bluuebunny/crossref_metadata_2025 huggingface dataset:
The Epstein-Barr Virus BILF1 Gene Encodes a G Protein-Coupled Receptor That Inhibits Phosphorylation of RNA-Dependent Protein Kinase
Authors: Beisser Patrick S. , Verzijl Dennis , Gruijthuijsen Yvonne K. , Beuken Erik , Smit Martine J. , Leurs Rob , Bruggeman Cathrien A. , Vink Cornelis
Published: December 2004

Epstein-Barr virus (EBV) infection is associated with many lymphoproliferative diseases, such as infectious mononucleosis and Burkitt's lymphoma. Consequently, EBV is one of the most extensively studied herpesviruses. Surprisingly, a putative G protein-coupled receptor (GPCR) gene of EBV, BILF1, has hitherto escaped attention, yet BILF1-like genes are conserved among all known lymphocryptovirus species, suggesting that they play a pivotal role in viral infection. To determine the function of EBV BILF1, the activity of this gene and its products was studied. BILF1-specific mRNA was detected in various EBV-positive cell types and found to be expressed predominantly during the immediate early and early phases of infection in vitro. Interestingly, in COS-7 cells transfected with BILF1 expression constructs, a decrease in forskolin-induced CRE-mediated transcription was measured, as well as an increase in NF-κB-mediated transcription. In contrast, CRE-mediated transcription was increased in EBV-positive Burkitt's lymphoma cells as well as EBV-positive lymphoblastoid B cells transfected with BILF1, whereas NF-κB-mediated transcription levels remained unaffected in these cells. All observed activities were sensitive to treatment with pertussis toxin, indicating that the BILF1-encoded protein mediates these activities by coupling to G proteins of the G
i/o
class. Finally, reduced levels of phosphorylated RNA-dependent antiviral protein kinase were observed in COS-7 and Burkitt's lymphoma cells transfected with BILF1. Neither of the observed effects required a ligand to interact with the BILF1 gene product, suggesting that BILF1 encodes a constitutively active GPCR capable of modulating various intracellular signaling pathways.
R5 Human Immunodeficiency Virus Type 1 Infection of Fetal Thymic Organ Culture Induces Cytokine and CCR5 Expression
Authors: Choudhary Shailesh K. , Choudhary Neelima R. , Kimbrell Katherine C. , Colasanti Jonathan , Ziogas Argyrios , Kwa David , Schuitemaker Hanneke , Camerini David
Published: December 2004

Late-stage CCR5 tropic human immunodeficiency virus type 1 (HIV-1) isolates (R5 HIV-1) can deplete nearly all CD4+thymocytes from human thymus/liver grafts, despite the fact that fewer than 5% of these cells express CCR5. To resolve this paradox, we studied the replication and cytopathic effects (CPE) of late-stage R5 HIV-1 biological clones from two progressors and two long-term nonprogressors (LTNP) in fetal thymic organ culture (FTOC) with and without added cytokines. We found that R5 HIV-1 clones from progressors but not LTNP were cytopathic in untreated FTOC. Moreover, R5 HIV-1 clones from progressors replicated to higher levels than LTNP-derived R5 HIV-1 clones in this system. In contrast, when FTOC was maintained in the presence of interleukin 2 (IL-2), IL-4, and IL-7, both progressor and LTNP clones exhibited similar replication and CPE, which were equal to or greater than the levels achieved by progressor-derived R5 HIV-1 clones in untreated FTOC. This finding was likely due to IL-2-induced CCR5 expression on CD4+thymocytes in FTOC. R5 HIV-1 clones showed greater pathogenesis for CCR5+cells but also showed evidence of CPE on CCR5−cells. Furthermore, infection of FTOC by R5 HIV-1 induced IL-10 and transforming growth factor β (TGF-β) expression. Both IL-10 and TGF-β in turn induced CCR5 expression in FTOC. Induction of CCR5 expression via cytokine induction by R5 HIV-1 infection of CCR5+thymocytes likely permitted further viral replication in newly CCR5+thymocytes. CCR5 expression, therefore, is a key determinant of pathogenesis of R5 HIV-1 in FTOC.
Posttranscriptional Suppression of Interleukin-6 Production by Human Cytomegalovirus
Authors: Gealy Claire , Denson Marian , Humphreys Christine , McSharry Brian , Wilkinson Gavin , Caswell Richard
Published: December 2004

