Damage to either area impaired acquisition and performance of TP but not of linear discriminations (e.g., A>B>C>X). Damage to areas TH/TF impaired performance of the DNML at all delays but only affected memory for objects at the longest delay, as measured by a delayed nonmatching-to-sample task (DNMS) (Nemanic et al., 2004). Damage to the PRh impaired performance of the DNMS but not of the DNML. The results present a dissociation in object and place memory for these two cortical regions and suggest a role for each in the cortical circuitry supporting configural/relational memory.
Spider Peripheral Mechanosensory Neurons Are Directly Innervated and Modulated by Octopaminergic Efferents
Authors: Widmer Alexandre , Höger Ulli , Meisner Shannon , French Andrew S. , Torkkeli Päivi H.
Published: February 2005

Octopamine is a chemical relative of noradrenaline providing analogous neurohumoral control of diverse invertebrate physiological processes. There is also evidence for direct octopaminergic innervation of some insect peripheral tissues. Here, we show that spider peripheral mechanoreceptors are innervated by octopamine-containing efferents. The mechanosensory neurons have octopamine receptors colocalized with synapsin labeling in the efferent fibers. In addition, octopamine enhances the electrical response of the sensory neurons to mechanical stimulation.

Spider peripheral mechanosensilla receive extensive efferent innervation. Many efferent fibers in the legs ofCupiennius saleiare GABAergic, providing inhibitory control of sensory neurons, but there is also evidence for other neurotransmitters. We used antibody labeling to show that some efferents contain octopamine and that octopamine receptors are concentrated on the axon hillocks and proximal soma regions of all mechanosensory neurons in the spider leg. Synaptic vesicles in efferent neurons were concentrated in similar areas.

Octopamine, or its precursor tyramine, increased responses of mechanically stimulated filiform (trichobothria) leg hairs. This effect was blocked by the octopamine antagonist phentolamine. The octopamine-induced modulation was mimicked by 8-Br-cAMP, a cAMP analog, and blocked by Rp-cAMPS, a protein kinase A inhibitor, indicating that spider octopamine receptors activate adenylate cyclase and increase cAMP concentration.

Frequency response analysis showed that octopamine increased the sensitivity of the trichobothria neurons over a broad frequency range. Thus, the major effect of octopamine is to increase its overall sensitivity to wind-borne signals from sources such as flying insect prey or predators.
A48G polymorphism in the D1 receptor genes associated with bipolar I disorder
Authors: Severino Giovanni , Congiu Donatella , Serreli Claudia , De Lisa Roberto , Chillotti Caterina , Del Zompo Maria , Piccardi Maria Paola
Published: February 2005

Several lines of evidence point to a role for dopamine in mood disorders and, in particular, in bipolar disorders. In line with a considerable amount of evidence, the dopamine D1 receptor gene (DRD1) is considered to be a good candidate gene for bipolar disorders. Several studies did not find any association between bipolar 1 patients and DRD1. In this study, we investigate a possible association between BP disorder and −48A/G polymorphism of the DRD1. We genotyped 107 bipolar 1 patients and 129 healthy control subjects of exclusively Sardinian descent. A statistically significant difference in genotype (χ2 = 6.29, df = 2, P = 0.042) and allele (χ2 = 5.46, df=1, P = 0.019; OR = 1.53, 95% CI = 1.08–2.16) frequencies was found, suggesting an association between the DRD1 gene and bipolar I disorder (BP I) in the Sardinian population. © 2005 Wiley‐Liss, Inc.
Bringing Back Community: Family Support From the Bottom Up
Authors: Wigfall Valerie
Published: February 2005

This paper presents findings of an evaluation of a one‐off, small scale, pilot project. Picking up where Sure Start, the government programme for families of newborns to threes, leaves off, ‘Families in Focus’ works with children aged four to 16 on a disadvantaged council estate in London. Through this route, the programme also reaches out to the families, providing a high level of on the spot local support. Feeding into the government's social exclusion agenda, the impact of the project has been significant, not least in restoring a strong sense of community to a previously alienated problem estate.
Stereoselective pharmacokinetics of RS‐8359, a selective and reversible MAO‐A inhibitor, by species‐dependent drug‐metabolizing enzymes
Authors: Takasaki Wataru , Yamamura Mayumi , Nozaki Akiko , Nitanai Takashi , Sasahara Kunihiro , Itoh Kunio , Tanaka Yorihisa
Published: February 2005

