bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional Characterization and Target Validation of Alternative Complex I of
Plasmodium falciparum
Mitochondria
Authors: Biagini Giancarlo A. , Viriyavejakul Parnpen , O'Neill Paul M. , Bray Patrick G. , Ward Stephen A.
Published: April 2006

This study reports on the first characterization of the alternative NADH:dehydrogenase (also known as alternative complex I or type II NADH:dehydrogenase) of the human malaria parasite
Plasmodium falciparum
, known as PfNDH2. PfNDH2 was shown to actively oxidize NADH in the presence of quinone electron acceptors CoQ
1
and decylubiquinone with an apparent

K
m

for NADH of approximately 17 and 5 μM, respectively. The inhibitory profile of PfNDH2 revealed that the enzyme activity was insensitive to rotenone, consistent with recent genomic data indicating the absence of the canonical NADH:dehydrogenase enzyme. PfNDH2 activity was sensitive to diphenylene iodonium chloride and diphenyl iodonium chloride, known inhibitors of alternative NADH:dehydrogenases. Spatiotemporal confocal imaging of parasite mitochondria revealed that loss of PfNDH2 function provoked a collapse of mitochondrial transmembrane potential (Ψ
m
), leading to parasite death. As with other alternative NADH:dehydrogenases, PfNDH2 lacks transmembrane domains in its protein structure, and therefore, it is proposed that this enzyme is not directly involved in mitochondrial transmembrane proton pumping. Rather, the enzyme provides reducing equivalents for downstream proton-pumping enzyme complexes. As inhibition of PfNDH2 leads to a depolarization of mitochondrial Ψ
m
, this enzyme is likely to be a critical component of the electron transport chain (ETC). This notion is further supported by proof-of-concept experiments revealing that targeting the ETC's Q-cycle by inhibition of both PfNDH2 and the
bc
1
complex is highly synergistic. The potential of targeting PfNDH2 as a chemotherapeutic strategy for drug development is discussed.
Curcumin-Artemisinin Combination Therapy for Malaria
Authors: Nandakumar Dalavaikodihalli Nanjaiah , Nagaraj Viswanathan Arun , Vathsala Palakkod Govindan , Rangarajan Pundi , Padmanaban Govindarajan
Published: April 2006

Artemisinin and curcumin show an additive interaction in killing
Plasmodium falciparum
in culture. In vivo, 3 oral doses of curcumin following a single injection of α,β-arteether to
Plasmodium berghei
-infected mice are able to prevent recrudescence due to α,β-arteether monotherapy and ensure almost 100% survival of the animals.
Antimicrobial Susceptibility Pattern of
Clostridium difficile
and Its Relation to PCR Ribotypes in a Swedish University Hospital
Authors: Aspevall Olle , Lundberg Annika , Burman Lars G. , Åkerlund Thomas , Svenungsson Bo
Published: April 2006

All 238
Clostridium difficile
isolates were susceptible to metronidazole and vancomycin, whereas 84% and 1% were resistant to clindamycin and fusidic acid. Etest MICs for metronidazole were lower than agar dilution MICs (
P
< 0.01) but without difference in susceptible-intermediate-resistant categorization. No particular PCR ribotype was associated with clindamycin or fusidic acid resistance.
Induction of Multifunctional Human Immunodeficiency Virus Type 1 (HIV-1)-Specific T Cells Capable of Proliferation in Healthy Subjects by Using a Prime-Boost Regimen of DNA- and Modified Vaccinia Virus Ankara-Vectored Vaccines Expressing HIV-1 Gag Coupled to CD8+T-Cell Epitopes
Authors: Goonetilleke Nilu , Moore Stephen , Dally Len , Winstone Nicola , Cebere Inese , Mahmoud Abdul , Pinheiro Susana , Gillespie Geraldine , Brown Denise , Loach Vanessa , Roberts Joanna , Guimaraes-Walker Ana , Hayes Peter , Loughran Kelley , Smith Carole , De Bont Jan , Verlinde Carl , Vooijs Danii , Schmidt Claudia , Boaz Mark , Gilmour Jill , Fast Pat , Dorrell Lucy , Hanke Tomas , McMichael Andrew J.
Published: April 2006

A double-blind randomized phase I trial was conducted in human immunodeficiency virus type 1 (HIV-1)-negative subjects receiving vaccines vectored by plasmid DNA and modified vaccinia virus Ankara (MVA) expressing HIV-1 p24/p17 gag linked to a string of CD8+T-cell epitopes. The trial had two groups. One group received either two doses of MVA.HIVA (2× MVA.HIVA) (n= 8) or two doses of placebo (2× placebo) (n= 4). The second group received 2× pTHr.HIVA followed by one dose of MVA.HIVA (n= 8) or 3× placebo (n= 4). In the pTHr.HIVA-MVA.HIVA group, HIV-1-specific T-cell responses peaked 1 week after MVA.HIVA vaccination in both ex vivo gamma interferon (IFN-γ) ELISPOT (group mean, 210 spot-forming cells/106cells) and proliferation (group mean stimulation index, 37), with assays detecting positive responses in four out of eight and five out of eight subjects, respectively. No HIV-1-specific T-cell responses were detected in either assay in the 2× MVA.HIVA group or subjects receiving placebo. Using a highly sensitive and reproducible cultured IFN-γ ELISPOT assay, positive responses mainly mediated by CD4+T cells were detected in eight out of eight vaccinees in the pTHr.HIVA-MVA.HIVA group and four out of eight vaccinees in the 2× MVA.HIVA group. Importantly, no false-positive responses were detected in the eight subjects receiving placebo. Of the 12 responders, 11 developed responses to previously identified immunodominant CD4+T-cell epitopes, with 6 volunteers having responses to more than one epitope. Five out of 12 responders also developed CD8+T-cell responses to the epitope string. Induced T cells produced a variety of anti-viral cytokines, including tumor necrosis factor alpha and macrophage inflammatory protein 1β. These data demonstrate that prime-boost vaccination with recombinant DNA and MVA vectors can induce multifunctional HIV-1-specific T cells in the majority of vaccinees.
NS1 Interaction with CKIIα: Novel Protein Complex Mediating Parvovirus-Induced Cytotoxicity
Authors: Nüesch Jürg P. F. , Rommelaere Jean
Published: April 2006