Human cytomegalovirus (HCMV) has evolved multiple strategies for suppression of the antiviral response of the infected cell. DNA array technology has revealed that HCMV clearly regulates host gene expression during the course of a productive infection by enhancing, sustaining, or suppressing steady-state levels of cellular transcripts. Interleukin-6 (IL-6) is a pleiotropic cytokine that plays a central role in the immune response to infection. Here we report a detailed study of the effects of HCMV infection on IL-6 expression by human fibroblasts. UV-inactivated virus was found to induce high levels of IL-6 mRNA and protein expression, and IL-6 mRNA remained abundant in cells 16 h after inoculation even though the level of ongoing IL-6 transcription was not significantly enhanced. In lytic HCMV infections, the onset of viral gene expression resulted in two apparently antagonistic effects on IL-6 expression: (i) transcriptional activation, mediated at least in part by the IE2p86 protein, and (ii) posttranscriptional suppression mediated by destabilization of IL-6 mRNA. Transcriptional activation was outweighed by the suppressive effect, such that cells undergoing productive infection produced less IL-6 than cells challenged with inactivated virus. Suppression of IL-6 expression was independent of the viral IL-10 homologue, cmvIL-10. Destabilization of IL-6 mRNA was observed to coincide with the enhanced expression and aberrant intracellular localization of HuR, an mRNA-binding protein known to interact with IL-6 and other mRNAs containing 3′ AU-rich elements. Our data suggest a novel mechanism for gene regulation by HCMV at the posttranscriptional level.
Epstein-Barr Virus-Encoded BILF1 Is a Constitutively Active G Protein-Coupled Receptor
Authors: Paulsen Sarah J. , Rosenkilde Mette M. , Eugen-Olsen Jesper , Kledal Thomas N.
Published: December 2004

Both beta- and gammaherpesviruses encode G protein-coupled receptors (GPCRs) with unique pharmacological phenotypes and important biological functions. An example is ORF74, the γ2-herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded GPCR, which is highly constitutively active and considered the key oncogene in Kaposi's sarcoma pathogenesis. In contrast, the current annotation of the Epstein-Barr virus (EBV) genome does not reveal any GPCR homolog encoded by this human oncogenic γ1-herpesvirus. However, by employing bioinformatics, we recognized that the previously established EBV open reading frame
BILF1
indeed encodes a GPCR. Additionally, BILF1 is a member of a new family of related GPCRs exclusively encoded by γ1-herpesviruses. Expression of hemagglutinin-tagged BILF1 in the HEK293 epithelial cell line revealed that BILF1 is expressed as an approximately 50-kDa glycosylated protein. Immunocytochemistry and confocal microscopy revealed that BILF1 localizes predominantly to the plasma membrane, similar to the localization of KSHV ORF74. Using chimeric G proteins, we found that human and rhesus EBV-encoded BILF1 are highly potent constitutively active receptors, activating Gα
i
. Furthermore, BILF1 is able to inhibit forskolin-triggered CREB activation via stimulation of endogenous G proteins in a pertussis toxin-sensitive manner, verifying that BILF1 signals constitutively through Gα
i
. We suggest that EBV may use BILF1 to regulate Gα
i
-activated pathways during viral lytic replication, thereby affecting disease progression.
Evolutionary Trace Residues in Noroviruses: Importance in Receptor Binding, Antigenicity, Virion Assembly, and Strain Diversity
Authors: Chakravarty Sugoto , Hutson Anne M. , Estes Mary K. , Prasad B. V. Venkataram
Published: December 2004

Noroviruses cause major epidemic gastroenteritis in humans. A large number of strains of these single-stranded RNA viruses have been reported. Due to the absence of infectious clones of noroviruses and the high sequence variability in their capsids, it has not been possible to identify functionally important residues in these capsids. Consequently, norovirus strain diversity is not understood on the basis of capsid functions, and the development of therapeutic compounds has been hampered. To determine functionally important residues in noroviruses, we have analyzed a number of norovirus capsid sequences in the context of the Norwalk virus capsid crystal structure by using the evolutionary trace method. This analysis has identified capsid protein residues that uniquely characterize different norovirus strains and provide new insights into capsid assembly and disassembly pathways and the strain diversity of these viruses. Such residues form specific three-dimensional clusters that may be of functional importance in noroviruses. One of these clusters includes residues known to participate in the proteolytic cleavage of these viruses at high pH. Other clusters are formed in capsid regions known to be important in the binding of antibodies to noroviruses, thereby indicating residues that may be important in the antigenicity of these viruses. The highly variable region of the capsid shows a distinct cluster whose residues may participate in norovirus-receptor interactions.
Effects of Febrile Temperature on Adenoviral Infection and Replication: Implications for Viral Therapy of Cancer
Authors: Thorne Stephen H. , Brooks Gabriel , Lee Yeun-Ling , Au Tina , Eng Lawrence F. , Reid Tony
Published: December 2004

We previously conducted a phase I/II study using arterial infusions of ONYX-015 (
dl
1520), a replication-selective adenoviral vector, with E1b deleted, for patients with metastatic colorectal cancer. No dose-limiting toxicities occurred, but >90% of the patients experienced fever. The effects of temperature on the replication of
dl
1520 in normal and transformed cells had not been studied. Therefore, replication and cell viability assays were performed with a panel of nontransformed and transformed cell lines cultured at 37 and 39.5°C and treated with adenovirus type 5 (Ad5) or
dl
1520. Ad5-mediated cytolytic effects were inhibited and production of infectious particles decreased by >1,000-fold in the nontransformed cells at 39.5°C. Seven of nine of the tumor cell lines retained significant cell-killing effects when treated with Ad5 at 39.5°C. When
dl
1520 was used, no cytolytic effects were observed at 39.5°C in the nontransformed cell lines; however, cytolytic effects occurred in six of nine tumor cell lines at 39.5°C. Notably, a subset of the tumor cell lines demonstrated increased
dl
1520-mediated cytolytic effect and replication at 39.5°C. Suppression of Ad5 and
dl
1520 replication at 39.5°C was not related to p53 status or HSP70 expression. Also, at 39.5°C, E1a expression was inhibited in nontransformed cells but was still abundant in the transformed cells, indicating that a novel early block in viral replication occurred in the nontransformed cells. Fever may therefore augment the therapeutic index of oncolytic viruses by inhibiting replication in normal cells while permitting or enhancing viral replication in some tumor cells.
Adenovirus Early Region 3 Transgenes Expressed in β Cells Prevent Autoimmune Diabetes in Nonobese Diabetic Mice: Effects of Deleting the Adenovirus Death Protein 11.6K
Authors: Pierce Melissa A. , Svetlanov Anton , Horwitz Marshall S. , Serreze David V.
Published: December 2004

