bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Mus81 and FANCB independently contribute to repair of DNA damage during replication
Authors: Nomura Yuji , Adachi Noritaka , Koyama Hideki
Published: September 2007

Recent studies suggest a crucial role for homologous recombination (HR) in repairing replication‐associated DNA lesions. In mammals, the Mus81 endonuclease and the Fanconi anemia (FA) pathway have been implicated in HR repair; however, their functional relationship has remained unexplored. Here, we knockout the genes for Mus81 and FANCB, a component of the FA core complex, in the human Nalm‐6 cell line. We show that Mus81 plays an important role in cell proliferation to suppress cell death when FANCB is missing, indicating a functional linkage between Mus81 and the FA pathway. In DNA cross‐link repair, roles for Mus81 and the FA pathway appear to have an overlapping function. Intriguingly, Mus81 and FANCB act independently in surviving exposure to camptothecin (CPT). Although CPT‐induced FANCD2 and Mus81 foci co‐localize with Rad51, loss of Mus81, but not FANCB, results in significantly decreased levels of spontaneous and CPT‐induced sister chromatid exchanges (SCEs). In addition, Mus81, unlike FANCB, has no significant role in gene targeting as well as in repairing hydroxyurea (HU)‐induced stalls of replication forks. Collectively, our results provide the first evidence for differential functions of Mus81 and the FA pathway in repair of DNA damage during replication in human cells.
Transcription‐coupled nucleoid architecture in bacteria
Authors: Ohniwa Ryosuke L. , Morikawa Kazuya , Takeshita Sayaka L. , Kim Joongbaek , Ohta Toshiko , Wada Chieko , Takeyasu Kunio
Published: September 2007

The circular bacterial genome DNA exists in cells in the form of nucleoids. In the present study, using genetic, molecular and structural biology techniques, we show that nascent single‐stranded RNAs are involved in the step‐wise folding of nucleoid fibers. In Escherichia coli, RNase A degraded thicker fibers (30 and 80 nm wide) into thinner fibers (10 nm wide), while RNase III and RNase H degraded 80‐nm fibers into 30‐nm (but not 10‐nm) fibers. Similarly in Staphylococcus aureus, RNase A treatment resulted in 10‐nm fibers. Treatment with the transcription inhibitor, rifampicin, in the absence of RNase A changed most nucleoid fibers to 10‐nm fibers. Proteinase‐K treatment of nucleoids exposed DNA. Thus, the smallest structural unit is an RNase A‐resistant 10‐nm fiber composed of DNA and proteins, and the hierarchical structure of the bacterial chromosome is controlled by transcription itself. In addition, the formation of 80‐nm fibers from 30‐nm fibers requires double‐stranded RNA and RNA–DNA hetero duplex. RNA is evident in the architecture of log‐phase uncondensed and stationary‐phase condensed nucleoids.
Type I platelet‐activating factor acetylhydrolase catalytic subunits over‐expression induces pleiomorphic nuclei and centrosome amplification
Authors: Yamaguchi Noritaka , Koizumi Hiroyuki , Aoki Junken , Natori Yumiko , Nishikawa Kiyotaka , Natori Yasuhiro , Takanezawa Yasukazu , Arai Hiroyuki
Published: September 2007

LIS1, a causative gene product for type I lissencephaly, binds to and regulates the dynein motor and the centrosome. LIS1 also forms a complex with the catalytic subunits α1 and α2 of type I platelet‐activating factor acetylhydrolase [PAF‐AH (I)]. However, the cellular function of the catalytic subunits remains unknown. In this study, we showed that over‐expression of the catalytic subunits, especially α2, in cultured cells induced dramatic phenotypical changes including nuclear shape change, centrosomal amplification and microtubule disorganization. We examined if these effects were due to the catalytic activity and/or binding of α2 to LIS1. Substitution of a single amino acid Glu39 of murine α1 and α2 by Asp (α2‐E39D) did not affect catalytic activity but completely abolished LIS1 binding. Over‐expression of either α2‐E39D or the catalytically inactive α2‐S48C revealed that α2‐E39D, but not α2‐S48C, lost its ability to induce above‐mentioned phenotypic changes. Biochemical analyses showed that LIS1 present in the precipitate fraction of murine brain homogenates could be translocated to the soluble fraction by α2, but not by α2‐E39D. These results suggest that over‐expression of the PAF‐AH (I) catalytic subunits induces centrosomal amplification and microtubule disorganization by disturbing intracellular localization of LIS1.
Degenerative structures that inhibit the emergence of communities of practice: a case study of knowledge management in the British Council
Authors: Venters Will , Wood Bob
Published: September 2007

Abstract. This paper presents the British Council’s knowledge management strategy. It outlines how, as part of this strategy, the organization attempted to engender communities of practice among a strategically significant group spread across the 110 countries in which the organization operates. Using a case study of this group, the paper explores ‘degenerative structures’ that impact on the ability to engender communities of practice and, through consideration of issues of individualization and risk, highlights a series of paradoxes that inhibited this organization’s attempt to move from a ‘hub‐and‐spoke’ structure to become a networked organization in which communities of practice flourish.
Closing the gap: towards a process model of post‐merger knowledge sharing
Authors: Yoo Youngjin , Lyytinen Kalle , Heo Dongcheol
Published: September 2007