During a productive infection, the prototype strain of the parvovirus minute virus of mice (MVMp) induces dramatic morphological alterations in permissive A9 fibroblasts, culminating in cell lysis at the end of infection. These cytopathic effects (CPE) result from rearrangements and destruction of the cytoskeletal micro- and intermediate filaments, while other structures such as the nuclear lamina and particularly the microtubule network remain protected throughout the infection (J. P. F. Nüesch et al., Virology
331:
159-174, 2005). In order to unravel the mechanism(s) by which parvoviruses trigger CPE, we searched for NS1 interaction partners by differential affinity chromatography, using distinct NS1 mutants debilitated specifically for this function. Thereby, we isolated an NS1 partner polypeptide, whose interaction with NS1 correlated with the competence of the viral product for CPE induction, and further identified it by tandem mass spectrometry and Western blotting analyses to consist of the catalytic subunit of casein kinase II, CKIIα. This interaction of NS1 with CKIIα suggested interference by the viral protein with intracellular signaling. Using permanent cell lines expressing dominant-negative CKIIα mutants, we were able to show that this kinase activity was indeed specifically involved in parvoviral CPE and progeny particle release. Furthermore, the NS1/CKIIα complex proved to be able to specifically phosphorylate viral capsids, indicating a mediator function of NS1 for CKII activity and specificity, at least in vitro. Altogether our data suggest that parvovirus-induced CPE is mediated by NS1 interference with intracellular CKII signaling.
Neutralizing Antibodies Do Not Mediate Suppression of Human Immunodeficiency Virus Type 1 in Elite Suppressors or Selection of Plasma Virus Variants in Patients on Highly Active Antiretroviral Therapy
Authors: Bailey Justin R. , Lassen Kara G. , Yang Hung-Chih , Quinn Thomas C. , Ray Stuart C. , Blankson Joel N. , Siliciano Robert F.
Published: April 2006

Neutralizing antibodies (NAb) against autologous virus can reach high titers in human immunodeficiency virus type 1 (HIV-1)-infected patients with progressive disease. Less is known about the role of NAb in HIV-1-infected patients with viral loads of <50 copies/ml of plasma, including patients on effective highly active antiretroviral therapy (HAART) and elite suppressors, who control HIV-1 replication without antiretroviral therapy. In this study, we analyzed full-length
env
sequences from plasma viruses and proviruses in resting CD4
+
T cells of HAART-treated patients, elite suppressors, and untreated HIV-1-infected patients with progressive disease. For each patient group, we assessed plasma virus neutralization by autologous, contemporaneous plasma. The degree of
env
diversity, the number of N-linked glycosylation sites, and the lengths of variable loops were all lower in elite suppressors than in HAART-treated and untreated viremic patients. Both elite suppressors and HAART-treated patients had lower titers of NAb against HIV-1 lab strains than those of untreated viremic patients. Surprisingly, titers of NAb against autologous, contemporaneous plasma viruses were similarly low in chronic progressors, elite suppressors, and HAART-treated patients. In elite suppressors and HAART-treated patients, titers of NAb against autologous plasma viruses also did not differ significantly from titers against autologous proviruses from resting CD4
+
T cells. These results suggest that high-titer NAb are not required for maintenance of viral suppression in elite suppressors and that NAb do not select plasma virus variants in most HAART-treated patients. Both drug-mediated and natural suppression of HIV-1 replication to levels below 50 copies/ml may limit the stimulation and maintenance of effective NAb responses.
Long-Term-Infected Telomerase-Immortalized Endothelial Cells: a Model for Kaposi's Sarcoma-Associated Herpesvirus Latency In Vitro and In Vivo
Authors: An Feng-Qi , Folarin Hope Merlene , Compitello Nicole , Roth Justin , Gerson Stanton L. , McCrae Keith R. , Fakhari Farnaz D. , Dittmer Dirk P. , Renne Rolf
Published: April 2006

Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman's disease. Most KS tumor cells are latently infected with KSHV and are of endothelial origin. While PEL-derived cell lines maintain KSHV indefinitely, all KS tumor-derived cells to date have lost viral genomes upon ex vivo cultivation. To study KSHV latency and tumorigenesis in endothelial cells, we generated
t
elomerase-
i
mmortalized human umbilical
v
ein
e
ndothelial (TIVE) cells. TIVE cells express all KSHV latent genes 48 h postinfection, and productive lytic replication could be induced by RTA/Orf50. Similar to prior models, infected cultures gradually lost viral episomes. However, we also obtained, for the first time, two endothelial cell lines in which KSHV episomes were maintained indefinitely in the absence of selection. Long-term KSHV maintenance correlated with loss of reactivation in response to RTA/Orf50 and complete oncogenic transformation. Long-term-infected TIVE cells (LTC) grew in soft agar and proliferated under reduced-serum conditions. LTC, but not parental TIVE cells, formed tumors in nude mice. These tumors expressed high levels of the latency-associated nuclear antigen (LANA) and expressed lymphatic endothelial specific antigens as found in KS (LYVE-1). Furthermore, host genes, like those encoding interleukin 6, vascular endothelial growth factor, and basic fibroblast growth factor, known to be highly expressed in KS lesions were also induced in LTC-derived tumors. KSHV-infected LTCs represent the first xenograft model for KS and should be of use to study KS pathogenesis and for the validation of anti-KS drug candidates.
N-Glycans on Nipah Virus Fusion Protein Protect against Neutralization but Reduce Membrane Fusion and Viral Entry
Authors: Aguilar Hector C. , Matreyek Kenneth A. , Filone Claire Marie , Hashimi Sara T. , Levroney Ernest L. , Negrete Oscar A. , Bertolotti-Ciarlet Andrea , Choi Daniel Y. , McHardy Ian , Fulcher Jennifer A. , Su Stephen V. , Wolf Mike C. , Kohatsu Luciana , Baum Linda G. , Lee Benhur
Published: April 2006

Nipah virus (NiV) is a deadly emerging paramyxovirus. The NiV attachment (NiV-G) and fusion (NiV-F) envelope glycoproteins mediate both syncytium formation and viral entry. Specific N-glycans on paramyxovirus fusion proteins are generally required for proper conformational integrity and biological function. However, removal of individual N-glycans on NiV-F had little negative effect on processing or fusogenicity and has even resulted in slightly increased fusogenicity. Here, we report that in both syncytium formation and viral entry assays, removal of multiple N-glycans on NiV-F resulted in marked increases in fusogenicity (>5-fold) but also resulted in increased sensitivity to neutralization by NiV-F-specific antisera. The mechanism underlying the hyperfusogenicity of these NiV-F N-glycan mutants is likely due to more-robust six-helix bundle formation, as these mutants showed increased fusion kinetics and were more resistant to neutralization by a fusion-inhibitory reagent based on the C-terminal heptad repeat region of NiV-F. Finally, we demonstrate that the fusogenicities of the NiV-F N-glycan mutants were inversely correlated with the relative avidities of NiV-F's interactions with NiV-G, providing support for the attachment protein “displacement” model of paramyxovirus fusion. Our results indicate that N-glycans on NiV-F protect NiV from antibody neutralization, suggest that this “shielding” role comes together with limiting cell-cell fusion and viral entry efficiencies, and point to the mechanisms underlying the hyperfusogenicity of these N-glycan mutants. These features underscore the varied roles that N-glycans on NiV-F play in the pathobiology of NiV entry but also shed light on the general mechanisms of paramyxovirus fusion with host cells.
Human Rhinovirus Attenuates the Type I Interferon Response by Disrupting Activation of Interferon Regulatory Factor 3
Authors: Peng Tao , Kotla Swathi , Bumgarner Roger E. , Gustin Kurt E.
Published: April 2006

The type I interferon (IFN) response requires the coordinated activation of the latent transcription factors NF-κB, interferon regulatory factor 3 (IRF-3), and ATF-2, which in turn activate transcription from the IFN-β promoter. Synthesis and subsequent secretion of IFN-β activate the Jak/STAT signaling pathway, resulting in the transcriptional induction of the full spectrum of antiviral gene products. We utilized high-density microarrays to examine the transcriptional response to rhinovirus type 14 (RV14) infection in HeLa cells, with particular emphasis on the type I interferon response and production of IFN-β. We found that, although RV14 infection results in altered levels of a wide variety of host mRNAs, induction of IFN-β mRNA or activation of the Jak/STAT pathway is not seen. Prior work has shown, and our results have confirmed, that NF-κB and ATF-2 are activated following infection. Since many viruses are known to target IRF-3 to inhibit the induction of IFN-β mRNA, we analyzed the status of IRF-3 in infected cells. IRF-3 was translocated to the nucleus and phosphorylated in RV14-infected cells. Despite this apparent activation, very little homodimerization of IRF-3 was evident following infection. Similar results in A549 lung alveolar epithelial cells demonstrated the biological relevance of these findings to RV14 pathogenesis. In addition, prior infection of cells with RV14 prevented the induction of IFN-β mRNA following treatment with double-stranded RNA, indicating that RV14 encodes an activity that specifically inhibits this innate host defense pathway. Collectively, these results indicate that RV14 infection inhibits the host type I interferon response by interfering with IRF-3 activation.
Alpha and Lambda Interferon Together Mediate Suppression of CD4 T Cells Induced by Respiratory Syncytial Virus
Authors: Chi Bo , Dickensheets Harold L. , Spann Kirsten M. , Alston Marc A. , Luongo Cindy , Dumoutier Laure , Huang Jiaying , Renauld Jean-Christophe , Kotenko Sergei V. , Roederer Mario , Beeler Judy A. , Donnelly Raymond P. , Collins Peter L. , Rabin Ronald L.
Published: April 2006