The incidence of type 1 diabetes (T1D) is decreased in nonobese diabetic mice expressing the complete cassette of adenovirus early region 3 (E3) immunomodulating genes in pancreatic β cells. Embedded among the antiapoptotic E3 genes is one encoding an adenovirus death protein (ADP), which contributes to release of virion particles by promoting cell lysis. Because removal of this proapoptotic protein might have further enhanced the ability of E3 proteins to prevent T1D, an ADP-inactivated E3 construct was tested. Significantly, deletion of ADP did not improve the diabetes-protective effect of an E3 gene cassette.
Human Immunodeficiency Virus Type 1 Nef Domains Required for Disruption of Major Histocompatibility Complex Class I Trafficking Are Also Necessary for Coprecipitation of Nef with HLA-A2
Authors: Williams Maya , Roeth Jeremiah F. , Kasper Matthew R. , Filzen Tracey M. , Collins Kathleen L.
Published: December 2004

Human immunodeficiency virus type 1 (HIV-1) Nef is a critical protein that is necessary for HIV pathogenesis. Its roles include the disruption of major histocompatibility complex class I (MHC-I) and CD4 trafficking to promote immune evasion and viral spread. Mutational analyses have revealed that separate domains of Nef are required to affect these two molecules. To further elucidate how Nef disrupts MHC-I trafficking in T cells, we examined the role of protein domains that are required for this function (N-terminal alpha helix, polyproline, acidic, and oligomerization domains). We found that each of these regions was required for Nef to disrupt the transport of HLA-A2 to the cell surface and for Nef to coprecipitate with HLA-A2.
Sindbis Virus with a Tricomponent Genome
Authors: Fayzulin Rafik , Gorchakov Rodion , Petrakova Olga , Volkova Evgenia , Frolov Ilya
Published: December 2004

We established a system for propagation of Sindbis virus (SIN)-based replicons in tissue culture in the form of a tricomponent genome virus. Three RNA fragments containing complementing genetic information required for virus replication are packaged into separate viral particles, and each cell produces at least 1,000 packaged replicons and the number of packaged helpers sufficient to perform the next passage. This system can be used to generate large stocks of packaged replicons. The formation of infectious recombinant SIN virus was not detected in any experiments. These features make multicomponent genome SIN an attractive system for a variety of research and biotechnology applications.
QUANTUM ERROR CORRECTION DRIVEN ENTANGLEMENT DYNAMICS IN THE PRESENCE OF CORRELATED NOISE
Authors: DE CHIARA GABRIELE , FAZIO ROSARIO , MACCHIAVELLO CHIARA , PALMA G. MASSIMO
Published: December 2004

The effects of quantum error correction (QEC) on the dynamics of entanglement between logical qubits in the presence of a dephasing interaction with a correlated environment is investigated. Such a correlated reservoir introduces entanglement between physical qubits which, for short times, is interpreted as error and suppressed by the QEC routine. However for longer times, although QEC is no longer able to correct errors, it enhances the rate of entanglement production due to the interaction with the environment.
ON NONLINEAR EVOLUTION AND SUPRALUMINAL COMMUNICATION BETWEEN FINITE QUANTUM SYSTEMS
Authors: FERRERO M. , SALGADO D. , SÁNCHEZ-GÓMEZ J. L.
Published: December 2004

We revise the 'no-signaling' condition for the supraluminal communication between two spatially separated finite quantum systems of arbitrary dimensions, thus generalizing a similar preceding approach for two-qubits: non-linear evolution does not necessarily imply the possibility of supraluminal communication between any sort of finite quantum systems.
Characterization of inorganic phosphate transport in osteoclast-like cells
Authors: Ito Mikiko , Matsuka Naoko , Izuka Michiyo , Haito Sakiko , Sakai Yuko , Nakamura Rie , Segawa Hiroko , Kuwahata Masashi , Yamamoto Hironori , Pike Wesley J. , Miyamoto Ken-ichi
Published: December 2004

