bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary human glomerular endothelial cells produce proteoglycans, and puromycin affects their posttranslational modification
Authors: Björnson Anna , Moses Jonatan , Ingemansson Annika , Haraldsson Börje , Sörensson Jenny
Published: December 2004

This article describes the possible role of the endothelial cell-surface coat, containing proteoglycans (PGs) with connected glycosaminoglycans (GAGs), in maintaining glomerular permselectivity. Primary human glomerular endothelial cells (HGEC) in culture were treated with the nephrosis-inducing agent puromycin aminonucleoside (PAN). Analysis was made by TaqMan real-time PCR, Western blot analysis, and by metabolic labeling with [35S]sulfate. The HGECs express several PGs: syndecan, versican, glypican, perlecan, decorin, and biglycan, which may contribute to the glomerular charge barrier. PAN treatment downregulated both the protein expression (by 25%) and the mRNA expression (by 37 ± 6%, P < 0.001, n = 8) of versican compared with control. Transferases important for chondroitin and heparan sulfate biosynthesis were also significantly downregulated by PAN, resulting in less sulfate groups, shorter GAG chains, and reduced PG net-negative charge. Moreover, analysis of the cell media after PAN treatment revealed a reduced content of [35S]sulfate-labeled PGs (40% of control). We conclude that PAN may cause proteinuria by affecting the endothelial cell-surface layer and not only by disrupting the foot process arrangement of the podocytes. Thus the endothelium may be a more important component of the glomerular barrier than hitherto acknowledged.
Genes controlling multiple functional pathways are transcriptionally regulated in connexin43 null mouse heart
Authors: Iacobas Dumitru A. , Iacobas Sanda , Li W. E. I. , Zoidl Georg , Dermietzel Rolf , Spray David C.
Published: December 2004

We have used mouse 27k cDNA arrays to compare gene expression patterns in four sets of three hearts each of neonatal wild types and four sets of three hearts each of littermates lacking the major cardiac gap junction protein, connexin43 (Cx43). Each individual set of hearts was hybridized against aliquots of an RNA standard prepared from selected mouse tissues, allowing calculation of variability and coordination of gene expression among the samples from both genotypes. Overall variance of gene expression was found to be markedly higher in wild-type hearts than in those from Cx43 null littermates. Expression levels of 586 of 5,613 adequately quantifiable distinct genes with known protein products were statistically altered in the Cx43 null hearts, 38 upregulated and 548 downregulated compared with wild types. Downregulation was confirmed for seven tested genes by quantitative RT-PCR. Functions of proteins encoded by the altered genes encompassed all functional categories, with largest percent changes in genes involved in intracellular transport and transcription factors. Among the downregulated genes in the Cx43 null hearts were those related to neuronal and glial function, suggesting that cardiac innervation might be compromised as a consequence of Cx43 deletion. This was supported by immunodetection of sympathetic innervation, using antibodies to the synaptic vesicle protein synaptophysin and to the adrenergic nerve terminal marker tyrosine hydroxylase. These findings reinforce the proposal that the cardiac abnormality in Cx43 null animals may be contributed by altered innervation and indicate that Cx43 deletion has consequences in addition to reduced intercellular communication.
Chemical preparation and crystal data for two condensed phosphates NiCs4(PO3)6 and NiK4(P3O9)2
Authors: Sbai Kacem , Belaaouad Said , Kenz Abdelkebir , Tace El Mostafa , Tridane Malika
Published: December 2004

Methods of chemical preparation and crystallographic data are reported for two new condensed phosphates: a polyphosphate of nickel and cesium, NiCs4(PO3)6, and a cyclotriphosphate of nickel and potassium, NiK4(P3O9)2. NiCs4(PO3)6 is rhombohedral with the following unit-cell dimensions: a=b=11.602(1) Å, c=9.078(1) Å, space group P−31c, V=1058.24(1) Å3, and Z=2. NiK4(P3O9)2 is triclinic with the following unit-cell dimensions: a=6.143(8) Å, b=6.80(1) Å, c=12.80(3) Å, α=102.8(3)°, β=89.7(2)°, γ=66.03(7)°, space group P−1, V=473.56(3) Å3, and Z=1.
X-ray powder diffraction data and Rietveld refinement of CrFe3NiSn5
Authors: Huang Jirong , Zeng Lingmin , Sun Zhihui
Published: December 2004

X-ray power diffraction data for CrFe3NiSn5 are reported. Indexing the XRD power pattern and Rietveld refinement shows that the compound crystallizes in the hexagonal crystal system, space group P6mm (No. 183) with lattice parameters a=5.3168(1) Å, c=4.4261(1) Å, z=0.6 and Dcalc=8.011 g cm−3. The crystal structure of CrFe3NiSn5 is of the CoSn structure type with Fe, Cr and Ni disordered in the Co position.
Powder X-ray diffraction data of a new calcium zirconium phosphate Ca7Zr(PO4)6
Authors: Fukuda Koichiro , Matsubara Hiroyuki , Fukutani Kazuko , Yoshida Hideto
Published: December 2004

X-ray powder diffraction data for a new calcium zirconium phosphate Ca7Zr(PO4)6are reported. The sample was prepared by heating mixtures of CaCO3, ZrO2, and NH4H2PO4in prescribed molar ratios at 1623 K. Powder diffraction data were collected with a laboratory X-ray source (CuKα) for refinement of unit-cell parameters and intensity measurement of individual reflections. Crystallographic data were Ca7Zr(PO4)6, cubic,I-43d(No. 220),a=0.98338(1) nm,V=0.95097(3) nm3,Z=2, andDx=3.29 Mg m−3. This compound is most probably isomorphous with eulytite.
Determination of crystal structures of polymorphic chlorothalonil using Monte Carlo simulated annealing and Rietveld refinement
Authors: Hu Xiurong , Yuan Ziqin , Lu Guanglie
Published: December 2004

