bluuebunny/crossref_metadata_2025 huggingface dataset:
Transfer of the HIV-1 cyclophilin-binding site to simian immunodeficiency virus from
Macaca mulatta
can confer both cyclosporin sensitivity and cyclosporin dependence
Authors: Bukovsky Anatoly A. , Weimann Andreas , Accola Molly A. , Göttlinger Heinrich G.
Published: July 2002

HIV-1 specifically incorporates the peptidyl prolyl isomerase cyclophilin A (CyPA), the cytosolic receptor for the immunosuppressant cyclosporin A (CsA). HIV-1 replication is inhibited by CsA as well as by nonimmunosuppressive CsA analogues that bind to CyPA and interfere with its virion association. In contrast, the related simian immunodeficiency virus SIV
mac
, which does not interact with CyPA, is resistant to these compounds. The incorporation of CyPA into HIV-1 virions is mediated by a specific interaction between the active site of the enzyme and the capsid (CA) domain of the HIV-1 Gag polyprotein. We report here that the transfer of HIV-1 CA residues 86–93, which form part of an exposed loop, to the corresponding position in SIV
mac
resulted in the efficient incorporation of CyPA and conferred an HIV-1-like sensitivity to a nonimmunosuppressive cyclosporin. HIV-1 CA residues 86–90 were also sufficient to transfer the ability to efficiently incorporate CyPA, provided that the length of the CyPA-binding loop was preserved. However, the resulting SIV
mac
mutant required the presence of cyclosporin for efficient virus replication. The results indicate that the presence or absence of a type II tight turn adjacent to the primary CyPA-binding site determines whether CyPA incorporation enhances or inhibits viral replication. By demonstrating that CyPA-binding-site residues can induce cyclosporin sensitivity in a heterologous context, this study provides direct
in
vivo
evidence that the exposed loop between helices IV and V of HIV-1 CA not merely constitutes a docking site for CyPA but is a functional target of this cellular protein.
Targeted deletion of alkylpurine-DNA-N-glycosylase in mice eliminates repair of 1,
N
6
-ethenoadenine and hypoxanthine but not of 3,
N
4
-ethenocytosine or 8-oxoguanine
Authors: Hang B. , Singer B. , Margison G. P. , Elder R. H.
Published: July 2002

It has previously been reported that 1,
N
6
-ethenoadenine (ɛA), deaminated adenine (hypoxanthine, Hx), and 7,8-dihydro-8-oxoguanine (8-oxoG), but not 3,
N
4
-ethenocytosine (ɛC), are released from DNA
in vitro
by the DNA repair enzyme alkylpurine-DNA-N-glycosylase (APNG). To assess the potential contribution of APNG to the repair of each of these mutagenic lesions
in vivo
, we have used cell-free extracts of tissues from APNG-null mutant mice and wild-type controls. The ability of these extracts to cleave defined oligomers containing a single modified base was determined. The results showed that both testes and liver cells of these knockout mice completely lacked activity toward oligonucleotides containing ɛA and Hx, but retained wild-type levels of activity for ɛC and 8-oxoG. These findings indicate that (
i
) the previously identified ɛA-DNA glycosylase and Hx-DNA glycosylase activities are functions of APNG; (
ii
) the two structurally closely related mutagenic adducts ɛA and ɛC are repaired by separate gene products; and (
iii
) APNG does not contribute detectably to the repair of 8-oxoG.
Variation in per capita interaction strength: Thresholds due to nonlinear dynamics and nonequilibrium conditions
Authors: Ruesink Jennifer L.
Published: July 2002

I measured the strength of interaction between a marine herbivore and its growing resource over a realistic range of absolute and relative abundances. The herbivores (hermit crabs:
Pagurus
spp.) have slow and/or weak functional and numerical responses to epiphytic diatoms (
Isthmia nervosa
), which show logistic growth in the absence of consumers. By isolating this interaction in containers in the field, I mimicked many of the physical and biological variables characteristic of the intertidal while controlling the densities of focal species. The per capita effects of consumers on the population dynamics of their resource (i.e., interaction strength) were defined by using the relationship between hermit crab density and proportional change in the resource. When this relationship is fit by a Weibull function, a single parameter distinguishes constant interaction strength from one that varies as a function of density. Constant interaction strength causes the proportion of diatoms to fall linearly or proportionally as hermit crab density increases whereas per capita effects that increase with density cause an accelerating decline. Although many mathematical models of species interactions assume linear dynamics and invariant parameters, at least near equilibrium, the per capita effects of hermit crabs on diatoms varied substantially, apparently crossing a threshold from weak to strong when consumption exceeded resource production. This threshold separates a domain of coexistence from one of local extinction of the resource. Such thresholds may help explain trophic cascades, resource compensation, and context-dependent interaction strengths, while indicating a way to predict trophic effects, despite nonlinearities, as a function of vital rates.
Targeted disruption of the interferon-γ receptor 2 gene results in severe immune defects in mice
Authors: Lu Binfeng , Ebensperger Christoph , Dembic Zlatko , Wang Yulin , Kvatyuk Marina , Lu Tianhong , Coffman Robert L. , Pestka Sidney , Rothman Paul B.
Published: July 2002