Osteoclasts possess inorganic phosphate (Pi) transport systems to take up external Pi during bone resorption. In the present study, we characterized Pi transport in mouse osteoclast-like cells that were obtained by differentiation of macrophage RAW264.7 cells with receptor activator of NF-κB ligand (RANKL). In undifferentiated RAW264.7 cells, Pi transport into the cells was Na+ dependent, but after treatment with RANKL, Na+-independent Pi transport was significantly increased. In addition, compared with neutral pH, the activity of the Na+-independent Pi transport system in the osteoclast-like cells was markedly enhanced at pH 5.5. The Na+-independent system consisted of two components with Km of 0.35 mM and 7.5 mM. The inhibitors of Pi transport, phosphonoformic acid, and arsenate substantially decreased Pi transport. The proton ionophores nigericin and carbonyl cyanide p-trifluoromethoxyphenylhydrazone as well as a K+ ionophore, valinomycin, significantly suppressed Pi transport activity. Analysis of BCECF fluorescence indicated that Pi transport in osteoclast-like cells is coupled to a proton transport system. In addition, elevation of extracellular K+ ion stimulated Pi transport, suggesting that membrane voltage is involved in the regulation of Pi transport activity. Finally, bone particles significantly increased Na+-independent Pi transport activity in osteoclast-like cells. Thus, osteoclast-like cells have a Pi transport system with characteristics that are different from those of other Na+-dependent Pi transporters. We conclude that stimulation of Pi transport at acidic pH is necessary for bone resorption or for production of the large amounts of energy necessary for acidification of the extracellular environment.
Conductance catheter-based assessment of arterial input impedance, arterial function, and ventricular-vascular interaction in mice
Authors: Segers Patrick , Georgakopoulos Dimitrios , Afanasyeva Marina , Champion Hunter C. , Judge Daniel P. , Millar Huntly D. , Verdonck Pascal , Kass David A. , Stergiopulos Nikos , Westerhof Nico
Published: December 2004

Global assessment of both cardiac and arterial function is important for a meaningful interpretation of pathophysiological changes in animal models of cardiovascular disease. We simultaneously acquired left ventricular (LV) and aortic pressure and LV volume (VLV) in 17 open-chest anesthetized mice (26.7 ± 3.2g) during steady-state (BL) and caval vein occlusion (VCO) using a 1.4-Fr dual-pressure conductance catheter and in a subgroup of eight animals during aortic occlusion (AOO). Aortic flow was obtained from numerical differentiation of VLV. AOO increased input impedance ( Zin) for the first two harmonics, increased characteristic impedance (0.025 ± 0.007 to 0.040 ± 0.011 mmHg·μl−1·s, P < 0.05), and shifted the minimum in Zin from the third to the sixth harmonic. For all conditions, the Zin could be well represented by a four-element windkessel model. The augmentation index increased from 116.7 ± 7.8% to 145.9 ± 19.5% ( P < 0.01) as well as estimated pulse-wave velocity (3.50 ± 0.94 to 5.95 ± 1.62 m/s, P < 0.05) and arterial elastance ( Ea, 4.46 ± 1.62 to 6.02 ± 1.43 mmHg/μl, P < 0.01). AOO altered the maximal slope ( Emax, 3.23 ± 1.02 to 5.53 ± 1.53 mmHg/μl, P < 0.05) and intercept (−19.9 ± 8.6 to 1.62 ± 13.51 μl, P < 0.01) of the end-systolic pressure-volume relation but not Ea/ Emax (1.44 ± 0.43 to 1.21 ± 0.37, not significant). We conclude that simultaneous acquisition of Zin and arterial function parameters in the mouse, based solely on conductance catheter measurements, is feasible. We obtained an anticipated response of Zin and arterial function parameters following VCO and AOO, demonstrating the sensitivity of the measuring technique to induced physiological alterations in murine hemodynamics.
Exercise-induced increase in skeletal muscle vasodilatory responses in obese Zucker rats
Authors: Xiang Lusha , Naik Jay , Hester Robert L.
Published: December 2004

The purpose of this study was to test the hypothesis that exercise training improves microvascular function in obese Zucker rats, a model of obesity and type II diabetes. Animals were divided into four age-matched groups: lean sedentary (LS), lean exercise (LE), obese sedentary (OS), and obese exercise (OE). The exercise groups were treadmill-exercised from 5 to 11 wk of age, including a 2-wk acclimation period. Mean arterial pressure (MAP) was not significantly different between any of the groups. The OS had significantly higher mean body weight, blood glucose, insulin, IL-6, and leptin levels compared with the LS, whereas the OE had significantly lower blood glucose, insulin, and IL-6 levels compared with the OS. Functional hyperemia and endothelial-dependent vasodilation were tested in the spinotrapezius muscle using intravital microscopy. Functional hyperemia and acetylcholine (0.1 μM, 1 μM, and 10 μM) responses were significantly attenuated in OS compared with the LS, while the contraction and ACh-induced (1 μM and 10 μM) vasodilation were significantly increased in both LE and OE compared with the sedentary animals. These results suggest that exercise training can improve vascular function in this model of type II diabetes. Moreover, the impaired vasodilation observed in 11-wk-old OZR suggests that the microvascular dysfunction is not likely due to an elevated blood pressure.
Cortical and Subcortical Correlates of Electroencephalographic Alpha Rhythm Modulation
Authors: Feige Bernd , Scheffler Klaus , Esposito Fabrizio , Di Salle Francesco , Hennig Jürgen , Seifritz Erich
Published: December 2004