RS‐8359, (±)‐4‐(4‐cyanoanilino)‐5,6‐dihydro‐7‐hydroxy‐7H‐cyclopenta[d]pyrimidine selectively and reversibly inhibits monoamine oxidase A (MAO‐A). After oral administration of rac‐RS‐8359 to rats, mice, dogs, monkeys, and humans, plasma concentrations of the (R)‐enantiomer were greatly higher than were those of the (S)‐enantiomer in all species studied. The AUC(R) to AUC(S) ratios were 2.6 in rats, 3.8 in mice, 31 in dogs, and 238 in monkeys, and the (S)‐enantiomer was almost negligible in human plasma. After intravenous administration of RS‐8359 enantiomers to rats, the pharmacokinetic parameters showed that the (S)‐enantiomer had a 2.7‐fold greater total clearance (CLt) and a 70% shorter half‐life (t1/2) than those for the (R)‐enantiomer but had no difference in distribution volume (Vd). No significant difference in the intestinal absorption rate was observed. The principal metabolites were the 2‐keto form, possibly produced by aldehyde oxidase, the cis‐diol form, and the 2‐keto‐cis‐diol form produced by cytochrome P450 in rats, the cis‐diol form in mice, RS‐8359 glucuronide in dogs, and the 2‐keto form in monkeys and humans. Thus, the rapid disappearance of the (S)‐enantiomer from the plasma was thought to be due to the rapid metabolism of the (S)‐enantiomer by different drug‐metabolizing enzymes, depending on species. Chirality 17:135–141, 2005. © 2005 Wiley‐Liss, Inc.
Assignment of absolute configuration of 3‐hydroxy β‐lactams by the NMR “mix and shake” method
Authors: Yang Yan , Kayser Margaret M. , Hooper Donald
Published: February 2005

The absolute configurations of several 3‐hydroxy β‐lactams were assigned by the NMR “mix and shake” methodology developed by Riguera and co‐workers. The results from the NMR study correlated perfectly with the absolute configurations obtained from X‐ray crystallographic structure analyses and chiral‐phase HPLC data. Chirality 17:131–134, 2005. © 2005 Wiley‐Liss, Inc.
Application of Mosher's method for absolute configuration assignment and resolution of 2‐hydroxypyrrolizidinones
Authors: Cordero Franca M. , Pisaneschi Federica , Salvati Maria , Valenza Silvia , Faggi Cristina , Brandi Alberto
Published: February 2005

Derivatization of racemic 2‐hydroxypyrrolizidinones with S‐(+)‐α‐methoxy‐α‐trifluoromethylphenylacetyl chloride (MTPA‐Cl) was successfully used for enantiomer separation and absolute configuration assignment. Chirality 17:149–153, 2005. © 2005 Wiley‐Liss, Inc.
Pharmacokinetics of theanine enantiomers in rats
Authors: Desai Meera J. , Gill Manmeet S. , Hsu Walter H. , Armstrong Daniel W.
Published: February 2005

Theanine, first discovered in tea, is a chiral nonproteinic amino acid that has been reported to have cardiovascular, neurological, and oncological effects. It is being considered as a therapeutic/medicinal agent and additive in consumer products. The present study evaluated the pharmacokinetics of d‐theanine, l‐theanine, and d,l‐theanine in plasma and urine using LC‐ESI/MS in rats after oral (p.o.) and intraperitoneal (i.p.) administration. Oral administration data indicated that gut absorption of d‐theanine was far less than that of l‐theanine. However, after i.p. administration, plasma theanine concentrations of l‐ and d‐theanine were similar. This indicated that d‐ and l‐theanine may exhibit a competitive effect with respect to intestinal absorption. Regardless of the route of administration, p.o. or i.p., the presence of the other enantiomer always decreased theanine plasma concentrations, indicating d,l‐theanine competition with respect to urinary reabsorption. Data on urinary concentrations of d‐theanine suggested that the d‐isomer may be eliminated with minimal metabolism. l‐Theanine appeared to be preferentially reabsorbed and metabolized by the kidney while d‐theanine was preferentially excreted. Clearly, the bioequivalencies of d,l‐theanine and its enantiomers were found to be quite different from one another. Consequently, the efficacy of commercial theanine products containing d‐theanine, l‐theanine, or d,l‐theanine may be quite different. Chirality 17:154–162, 2005. © 2005 Wiley‐Liss, Inc.
Role of Drosophila HP1 in euchromatic gene expression
Authors: Cryderman Diane E. , Grade Stephanie K. , Li Yuhong , Fanti Laura , Pimpinelli Sergio , Wallrath Lori L.
Published: February 2005