The mechanism by which respiratory syncytial virus (RSV) suppresses T-cell proliferation to itself and other antigens is poorly understood. We used monocyte-derived dendritic cells (MDDC) and CD4 T cells and measured [3H]thymidine incorporation to determine the factors responsible for RSV-induced T-cell suppression. These two cell types were sufficient for RSV-induced suppression of T-cell proliferation in response to cytomegalovirus orStaphylococcusenterotoxin B. Suppressive activity was transferable with supernatants from RSV-infected MDDC and was not due to transfer of live virus or RSV F (fusion) protein. Supernatants from RSV-infected MDDC, but not MDDC exposed to UV-killed RSV or mock conditions, contained alpha interferon (IFN-α; median, 43 pg/ml) and IFN-λ (approximately 1 to 20 ng/ml). Neutralization of IFN-α with monoclonal antibody (MAb) against one of its receptor chains, IFNAR2, or of IFN-λ with MAb against either of its receptor chains, IFN-λR1 (interleukin 28R [IL-28R]) or IL-10R2, had a modest effect. In contrast, blocking the two receptors together markedly reduced or completely blocked the RSV-induced suppression of CD4 T-cell proliferation. Defining the mechanism of RSV-induced suppression may guide vaccine design and provide insight into previously uncharacterized human T-cell responses and activities of interferons.
Isolation and Genetic Characterization of New Reassortant H3N1 Swine Influenza Virus from Pigs in the Midwestern United States
Authors: Ma Wenjun , Gramer Marie , Rossow Kurt , Yoon Kyoung-Jin
Published: April 2006

Since the introduction of H3N2 swine influenza viruses (SIVs) into U.S. swine in 1998, H1N2 and H1N1 reassortant viruses have emerged from reassortment between classical H1N1 and H3N2 viruses. In 2004, a new reassortant H3N1 virus (A/Swine/Minnesota/00395/2004) was identified from coughing pigs. Phylogenetic analyses revealed a hemagglutinin segment similar to those of contemporary cluster III H3N2 SIVs and a neuraminidase sequence of contemporary H1N1 origin. The internal genes were of swine, human, and avian influenza virus origin, similar to those of contemporary U.S. cluster III H3N2 SIVs. The recovery of H3N1 is further evidence of reassortment among SIVs and justifies continuous surveillance.
Immunoglobulin GM and KM Allotypes and Prevalence of Anti-LKM1 Autoantibodies in Patients with Hepatitis C Virus Infection
Authors: Muratori Paolo , Sutherland Susan E. , Muratori Luigi , Granito Alessandro , Guidi Marcello , Pappas Georges , Lenzi Marco , Bianchi Francesco B. , Pandey Janardan P.
Published: April 2006

GM and KM allotypes—genetic markers of immunoglobulin (Ig) γ and κ chains, respectively—are associated with humoral immunity to several infection- and autoimmunity-related epitopes. We hypothesized that GM and KM allotypes contribute to the generation of autoantibodies to liver/kidney microsomal antigen 1 (LKM1) in hepatitis C virus (HCV)-infected persons. To test this hypothesis, we characterized 129 persons with persistent HCV infection for several GM and KM markers and for anti-LKM1 antibodies. The heterozygous GM 1,3,17 23 5,13,21 phenotype was significantly associated with the prevalence of anti-LKM1 antibodies (odds ratio, 5.13;P= 0.002), suggesting its involvement in this autoimmune phenomenon in HCV infection.
POLYVECTOR SUPER-POINCARÉ ALGEBRAS, M, F THEORY ALGEBRAS AND GENERALIZED SUPERSYMMETRY IN CLIFFORD-SPACES
Authors: CASTRO CARLOS
Published: April 2006

Starting with a review of the Extended Relativity Theory in Clifford-Spaces, and the physical motivation behind this novel theory, we provide the generalization of the nonrelativistic supersymmetric point-particle action in Clifford-space backgrounds. The relativistic supersymmetric Clifford particle action is constructed that is invariant under generalized supersymmetric transformations of the Clifford-space background's polyvector-valued coordinates. To finalize, the Polyvector super-Poincaré and M, F theory superalgebras, in D = 11, 12 dimensions, respectively, are discussed followed by our final analysis of the novel Clifford-superspace realizations of generalized supersymmetries in Clifford spaces.
GRAVITATIONAL COLLAPSE OF A MASSLESS SCALAR FIELD AND A PERFECT FLUID WITH SELF-SIMILARITY OF THE SECOND KIND IN (2 + 1) DIMENSIONS
Authors: PEREIRA F. I. M. , CHAN R. , WANG AN ZHONG
Published: April 2006

Self-similar solutions of a collapsing perfect fluid and a massless scalar field with kinematic self-similarity of the second kind in (2 + 1) dimensions are obtained. The local and global properties of the solutions are studied. It is found that some of them represent gravitational collapse, in which black holes are always formed, and some may be interpreted as representing cosmological models.
ROTATING BLACK HOLES IN HIGHER DIMENSIONAL BRANE WORLDS
Authors: SENGUPTA GAUTAM
Published: April 2006

A black string generalization of the Myers–Perry N-dimensional rotating black hole is considered in an (N + 1)-dimensional Randall–Sundrum brane world. The black string intercepts the (N - 1) brane in a N-dimensional rotating black hole. We examine the diverse cases arising for various non-zero rotation components and obtain the geodesic equations for these space–times. The causal structure and asymptotics of the resulting brane world geometries are analyzed.
Muscle-specific overexpression of wild type and R225Q mutant AMP-activated protein kinase γ3-subunit differentially regulates glycogen accumulation
Authors: Yu Haiyan , Hirshman Michael F. , Fujii Nobuharu , Pomerleau Jason M. , Peter Lauren E. , Goodyear Laurie J.
Published: April 2006