Neural correlates of electroencephalographic (EEG) alpha rhythm are poorly understood. Here, we related EEG alpha rhythm in awake humans to blood-oxygen-level-dependent (BOLD) signal change determined by functional magnetic resonance imaging (fMRI). Topographical EEG was recorded simultaneously with fMRI during an open versus closed eyes and an auditory stimulation versus silence condition. EEG was separated into spatial components of maximal temporal independence using independent component analysis. Alpha component amplitudes and stimulus conditions served as general linear model regressors of the fMRI signal time course. In both paradigms, EEG alpha component amplitudes were associated with BOLD signal decreases in occipital areas, but not in thalamus, when a standard BOLD response curve (maximum effect at ∼6 s) was assumed. The part of the alpha regressor independent of the protocol condition, however, revealed significant positive thalamic and mesencephalic correlations with a mean time delay of ∼2.5 s between EEG and BOLD signals. The inverse relationship between EEG alpha amplitude and BOLD signals in primary and secondary visual areas suggests that widespread thalamocortical synchronization is associated with decreased brain metabolism. While the temporal relationship of this association is consistent with metabolic changes occurring simultaneously with changes in the alpha rhythm, sites in the medial thalamus and in the anterior midbrain were found to correlate with short time lag. Assuming a canonical hemodynamic response function, this finding is indicative of activity preceding the actual EEG change by some seconds.
Sluggish and Brisk Ganglion Cells Detect Contrast With Similar Sensitivity
Authors: Xu Ying , Dhingra Narender K. , Smith Robert G. , Sterling Peter
Published: December 2004

Roughly half of all ganglion cells in mammalian retina belong to the broad class, termed “sluggish.” Many of these cells have small receptive fields and project via lateral geniculate nuclei to visual cortex. However, their possible contributions to perception have been largely ignored because sluggish cells seem to respond weakly compared with the more easily studied “brisk” cells. By selecting small somas under infrared DIC optics and recording with a loose seal, we could routinely isolate sluggish cells. When a spot was matched spatially and temporally to the receptive field center, most sluggish cells could detect the same low contrasts as brisk cells. Detection thresholds for the two groups determined by an “ideal observer” were similar: threshold contrast for sluggish cells was 4.7 ± 0.5% (mean ± SE), and for brisk cells was 3.4 ± 0.3% (Mann-Whitney test: P > 0.05). Signal-to-noise ratios for the two classes were also similar at low contrast. However, sluggish cells saturated at somewhat lower contrasts (contrast for half-maximum response was 14 ± 1 vs. 19 ± 2% for brisk cells) and were less sensitive to higher temporal frequencies (when the stimulus frequency was increased from 2 to 4 Hz, the response rate fell by 1.6-fold). Thus the sluggish cells covered a narrower dynamic range and a narrower temporal bandwidth, consistent with their reported lower information rates. Because information per spike is greater at lower firing rates, sluggish cells may represent “cheaper” channels that convey less urgent visual information at a lower energy cost.
Public administration versus public management: parallels, divergences, convergences and who benefits?
Authors: Sindane Abakholwa Moses
Published: December 2004

In this article, the author argues that the New Public Management approach to state and public affairs can only succeed in perpetuating the already unacceptable level of inequalities, exclusions and poverty, both domestically and globally, instead of reversing them. The existence of institutions such as the G8 implies that there is inequality and exclusions even among the developed countries of the world. In emerging democracies, especially in Africa, the situation is rendered worse by the level of poverty, lack of or inadequate education and political instability. In such situations, the role of the state and its machinery, i.e. public administration, assumes greater proportions in the promotion of the general welfare of the population. Such situations cannot be left to economic imperatives as suggested by New Public Management approaches. Marketization is, by nature, exclusive and how it can be reconciled with the pursuit of the promotion of the general welfare and concerns with social issues and public policies beats imagination. Thus, public administration, being time, place and culture bound, demands that the design of its curricula takes the developmental level of the country and its population into account while being mindful of international trends for its adaptation at a pace suited for the specific country.
A Life-Course Analysis of Military Service in Vietnam
Authors: Wright John Paul , Carter David E. , Cullen Francis T.
Published: December 2004

Prior research demonstrates that military service disconnects men from past social and personal disadvantages and thus potentially alters normal life-course patterns of development. Much of this research, however, has been conducted only with World War II veterans. Relatively fewstudies have examined the influence of military service in Vietnam and its impact on altering individual trajectories of development. Through latent growth curve models, the authors examine the impact of military service in Vietnam on drug use and arrests across the life-course. Longitudinal data collected by the Marion County Youth study (1964-1979) were used to track a sample of men over a 15-year period. Analyses of these data revealed substantial nonrandom selection effects associated with service in Vietnam. Lower-class youths with already established delinquent patterns were significantly more likely to have served in Vietnam. It also appears, however, that service in Vietnam significantly increased individual drug use and, hence, offending rates.
In Vivo Disintegration Profiles of Encapsulated and Nonencapsulated Sumatriptan: Gamma Scintigraphy in Healthy Volunteers
Authors: Wilding Ian R. , Clark Darren , Wray Heather , Alderman Jeff , Muirhead Nancy , Sikes Carolyn R.
Published: December 2004