To study the role of the interferon- (IFN) γR2 chain in IFN-γ signaling and immune function, IFN-γR2-deficient mice have been generated and characterized. Cells derived from IFN-γR2 −/− mice are unable to activate either JAK/STAT signaling proteins or gene transcription in response to IFN-γ. The lack of IFN-γ responsiveness alters IFN-γ-induced Ig class switching by B cells from these mice.In vitrocultures of T cells demonstrate that the T cells from the IFN-γR2 −/− mice have a defect in Th1 cell differentiation. The IFN-γR2 (−/−) mice also produce lower amounts of IFN-γ in response to antigenic challenge. In addition, IFN-γR2 −/− mice are defective in contact hypersensitivity and are highly susceptible to infection byListeria monocytogenes. These results demonstrate that the IFN-γR2 is essential for IFN-γ-mediated immune responsesin vivo.
β-Chemokines and neutralizing antibody titers correlate with sterilizing immunity generated in HIV-1 vaccinated macaques
Authors: Heeney Jonathan L. , Teeuwsen Vera J. P. , van Gils Mariélle , Bogers Willy M. J. M. , Morghen Carlo De Giuli , Radaelli Antonia , Barnett Susan , Morein Bror , Åkerblom Lennart , Wang Yufei , Lehner Thomas , Davis David
Published: July 2002

One of the obstacles to AIDS vaccine development is the variability of HIV-1 within individuals and within infected populations, enabling viral escape from highly specific vaccine induced immune responses. An understanding of the different immune mechanisms capable of inhibiting HIV infection may be of benefit in the eventual design of vaccines effective against HIV-1 variants. To study this we first compared the immune responses induced in Rhesus monkeys by using two different immunization strategies based on the same vaccine strain of HIV-1. We then utilized a chimeric simian/HIV that expressed the envelope of a dual tropic HIV-1 escape variant isolated from a later time point from the same patient from which the vaccine strain was isolated. Upon challenge, one vaccine group was completely protected from infection, whereas all of the other vaccinees and controls became infected. Protected macaques developed highest titers of heterologous neutralizing antibodies, and consistently elevated HIV-1-specific T helper responses. Furthermore, only protected animals had markedly increased concentrations of RANTES, macrophage inflammatory proteins 1α and 1β produced by circulating CD8
+
T cells. These results suggest that vaccine strategies that induce multiple effector mechanisms in concert with β-chemokines may be desired in the generation of protective immune responses by HIV-1 vaccines.
Second-order correction to the Bigeleisen–Mayer equation due to the nuclear field shift
Authors: Bigeleisen Jacob
Published: July 2002

The nuclear field shift affects the electronic, rotational, and vibrational energies of polyatomic molecules. The theory of the shifts in molecular spectra has been studied by Schlembach and Tiemann [Schlembach, J. & Tiemann, E. (1982)
Chem. Phys.
68, 21]; measurements of the electronic and rotational shifts of the diatomic halides of Pb and Tl have been made by Tiemann
et al.
[Tiemann, E., Knöckel, H. & Schlembach, J. (1982)
Ber. Bunsenges. Phys. Chem.
86, 821]. These authors have estimated the relative shifts in the harmonic frequencies of these compounds due to the nuclear field shift to be of the order of 10
−6
. I have used this estimate of the relative shift in vibrational frequency to calculate the correction to the harmonic oscillator approximation to the isotopic reduced partition-function ratio
208
Pb
32
S/
207
Pb
32
S. The correction is 0.3% of the harmonic oscillator value at 300 K. In the absence of compelling evidence to the contrary, it suffices to calculate the nuclear field effect on the total isotopic partition-function ratio from its shift of the electronic zero point energy and the unperturbed molecular vibration.
An inactive open complex mediated by an UP element at
Escherichia
coli
promoters
Authors: Tagami Hideaki , Aiba Hiroji
Published: July 2002

A specific interaction between the α subunit of RNA polymerase and an A+T-rich upstream sequence (UP element) stimulates transcription at some promoters in
Escherichia coli
. We found that RNA polymerase formed a heparin-resistant nonproductive initiation complex at the
malT
promoter which has an A+T-rich upstream sequence that begins 9 bp upstream of the −35 region. Substitution of other sequences for the A+T-rich sequence eliminated both the formation of heparin-resistant complexes and α binding to the
malT
promoter. A 5-bp deletion between the A+T-rich sequence and the −35 region increased promoter activity. The UP element derived from the
rrnB
P1 promoter stimulated transcription of the
malT
core promoter when placed 4 bp upstream from the
malT
−35 region, but insertion of an additional 4 bp between the
rrnB
P1 UP element and the −35 element eliminated transcription activity without eliminating heparin-resistant complex formation. Similar UP element effects were observed in hybrids with the
lac
core promoter, even though the region around the transcription start site was melted in both productive and nonproductive complexes. We conclude that UP elements can mediate the formation of both productive and nonproductive open complexes, depending on their location with respect to the core promoter.
Cognitive changes and modified processing of amyloid precursor protein in the cortical and hippocampal system after cholinergic synapse loss and muscarinic receptor activation
Authors: Lin L. , Georgievska B. , Mattsson A. , Isacson O.
Published: July 2002