Crystal structures of types II and III chlorothalonil, 2,4,5,6-tetrachloro-1,3-dicyanobenzene, (C8Cl4N2) were solved by applying Monte Carlo simulated annealing techniques to X-ray powder diffraction data and refined using the Rietveld method. Both types of chlorothalonil crystallize in monoclinic symmetry (space group P21and two molecules per unit cell). Lattice parameters are:a=8.1615(18) Å,b=9.4191(19) Å,c=6.4728(14) Å,β=93.7307(64)° andV=497.8 Å3for type II, anda=8.6003(10) Å,b=9.2382(11) Å,c=6.3024(7) Å,β=96.2152(60)° andV=498.5 Å3for type III. The structures of both types of chlorothalonil are stacked by two coplanar molecular sheets paralleled to the b-axis. The adjacent two paralleled molecules in type II are on the same plane, while those in type III are on two different parallel planes.
Contribution of capsaicin-sensitive sensory neurons to antithrombin-induced reduction of ischemia/reperfusion-induced liver injury in rats
Authors: Harada Naoaki , Yuksel Mehtap , Isobe Hirotaka , Okajima Kenji
Published: December 2004

We previously reported that antithrombin (AT) reduced ischemia/ reperfusion (I/R)-induced liver injury in rats by increasing endothelial production of prostacyclin (PGI2). However, the mechanism(s) underlying this phenomenon remains to be fully elucidated. We also demonstrated that activation of capsaicinsensitive sensory neurons increased endothelial production of PGI2 by releasing calcitonin gene-related peptide (CGRP) in rats subjected to hepatic I/R. In the present study, we investigated whether AT increases endothelial production of PGI2 through activation of the sensory neurons in rats subjected to hepatic I/R. AT significantly enhanced the I/R-induced increases in hepatic tissue levels of CGRP in rats. Increases in hepatic tissue levels of 6-keto-PGF1α, a stable metabolite of PGI2 , the increase in hepatic-tissue blood flow, and attenuation of both hepatic local inflammatory responses and liver injury in rats administered AT were completely reversed by administration of capsazepine, an inhibitor of sensory neuron activation and CGRP(8–37), a CGRP antagonist.AT did not show any protective effect on liver injury in animals undergoing functional denervation by administration of a large amount of capsaicin.AT significantly increased CGRP release from cultured dorsal root ganglion neurons isolated from rats in the presence of capsaicin.Taken together,these observations strongly suggested that AT might increase hepatic tissue levels of PGI2 via enhancement of hepatic I/R-induced activation of capsaicin-sensitive sensory neurons,thereby reducing liver injury in rats. In this process, CGRP-induced activation of both endothelial nitric oxide synthase and cyclooxygenase-1 might be critically involved.
Haemostatic abnormalities and thrombotic disorders in malignant lymphoma
Authors: Sase Tomohiro , Yamaguchi Motoko , Ogawa Shoko , Kamikura Yuko , Nishikawa Masakatsu , Kaneko Toshihiro , Abe Yasunori , Nishioka Junji , Nobori Tsutomu , Shiku Hiroshi , Wada Hideo
Published: December 2004

We examined haemostatic abnormalities and thrombotic disorders in 217 patients with malignant lymphoma. Plasma levels of fibrinogen and D-dimer were significantly higher in patients with malignant lymphoma than in healthy subjects.The incidence of severe complications, such as disseminated intravascular coagulation (DIC) and interstitial pneumonia (IP), differed with each clinical stage or histological type, but they occurred frequently in stage IV or natural killer (NK) cell lymphoma. Plasma levels of fibrinogen degradation products (FDP) and D-dimer, leukocyte tissue factor (TF) mRNA and plasma TF antigen were significantly higher in stage IV than in stage I, II or III. Plasma levels of FDP, D-dimer, and leukocyte TF mRNA in NK cell lymp homa were markedly higher than in other types of lymphoma. Immunohistochemical staining of NK cell lymphoma revealed that granulocyte macrophage colony-stimulating factor was positive in tumour cells, whereas von Willebrand factor and TF were positive in vascular endothelial cells of surrounding tissue. Our results suggested that patients with stage IV disease and NK cell lymphoma were in abnormal thrombotic and haemostatic state, and may frequently develop DIC and IP. One of the mechanisms of DIC and IP may involve elevated cytokine production by lymphoma cells, which can stimulate the expression of TF in blood cells or surrounding tissue.
High incidence of thrombosis in African-American and Latin-American patients with Paroxysmal Nocturnal Haemoglobinuria
Authors: Thaler Howard , Luzzatto Lucio , Araten David
Published: December 2004

Paroxysmal Nocturnal Haemoglobinuria (PNH) results in a marked thrombophilic state by unknown mechanisms. Geographic differences in thrombosis incidence in PNH have been observed. We have reviewed 64 patients with “Classic PNH” from a single institution in order to determine the rate of thrombosis in different ethnic groups.When we compared African- Americans (n=11) and Latin-Americans (n=8) with other patients (n= 45), we found that African-American and Latin-American patients are at increased risk [Hazard ratio 3.66 (p=0.005) and 3.52, (p= 0.035) respectively by Cox regression]. Our data also suggest that this difference in the rate of thrombosis has an impact on length of survival.These findings demonstrate that ethnicity is a risk factor for thrombosis in PNH and have implications for decision-making regarding the management of these patients,including the prevention of thrombosis.
Tissue factor pathway inhibitor on circulating microparticles in acute myocardial infarction
Authors: Steppich Birgit , Mattisek Christoph , Sobczyk Dean , Kastrati Adnan , Schömig Albert , Ott Ilka
Published: December 2004