Abstract. We develop a process model of post‐merger knowledge sharing based on distributed cognition, a systems perspective and path dependence. The framework conceptualizes knowledge sharing by layers of management choice and employee appropriation of knowledge resources seen as knowledge as content and knowledge as connection. We use the framework to study a merger of two polymer companies. The study reveals that mergers represent a discontinuity in knowledge sharing. Yet, chosen strategies often mirror the learned knowledge‐sharing practices of one of the merged companies and match poorly with the post‐merger knowledge‐sharing needs. Five factors emerged contribute to this knowledge gap: (a) the nature of the merger; (b) a lack of shared context; (c) the incompatibility of existing knowledge systems; (d) the tacit dimension of knowledge; and (e) time pressures of the merger. Our study shows that, employees enacted knowledge new sharing practices that differed significantly from the official strategy to close to the post‐merger knowledge gap.
Counter‐networks in standardization: a perspective of developing countries
Authors: Gao Ping
Published: September 2007

Abstract. Present information systems studies focus on technology from developed countries. Little is known about the development and implementation of indigenous technology in the developing world. This paper investigates China's experience of developing and deploying wireless local‐area network (WLAN) standards. First, drawing upon actor‐network theory, I interpret WLAN Authentication and Privacy Infrastructure (WAPI) standardization as a process of the actor‐network formation. Specifically, different actors were enrolled into two counter‐networks, namely the defensive network and the challenging network. These actors and the two counter‐networks struggled to dominate the interest inscriptions in the strategy of WLAN standardization. China's WAPI initiative failed because it could not establish a strong defensive network. Furthermore, I analyse the social, institutional and technological elements that determined the process of WAPI standardization. This case study demonstrates that counter‐network is a useful concept to analyse the mechanism of actor‐network formation. My analytical model in which the macro contexts are connected with the micro network dynamics can be drawn upon by other actor‐network studies on technology design and implementation. Practical implications for developing countries to develop the indigenous technologies have been given.
Multi‐metaphor method: organizational metaphors in information systems development
Authors: Oates Briony June , Fitzgerald Brian
Published: September 2007

Abstract.  Conventional methods have been criticized for their positivist philosophy and for either ignoring the organizational context of information systems development (ISD) or using only a simplistic, machine‐based conceptual model of organizations. We have developed an approach to enable systems developers to use a richer view of organizations and a more interpretive approach. Multi‐Metaphor Method (MMM) supports developers via a range of metaphors as cognitive structuring devices to understand an organization so that developers can learn to move between different ways of ‘reading’ the social context in which ISD occurs. We explain the rationale and theoretical underpinnings of MMM and then discuss our action research to investigate the viability and relevance of MMM during ISD practice. We show how the developers’ use of organizational metaphors via MMM did not just enable rich conceptualizations of the client organizations but also influenced the ISD process and final product. We review the learning outcomes and discuss the implications for systems development practice of our research.
Isolation and Characterisation of Four cDNAs Encoding Neuromedin U (NMU) From the Brain and Gut of Goldfish, and the Inhibitory Effect of a Deduced NMU on Food Intake and Locomotor Activity
Authors: Maruyama K. , Konno N. , Ishiguro K. , Wakasugi T. , Uchiyama M. , Shioda S. , Matsuda K.
Published: September 2007

In rodents, neuromedin U (NMU; U for its original effects examined in the uterus) is a multifunctional neuropeptide implicated in the regulation of the circulatory and digestive systems and energy homeostasis, especially appetite. However, there is no available information on the nature and physiological roles of NMU in fish. Therefore, we attempted to isolate and characterise transcripts encoding NMU from the brain and gut of the goldfish, and to examine the involvement of NMU in the regulation of feeding behaviour in this species. We identified four cDNAs encoding three NMU orthologs from the brain and gut. Putative peptides consisting of 21, 25 and 38 amino acid residues (NMU‐21, NMU‐25 and NMU‐38) were deduced from their nucleotide sequences. Two mRNAs for NMU‐25 were strongly expressed in the gut and weakly expressed in the brain and testis. By contrast, mRNA for NMU‐21 was strongly expressed in the brain and weakly expressed in the peripheral tissues. Expression of mRNA for NMU‐38 was weakly expressed only in the brain. Therefore, we examined the effect of feeding status on the expression of NMU‐21 mRNA in the brain. Fasting for 7 days induced a significant decrease in the expression levels of NMU‐21 mRNA in the brain. We also synthesised NMU‐21 after deducing its C‐terminal amide from the NMU‐21 mRNA, and then investigated the effect of intracerebroventricular (i.c.v.) administration of NMU‐21 on food intake and locomotor activity in the goldfish. NMU‐21, injected i.c.v., suppressed food intake and locomotor activity in a dose‐dependent manner. These results suggest that NMU orthologs exist in fish, and that the NMU‐21 deduced from them can potently inhibit food intake and locomotor activity in goldfish.
Downregulated hypothalamic 5‐HT3 receptor expression and enhanced 5‐HT3 receptor antagonist‐mediated improvement in fatigue‐like behaviour in cholestatic rats
Authors: Nguyen H. , Wang H. , Le T. , Ho W. , Sharkey K. A. , Swain M. G.
Published: September 2007