Heterochromatin protein 1 (HP1), a gene silencing protein, localizes to centric heterochromatin through an interaction with methylated K9 of histone H3, a modification generated by the histone methyl transferase SU(VAR)3‐9. On Drosophila polytene chromosomes, HP1 also localizes to 200 sites scattered throughout euchromatin. To address the role of HP1 in euchromatic gene regulation, mRNAs from wild‐type and Su(var)2‐5 mutants lacking HP1 were compared. Genes residing within a 550‐kb genomic region enriched in HP1 that show altered expression in the Su(var)2‐5 mutant were analyzed in detail. Three genes within this region, Pros35, CG5676, and cdc2, were found to associate with HP1 by chromatin immunoprecipitation. Surprisingly, these genes require HP1 for expression, suggesting a positive role for HP1 in euchromatic gene expression. Of these genes, only cdc2 is packaged with methylated K9 H3. Furthermore, none of the genes show altered expression in a Su(var)3‐9 mutant. Collectively, these data demonstrate multiple mechanisms for HP1 localization within euchromatin and show that some genes associated with HP1 are not affected by alterations in Su(var)3‐9 dosage. Developmental Dynamics 232:767–774, 2005. © 2005 Wiley‐Liss, Inc.
Genome wide analysis of transcript levels after perturbation of the EGFR pathway in the Drosophila ovary
Authors: Jordan Katherine C. , Hatfield Steven D. , Tworoger Michael , Ward Ellen J. , Fischer Karin A. , Bowers Stuart , Ruohola‐Baker Hannele
Published: February 2005

Defects in the epidermal growth factor receptor (EGFR) pathway can lead to aggressive tumor formation. Activation of this pathway during normal development produces multiple outcomes at the cellular level, leading to cellular differentiation and cell cycle activation. To elucidate the downstream events induced by this pathway, we used genome‐wide cDNA microarray technology to identify potential EGFR targets in Drosophila oogenesis. We focused on genes for which the transcriptional responses due to EGFR pathway activation and inactivation were in opposite directions, as this is expected for genes that are directly regulated by the pathway in this tissue type. We perturbed the EGFR pathway in epithelial follicle cells using seven different genetic backgrounds. To activate the pathway, we overexpressed an activated form of the EGFR (UAS‐caEGFR), and an activated form of the signal transducer Raf (UAS‐caRaf); we also over‐ or ectopically expressed the downstream homeobox transcription factor Mirror (UAS‐mirr) and the ligand‐activating serine protease Rhomboid (UAS‐rho). To reduce pathway activity we used loss‐of‐function mutations in the ligand (gurken) and receptor (torpedo). From microarrays containing 6,255 genes, we found 454 genes that responded in an opposite manner in gain‐of‐function and loss‐of‐function conditions among which are many Wingless signaling pathway components. Further analysis of two such components, sugarless and pangolin, revealed a function for these genes in late follicle cell patterning. Of interest, components of other signaling pathways were also enriched in the EGFR target group, suggesting that one reason for the pleiotropic effects seen with EGFR activity in cancer progression and development may be its ability to regulate many other signaling pathways. Developmental Dynamics 232:709–724, 2005. © 2005 Wiley‐Liss, Inc.
On‐line signature verification based on subband decomposition by DWT and adaptive signal processing
Authors: Nakanishi Isao , Nishiguchi Naoto , Itoh Yoshio , Fukui Yutaka
Published: February 2005