In acute myocardial infarction (AMI), increased Tissue Factor (TF) expression on circulating monocytes and microparticles (MP) may contribute to thrombotic events. Because surfaceboundTissue Factor Pathway Inhibitor-1 (TFPI) inhibitsTF activity on monocytes and endothelial cells decreased TFPI expression may reinforce the procoagulant activity of circulating MP.Aim of the study was to analyze TFPI expression and TF activity after stenting and thrombolysis inAMI.Thirty-nine patients of a randomized study comparing intravenous thrombolysis (n = 19) and stenting (n = 20) were included. Before and after therapy blood samples for analysis of MPs, TF antigen and activity, prothrombin fragment F1+2 and D-dimer were obtained.TFPI expression on TF positive MPs was decreased after thrombolysis but not after stenting. In contrast, TF plasma levels and TF positive MP remained unchanged in both treatment groups. After thrombolysis increased D-dimer and F1+2 plasma concentrations indicated activation of fibrinolysis and coagulation. Significance of MPTFPI for inhibition ofTF activity was measured using inhibitory TFPI antibodies. Membrane-associated TFPI inhibited TF activity on circulating MPs. After thrombolysis inhibition of TF activity by TFPI was decreased as compared to stenting. Correlation of circulating TF with F1+2 only after thrombolysis, suggests a role forTF-induced activation of coagulation after thrombolysis. Enhanced TF activity on circulating MPs inAMI is inhibited by endogenous surface-boundTFPI.After thrombolysis but not after stenting MPTFPI is degraded and may induce thrombin generation due to unopposed tissue factor activity. Anti-TF therapies during thrombolysis may reduce thrombin generation in AMI.
Regulation of chemotaxis by the cytoplasmic domain of tissue factor
Authors: Johnell Matilda , Sorensen Brit , Petersen Lars , Heldin Carl-Henrik , Siegbahn Agneta
Published: December 2004

We previously demonstrated that FVIIa bound to tissue factor (TF) induces a hyperchemotactic response towards PDGF-BB. The aim of the present study was to investigate the role of the cytoplasmic domain of TF in cell migration. Porcine aortic endothelial (PAE) cells expressing human PDGF β -receptors (PAE/ PDGFR β ) were transfected for expression of human wildtype TF (PAE/PDGFRβ ,TF), a construct lacking the cytoplasmic domain (PAE/PDGFRβ ,TF ∆ cyto), a construct with alanine replacement of serine 258 (PAE/PDGFRβ ,TFS258A), or a construct with alanine replacement of serine 253, 258 and 263 in the cytoplasmic domain (PAE/PDGFRβ ,TF3SA). All stably transfected cell lines expressed functional TF. Chemotaxis was analyzed in a modified Boyden chamber assay. PAE/PDGFRβ ,TF cells stinulated with FVIIa migrated towards a 100-fold lower concentration of PDGF-BB than in the absence of FVIIa,however,hyperchemotaxis was not seen in PAE/PDGFRβ ,TF ∆ cyto cells. PAE/ PDGFR β /TFS258A and PAE/PDGFRβ ,TF3SA cells responded to low levels of PDGF-BB, but migrated a significantly shorter distance than PAE/PDGFRβ ,TF cells. Thus, hyperchemotaxis towards PDGF-BB is likely to depend in part on phosphorylation of the cytoplasmic domain of TF.We conclude that the cytoplasmic domain of TF plays a pivotal role in modulating cellular migration response.Our results suggest that the FVIIa/TF complex mediates intracellular signaling by alternative signal transduction pathway(s).
The Role of the Carnitine System in Human Metabolism
Authors: FOSTER DANIEL W.
Published: December 2004

Abstract:Metabolism cycles daily between the fed and fasted states. The pathways of energy production are reversible and distinct. In the anabolic (fed) state, the liver stores glucose as glycogen, and fatty acid/triglyceride synthesis is active. In the catabolic (fasted) state, the liver becomes a glucose producer, lipogenesis is slowed, and fatty acid oxidation/ketogenesis is activated. The rate‐limiting step for the latter is vested in the carnitine/carnitine palmitoyltransferase (CPT) system, and the off/on regulator of this is malonyl CoA. The AMP‐induced protein kinase primarily determines the concentration of malonyl CoA. Four other systems have significant influence: two on fatty acid oxidation and two on lipogenesis. Peroxisome proliferator‐activated receptor γ‐1α, a master regulator of metabolism, induces hepatic gluconeogenesis and fatty acid oxidation in the catabolic phase. Deficiency of stearoyl CoA desaturase, although having no role in gluconeogenesis, powerfully induces fatty acid oxidation and weight loss despite increased food intake in rodents. Major stimulators of lipogenesis are carbohydrate‐responsive element binding protein and the Insig system. The malonyl CoA‐regulated CPT system has been firmly established in humans. The other systems have not yet been confirmed in humans, but likely are active there as well. Activation of fatty acid oxidation has considerable clinical promise for the treatment of obesity, type 2 diabetes, steatohepatitis, and lipotoxic damage to the heart.
Modulatory Effects of l‐Carnitine on Glucocorticoid Receptor Activity
Authors: MANOLI IRINI , de MARTINO MASSIMO U. , KINO TOMOSHIGE , ALESCI SALVATORE
Published: December 2004