Abstract  The serotonin neurotransmitter system, including the 5‐HT3 receptor, has been implicated in the genesis of fatigue in patients with liver disease. Therefore, we examined the possible role of 5‐HT3 receptors in cholestasis‐associated fatigue. Rats were either bile duct resected (BDR) or sham resected and studied 10 days postsurgery. A significant decrease in hypothalamic 5‐HT3 receptor expression was detected by immunohistochemistry and Western blot in BDR vs sham rats, coupled with increased hypothalamic serotonin turnover identified by an elevated 5‐hydroxyindoleacetic acid (5‐HIAA) to 5‐HT ratio in BDR vs sham rats. To examine fatigue‐like behaviour, an activity meter was used. BDR rats exhibited significantly lower locomotor activity than did sham animals. Subcutaneous injection of the 5‐HT3 receptor antagonist tropisetron (0.1 mg kg−1) resulted in significantly increased locomotor activity in BDR rats compared to the activity in saline‐treated controls, but was without effect in sham rats. However, a 10‐fold higher dose of tropisetron significantly increased locomotor activity in both BDR and sham rats compared to saline‐injected controls. These findings indicate that cholestasis in the rat is associated with increased hypothalamic serotonin turnover, decreased hypothalamic 5‐HT3 receptor expression, and enhanced sensitivity to locomotor activation induced by 5‐HT3 receptor antagonism, thereby implicating the 5‐HT3 receptor system in cholestasis associated fatigue.
Expression of the Rai (Shc C) adaptor protein in the human enteric nervous system
Authors: Villanacci V. , Bassotti G. , Ortensi B. , Fisogni S. , Cathomas G. , Maurer C. A. , Galletti A. , Salerni B. , Pelicci G.
Published: September 2007

Abstract  The adaptor protein Rai (ShcC/N‐Shc) is almost exclusively present in the nervous system, although little is documented about its expression in the gut and the enteric nervous system (ENS). As Rai is a physiological substrate of Ret, an important factor for the development of ENS, we have evaluated the expression of Rai in the ENS in various segments of the human gastrointestinal tract. The expression of Rai was assessed by immunohistochemistry in disease‐free human gut samples (oesophagus, stomach, small bowel and colon) obtained from subjects undergoing surgical procedures. Rai was not expressed in the epithelia or lymphoid tissue, whereas a moderate level of expression was observed in the endothelial cells of blood vessels and on the outer membrane of smooth muscle cells in both the muscularis mucosae and the muscularis propria. In the ENS, strong positivity was observed only in enteric glial cells, overlapping with GFAP and S100. In conclusion, Rai is expressed in the human gut, especially in the enteric glial cells. We conclude that Rai may provide an additional marker for this cell type.
Cavitation resistance and seasonal hydraulics differ among three arid Californian plant communities
Authors: JACOBSEN ANNA L. , PRATT R. BRANDON , DAVIS STEPHEN D. , EWERS FRANK W.
Published: September 2007

Vulnerability to water stress‐induced cavitation was measured on 27 woody shrub species from three arid plant communities including chaparral, coastal sage and Mojave Desert scrub. Dry season native embolism and pre‐dawn water potential, and both wet and dry season xylem specific hydraulic conductivity (Ks) were measured. Cavitation resistance, estimated as water potential at 50% loss in conductivity (Ψ50), was measured on all species during the wet season and on a subset of species during the dry season. Cavitation resistance varied with sampling season, with 8 of 13 sampled species displaying significant seasonal shifts. Native embolism and water potential were useful in identification of species displaying seasonal shifts. The Ks was not different among sites or seasons. The Ψ50 varied among species and communities. Within communities, interspecific variation may be partially explained by differences in rooting depth or leaf habit (evergreen, semi‐deciduous, deciduous). Communities diverged in their Ψ50 with chaparral species displaying the greatest cavitation resistance regardless of sampling season. The greater cavitation resistance of chaparral species is surprising, considering the greater aridity of the Mojave Desert site. Adaptation to arid environments is due to many plant traits, and aridity does not necessarily lead to convergence in cavitation resistance.
Aquaporins and unloading of phloem‐imported water in coats of developing bean seeds
Authors: ZHOU YUCHAN , SETZ NATHAN , NIEMIETZ CHRISTA , QU HONGXIA , OFFLER CHRISTINA E. , TYERMAN STEPHEN D. , PATRICK JOHN W.
Published: September 2007

Nutrients are imported into developing legume seeds by mass flow through the phloem, and reach developing embryos following secretion from their symplasmically isolated coats. To sustain homeostasis of seed coat water relations, phloem‐delivered nutrients and water must exit seed coats at rates commensurate with those of import through the phloem. In this context, coats of developing French bean seeds were screened for expression of aquaporin genes resulting in cloning PvPIP1;1, PvPIP2;2 and PvPIP2;3. These genes were differentially expressed in all vegetative organs, but exhibited their strongest expression in seed coats. In seed coats, expression was localized to cells of the nutrient‐unloading pathway. Transport properties of the PvPIPs were characterized by expression in Xenopus oocytes. Only PvPIP2;3 showed significant water channel activity (Pos = 150–200 µm s−1) even when the plasma membrane intrinsic proteins (PIPs) were co‐expressed in various combinations. Permeability increases to glycerol, methylamine and urea were not detected in oocytes expressing PvPIPs. Transport active aquaporins in native plasma membranes of seed coats were demonstrated by measuring rates of osmotic shrinkage of membrane vesicles in the presence and absence of mercuric chloride and silver nitrate. The functional significance of aquaporins in nutrient and water transport in developing seeds is discussed.
A rapid gel agglutination test for the determination of fetomaternal haemorrhage
Authors: Agaylan A. , Meyer O. , Ahrens N. , Dudenhausen J. , Bombard S. , Salama A.
Published: September 2007