AMP-activated protein kinase (AMPK) is a heterotrimeric complex that works as an energy sensor to integrate nutritional and hormonal signals. The naturally occurring R225Q mutation in the γ3-subunit in pigs is associated with abnormally high glycogen content in skeletal muscle. Becauses skeletal muscle accounts for most of the body's glucose uptake, and γ3 is specifically expressed in skeletal muscle, it is important to understand the underlying mechanism of this mutation in regulating glucose and glycogen metabolism. Using skeletal muscle-specific transgenic mice overexpressing wild type γ3 (WTγ3) and R225Q mutant γ3 (MUTγ3), we show that both WTγ3 and MUTγ3 mice have 1.5- to 2-fold increases in muscle glycogen content. In WTγ3 mice, increased glycogen content was associated with elevated total glycogen synthase activity and reduced glycogen phosphorylase activity, whereas alterations in activities of these enzymes could not explain elevated glycogen in MUTγ3 mice. Basal, 5-aminoimidazole- AICAR- and phenformin-stimulated AMPKα2 isoform-specific activities were decreased only in MUTγ3 mice. Basal rates of 2-DG glucose uptake were decreased in both WTγ3 and MUTγ3 mice. However, AICAR- and phenformin-stimulated 2-DG glucose uptake were blunted only in MUTγ3 mice. In conclusion, expression of either wild type or mutant γ3-subunit of AMPK results in increased glycogen concentrations in muscle, but the mechanisms underlying this alteration appear to be different. Furthermore, mutation of the γ3-subunit is associated with decreases in AMPKα2 isoform-specific activity and impairment in AICAR- and phenformin-stimulated skeletal muscle glucose uptake.
Metabolic programming: fetal origins of obesity and metabolic syndrome in the adult
Authors: Ismail-Beigi Faramarz , Catalano Patrick M. , Hanson Richard W.
Published: April 2006

Exposure of the fetus to the intrauterine milieu can have profound effects on the health of the offspring in adulthood. Results of a series of studies demonstrate the powerful influence of the mother's metabolic state on whether the emerging adult develops obesity and hyperinsulinemia. Importantly, these attributes can be passed on to the next generation nongenetically and can be reversed and prevented.
Cholinergic regulation of fuel-induced hormone secretion and respiration of SUR1−/− mouse islets
Authors: Doliba Nicolai M. , Qin Wei , Vatamaniuk Marko Z. , Buettger Carol W. , Collins Heather W. , Magnuson Mark A , Kaestner Klaus H. , Wilson David F. , Carr Richard D. , Matschinsky Franz M.
Published: April 2006

Neural and endocrine factors (i.e., Ach and GLP-1) restore defective glucose-stimulated insulin release in pancreatic islets lacking sulfonylurea type 1 receptors (SUR1−/−) (Doliba NM, Qin W, Vatamaniuk MZ, Li C, Zelent D, Najafi H, Buettger CW, Collins HW, Carr RD, Magnuson MA, and Matschinsky FM. Am J Physiol Endocrinol Metab 286: E834–E843, 2004). The goal of the present study was to assess fuel-induced respiration in SUR1−/− islets and to correlate it with changes in intracellular Ca2+, insulin, and glucagon secretion. By use of a method based on O2 quenching of phosphorescence, the O2 consumption rate (OCR) of isolated islets was measured online in a perifusion system. Basal insulin release (IR) was 7–10 times higher in SUR1−/− compared with control (CON) islets, but the OCR was comparable. The effect of high glucose (16.7 mM) on IR and OCR was markedly reduced in SUR1−/− islets compared with CON. Ach (0.5 μM) in the presence of 16.7 mM glucose caused a large burst of IR in CON and SUR1−/− islets with minor changes in OCR in both groups of islets. In SUR1−/− islets, high glucose failed to inhibit glucagon secretion during stimulation with amino acids or Ach. We conclude that 1) reduced glucose responsiveness of SUR1−/− islets may be in part due to impaired energetics, as evidenced by significant decrease in glucose-stimulated OCR; 2) elevated intracellular Ca2+ levels may contribute to altered insulin and glucagon secretion in SUR1−/− islets; and 3) The amplitudes of the changes in OCR during glucose and Ach stimulation do not correlate with IR in normal and SUR1−/− islets suggesting that the energy requirements for exocytosis are minor compared with other ATP-consuming reactions.
Latency and Initiation of the Human Vestibuloocular Reflex to Pulsed Galvanic Stimulation
Authors: Aw Swee T. , Todd Michael J. , Halmagyi G. Michael
Published: April 2006

Cathodal galvanic currents activate primary vestibular afferents, whereas anodal currents inhibit them. Pulsed galvanic vestibular stimulation (GVS) was used to determine the latency and initiation of the human vestibuloocular reflex. Three-dimensional galvanic vestibuloocular reflex (g-VOR) was recorded with binocular dual-search coils in response to a bilateral bipolar 100-ms rectangular pulse of current at 0.9 (near-threshold), 2.5, 5.0, 7.5, and 10.0 mA in 11 normal subjects. The g-VOR consisted of three components: conjugate torsional eye rotation away from cathode toward anode; vertical divergence (skew deviation) with hypertropia of the eye on the cathodal and hypotropia of the eye on the anodal sides; and conjugate horizontal eye rotation away from cathode toward anode. The g-VOR was repeatable across all subjects, its magnitude a linear function of the current intensity, its latency about 9.0 ms with GVS of ≥2.5 mA, and was not suppressed by visual fixation. At 10-mA stimulation, the g-VOR [ x, y, z] on the cathodal side was [0.77 ± 0.10, −0.05 ± 0.05, −0.18 ± 0.06°] (mean ± 95% confidence intervals) and on the anodal side was [0.79 ± 0.10, 0.16 ± 0.05, −0.19 ± 0.06°], with a vertical divergence of 0.20°. Although the horizontal g-VOR could have arisen from activation of the horizontal semicircular canal afferents, the vertical-torsional g-VOR resembled the vestibuloocular reflex in response to roll-plane head rotation about an Earth-horizontal axis and might be a result of both vertical semicircular canal and otolith afferent activations. Pulsed GVS is a promising technique to investigate latency and initiation of the human vestibuloocular reflex because it does not require a large mechanical apparatus nor does it pose problems of head inertia or slippage.
Are “Great Salinity Anomalies” Advective?
Authors: Wadley Martin R. , Bigg Grant R.
Published: April 2006