Abstract: l‐Carnitine (3‐hydroxy‐4‐N,N,N‐trimethylaminobutyrate) is a conditionally essential nutrient with a major role in cellular energy metabolism. It is available in the United States as both a prescription drug and an over‐the‐counter nutritional supplement. Accumulating evidence from both animal and human studies indicates that pharmacologic doses of l‐carnitine (LCAR) have immunomodulatory effects resembling those of glucocorticoids (GC). On the other hand, in contrast to GC, which cause bone loss, LCAR seems to have positive effects on bone metabolism. To explore the molecular bases of this GC‐like activity of LCAR, we investigated its effects on glucocorticoid receptor (GR)‐modulated cytokine release ex vivo, and on the transcriptional activity, intracellular trafficking, and binding of GR in vitro. At high noncytotoxic doses, LCAR (a) suppressed the lipopolysaccharide‐stimulated release of tumor necrosis factor α and interleukin‐12 from primary human monocytes in a GC‐like fashion, (b) stimulated the transcriptional activity of GR on the GC‐responsive promoters, (c) triggered nuclear translocation of green fluorescent protein (GFP)‐fused GR, and (d) reduced the whole cell binding of [3H]‐dexamethasone to GR. These results suggest that LCAR is a “nutritional modulator” of the GR, by acting as an agonist‐like compound. Since LCAR appears to have positive effects on bone metabolism, in contrast to GC, LCAR may share some of the therapeutic properties of GC, particularly on the immune system, but not their deleterious side effects on some of other organs/tissues. Thus, LCAR is potentially a useful alternative compound of GC in particular therapeutic situations. The clinical and therapeutic implications of these findings, as well as a better understanding of their mechanisms, warrant further research.
Model Describing the Relationship Between Pharmacokinetics and Hematologic Toxicity of the Epirubicin-Docetaxel Regimen in Breast Cancer Patients
Authors: Sandström M. , Lindman H. , Nygren P. , Lidbrink E. , Bergh J. , Karlsson M.O.
Published: December 2004

Purpose

The aims of the present study were (1) to characterize the pharmacokinetics of both component drugs and (2) to describe the relationship between the pharmacokinetics and the dose-limiting hematologic toxicity for the epirubicin (EPI)/docetaxel (DTX) regimen in breast cancer patients.

Patients and Methods

Forty-four patients with advanced disease received EPI and DTX every 3 weeks for up to nine cycles. The initial doses (EPI/DTX) were 75/70 mg/m2. Based on leukocyte (WBC) and platelet counts, the subsequent doses were, stepwise, either escalated (maximum, 120/100 mg/m2) or reduced (minimum, 40/50 mg/m2). Hematologic toxicity was monitored in all patients, whereas pharmacokinetics was studied in 16 patients. A semiphysiological model, including physiological parameters as well as drug-specific parameters, was used to describe the time course of WBC count following treatment.

Results

In the final pharmacokinetic model, interoccasion variability was estimated to be less than interindividual variability in the clearances for both drugs. The sum of the individual EPI and DTX areas under concentration-time curve correlated stronger to WBC survival fraction than did the corresponding sum of doses. A pharmacokinetic-pharmacodynamic (PK-PD) model with additive effects of EPI and DTX could adequately describe the data.

Conclusion

The final PK-PD model might provide a tool for calculation of WBC time course, and hence, for prediction of nadir day and duration of leukopenia in breast cancer patients treated with the EPI/DTX regimen.
Ice2p is important for the distribution and structure of the cortical ER network in Saccharomyces cerevisiae
Authors: de Martin Paula Estrada , Du Yunrui , Novick Peter , Ferro-Novick Susan
Published: December 2004

In Saccharomyces cerevisiae, the endoplasmic reticulum (ER) is found along the cell periphery (cortical ER) and nucleus (perinuclear ER). In this study, we characterize a novel ER protein called Ice2p that localizes to the cortical and perinuclear ER. Ice2p is predicted to be a type-III transmembrane protein. Cells carrying a genomic disruption of ICE2 display defects in the distribution of cortical ER in mother and daughter cells. Furthermore, fluorescence imaging of ice2Δ cells reveals an abnormal cortical ER tubular network morphology in both the mother cell and the developing bud. Subcellular fractionation analysis using sucrose gradients corroborate the data from the fluorescence studies. Our findings indicate that Ice2p plays a role in forming and/or maintaining the cortical ER network in budding yeast.
Stroma is not a major target in DMBA-mediated tumorigenesis of mouse mammary preneoplasia
Authors: Medina Daniel , Kittrell Frances
Published: December 2004

Carcinogenesis in the mammary gland is thought to involve carcinogen-induced initiation in mammary epithelial cells. Recent experiments have demonstrated that the mammary stroma can be a target of carcinogenic agents, which results in the stroma positively affecting carcinogenesis. To determine whether the stroma or epithelium is the primary target in chemically induced mouse mammary tumorigenesis, we used transplantation of untreated or 7,12-dimethylbenzanthracene (DMBA)-treated immortalized preneoplastic mammary cells into untreated or DMBA-treated stroma. The results demonstrate that the chemical-carcinogen treated stroma did not enhance mammary tumorigenesis in this model and that carcinogen treatment of the mammary epithelium was essential for tumorigenesis.
The Photographic Medium: Representation, Reconstitution, Consciousness, and Collaboration in Early-Twentieth-Century Spiritualism
Authors: Harvey John
Published: December 2004