The goal of this exploratory pilot study was to use gamma scintigraphy to evaluate, under physiological conditions, disintegration profiles of encapsulated and nonencapsulated formulations of 100 mg sumatriptan. Using a crossover design, healthy volunteers (n = 10) ingested 100‐mg doses of sumatriptan tablets radiolabeled with 111Indium, as well as encapsulated sumatriptan tablets that were prepared similarly, then placed within a gelatin capsule and backfilled with an excipient blend radiolabeled with 99mTechnetium. A gamma camera recorded scintigraphic images until 5 hours postdose. Initial disintegration of the gelatin capsule was observed at a mean (range) of 5 minutes (1–11 minutes); disintegration was complete within 14 minutes (5–24 minutes). For nonencapsulated versus encapsulated tablets, the mean (± standard deviation) time to initial disintegration (6 ± 5 minutes vs 8 ± 5 minutes) and time to complete disintegration (18 ± 14 minutes vs 16 ± 7 minutes) were comparable. Results of this study demonstrate that encapsulated and nonencapsulated sumatriptan have equivalent in vivo dissolution rates.
Free software and the digital divide: opportunities and constraints for developing countries
Authors: James Jeffrey
Published: December 2004

Our focus in this paper is mainly on the GNU/LINUX operting system and the advantages that it affords developing countries seeking to bridge the global digital divide. In the early parts of the paper we argue that, although GNU/LINUX can generate substantial savings when used instead of the proprietary alternative in numerous institutional settings, the most telling opportunities for developing countries arise when this system is combined with other ways of reducing computing costs. Policy, therfore, should not only consist of substituting GNU/LINUX for proprietary software in running the latest and most expensive hardware, but also of lowering these latter costs themselves. Later sections focus on the link between the choice of software and path-dependency (i.e. the notion that if one system gets ahead, it tends to lock out alternatives in the manner described by Brian Arthur). We suggest that the problem of proprietary lock-in in developing countries has been greatly accentuated by piracy of Microsoft operating systems and that the result is a stagnation of the technological capabilities in software that these countries need so badly.
A model to minimize joint total costs for industrial waste producers and waste management companies
Authors: Tietze-Stöckinger Ingela , Fichtner Wolf , Rentz Otto
Published: December 2004

The model LINKopt is a mixed-integer, linear programming model for mid- and long-term planning of waste management options on an inter-company level. There has been a large increase in the transportation of waste material in Germany, which has been attributed to the implementation of the European Directive 75/442/EEC on waste. Similar situations are expected to emerge in other European countries. The model LINKopt has been developed to determine a waste management system with minimal decision-relevant costs considering transportation, handling, storage and treatment of waste materials. The model can serve as a tool to evaluate various waste management strategies and to obtain the optimal combination of investment options. In addition to costs, ecological aspects are considered by determining the total mileage associated with the waste management system. The model has been applied to a German case study evaluating different investment options for a co-operation between Daimler-Chrysler AG at Rastatt, its suppliers, and the waste management company SITA P+R GmbH. The results show that the installation of waste management facilities at the premises of the waste producer would lead to significant reductions in costs and transportation.
Managing Time in Domestic Space
Authors: Osnowitz Debra
Published: December 2004

Much research shows that paid work performed at home supports a gendered division of household labor, leaving women disproportionately responsible for unpaid domestic work. For contract professionals, however, the flexibility to manage working time outside the constraints of a standard job allows both men and women to meld paid employment with household responsibilities. Interspersing paid and unpaid work, home-based contractors—both women and men—accommodate family needs. They arrange daily schedules to be available parents and household managers, and they develop longer-term career trajectories that allow adjustment over time. For women, however, long-standing notions of domesticity make such accommodation invisible, normative, and unremarkable. For men, in contrast, home-based contracting can create the space with which to challenge gender norms. For these home workers, therefore, the same arrangement simultaneously reinforces and resists conventional constructions of gender.
Close Your Eyes and Think of England
Authors: Brown Jessica Autumn , Ferree Myra Marx
Published: December 2004

Faced with declining fertility rates, media in Britain are reacting with anxiety about cultural annihilation. To look at how nationalism inflects concerns over biological and cultural reproduction, the authors analyze coverage of falling fertility and rising immigration in Great Britain in major newspapers in 2000-2. They find pronatalist appeals to be commonand especially directed at women but varying in how women’s duty to the nation is framed. Appeals characterized as begging, lecturing, threatening, and bribing express different relationships between individual interest and the national good and offer positive and negative views of women. The political leanings of specific newspapers affect how they connect biological reproduction to the cultural threat seen in immigration. Even positive views of women as making rational reproductive choices are tainted by alarmist views of immigration as a threat to national survival.
Sisyphus Meets the Borg
Authors: Lowery David , Gray Virginia , Fellowes Matthew
Published: December 2004

Recent interpretations of the changing diversity of state interest communities emphasize the distinctive ways that the numbers of organizations representing different kinds of substantive interests grow in response to economic growth. Some guilds readily add new lobbying organizations as economies become larger, while many others grow hardly at all. As economies become larger, then, the relative composition of interest communities can change in ways having little to do with the distribution of interests in society. We develop and test four explanations of the changing diversity of interest communities using the first derivatives of the gross state product (GSP) response functions of 17 guilds of state interest organizations in 1997 as a dependent variable. Our results suggest that some guilds - including several major traditional economic interests - have a demographic advantage over social and public organizations that will make it very difficult for the latter to keep pace with the former as state economies grow.
Informational Party Primaries and Strategic Ambiguity
Authors: Meirowitz Adam
Published: December 2004