“Great Salinity Anomalies” (GSAs) have been observed to propagate around the North Atlantic subpolar gyre. Similar anomalies occur in the Third Hadley Centre Coupled Atmosphere–Ocean GCM (HadCM3) of preindustrial climate. It has been hypothesized that these salinity anomalies result from the advection of anomalously low salinity waters around the subpolar gyre. Here, the consequences of using passive tracers in the HadCM3 climate model to tag the anomalously low salinity water associated with a GSA in the Greenland and Labrador Seas are reported. Rather than predominantly advecting around the modeled subpolar gyre in accordance with the upper-ocean salinity anomaly, the tracers mix to intermediate depths, before becoming incorporated into the model's North Atlantic Deep Water. Horizontal advection of the tracer in the upper ocean is limited to around 1000 km, compared with the gyre-scale propagation of the salinity anomalies. It is concluded that GSAs are unlikely to be caused by the advection of salinity anomalies; rather anomalous oceanic currents or surface fluxes are responsible.
Twenty-First-Century Climate Impacts from a Declining Arctic Sea Ice Cover
Authors: Singarayer Joy S. , Bamber Jonathan L. , Valdes Paul J.
Published: April 2006

A steady decline in Arctic sea ice has been observed over recent decades. General circulation models predict further decreases under increasing greenhouse gas scenarios. Sea ice plays an important role in the climate system in that it influences ocean-to-atmosphere fluxes, surface albedo, and ocean buoyancy. The aim of this study is to isolate the climate impacts of a declining Arctic sea ice cover during the current century. The Hadley Centre Atmospheric Model (HadAM3) is forced with observed sea ice from 1980 to 2000 (obtained from satellite passive microwave radiometer data derived with the Bootstrap algorithm) and predicted sea ice reductions until 2100 under one moderate scenario and one severe scenario of ice decline, with a climatological SST field and increasing SSTs. Significant warming of the Arctic occurs during the twenty-first century (mean increase of between 1.6° and 3.9°C), with positive anomalies of up to 22°C locally. The majority of this is over ocean and limited to high latitudes, in contrast to recent observations of Northern Hemisphere warming. When a climatological SST field is used, statistically significant impacts on climate are only seen in winter, despite prescribing sea ice reductions in all months. When correspondingly increasing SSTs are incorporated, changes in climate are seen in both winter and summer, although the impacts in summer are much smaller. Alterations in atmospheric circulation and precipitation patterns are more widespread than temperature, extending down to midlatitude storm tracks. Results suggest that areas of Arctic land ice may even undergo net accumulation due to increased precipitation that results from loss of sea ice. Intensification of storm tracks implies that parts of Europe may experience higher precipitation rates.
Granger Causality of Coupled Climate Processes: Ocean Feedback on the North Atlantic Oscillation
Authors: Mosedale Timothy J. , Stephenson David B. , Collins Matthew , Mills Terence C.
Published: April 2006

This study uses a Granger causality time series modeling approach to quantitatively diagnose the feedback of daily sea surface temperatures (SSTs) on daily values of the North Atlantic Oscillation (NAO) as simulated by a realistic coupled general circulation model (GCM). Bivariate vector autoregressive time series models are carefully fitted to daily wintertime SST and NAO time series produced by a 50-yr simulation of the Third Hadley Centre Coupled Ocean–Atmosphere GCM (HadCM3). The approach demonstrates that there is a small yet statistically significant feedback of SSTs on the NAO. The SST tripole index is found to provide additional predictive information for the NAO than that available by using only past values of NAO—the SST tripole is Granger causal for the NAO. Careful examination of local SSTs reveals that much of this effect is due to the effect of SSTs in the region of the Gulf Steam, especially south of Cape Hatteras. The effect of SSTs on NAO is responsible for the slower-than-exponential decay in lag-autocorrelations of NAO notable at lags longer than 10 days. The persistence induced in daily NAO by SSTs causes long-term means of NAO to have more variance than expected from averaging NAO noise if there is no feedback of the ocean on the atmosphere. There are greater long-term trends in NAO than can be expected from aggregating just short-term atmospheric noise, and NAO is potentially predictable provided that future SSTs are known. For example, there is about 10%–30% more variance in seasonal wintertime means of NAO and almost 70% more variance in annual means of NAO due to SST effects than one would expect if NAO were a purely atmospheric process.
Mechanism-based Failure Laws for Biaxially Compressed IM7/8551-7 Graphite–Epoxy Laminates
Authors: Chen Xu , Gupta Vijay , Tian Jun
Published: April 2006