This paper presents an on‐line signature verification method based on the Discrete Wavelet Transform (DWT) and adaptive signal processing. Time‐varying pen‐position signals of the on‐line signature are decomposed into subband signals by using the DWT. Individual features are extracted as high‐frequency signals in subbands. Verification is achieved in each subband by determining whether the adaptive weight converges to unity. The overall verification decision is made by averaging the verification results in lower subbands. Experimental results show that the verification rate was 95% even if the writer was not permitted to refer to his/her own signature or if a forger traced the genuine signature. © 2005 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 88(6): 1–11, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.20143
Node mobility protocols in the Internet
Authors: Teraoka Fumio
Published: February 2005

In this paper, the various protocols used to achieve node mobility on the Internet are compared and evaluated. Node mobility can be defined as hiding from the application or user changes in the connection point to the Internet of the terminal. Node mobility can be broken down into two forms of mobility: wide area mobility and local mobility. Wide area mobility can be achieved by satisfying two factors: mobile node reachability and communication continuity. Local mobility can be achieved by satisfying two factors: packet loss avoidance and control traffic suppression. In this paper, the various proposed protocols for achieving node mobility are analyzed, and the methods used to satisfy the above factors are classified. Each classified method is then analyzed and evaluated from the standpoint of communication efficiency, scalability, security, fault tolerance, and ease of implementation. In addition, specific examples are given for the representative protocols. © 2005 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 88(6): 39–59, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.20173
Mapping structural differences of the corpus callosum in individuals with 18q deletions using targetless regional spatial normalization
Authors: Kochunov Peter , Lancaster Jack , Hardies Jean , Thompson Paul M. , Woods Roger P. , Cody Jannine D. , Hale Daniel E. , Laird Angela , Fox Peter T.
Published: February 2005

Individuals with a constitutional chromosome abnormality consisting of a deletion of a portion of the long arm of chromosome 18 (18q−) have a high incidence (∼95%) of dysmyelination. Neuroradiologic findings in affected children report a smaller corpus callosum, but this finding has not been quantified. This is in part due to the large intersubject variability of the corpus callosum size and shape and the small number of subjects with 18q−, which leads to low statistical power for comparison with typically developing children. An analysis method called targetless spatial normalization (TSN) was used to improve the sensitivity of statistical testing. TSN converges all images in a group into what is referred as group common space. The group common space conserves common shape, size, and orientation while reducing intragroup variability. TSN in conjunction with a Witelson vertical partitioning scheme was used to assess differences in corpus callosum size between 12 children with 18q− and 12 age‐matched normal controls. Significant global and regional differences in corpus callosum size were seen. The 18q− group showed an overall smaller (25%) corpus callosum (P< 10−7), even after correction for differences in brain size. Regionally, the posterior portions of corpus callosum (posterior midbody, isthmus, and splenium), which contain heavily myelinated fibers, were found to be 25% smaller in the population with 18q−. Hum Brain Mapping 24:325–331, 2005. © 2005 Wiley‐Liss, Inc.
Gender differences in the functional neuroanatomy of emotional episodic autobiographical memory
Authors: Piefke Martina , Weiss Peter H. , Markowitsch Hans J. , Fink Gereon R.
Published: February 2005

Autobiographical memory is based on interactions between episodic memory contents, associated emotions, and a sense of self‐continuity along the time axis of one's life. The functional neuroanatomy subserving autobiographical memory is known to include prefrontal, medial and lateral temporal, as well as retrosplenial brain areas; however, whether gender differences exist in neural correlates of autobiographical memory remains to be clarified. We reanalyzed data from a previous functional magnetic resonance imaging (fMRI) experiment to investigate gender‐related differences in the neural bases of autobiographical memories with differential remoteness and emotional valence. On the behavioral level, there were no significant gender differences in memory performance or emotional intensity of memories. Activations common to males and females during autobiographical memory retrieval were observed in a bilateral network of brain areas comprising medial and lateral temporal regions, including hippocampal and parahippocampal structures, posterior cingulate, as well as prefrontal cortex. In males (relative to females), all types of autobiographical memories investigated were associated with differential activation of the left parahippocampal gyrus. By contrast, right dorsolateral prefrontal cortex was activated differentially by females. In addition, the right insula was activated differentially in females during remote and negative memory retrieval. The data show gender‐related differential neural activations within the network subserving autobiographical memory in both genders. We suggest that the differential activations may reflect gender‐specific cognitive strategies during access to autobiographical memories that do not necessarily affect the behavioral level of memory performance and emotionality. Hum Brain Mapping 24:313–324, 2005. © 2005 Wiley‐Liss, Inc.
Classification of cancer types by measuring variants of host response proteins using SELDI serum assays
Authors: Fung Eric T. , Yip Tai‐Tung , Lomas Lee , Wang Zheng , Yip Christine , Meng Xiao‐Ying , Lin Shanhua , Zhang Fujun , Zhang Zhen , Chan Daniel W. , Weinberger Scot R.
Published: February 2005