summary Determination of fetomaternal haemorrhage (FMH) remains an area of difficulty. In most cases, prophylactic Rh immunoglobulin is usually administered to affected women without testing for foetal red blood cells (RBC). Here, we describe a new particle gel immunoassay (PaGIA) for the determination FMH (FMH‐PaGIA). Superparamagnetic particles were coated with monoclonal anti‐D and mixed with ethylenediaminetetraacetic acid‐anticoagulated blood samples from D‐negative pregnant women. The particles were isolated using a magnetic particle concentrator and then placed into the reaction chamber of a gel card. Agglutinated particles on top or dispersed through the gel matrix indicated the presence of D‐positive cells. After the test was adapted to detect ≥0·3% D‐positive RBC, randomly selected postpartum samples from 208 women were analysed in parallel with the Kleihauer–Betke test (KBT). In addition, all discrepancies were further analysed by flow cytometry. A total of 203 of the 208 postpartum samples were negative in both tests. One sample reacted positive with both assays. Two samples were strongly positive in the new FMH‐PaGIA, but negative in the KBT. A serological re‐examination revealed that both women were D positive. The KBT gave a false‐positive result in two cases because of hereditary persistence of haemoglobin F. The new test is specific, easy to perform and can be done at any time in all laboratories.
Market and Welfare Effects of Second‐Generation, Consumer‐Oriented GM Products
Authors: Giannakas Konstantinos , Yiannaka Amalia
Published: September 2007

We examine the economic effects of the introduction of consumer‐oriented genetically modified (GM) products into the food system by developing a model of heterogeneous consumers and producers that allows for vertical and horizontal differentiation between the products available to consumers. The model facilitates the estimation of consumer and producer surpluses in the product/utility and product/net returns spaces. Results show that the introduction of consumer‐oriented GM products can change the relationship between GM and conventional and organic products from one of vertical to one of horizontal product differentiation and can enhance both economic welfare and the market acceptance and growth of agricultural biotechnology.
Experiments on Damage‐Based Ambient Taxes for Nonpoint Source Polluters
Authors: Suter Jordan F. , Vossler Christian A. , Poe Gregory L. , Segerson Kathleen
Published: September 2007

This article presents experimental tests of a linear and a nonlinear ambient tax mechanism that involve modest information requirements for the regulator. When agents are not allowed to communicate, both tax mechanisms result in emission levels that approximate the social optimum. When agents can communicate, emissions are considerably below the optimum, but we show that the tax function can be scaled to achieve social efficiency. Finally, by disaggregating the overall efficiency measure, we show that changing the pollution threshold that triggers the tax increases the inefficiency resulting from variation in agent‐level decisions, but does not affect average emissions.
Farmers' Perceived Costs of Wetlands: Effects of Wetland Size, Hydration, and Dispersion
Authors: Gelso Brett R. , Fox John A. , Peterson Jeffrey M.
Published: September 2007

We survey landowners to investigate the costs associated with the presence of permanent or seasonal wetland areas in cropland. We find, as predicted by our conceptual model, that dispersion of wetland areas imposes substantial inconvenience costs for producers but that costs respond nonlinearly and irregularly to changes in the frequency of hydration. Producer attitudes toward conservation and environmental regulation have a significant impact on perceived costs, as do some demographic attributes. The analysis suggests that incentives to aggregate dispersed wetlands into larger contiguous areas could benefit landowners and at the same time provide a net increase in wetland area.
Pesticide Use and Fish Harvests in Vietnamese Rice Agroecosystems
Authors: Klemick Heather , Lichtenberg Erik
Published: September 2007

Criticisms of the Green Revolution have focused on environmental and human health problems associated with pesticides. Pesticides may also have adverse effects on wild fish and other aquatic animals in rice paddies that supply an additional source of food and income for some farm households and provide natural pest control. We use survey data from the Mekong Delta region of Vietnam to estimate the impact of pesticides on fish harvests from rice fields. The results confirm findings of ecological studies that pesticide use harms fish populations. However, fish harvest losses are small enough that ignoring them is likely economically rational.
Traceability, Liability, and Incentives for Food Safety and Quality
Authors: Pouliot Sébastien , Sumner Daniel A.
Published: September 2007

Recent food scares such as the discoveries of Bovine Spongiform Encephalopathy and E. coli‐contaminated spinach have heightened interest in food traceability. Here, we show how exogenous increases in food traceability create incentives for farms and marketing firms to supply safer food by increasing liability costs. We model a stylized marketing chain composed of farms, marketers, and consumers. Unsafe food for consumers can be caused by either marketers or farms. We show that food safety declines with the number of farms and marketers and imperfect traceability from consumers to marketers dampens liability incentives to supply safer food by farms.
Bilateral Trade Agreements*
Authors: Menon Jayant
Published: September 2007

Bilateral Trade Agreements (BTAs) have been proliferating. Why are they so popular? What are their impacts on multilateralism and the world trade system? The article identifies the general and specific factors driving the growth in BTAs, and examines how BTAs in general and different types of BTAs are affecting the world trade system. Although the sheer number of BTAs is fragmenting the world trade system, the impact of individual BTAs often depends on their underlying motivation. The article also portrays scenarios for the future landscape of world trade and possible responses. Is the consolidation of BTAs into region‐wide agreements a solution or simply a new problem? How can we multilateralise bilateralism and repair the world trade system? The article attempts to answer these questions, with or without Doha.
Modern Statistics for Spatial Point Processes*
Authors: MØLLER JESPER , WAAGEPETERSEN RASMUS P.
Published: September 2007