This article discusses the image of the ghost as adapted by and to photography. It focuses on the evolution of the photographic ghost in relation to a distinctive manifestation of psychic photography (or spirit photography) prevalent during the early twentieth century. Psychic investigators
observed that in some photographs the faces of spirits that developed on the glass-plate negatives appeared to have been handmade.1 More specifically, they looked like collages, composed of fragments of existing portrait photographs and prints, and of everyday materials, re-photographed, and
superimposed on the plate in the manner of a double-exposure (Fig. 1). Several notable investigators advocated that this phenomenon need not be construed as evidence of fakery. There was another explanation: that psychic photographs contained portraits not of but by disincarnate souls, made
from images drawn from the Spiritualist medium’s or the spirit’s visual memories of photographs of themselves, others, and objects, which were assembled, reproduced, and imprinted upon the photographic plate. Thus, psychic photographs were interpreted as being fabricated artefacts,
born of an interactive collaboration between disincarnate and embodied consciousness, created (somehow) in the ether or a psychic aura, mediated via the camera (in some cases), and made tangible on the sensitized emulsion. This paper examines the unique and overlooked interaction between science
and spirit, apparatus and appearances, and matter and minds, involving and connecting attendant and (purportedly) remote psyches.
Book Reviews
Authors: Sharir Yacov
Published: December 2004

New Visions in Performance: The Impact of Digital Technologies, Gavin Carver and Colin Beardon (eds.) (2003) . Lisse: Swets & Zeitlinger, 195 pp., 57 illustrations, ISBN 9026519664, Hardback, $87.
Synnoetics and self: the construction of planetary identity as an aesthetic oeuvre
Authors: Little Gregory
Published: December 2004

In this article an expanded model of a constructed planetary self is sought, informed by the meta-discipline of “synnoetics”-a term coined in 1961 by Louis Fein in unpublished documents, to describe “the cooperative interaction, or symbiosis of people, mechanisms,
plant or animal organisms, and automata into a system that results in a mental power (power of knowing) greater than that of its individual components.” (Fein, 1960) As the Net has brought about the death of the Cartisian cogito and the collapse of the Oedipal narrative, monolithic identity
is renounced and replaced by a constructed identity of ubiquity. Synnoetics takes us one step further, as we are able to consciously construct a Synnoetic self as an aesthetic oeuvre, further challenging traditional notions of singular, monolithic identity and extending notions of the postmodern,
decentered self into simultaneously new and ancient selves defined by shape-shifting, Psi-interaction, and cumulative, distributed, inter-species knowing. It is my position in this paper that the parallel trajectories of development in nanotechnologies; research in Psi and anomolous phenomena,
and the proliferation of ubiquitous technologies has created a medium for the creation of a synnoetic self. The merger of these research agendas represent a fourth stage in the development of cybernetics, as the research facilitates an entirely new channel for information exchange and communication
between humans, plants, animals, and machines, and consequently, for the construction of a planetary, aesthetic, beyond the human, self. The role of technology shifts, as it is used not to augment or extend human consciousness, but to measure the extent to which the boundaries of human, plant,
animal, and machine consciousness are not known. For example, in Psi phenomena, consciousness needs sensitive technology to be understood and directed, thus consciousness augments technology, not the other way round. Psi phenomena as a form of wireless communication may be of profound importance
to the future development of interactive ubiquitious interfaces, synnoetic intra-species minds, and a new, undefined context for aesthetic experience.
Soft buildings
Authors: Phillips Mike
Published: December 2004

Buildings are solid, monolithic, static structures of steel, stone and glass. Buildings are at their most dynamic during the phases of construction and ossify from the point of completion. They occupy a different timescale to the rest of us, unlike the mayfly that enacts its lifespan
in the space of a day, or our three score and ten, buildings emerge from a long gestation to face the elements for periods that can span a thousand years. Or they used to - increasingly the contemporary built environment ebbs and flows, generating a dynamically changing landscape as buildings
are designed, constructed and demolished in the time it used to take to construct a model. This state of flux is enhanced by the addition of surveillance systems, telematic communication networks and environmental monitoring and control technologies. All these factors provide a new tangible
dimensionality to contemporary architecture. Arch-OS is an ‘operating system’ that harnesses these new architectural, technological and social dimensions. Arch-OS, ‘software for buildings’, has been developed to manifest the social, technological and environmental life
of a building and provide a living laboratory for cultivating transdisciplinary knowledge. Arch-OS buildings will be permanently in a state of flux. By feeding on the diverse forms of dynamic data that are generated by a building, its environment and its occupants, Arch-OS transforms the architect’s
drawings, the brick, steel, glass and fibre-optic infrastructure into a living, breathing environment. Arch- OS provides users of buildings with a spatial and temporal consciousness, essentially re-programming human activity through a heightened social, architectural awareness. Arch-OS combines
a rich mix of the physical and virtual into a new dynamic architecture, an ‘intelligent’ entity, that interacts, responds and anticipates: Arch-OS is a nervous system for multidimensional buildings. ‘Soft Buildings’ explores some of the ‘dimensions’ made
manifest by Arch-OS. Specifically the generation of new kinds of space, a new kind of model, generated by a soft building.
The Declining Value‐relevance of Accounting Information and Non‐Information‐based Trading: An Empirical Analysis*
Authors: DONTOH ALEX , RADHAKRISHNAN SURESH , RONEN JOSHUA
Published: December 2004