While scholars have thoroughly explored the logic of two candidate electoral competition, much less has been accomplished in gaining an understanding of the role of party primaries. This paper presents an incomplete information model of primary and general elections and argues that party primaries do more than select party candidates. Party primaries serve an informational function. In an environment where candidates are uncertain about the preferences of voters, selection of desirable policy platforms is a risky, if not difficult, undertaking. Primary elections offer voters an early opportunity to signal their preferences to candidates. Before primary elections, the candidates, aware that information about voter preferences is forthcoming, have an incentive to remain ambiguous about their policy platforms. Early commitment makes them vulnerable to better informed candidates that they might face in the general election. The fully revealing equilibrium of the game yields a joint explanation of the role of party primaries and candidate ambiguity. Primaries aggregate information about voter preferences and candidate ambiguity has an option value.
Get rid of those election blues
Authors: Robinson Nick
Published: December 2004

Journalists who could barely contain their excitement about the US elections now look ahead with almost universal gloom to the long British campaign ahead, writes the political editor of ITV News. While set and graphic designers gurgle with delight at their quadrennial licensed excess - election night sets that put the Pompidou Centre to shame, magical graphics that can fly you down the chimney of Number Ten right into Tony Blair's bedroom - reporters and producers are carping into their cappuccinos: "It's going to be so dull...I don't think I can bear it." Well, move aside for someone who understands that there is something special - magical even - about the moment the country makes its choice of who should lead it and, just as important, we all choose who should represent us where we live.

Robinson presents his propositions designed to allay those pre-election blues.
Color Categories Are Culturally Diverse in Cognition as Well as in Language
Authors: Roberson Debi
Published: December 2004

Categorization is a fundamental property of human cognition. This article presents a summary of recent research that has reexamined the nature of linguistic and nonlinguistic color categories and the relationship between them. Improvements in experimental paradigms combined with a better understanding of the relationship between physiology and higher level cognition have led to a clearer understanding of the complexities of the relationship between culture, language, cognition, and perception. It is concluded that possession of linguistic color categories facilitates recognition and influences perceptual judgments, even in languages with terms that are less abstract than English. Cognitive categories for color appear to be tightly tied to the linguistic terms used to describe them.
Deadly Violence in the Heartland
Authors: Weisheit Ralph A. , Wells L. Edward
Published: December 2004

In the study of homicide, one common research finding is the strong association between urbanization and homicide rates. The strength of the association between urbanism and homicide rates should have led to a large body of research comparing rural and urban homicide, but it has not. This is an exploratory study using the FBI’s Uniform Crime Reports data on homicide and the FBI’s Supplemental Homicide Reports merged with data from the U.S. Bureau of the Census to examine predictors of nonmetropolitan and metropolitan homicide rates and to consider the implications of these findings. Although homicides display some general patterns across the United States, rural-urban differences modify the typical attributes of homicide incidents as well as the community dynamics of homicide rates. The analysis shows that models with very high predictive power in the largest metropolitan areas have much less success in accounting for homicide differences in the most rural areas.
The globalization of crime control—the case of youth and juvenile justice
Authors: Muncie John
Published: December 2004

The concept of globalization has gradually permeated criminology, but more so as applied to transnational organized crime, international terrorism and policing than in addressing processes of criminal justice reform. Based on a wide range of bibliographic and web resources, this article assesses the extent to which a combination of neo-liberal assaults on the social logics of the welfare state and public provision, widespread experimentation with restorative justice and the prospect of rehabilitation through mediation and widely ratified international directives, epitomized by the United Nations Convention on the Rights of the Child, have now made it possible to talk of a global juvenile/youth justice. Conversely it also reflects on how persistent national and local divergences, together with the contradictions of contemporary reform, may preclude any aspiration for the delivery of a universal and consensual product
Methodological Issues in the Effects of Attrition: Simple Solutions for Social Scientists
Authors: Ahern Kathy , Le Brocque Robyne
Published: December 2004

Participant attrition from longitudinal research studies is a concern for social scientists because loss of certain subgroups of participants may result in subsequent data collection phases becoming increasingly biased. This article examines whether attrition has been given due consideration in selected reports of longitudinal research undertaken by social scientists. Results of a review of the literature found that less than one-quarter of the studies described how data were examined for patterns of attrition. On the other hand, those articles that described the treatment of attrition used solutions that were varied and often simple and effective. Recommendations for statistical and nonstatistical ways of dealing with sample attrition used by social scientists are provided.
C. Wright Mills, the Bureau for Applied Social Research, and the Meaning of Critical Scholarship
Authors: Sterne Jonathan
Published: December 2004

This article argues that C. Wright Mills’s time at Columbia University’s Bureau for Applied Social Research provided a crucial intellectual and institutional basis for his later work, and it uses Mills’s career as an allegory for the history and self-understanding of modern-day, self-described “ critical” scholars. Mills’s own published writings, along with those of his biographers, encourage a view of his time at the bureau as an aberration. Yet, a careful examination of his letters and his work reveals that the critical position for which Mills is famous was actually nourished by his use of surveys, statistics, research teams, and other trappings of administrative research while at the bureau. The article explores the implications of this history for our own understandings of critical research today.
Teach Feminist: Pedagogy, Politics, and Process in Women’s Studies
Authors: Uppal Jyotsna , English Hugh
Published: December 2004