Abstract. We summarize and discuss the current state of spatial point process theory and directions for future research, making an analogy with generalized linear models and random effect models, and illustrating the theory with various examples of applications. In particular, we consider Poisson, Gibbs and Cox process models, diagnostic tools and model checking, Markov chain Monte Carlo algorithms, computational methods for likelihood‐based inference, and quick non‐likelihood approaches to inference.
HOMEOWNERSHIP IN AN UNCERTAIN WORLD WITH SUBSTANTIAL TRANSACTION COSTS*
Authors: Smith Margaret H. , Smith Gary
Published: September 2007

ABSTRACT This paper presents a dynamic model of residential real estate tenure decisions that takes into account the substantial transaction costs and the uncertain time paths of rents and prices. By temporarily postponing decisions, buyers and sellers obtain additional information and may avoid transactions that are costly to reverse. One implication is that the combination of high transaction costs and substantial uncertainty can create a large wedge between a household's reservation prices for buying and selling a home, which can explain why households do not switch back and forth between owning and renting as home prices fluctuate.
Algorithms for Optimal Allocation of Bets on Many Simultaneous Events
Authors: Whitrow Chris
Published: September 2007

The problem of optimizing a number of simultaneous bets is considered, using primarily log-utility. Stochastic gradient-based algorithms for solving this problem are developed and compared with the simplex method. The solutions may be regarded as a generalization of ‘Kelly staking’ to the case of many simultaneous bets. Properties of the solutions are examined in two example cases using real odds from sports bookmakers. The algorithms that are developed also have wide applicability beyond sports betting and may be extended to general portfolio optimization problems, with any reasonable utility function.
HISTORY IN THE SIKH PAST1
Authors: MURPHY ANNE
Published: September 2007

This article offers a reading of an early eighteenth‐century Punjabi text—Gur Sobha or “The Splendor of the Guru”—as a form of historical representation, suggesting reasons for the importance of the representation of the past as history within Sikh discursive contexts. The text in question provides an account of the life, death, and teachings of the last of the ten living Sikh Gurus or teachers, Guru Gobind Singh. The article argues that the construction of history in this text is linked to the transition of the Sikh community at the death of the last living Guru whereby authority was invested in the canonical text (granth) and community (panth). As such a particular rationale for history was produced within Sikh religious thought and intellectual production around the discursive construction of the community in relation to the past and as a continuing presence. As such, the text provides an alternative to modern European forms of historical representation, while sharing some features of the “historical” as defined in that context. The essay relates this phenomenon to a broader exploration of history in South Asian contexts, to notions of historicality that are plural, and to issues particular to the intersection of history and religion. Later texts, through the middle of the nineteenth century, are briefly considered, to provide a sense of the significance of Gur Sobha within a broader, historically and religiously constituted Sikh imagination of the past.
Reversal of heroin neurobehavioral teratogenicity by grafting of neural progenitors
Authors: Katz Sophia , Ben‐hur Tamir , Ben‐Shaanan Tamar L. , Yanai Joseph
Published: September 2007

A major objective in identifying the mechanisms underlying neurobehavioral teratogenicity in an animal model is the possibility of designing therapies that reverse or offset teratogen‐induced neural damage. In our previous studies, we identified deficits in hippocampal muscarinic cholinergic receptor‐induced translocation of protein kinase C (PKC) γ as the likely central factor responsible for the adverse behavioral effects of pre‐natal heroin exposure. Neural progenitors (NP) have the ability to recover behavioral deficits after focal hippocampal damage. Therefore, we explored whether behavioral and synaptic defects could be reversed in adulthood by neural progenitor grafting. Pregnant mice were injected daily with 10 mg/kg of heroin on gestational days 9–18. In adulthood, offspring showed deficits in the Morris maze, a behavior dependent on the integrity of septohippocampal cholinergic synaptic function, along with the loss of the PKCγ and PKCβII responses to cholinergic stimulation. Mice that were exposed pre‐natally to heroin and vehicle control mice were then grafted in adulthood with NP. Importantly, most grafted cells differentiated to astrocytes. NP reversed the behavioral deficits (p = 0.0043) and restored the normal response of hippocampal PKCγ and PKCβII (p = 0.0337 and p = 0.0265 respectively) to cholinergic receptor stimulation. The effects were specific as the PKCα isoform, which is unrelated to the behavioral deficits, showed almost no changes. Neural progenitor grafting thus offers an animal model for reversing neurobehavioral deficits originating in septohippocampal cholinergic defects elicited by pre‐natal exposure to insults.
Hsp70 suppresses apoptosis in sympathetic neurones by preventing the activation of c‐Jun
Authors: Bienemann A. S. , Lee Y. B. , Howarth J. , Uney J. B
Published: September 2007