Failure mechanisms and stress–strain behaviors have been investi- gated for [15]6s,[30]12s, and [45]12s graphite–epoxy (IM7/8551-7) laminates under in-plane biaxial compression using a cruciform biaxial test frame and microscopic examination of the load-interrupted samples. The loading confinement ratio R is varied from 0 to nearly 1.0 to measure the sensitivity of sample failure mechanisms and stress–strain behaviors to different stress states. The failure modes for each orientation are found to be strongly confinement-ratio-dependent. For R 1/4 0, all the samples failed by in-plane shearing on a plane aligned with the fiber direction. As the confinement ratio is increased, the in-plane failure mode in [30]12s, and [45]12s samples transitioned to out-of-plane shearing at R 1/4 0.25 and 0.5, and multiple delamination at R 1/4 0.75 and 1.0. For the [15]6s samples, the failure modes transition to fiber buckling at R 1/4 0.25 and then out-of-plane shearing at R 1/4 0.5, 0.75, and 1.0. Microscopic examination of the load-interrupted samples confirms the source of the individual delaminations to be the wing cracks associated with the angled shear cracks in the out-of-plane direction. The classical laminate theory in combination with the standard rule of mixture is used to calculate the maximum shear stress in the matrix and the fibers. The failure data conform well with a Mohr–Coulomb-type shear failure law when applied to the fibers but not to the matrix. Thus, fiber shearing appears to be the failure-setting mechanism in this material under all material orientations and biaxiality ratios.
Rhetorical Question Use and Resistance to Persuasion: An Attitude Strength Analysis
Authors: Blankenship Kevin L. , Craig Traci Y.
Published: April 2006

Although previous research has provided indirect evidence that rhetorical questions can increase attitudinal resistance, what little work that was done was not specifically designed to examine the issue. Current models of attitude change suggest that rhetorical questions can increase persuasion and message processing, creating a relatively strong, resistant attitude. These processing and resistance effects in turn may be mediated by a property of attitude strength such as participants’ cognitive responses. In Study 1, placing rhetorical questions in a message increased participants’ message processing and counterargument generation relative to a control message. In addition, participants’ attitudes were mediated by participants’ cognitive responses. Study 2 found that a message containing rhetorical questions increased participants’ attitudinal resistance to an attacking message more than a control message, and the resistance effects were related to participants’ cognitive responses. These results provide the first direct evidence for the resistance effects of rhetorical question use and for mediators.
UV Radiation Exposure to Body Sites of Golfers and Effects of Clothing
Authors: Sung Heewon , Slocum Ann C.
Published: April 2006

This study focused on cumulative ultraviolet radiation (UVR) exposure to specific body sites of golfers and the effects of clothing in reducing UVR. Polysulphone film badges were used to measure personal exposure to UVB. Two experiments were conducted, in August and in October, at a midwestern golf course. Findings indicated that the upper back of golfers, such as the shoulders, back of the neck, and posterior arms, were more exposed to UVR than the front of the body such as the chest. Under clothing, the two most exposed areas were the back and front of the neck. However, the other body sites under the clothing received a limited amount of UVR, suggesting the importance of clothing in reducing UVR transmission.
Cumulvs: Interacting with High-Performance Scientific Simulations, for Visualization, Steering and Fault Tolerance
Authors: Kohl James A. , Wilde Torsten , Bernholdt David E.
Published: April 2006

High-performance computer simulations are an increasingly popular alternative or complement to physical experiments or prototypes. However, as these simulations grow more massive and complex, it becomes challenging to monitor and control their execution. CUMULVS is a middleware infrastructure for visualizing and steering scientific simulations while they are running. Front-end “viewers” attach dynamically to simulation programs, to extract and collect intermediate data values, even if decomposed over many parallel tasks. These data can be graphically viewed or animated in a variety of commercial or custom visualization environments using a provided viewer library. In response to this visual feedback, scientists can “close the loop” and apply interactive control using computational steering of any user-defined algorithmic or model parameters. The data identification interfaces and gathering protocols can also be applied for parallel data exchange in support of coupled simulations, and for application-directed collection of key program data in checkpoints, for automated restart in response to software or hardware failures. CUMULVS was originally based on PVM, but interoperates well with simulations that use MPI or other parallel environments. Several alternate messaging systems are being integrated with CUMULVS to ease its applicability, e.g. to MPI. CUMULVS has recently been integrated with the Common Component Architecture (CCA) for visualization and parallel data redistribution (referred to as “MxN”), and also with Global Arrays. This paper serves as a comprehensive overview of the CUMULVS capabilities, their usage, and their development over several years.
Just What Is It That Makes Capsule Homes So Different, So Appealing? Domesticity and the Technological Sublime, 1945 to 1975
Authors: Leslie Thomas
Published: April 2006

Of the various technical, domestic, and urban developments in 1960s architecture, none seems as bizarre or ill-conceived as the fascination with capsules and gantries as models for domestic living. Inspired by the fetishistic hardware of NASA and associated military organizations, capsule houses and their service towers celebrated the technological nihilism of the existenzminimum rendered in profoundly late-modern terms. Latent in these radical proposals was the suggestion of a postmechanical sublime, a denial of humane space and experience in favor of systematizing biological and anthropomorphic requirements. This article focuses on capsule home proposals by the Japanese metabolists and contemporaries in Britain, France, and America, including proposals for domestic environments in aerospace situations and domestic capsule-gantry experiments by Kisho Kurokawa and Archigram. Kurokawa's essay “Capsule Declaration” serves as a convenient conceptual summary for an exploration of technical models from aerospace, cultural, and political influences on the capsule-gantry ideal and suggests the lingering influence of this odd yet compelling chapter in the architecture of the 1960s.
Toward a Cultural-Ecological Revival of Military Bases
Authors: Hong Seongtae
Published: April 2006