Recently, a growing body of literature has suggested that financial statements have lost their value‐relevance because of a shift from a traditional capital‐intensive economy to a high‐technology, service‐oriented economy. These conclusions are based on studies that find a temporal decline in the association between stock prices and accounting information (earnings and book values). This paper empirically tests a theoretical prediction arising from the noisy rational expectations equilibrium model that suggests that the decline could be driven by non‐information‐based (NIB) trading activity, because such trading reduces the ability of stock prices to reflect accounting information. Specifically, Dontoh, Radhakrishnan, and Ronen (2004) show that when NIB trading increases, the R2s of a regression of stock price on accounting information declines. Our empirical tests confirm this prediction; that is, the decline in the association between stock prices and accounting information as measured by R2s is driven by an increase in NIB trading.
The Walk‐down to Beatable Analyst Forecasts: The Role of Equity Issuance and Insider Trading Incentives*
Authors: RICHARDSON SCOTT , TEOH SIEW HONG , WYSOCKI PETER D.
Published: December 2004

It has been alleged that firms and analysts engage in an "earnings‐guidance game" where analysts first issue optimistic earnings forecasts and then "walk down" their estimates to a level that firms can beat at the official earnings announcement. We examine whether the walk‐down to beatable targets is associated with managerial incentives to sell stock after earnings announcements on the firm's behalf (through new equity issuance) or from their personal accounts (through option exercises and stock sales). Consistent with these hypotheses, we find that the walk‐down to beatable targets is most pronounced when firms or insiders are net sellers of stock after an earnings announcement. These findings provide new insights on the impact of capital‐market incentives on communications between managers and analysts.
Managers' Commitment to the Goals Contained in a Strategic Performance Measurement System*
Authors: WEBB R. ALAN
Published: December 2004

A strategic performance measurement system (SPMS) is a set of causally linked nonfinancial and financial objectives, performance measures, and goals designed to align managers' actions with an organization's strategy. This study identifies and tests features unique to the cause‐effect structure of an SPMS likely to affect an important antecedent to managerial performance: goal commitment. Companies often set difficult goals for the multiple performance measures contained in an SPMS, but research shows difficult goals are significantly more likely to lead to performance gains if individuals are committed to achieving them. Two features central to the SPMS approach are predicted to affect goal commitment: (1) the strength of the cause‐effect links among the nonfinancial and financial performance measures contained in an SPMS and (2) managers' beliefs in their ability to achieve the SPMS nonfinancial goals. Results from an experiment conducted with experienced managers show both SPMS features have a positive effect on goal commitment.
The Riskiness of Large Audit Firm Client Portfolios and Changes in Audit Liability Regimes: Evidence from the U.S. Audit Market*
Authors: CHOI JONG‐HAG , DOOGAR RAJIB K. , GANGULY ANANDA R.
Published: December 2004

We investigate whether the financial riskiness of large U.S. audit firm clienteles varied with the changing audit litigation liability environment during the period 1975‐99. Partitioning the period of study into four distinct periods (a benchmark period (1975‐84), a period of increasing concerns about litigation liability (1985‐89), a period of lobbying for reform (1990‐94), and a post‐relief period (1995‐99)), we find some evidence of risk decreases during 1985‐89, strong evidence of risk decreases during 1990‐94, and strong evidence of risk increases during 1995‐99. However, we also find that over the period of our study, a time during which Big 6 market shares grew appreciably, the proportion of litigious‐industry clients in Big 6 client portfolios grew at about the same rate as the proportion of such clients in the population. Moreover, the Big 6 share of the financially riskiest clients in the economy did not grow as fast as the overall Big 6 market share. In sum, although our evidence is consistent with the hypothesis that the riskiness of Big 6 client portfolios responded to changes in the audit litigation liability environment, we find no systematic evidence of a "race to the bottom" or "bottom fishing" by these firms in a bid to increase their market shares.
Programmed Cell Death of Adult-Generated Hippocampal Neurons Is Mediated by the Proapoptotic Gene Bax
Authors: Sun Woong , Winseck Adam , Vinsant Sharon , Park Ok-hee , Kim Hyun , Oppenheim Ronald W.
Published: December 2004

In the dentate gyrus (DG) of the adult mouse hippocampus, a substantial number of new cells are generated daily, but only a subset of these survive and differentiate into mature neurons, whereas the majority undergo programmed cell death (PCD). However, neither the intracellular machinery required for adult stem cell-derived neuronal death nor the biological implications of the significant loss of these newly generated cells have been examined. Several markers for apoptosis failed to reveal cell death in Bax-deficient mice, and this, together with a progressive increase in neuron number in the DG of the Bax knock-out, indicates that Bax is critical for the PCD of adult-generated hippocampal neurons. Whereas the proliferation of neural progenitor cells was not altered in the Bax-knock-out, there was an accumulation of doublecortin, calretinin+, and neuronal-specific nuclear protein+postmitotic neurons, suggesting that Bax-mediated PCD of adult-generated neurons takes place during an early phase of differentiation. The absence of PCD in the adult also influenced the migration and maturation of adult-generated DG neurons. These results suggest that PCD in the adult brain plays a significant role in the regulation of multiple aspects of adult neurogenesis.
Role of α-Synuclein in Presynaptic Dopamine Recruitment
Authors: Yavich Leonid , Tanila Heikki , Vepsäläinen Saila , Jäkälä Pekka
Published: December 2004

Real-time monitoring of stimulated dopamine release in mice with different α-synuclein expression was used to study the role of α-synuclein in presynaptic dopamine recruitment. Repeated electrical stimulations of ascending dopaminergic pathways decreased the capacity of the readily releasable pool (RRP) and temporarily increased its refilling rate, significantly slowing the rate of dopamine decline in mice with normally expressed α-synuclein. Mice with α-synuclein null mutation demonstrated a permanent increase of the refilling rate. This increase maintained stable dopamine release during stimulation (which induced dopamine decline in other animals) and served as an adaptation to altered dopamine compartmentalization. Mice without α-synuclein and with overexpression of human A30P mutated α-synuclein had a lower capacity of the dopamine storage pool than other animals. Reducing capacity of the storage pool in transgenic A30P mice led to paradoxical effects ofl-dopa, which elevated dopamine release in response to single stimulation but decreased the refilling rate of the RRP.
Spontaneous Opening of T-Type Ca2+Channels Contributes to the Irregular Firing of Dopamine Neurons in Neonatal Rats
Authors: Cui Guohong , Okamoto Takashi , Morikawa Hitoshi
Published: December 2004