The anti‐apoptotic effects of heat‐shock protein (Hsp70) were assessed in SCG neurones following nerve growth factor (NGF) withdrawal. The results showed that the virally mediated expression of Hsp70 mirrored the effects of the c‐Jun‐N‐terminal kinase (JNK) binding domain (JBD) of JNK interacting protein (an inhibitor of JNK and c‐Jun activation) and suppressed the phosphorylation of c‐Jun. Preventing c‐Jun transcriptional activity subsequently led to reduced cytochrome c release and prevented caspase activation as indicated by a decrease in poly (ADP‐ribose) polymerase‐1 (PARP) cleavage. Together, these results show that Hsp70 is a highly effective inhibitor of apoptosis in sympathetic neurones and that it mediates this effect primarily by suppressing c‐Jun transcriptional signalling.
Effect of Analysts' Optimism on Estimates of the Expected Rate of Return Implied by Earnings Forecasts
Authors: EASTON PETER D. , SOMMERS GREGORY A.
Published: September 2007

Recent literature has used analysts' earnings forecasts, which are known to be optimistic, to estimate implied expected rates of return, yielding upwardly biased estimates. We estimate that the bias, computed as the difference between the estimates of the implied expected rate of return based on analysts' earnings forecasts and estimates based on current earnings realizations, is 2.84%. The importance of this bias is illustrated by the fact that several extant studies estimate an equity premium in the vicinity of 3%, which would be eliminated by the removal of the bias. We illustrate the point that cross‐sample differences in the bias may lead to the erroneous conclusion that cost of capital differs across these samples by showing that analysts' optimism, and hence, bias in the implied estimates of the expected rate of return, differs with firm size and with analysts' recommendation. As an important aside, we show that the bias in a value‐weighted estimate of the implied equity premium is 1.60% and that the unbiased value‐weighted estimate of this premium is 4.43%.
Contact metamorphism in the Malashan dome, North Himalayan gneiss domes, southern Tibet: an example of shallow extensional tectonics in the Tethys Himalaya
Authors: KAWAKAMI T. , AOYA M. , WALLIS S. R. , LEE J. , TERADA K. , WANG Y. , HEIZLER M.
Published: September 2007

Combined petrographic, structural and geochronological study of the Malashan dome, one of the North Himalayan gneiss domes, reveals that it is cored by a Miocene granite, the Malashan granite, that intruded into the Jurassic sedimentary rocks of Tethys Himalaya. Two other granites in the area are referred to as the Paiku and Cuobu granites. New zircon SHRIMP U‐Pb and muscovite and biotite40Ar‐39Ar dating show that the Paiku granite was emplaced during 22.2–16.2 Ma (average 19.3 ± 3.9 Ma) and cooled rapidly to 350–400 °C at around 15.9 Ma. Whole‐rock granite chemistry suggests the original granitic magma may have formed by muscovite dehydration melting of a protolith chemically similar to the High Himalayan Crystalline Sequence. Abundant calcareous metasedimentary rocks and minor garnet‐staurolite‐biotite‐muscovite ± andalusite schists record contact metamorphism by three granites that intruded intermittently into the Jurassic sediments between 18.5 and 15.3 Ma. Two stages of widespread penetrative ductile deformation, D1 and D2, can be defined. Microstructural studies of metapelites combined with geothermobarometry and pseudosection analyses yieldP–Tconditions of 4.8 ± 0.8 kbar at 550 ± 50 °C during a non‐deformational stage between D1 and D2, and 3.1–4.1 kbar at 530–575 °C during syn‐ to post‐D2. The pressure estimates for the syn‐ to post‐D2 growth of andalusite suggest relatively shallow (depth of ∼15.2 km) extensional ductile deformation that took place within a shear zone of the South Tibetan Detachment System. Close temporal association between intrusion of the Malashan granite and onset of D2 suggests extension may have been triggered by the intrusion of the Malashan granite.
Autosomal dominant nocturnal frontal lobe epilepsy with a mutation in the CHRNB2 gene
Authors: Díaz‐Otero Fernando , Quesada Mar , Morales‐Corraliza José , Martínez‐Parra Carlos , Gómez‐Garre Pilar , Serratosa José M
Published: September 2007

Summary

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE; MIM 600513) has been associated with mutations in the genes coding for the alfa‐4 (CHRNA4), beta‐2 (CHRNB2), and alpha‐2 (CHRNA2) subunits of the neuronal nicotinic acetylcholine receptor (nAChR) and for the corticotropin‐releasing hormone (CRH). A four‐generation ADNFLE family with six affected members was identified. All affected members presented the clinical characteristics of ADNFLE. Interictal awake and sleep EEG recordings showed no epileptiform abnormalities. Ictal video‐EEG recordings showed focal seizures with frontal lobe semiology. Mutation analysis of the CHRNB2 gene revealed a c.859G>A transition (Val287Met) within the second transmembrane domain, identical to that previously described in a Scottish ADNFLE family. To our knowledge, this is the third family reported presenting a mutation in CHRNB2. The clinical phenotype appears similar to that described with mutations in CHRNA4, suggesting that mutations in these two subunits lead to similar functional alterations of the nAChR.
Ictal asystole: A benign condition?
Authors: Schuele Stephan U. , Bermeo Adriana C. , Locatelli Eduardo , Burgess Richard C. , Lüders Hans O.
Published: September 2007