The authors reflect on organizing Teach Feminist, an interdisciplinary conference for faculty and students organized within theWomen’s Studies program at Queens College–City University of New York. By focusing on the implications of certain forms used in organizing—in particular, the use of a Listserv, efforts to focus attention explicitly on pedagogy, and understandings of faculty work within the academy—the authors consider how their work as organizers was limited by certain institutional logics, and they advocate forms of understanding that can articulate how educators inhabit institutions, while also recognizing that there must be sites of intervention that exceed institutional forms and logics, strategies that engage the possibility of exceeding the structures within which they emerge.
Homegrown Democracy, Homegrown Democrats
Authors: Denzin Norman K.
Published: December 2004

Written on the eve of the 2004 American presidential election, this political narrative offers a critical reading of two models of democracy: Instant-Mix imperial democracy (bring to a boil, add oil, then bomb), criticized by Arundhati Roy, and Garrison Keillor’s Homegrown Democrat. Keillor’s pastoral view of democracy is anchored in LakeWobegon, his imaginary utopian community. His homegrown democracy is narrow, provincial, and White. The author concludes that he must look elsewhere for his alternative view of democracy.
Temozolomide for malignant gliomas in British Columbia: A population-based cost-effectiveness analysis
Authors: Greanya ED , Taylor SCM , BscPharm F Hu , Barnett J , Thiessen B
Published: December 2004

Study objectives. To evaluate the cost-effectiveness and outcomes achieved in patients with recurrent malignant glioma treated with temozolomide in British Columbia, as compared to previous lomustine use in the same patient population, and to temozolomide literature reports. Outcomes assessed included median overall survival, 6-month overall survival and 6-month progression free survival.

Methods. A retrospective analysis was conducted to identify patients who received single-agent temozolomide or lomustine during successive, prespecified time periods. Data was collected on survival, disease progression, duration of therapy, cost of drug, labour and supplies, and successive or prior chemotherapy.

Results. Six-month progression free survival (PFS) occurred in 52% and 42.9% of patients in the temozolomide and lomustine cohorts, respectively (P=0.44). Six-month overall survival and median overall survival (OS) were 72% and 40.86 weeks for temozolomide patients and 64.3% and 46.7 weeks for lomustine patients. These outcomes were not statistically different between the two treatment groups. Associated with these outcomes, temozolomide patients received a median of six cycles of drug treatment, with a median cost per patient of $11 660 (CAN). Alternatively, lomustine patients received a median of four cycles with a median cost per patient of $189 (CAN). In the cost-effectiveness analysis for median OS, temozolomide was not a cost-effective alternative, and for 6-month PFS, the incremental cost effectiveness ratio (ICER) of temozolomide was $1261 (CAN) for each additional percent of patients progression free at 6-months. Sensitivity analysis varying both median OS and 6-month PFS resulted in ICER’s of temozolomide ranging from $332 to $3277.

Conclusions. No significant differences in outcomes were observed between patients treated with single-agent lomustine or temozolomide. Temozolomide therapy has an incremental cost increase over lomustine of $11 471 per patient. It appears when only survival outcomes and direct treatment costs are considered, lomustine is a more cost-effective treatment strategy in the specific setting of recurrent malignant glioma.
Identification of IgG2‐Specific Antigens in MexicanAnaplasma marginaleStrains
Authors: BARIGYE R , GARCÍA‐ORTIZ M A , ROJAS RAMÍREZ E E , RODRÍGUEZ S D
Published: December 2004

Abstract:To identify novel antigens with immunoglobulin G2 (IgG2) specificity and immunostimulant properties for bovine Th1 cells, humoral and cellular responses were studied in cattle inoculated with initial bodies from a Mexican isolate ofAnaplasma marginaleand challenged with a heterologous strain. Analysis of post‐immunization sera by ELISA and assaying ofin vitrocellular responses in peripheral blood mononuclear cells (PBMCs) cultured in the presence of protein extracts from threeAnaplasma marginalestrains showed positive values of optical density ELISA readings and stimulation indices in the immunized but not control cattle. Post‐immunization and post‐challenge sera recognized in Western blots several proteins with molecular weights ranging from 15 to 209 kDa, twelve of which were recognized by IgG2 in the threeAnaplasma marginalestrains. Seven of these are novel and have not been previously reported for their IgG2 specificity; three are confirmed to be major surface proteins (MSP‐1a, MSP‐2, and MSP‐5); and the others correspond to other well‐studied MSPs but were not confirmed. Partially purified fractions of protein extracts of the Mex‐17 strain were tested against PBMCs culturedin vitro. One out of the seven novel proteins induced detectable lymphoproliferation (LP) of PBMCs, and interferon‐γ was detected in supernatants of PBMC cultured in the presence of two protein fractions, including the one that caused LP. It is concluded that novel antigens, particularly the 28‐kDa protein, played an additional role in the protection of immunized cattle and should be considered vaccine candidates afterin vivoimmunization experiments are concluded.