During early postnatal development, midbrain dopamine (DA) neurons display anomalous firing patterns and amphetamine response. Spontaneous miniature hyperpolarizations (SMHs) are observed in DA neurons during the same period but not in adults. These hyperpolarizations have been shown to be dependent on the release of Ca2+from internal stores and the subsequent activation of Ca2+-sensitive K+channels. However, the triggering mechanism and the functional significance of SMHs remain poorly understood. To address these issues, using brain slices, we recorded spontaneous miniature outward currents (SMOCs) in DA neurons of neonatal rats. Two types of SMOCs were identified based on the peak amplitude. Both types were suppressed by intracellular dialysis of ruthenium red, a ryanodine receptor (RyR) antagonist, yet none of the known Ca2+-releasing messengers were involved. T-type Ca2+channel blockers (Ni2+and mibefradil) inhibited large-amplitude SMOCs without affecting the small-amplitude ones. The voltage dependence of SMOCs displayed a peak of approximately -50 mV, consistent with the involvement of low-threshold T-type Ca2+channels. Blockade of SMOCs with cyclopiazonic acid or ryanodine converted the irregular firing of DA neurons in neonatal rats into an adult-like pacemaker pattern. This effect was reversed by the injection of artificial currents mimicking SMOCs. Finally, amphetamine inhibited SMOCs and transformed the irregular firing pattern into a more regular one. These data demonstrate that Ca2+influx through T-type Ca2+channels, followed by Ca2+-induced Ca2+release via RyRs, contributes to the generation of SMOCs. We propose that SMOCs-SMHs may underlie the anomalous firing and amphetamine response of DA neurons during the postnatal developmental period.
Sodium Influx Pathways during and after Anoxia in Rat Hippocampal Neurons
Authors: Sheldon Claire , Diarra Abdoullah , Cheng Y. May , Church John
Published: December 2004

Mechanisms that contribute to Na+influx during and immediately after 5 min anoxia were investigated in cultured rat hippocampal neurons loaded with the Na+-sensitive fluorophore sodium-binding benzofuran isophthalate. During anoxia, an influx of Na+in the face of reduced Na+,K+-ATPase activity caused a rise in [Na+]i. After the return to normoxia, Na+,K+-ATPase activity mediated the recovery of [Na+]idespite continued Na+entry. Sodium influx during and after anoxia occurred through multiple pathways and increased the longer neurons were maintained in culture. Under the experimental conditions used, Na+entry during anoxia did not reflect the activation of ionotropic glutamate receptors, TTX- or lidocaine-sensitive Na+channels, plasmalemmal Na+/Ca2+exchange, Na+/H+exchange, or\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{HC}\mathrm{O}_{3}^{-}\) \end{document}-dependent mechanisms; rather, contributions were received from a Gd3+-sensitive pathway activated by reactive oxygen species and Na+/K+/2Cl-cotransport in neurons maintained for 6-10 and 11-14 din vitro(DIV), respectively. Sodium entry immediately after anoxia was not attributable to the activation of ionotropic glutamate receptors, voltage-activated Na+channels, or Na+/K+/2Cl-cotransport; rather, it occurred via Na+/Ca2+exchange, Na+/H+exchange, and a Gd3+-sensitive pathway similar to that observed during anoxia; 11-14 DIV neurons received an additional contribution from an\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{HC}\mathrm{O}_{3}^{-}\) \end{document}-dependent mechanism(s). The results provide insight into the intrinsic mechanisms that contribute to disturbed internal Na+homeostasis during and immediately after anoxia in rat hippocampal neurons and, in this way, may play a role in the pathogenesis of anoxic or ischemic cell injury.
Insulin-Degrading Enzyme as a Downstream Target of Insulin Receptor Signaling Cascade: Implications for Alzheimer's Disease Intervention
Authors: Zhao Lixia , Teter Bruce , Morihara Takashi , Lim Giselle P. , Ambegaokar Surendra S. , Ubeda Oliver J. , Frautschy Sally A. , Cole Greg M.
Published: December 2004

Insulin-degrading enzyme (IDE) is one of the proteins that has been demonstrated to play a key role in degrading β-amyloid (Aβ) monomerin vitroandin vivo, raising the possibility of upregulating IDE as an approach to reduce Aβ. Little is known, however, about the cellular and molecular regulation of IDE protein. Because one of the main functions of IDE is to degrade insulin, we hypothesized that there is a negative feedback mechanism whereby stimulation of insulin receptor-mediated signaling upregulates IDE to prevent chronic activation of the pathway. We show that treatment of primary hippocampal neurons with insulin increased IDE protein levels by ∼25%. Insulin treatment also led to phosphatidylinositol-3 (PI3) kinase activation evidenced by Akt phosphorylation, which was blocked by PI3 kinase inhibitors, wortmannin and LY 294002. Inhibition of PI3 kinase abolished the IDE upregulation by insulin, indicating a cause-effect relationship between insulin signaling and IDE upregulation. Further support for this link was provided by the findings that deficient insulin signaling (decreased PI3 kinase subunit P85) was correlated with reduced IDE in Alzheimer's disease (AD) brains and in Tg2576 Swedish amyloid precursor protein transgenic mice fed a safflower oil-enriched (“Bad”) diet used to accelerate pathogenesis. Consistent with IDE function in the degradation of Aβ monomer, the IDE decrease in the Bad diet-fed Tg2576 mice was associated with increased Aβ monomer levels. Thesein vitroandin vivoanalyses validate the use of enhanced CNS insulin signaling as a potential strategy for AD intervention to correct the IDE defects occurring in AD.
Spatial and Temporal Organization of Ensemble Representations for Different Odor Classes in the Moth Antennal Lobe
Authors: Lei Hong , Christensen Thomas A. , Hildebrand John G.
Published: December 2004