Summary

Ictal asystole (IA) has been implicated as a preventable cause of sudden unexplained death in epilepsy presumably provoked by a direct autonomic effect of the electrical stimulus on the heart. An electronic database search of patients with IA was performed comparing heart rate (HR) characteristics to a group of patients with vasovagal asystole. IA was seen in eight patients, all with temporal lobe epilepsy. No statistical difference was found in duration of asystole, bradycardia, and baseline HR characteristics except of a higher HR acceleration postasystole in the controls. None of the six patients with IA who underwent pacemaker implantation had recurrence of asystolic events during mean follow‐up of 5 years. This study in a small group of patients suggests that the epileptic activation leading to IA is possibly mediated through a transient increase in vagal tone and not by a direct autonomic effect on the heart.
Extracorporeal photophoresis increases sensitivity of monocytes from patients with graft‐versus‐host disease to HLA‐DR–mediated cell death
Authors: Setterblad Niclas , Garban Frédéric , Weigl Roman , Assier Eric , Drillat Philippe , Charron Dominique , Dickinson Anne , Greinix Hildegard , Mooney Nuala
Published: September 2007

BACKGROUND: Graft‐versus‐host disease (GVHD) remains a cause of long‐term morbidity after allogeneic hematopoietic stem cell transplantation, and recent studies indicate that extracorporeal photophoresis (ECP) is useful for treatment of steroid‐refractory GVHD although the mechanisms are unclear. Antigen‐presenting cells (APCs) such as dendritic cells have a central role in GVHD, and apoptosis of APCs by HLA‐DR monoclonal antibody (MoAb) has been documented in vitro and in vivo. Monocytes have been identified as precursors of dendritic cells in vivo and particularly under conditions of inflammation.

STUDY DESIGN AND METHODS: This study examined whether ECP altered the survival of peripheral blood monocytes from patients with GVHD, monocyte apoptosis after engagement of HLA‐DR antigens with MoAb, and monocyte apoptosis after allointeraction with primary CD4+ T lymphocytes. Samples from patients from two centers were studied.

RESULTS: It is reported here that ECP induced apoptosis of monocytes over a period of at least 48 hours. ECP also clearly increased cell death of monocytes after engagement of HLA‐DR antigens with MoAb. In contrast, engagement of HLA‐DR by allointeraction failed to induce significant cell death of monocytes, and this was unaltered by ECP treatment.

CONCLUSION: These data reveal that monocytes from patients with GVHD are sensitive to HLA‐DR–mediated apoptosis and that ECP treatment increases sensitivity to both spontaneous and HLA‐DR–mediated apoptosis. Therefore, ECP treatment in combination with HLA‐DR MoAbs could rapidly deplete monocytes and thereby reduce the contribution of monocyte‐derived dendritic cells to GVHD.
Neutralization of human parvovirus B19 by plasma and intravenous immunoglobulins
Authors: Modrof Jens , Berting Andreas , Tille Björn , Klotz Andreas , Forstner Christina , Rieger Sandra , Aberham Claudia , Gessner Matthias , Kreil Thomas R.
Published: September 2007

BACKGROUND: Human parvovirus B19 (B19V) is a highly prevalent pathogen, and plasma pools for manufacturing of plasma‐derived products have been shown to contain antibodies against B19V (B19V immunoglobulin G [IgG]).

STUDY DESIGN AND METHODS: The megakaryoblastic cell line UT7/Epo‐S1 can be infected with B19V Genotype 1 and as demonstrated here by immunocytochemistry, Western blot, and reverse transcription–polymerase chain reaction (RT‐PCR) of B19V‐specific mRNA, also with the more recently discovered Genotype 2. Based on B19V RT‐PCR analysis of infected UT7/Epo‐S1 cells, an infectivity assay was established and implemented for a B19V neutralization assay. To investigate the role of B19V neutralization in relation to B19V IgG titers, more than 1000 manufacturing plasma pools were tested by enzyme‐linked immunosorbent assay.

RESULTS: Plasma pools were found to contain a mean B19V IgG titer of 33 ± 9 IU per mL, with the lowest titer at 11 IU per mL. These 11 IU per mL B19V IgG neutralized 4.6 log B19V Genotype 1 and greater than 3.9 log Genotype 2 infectivity. Accordingly, a 10 percent intravenous immunoglobulin (IVIG) product prepared from such pools was found to contain an even higher B19V neutralization capacity.

CONCLUSION: A high capacity of B19V Genotypes 1 and 2 neutralization was demonstrated in plasma pools for fractionation, an inherent feature based on the constantly high titer of B19V IgG in these pools. The neutralizing activity of B19V IgG was shown to be maintained in the 10 percent IVIG product tested.
Correlation between serology and genetics of weak D types in Denmark
Authors: Christiansen Mette , Samuelsen Betina , Christiansen Lene , Morbjerg Trine , Bredahl Conny , Grunnet Niels
Published: September 2007

BACKGROUND: To date more than 100 variant D types have been reported and the frequencies vary among populations. Blood donor typing should reveal all donors expressing D antigens, while patient typing should prevent the development of anti‐D in patients with a D– or variant D blood type. Serotyping is the standard method to assign transfusion strategies, whereas molecular classification offers a more specific grouping of weak and partial D.

STUDY DESIGN AND METHODS: Blood donor and patient samples with discrepant results of D phenotyping were collected to investigate the frequency of weak D subtypes in Denmark and to evaluate currently used serologic methods.

RESULTS: Nine different weak D types were identified among the 101 samples. Weak D Types 1, 2, and 3 constituted 80 percent of the analyzed samples and 10 percent of the samples identified as weak D from serology were actually partial D.