Protein expression profiling has been increasingly used to discover and characterize biomarkers that can be used for diagnostic, prognostic or therapeutic purposes. Most proteomic studies published to date have identified relatively abundant host response proteins as candidate biomarkers, which are often dismissed because of an apparent lack of specificity. We demonstrate that 2 host response proteins previously identified as candidate markers for early stage ovarian cancer, transthyretin and inter‐alpha trypsin inhibitor heavy chain 4 (ITIH4), are posttranslationally modified. These modifications include proteolytic truncation, cysteinylation and glutathionylation. Assays using Surface Enhanced Laser Desorption/Ionization Time of Flight Mass Spectrometry (SELDI‐TOF‐MS) may provide a means to confer specificity to these proteins because of their ability to detect and quantitate multiple posttranslationally modified forms of these proteins in a single assay. Quantitative measurements of these modifications using chromatographic and antibody‐based ProteinChip® array assays reveal that these posttranslational modifications occur to different extents in different cancers and that multivariate analysis permits the derivation of algorithms to improve the classification of these cancers. We have termed this process host response protein amplification cascade (HRPAC), since the process of synthesis, posttranslational modification and metabolism of host response proteins amplifies the signal of potentially low‐abundant biologically active disease markers such as enzymes. © 2005 Wiley‐Liss, Inc.
International patterns and trends in testis cancer incidence
Authors: Purdue Mark P. , Devesa Susan S. , Sigurdson Alice J. , McGlynn Katherine A.
Published: February 2005

Although the incidence of testis cancer has risen markedly in many Western populations over the past half‐century, it is not clear whether rates in other populations also have increased. To clarify this issue, we examined testis cancer incidence rates over the 25‐year time period of 1973–1997 for selected populations around the world. Age‐standardized incidence rates for 21 registries in the Americas, Asia, Europe and Oceania over successive 5‐year time periods were obtained from volumes 4–8 of Cancer Incidence in Five Continents. Testis cancer rates rose between 1973 and 1997 in most populations worldwide, although the increases were strongest and most consistent among populations of European ancestry. Rates appear to be leveling off in some populations. The increases in testis cancer remain unexplained, although changes in the prevalence of important risk factors for this disease may be responsible. Published 2005 Wiley‐Liss, Inc.
Familial risks for colorectal cancer show evidence on recessive inheritance
Authors: Hemminki Kari , Chen Bowang
Published: February 2005

Recent molecular genetic data have become available on a recessive inheritance in colorectal cancer (CRC). We wanted to search for evidence for recessive inheritance from a population‐based family data set, which is not sensitive to reporting or ascertainment bias. The nationwide Swedish Family‐Cancer Database covered 10.3 million individuals whose invasive CRCs of adenocarcinoma histology were followed from 1991 to 2000. Age of the offspring and parental populations was limited to less than 69 years. Standardized incidence ratios (SIRs) were calculated for site‐specific CRC in offspring whose parents or siblings were diagnosed with CRC. A total of 6,774 offspring were recorded with CRC, whose risk was 2.13 when a parent was diagnosed with CRC and it was 2.75 when a sibling was affected. The SIRs for right‐sided colon cancer were 7.53 among siblings and 3.66 among offspring of affected parents, giving a 1.8‐fold excess familial risk among siblings. Colon cancer among the 0‐ to 68‐year‐old population accounted for about 25% of all colon cancers. Examination of all cancers in family members of the affected siblings did not reveal large contribution by known syndromes, such as hereditary nonpolyposis colorectal cancer. The most likely explanation to the high risk of right‐sided colon cancer among siblings is a recessive inheritance, which would account for 0.75% of all CRCs. Its high prevalence and predilection to right‐sided colon suggest that only a small proportion of this familial aggregation could be due to MYH mutations. © 2005 Wiley‐Liss, Inc.