In the insect antennal lobe, odor discrimination depends on the ability of the brain to read neural activity patterns across arrays of uniquely identifiable olfactory glomeruli. Less is understood about the complex temporal dynamics and interglomerular interactions that underlie these spatial patterns. Using neural-ensemble recording, we show that the evoked firing patterns within and between groups of glomeruli are odor dependent and organized in both space and time. Simultaneous recordings from up to 15 units per ensemble were obtained from four zones of glomerular neuropil in response to four classes of odorants: pheromones, monoterpenoids, aromatics, and aliphatics. Each odor class evoked a different pattern of excitation and inhibition across recording zones. The excitatory response field for each class was spatially defined, but inhibitory activity was spread across the antennal lobe, reflecting a center-surround organization. Some chemically related odorants were not easily distinguished by their spatial patterns, but each odorant evoked transient synchronous firing across a uniquely different subset of ensemble units. Examination of 535 cell pairs revealed a strong relationship between their recording positions, temporal correlations, and similarity of odor response profiles. These findings provide the first definitive support for a nested architecture in the insect olfactory system that uses both spatial and temporal coordination of firing to encode chemosensory signals. The spatial extent of the representation is defined by a stereotyped focus of glomerular activity for each odorant class, whereas the transient temporal correlations embedded within the ensemble provide a second coding dimension that can facilitate discrimination between chemically similar volatiles.
Interactions of Postsynaptic Density-95 and the NMDA Receptor 2 Subunit Control Calpain-Mediated Cleavage of the NMDA Receptor
Authors: Dong Yi Na , Waxman Elisa A. , Lynch David R.
Published: December 2004

The calcium-dependent protease calpain cleaves the NMDA receptor 2 (NR2) subunit of the NMDA receptor bothin vitroandin vivoand thus potentially modulates NMDA receptor function and turnover. We examined the ability of postsynaptic density-95 (PSD-95) protein to alter the calpain-mediated cleavage of NR2A and NR2B. Coexpression of PSD-95 with NMDA receptors in human embryonic kidney 293 cells blocked cleavage of NR2A and NR2B by NMDA receptor-activated calpain. NR2A cleavage by calpain occurred in the cell surface and intracellular fractions and required the presence of NR1 subunits. The blocking effect of PSD-95 did not result from decreased calpain activity, lowered intracellular calcium responses, or the blockade of internalization. Instead, this effect was eliminated by deletion of the C-terminal ESDV motif of NR2A or by overexpression of a palmitoylation-deficient PSD-95 mutant lacking the ability to cluster and to interact with NMDA receptorsin situ, suggesting a role for association between the C terminus of NR2A and clustered PSD-95. Synapse-associated protein 102, a membrane-associated guanylate kinase interacting with NR2A but lacking palmitoylation motifs and the ability to cluster, did not protect NR2A from cleavage by calpain. Pharmacological inhibition of palmitoylation disrupted the interaction of PSD-95 with NMDA receptors in cortical neurons and allowed NR2A to be cleaved by calpain, whereas NR2A could not be cleaved in untreated neurons. These results indicate that PSD-95 clustering and direct association of NR2A and PSD-95 mediate the blocking effect of PSD-95 on calpain cleavage. PSD-95 could regulate the susceptibility of NMDA receptors to calpain-mediated cleavage during synaptic transmission and excitotoxicity.
Perirhinal and Postrhinal Contributions to Remote Memory for Context
Authors: Burwell Rebecca D. , Bucci David J. , Sanborn Matthew R. , Jutras Michael J.
Published: December 2004

The perirhinal (PER) and postrhinal (POR) cortices, two components of the medial temporal lobe memory system, are reciprocally connected with the hippocampus both directly and via the entorhinal cortex. Damage to PER or POR before or shortly after training on a contextual fear conditioning task causes deficits in the subsequent expression of contextual fear, implicating these regions in the acquisition or expression of contextual memory. Here, we examined the contribution of PER and POR to the processing of remotely learned contextual information. Male Long-Evans rats were trained in an unsignaled contextual fear conditioning paradigm. After training, rats received bilateral neurotoxic lesions to PER or POR or sham control surgeries at three different training-to-lesion intervals: 1, 28, or 100 d after training. Two weeks after surgery, lesioned and control rats were returned to the training context to assess contextual fear as measured by freezing. Rats with PER or POR damage froze significantly less in the training context than control rats but were not different from each other. The severity of the deficit did not differ across training-to-lesion intervals for any group. This pattern of deficits differs from that of posttraining hippocampal lesions, for which longer training-to-lesion intervals produce significantly more fear-conditioned contextual freezing than shorter training-to-lesion intervals. In the absence of such a retrograde gradient in the present study, our interpretation is that PER and POR have an ongoing role in the storage or retrieval of representations for context. Alternatively, these regions may be involved in a more extended consolidation process that becomes apparent beyond 100 d after learning.