CONCLUSION: The distribution of weak D types in Denmark was found to resemble the distribution in Northern Germany in respect to the three most prevalent weak D types. Correctly defining all samples that show weak reactions in D typing as weak D or partial D is not possible with serotyping alone; genotyping offers the only exact categorization. Serology is superior for routine blood typing, however.
Two Techniques to Avoid Surgery for Cardiac Tamponade Occurring During Catheter Ablation of Atrial Fibrillation
Authors: O'NEILL MARK D. , JAÏS PIERRE , DERVAL NICOLAS , HOCINI MÉLÈZE , HAÏSSAGUERRE MICHEL
Published: September 2007

Catheter ablation of atrial fibrillation (AF) is associated with cardiac tamponade in between 0.1% and 2.4% of patients when performed in experienced centers. In the vast majority of cases, the tamponade can be managed conservatively; however, occasionally, urgent sternotomy and open repair are needed. In this report, we describe two techniques for pericardial drainage in patients who, without their use, would almost certainly have required an open exploration and surgical repair.
Quantitative Assessment of Angiographic Right Ventricular Wall Motion in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C)
Authors: INDIK JULIA H. , WICHTER THOMAS , GEAR KATHLEEN , DALLAS WILLIAM J. , MARCUS FRANK I.
Published: September 2007

Introduction: Angiography of the right ventricle (RV) is a standard, reference technique to diagnose wall motion abnormalities in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). RV wall motion is usually assessed by qualitative, visual impression, and has lacked a quantitative basis for defining abnormalities. Since the normal RV has a markedly asymmetric movement, angiographic interpretation can differ, even among experienced clinicians. The purpose of this study was to quantify RV wall motion based on contrast ventriculography in patients with ARVD/C and to specify the severity and location of wall motion abnormalities, as compared with normal subjects.

Methods and Results: We analyzed the angiographic contours of the RV in three views from 19 normal subjects and 23 subjects with ARVD/C. Contour area movement during contraction was calculated circumferentially and further analyzed in nine zones. RV ejection fraction was also computed. Wall motion in ARVD/C was depressed by more than 30% at the tricuspid valve and inferior wall regions (P < 0.001) and significantly reduced at the apex (P = 0.003). However, the RVOT and anterior wall motion were not significantly reduced. RV ejection fraction was depressed from 60 ± 11% in normal subjects to 41 ± 12% in ARVD/C patients (P < 0.001).

Conclusion: Wall motion abnormalities in ARVD/C can be quantified and compared with normal controls, showing primarily reduced movement in the tricuspid and inferior wall regions. This study delineates objective measurements that can be used to aid in the diagnosis of ARVD/C. In addition, they may be incorporated in future refinements of criteria to diagnose ARVD/C.
Pain and Anatomical Locations of Radiofrequency Ablation as Predictors of Esophageal Temperature Rise During Pulmonary Vein Isolation
Authors: ARYANA ARASH , HEIST E. KEVIN , D'AVILA ANDRE , HOLMVANG GODTFRED , CHEVALIER JIANPING , RUSKIN JEREMY N. , MANSOUR MOUSSA C.
Published: September 2007

Introduction: Esophageal temperature rise (ETR) during ablation inside left atrium has been reported as a marker for esophageal thermal injury. We sought to investigate the possible relationships between chest pain and ETR during radiofrequency (RF) ablation, and ETR and locations of RF application, in patients undergoing pulmonary vein (PV) isolation under moderate sedation.

Methods and Results: We analyzed anatomical locations of each RF application and its association with esophageal temperature and presence/absence of pain. Data from 40 consecutive patients (mean age: 56 ± 10 years) were analyzed. There were a total of 4,071 RF applications resulting in 291 episodes of pain (7.1%) and 223 ETRs (5.5%). Thirty‐five patients (87.5%) experienced at least one pain episode and 32 (80.0%) had at least one ETR. While 77.4% of posterior wall applications that caused pain also corresponded to an ETR (P < 0.0001), only 0.8% of pain‐free posterior wall applications were associated with ETRs (P < 0.0001). The sensitivity and specificity of pain during ablation for ETR were 94% and 98%, respectively. No ETRs were observed during anterior wall applications. ETRs occurred more frequently during ablation on the left (86.1%) versus the right (13.9%), and in inferior (70.4%) versus superior (29.6%) segments.

Conclusion: In patients undergoing PV isolation, ETR was encountered when ablating in the posterior left atrium with the distribution left > right and inferior > superior. Pain during ablation was associated with ETR, and lack of pain was strongly associated with absence of ETR. Pain during RF ablation may thus serve as a predictor of esophageal heating and potential injury.
A Semiparametric Response Surface Model for Assessing Drug Interaction
Authors: Kong Maiying , Lee J. Jack
Published: September 2007

Summary When multiple drugs are administered simultaneously, investigators are often interested in assessing whether the drug combinations are synergistic, additive, or antagonistic. Existing response surface models are not adequate to capture the complex patterns of drug interactions. We propose a two‐component semiparametric response surface model with a parametric function to describe the additive effect of a combination dose and a nonparametric function to capture the departure from the additive effect. The nonparametric function is estimated using the technique developed in thin plate splines, and the pointwise bootstrap confidence interval for this function is constructed. The proposed semiparametric model offers an effective way of formulating the additive effect while allowing the flexibility of modeling a departure from additivity. Example and simulations are given to illustrate that the proposed model provides an excellent estimation for different patterns of interactions between two drugs.