“Ecological revival of military space” does not merely mean the restoration of ecologically contaminated, destroyed military spaces. It includes utilizing military space as a means to actively respond to ecological crisis. If no effort is made to restore such spaces using lots of time and money, that space will become an almost permanent space of death. Even though ecological restoration can succeed through a judicious deployment of time and money, reckless development will surely turn the space again into a lifeless site. This is the reason that we should engage such sites using a cultural-ecological politics whose aim is to create cultural-ecological spaces. This article will make the case that the U.S. Yongsan Garrison in Seoul could be culturally and ecologically rejuvenated by transforming the whole site into a natural forest. Such a project would contribute to the lives of not only the people presently living in Seoul but also their descendants. The natural forest in this conception is a slow space as well as a natural space. Such a space would provide a welcome respite to time-starved, speed-driven urban dwellers and would provide the people of Seoul with the opportunity to reflect on some of the more inhuman aspects of their accelerated lives. The culturalecological-space concept can be brought into being through a project that seeks to transform time and space. Such a project inevitably becomes a political issue. Thus, an approach is needed that regards cultural-ecological politics as cultural politics for the sake of ecological revival.
Ocular adnexal lymphoma: a review of clinicopathologic features and treatment options
Authors: Decaudin Didier , de Cremoux Patricia , Vincent-Salomon Anne , Dendale Remi , Rouic Livia Lumbroso-Le
Published: April 2006

The recent literature shows that interest in ocular adnexal lymphomas and their biologic and clinical characteristics—along with their possible association with Chlamydia psittaci infection and therapeutic management with rituximab or anti-Chlamydia psittaci antibiotic therapy—is considerable. These new data have modified the previously reported features of this disease and have made an updated review of the literature necessary. The aims of this review are to present the current knowledge on the biology of these lymphomas, their clinical features and prognostic factors, and the panel of all available treatment options.
Differential effects of antigens from L. braziliensis isolates from disseminated and cutaneous leishmaniasis on in vitro cytokine production
Authors: Leopoldo Paulo TG , Machado Paulo RL , Almeida Roque P , Schriefer Albert , Giudice Angela , de Jesus Amélia Ribeiro , Ho John L , Guimarães Luiz Henrique , Bacellar Olívia , Carvalho Edgar M
Published: April 2006

Background

Disseminated leishmaniasis is an emerging infectious disease, mostly due toL. braziliensis, which has clinical and histopathological features distinct from cutaneous leishmaniasis.

Methods

In the current study we evaluated thein vitroproduction of the cytokines IFN-γ, TNF-α, IL-5 and IL-10 by peripheral blood mononuclear cells (PBMC) from 15 disseminated leishmaniasis and 24 cutaneous leishmaniasis patients upon stimulation withL. braziliensisantigens genotyped as disseminated leishmaniasis or cutaneous leishmaniasis isolates.

Results

Regardless of the source ofL. braziliensisantigens, PBMC from cutaneous leishmaniasis patients produced significantly higher IFN-γ than PBMC from disseminated leishmaniasis patients. Levels of TNF-α by PBMC from cutaneous leishmaniasis patients were significantly higher than disseminated leishmaniasis patients only when stimulated by genotyped cutaneous leishmaniasis antigens. The levels of IL-5 and IL-10 production by PBMC were very low and similar in PBMCs from both disseminated leishmaniasis and cutaneous leishmaniasis patients. The immune response of each patient evaluated by the twoL. braziliensisantigens was assessed in a paired analysis in which we showed thatL. braziliensisgenotyped as disseminated leishmaniasis isolate was more potent thanL. braziliensisgenotyped as cutaneous leishmaniasis isolate in triggering IFN-γ and TNF-α production in both diseases and IL-5 only in cutaneous leishmaniasis patients.

Conclusion

This study provides evidence that antigens prepared from genotypically distinct strains ofL. braziliensisinduce different degrees of immune response. It also indicates that both parasite and host play a role in the outcome ofL. braziliensisinfection.
Cerebrovascular disease associated with antiphospholipid antibodies: more questions than answers
Authors: Hawkins Carolyn , Gatenby Paul , Tuck Roger , Danta Gytis , Andrews Colin
Published: April 2006

Neurological syndromes occur in a significant number of patients with antiphospholipid antibodies. The optimal management for these patients however remains uncertain.

Our study is a descriptive analysis looking retrospectively at 45 patients who presented to the principal tertiary referral centre in the Australian Capital Territory, with either cerebral arterial or venous thrombosis for which there was no obvious cause for their presentation when initially reviewed. The diagnosis was based on the clinical findings made by one of three neurologists attached to our centre. Radiological findings and the presence of either IgM or IgG anticardiolipin antibodies, IgG anti-beta-2 glycoprotein 1 antibodies or a lupus anticoagulant were then documented.

In this group of patients three subgroups were identified:

1. Individuals that fulfilled the Sapporo Classification Criteria

2. Individuals with transiently positive antiphospholipid antibodies and

3. Individuals with persistently low positive antiphospholipid antibodies.

The most interesting of these three groups are those individuals with transiently positive antiphospholipid antibodies. A potential cause for presentation was identified in only one patient of this group with documented infective endocarditis and bacteraemia. Comparison with the other two groups suggested that there was little in terms of clinical presentation, radiological findings or intercurrent risk factors for thrombotic disease to distinguish between them. With disappearance of antiphospholipid antibodies, the individuals within this group have not had further thrombotic events.

Our observations emphasise the problems that continue to exist in relation to the occurrence of cerebrovascular disease in the context of antiphospholipid antibodies and the optimal management of these stratified groups. Our findings also raise an as yet unanswered question as to the signficance of these transiently positive antiphospholipid antibodies. In the absence of significant intercurrent risk factors our findings would suggest that in the group we describe that they are likely to be of clinical significance.