A number of
in vitro
studies have shown that activation of muscarinic receptors by cholinergic agonists stimulates the nonamyloidogenic, α-secretase-processing pathway of amyloid precursor protein (APP). To determine whether increased cholinergic neurotransmission can modify the APP processing
in vivo
, we administered a muscarinic receptor agonist (RS86) to normal or aged rats and rats with severe basal forebrain cholinergic deficits (induced by 192 IgG-saporin). The levels of the cell-associated APP in neocortex, hippocampus, and striatum, as well as the secreted form of APP (APPs) in cerebrospinal fluid, were examined by Western blots. Additionally, we investigated the association between the altered APP levels and behavioral deficits caused by cholinergic lesions. We found that treatment with muscarinic receptor agonist resulted in decreased APP levels in neocortex and hippocampus and increased levels of APPs in cerebrospinal fluid. Regulation of APP processing by the muscarinic agonist treatment occurred not only in normal rats, but also in aged and cholinergic denervated rats that model this aspect of Alzheimer’s disease. Interestingly, we found that elevation of APP in neocortex correlated with the cognitive deficits in water-maze testing of rats with cholinergic dysfunction. These data indicate that increased cholinergic neurotransmission can enhance nonamyloidogenic APP processing in intact and lesioned rats and that APP may be involved in cognitive performance.
The sociocultural and psychological adaptation of Chinese migrant adolescents in Australia and Canada
Authors: Leung Cynthia
Published: July 2002

This study aimed to investigate the adaptation of Chinese migrant adolescents in Australia and Canada, in terms of their academic achievement, parent—child conflict, and stress, in the light of various societal, situational, and individual variables. The participants included 75 Chinese‐Canadian and 92 Chinese‐Australian high school students. The results suggested that academic achievement in the host society was influenced by societal level variables such as auspices of immigration, and situational and individual variables such as amount of social support available, age, and their definitions of success. For parent—child conflict and stress level, they were related to the situational variable, social support, rather than to societal variables. There was also some evidence to indicate that the three adaptation outcome variables were related.
β2-microglobulin–deficient Mice Are Resistant to Bullous Pemphigoid
Authors: Liu Zhi , Roopenian Derry C. , Zhou Xiaoye , Christianson Greg J. , Diaz Luis A. , Sedmak Daniel D. , Anderson Clark L.
Published: July 2002

Recent understanding of the mechanism of immunoglobulin G (IgG) catabolism has yielded new insight into antibody-mediated diseases. We proposed that β2-microglobulin (β2m)–deficient mice have been protected from systemic lupus erythematosis (SLE)–like syndromes because they lack the β2m-associated IgG protection receptor (FcRn) and therefore catabolize IgG, including pathogenic IgG autoantibodies, considerably more rapidly than normal mice. Such an hypothesis would predict that β2m-deficient mice would also be resistant to experimental bullous pemphigoid, a disease with a pathogenesis thought to be much simpler than SLE, being the result of antibody directed toward a pathogenic epitope on the epidermal hemidesmosome that anchors basal keratinocytes to the basement membrane. To test this hypothesis, we administered pathogenic rabbit antibody directed toward the hemidesmosome to β2m-deficient mice and to normal control mice, both intraperitoneally and intradermally, and assessed the mice clinically, histologically, and immunologically for manifestations of skin disease. We found that the β2m-deficient mice were protected when the antibody was given intraperitoneally whereas intradermal administration resulted in blisters only slightly less severe than those seen in normal mice. These data would indicate that autoantibody-mediated inflammation might be prevented or controlled by appropriate modulation of FcRn function.
Mucosal Adjuvanticity and Immunogenicity of LTR72, a Novel Mutant of Escherichia coli Heat-labile Enterotoxin with Partial Knockout of ADP-ribosyltransferase Activity
Authors: Giuliani Marzia Monica , Del Giudice Giuseppe , Giannelli Valentina , Dougan Gordon , Douce Gill , Rappuoli Rino , Pizza Mariagrazia
Published: July 2002

Heat-labile Escherichia coli enterotoxin (LT) has the innate property of being a strong mucosal immunogen and adjuvant. In the attempt to reduce toxicity and maintain the useful immunological properties, several LT mutants have been produced. Some of these are promising mucosal adjuvants. However, so far, only those that were still toxic maintained full adjuvanticity. In this paper we describe a novel LT mutant with greatly reduced toxicity that maintains most of the adjuvanticity. The new mutant (LTR72), that contains a substitution Ala → Arg in position 72 of the A subunit, showed only 0.6% of the LT enzymatic activity, was 100,000-fold less toxic than wild-type LT in Y1 cells in vitro, and was at least 20 times less effective than wild-type LT in the rabbit ileal loop assay in vivo. At a dose of 1 μg, LTR72 exhibited a mucosal adjuvanticity, similar to that observed with wild-type LT, better than that induced by the nontoxic, enzymatically inactive LTK63 mutant, and much greater than that of the recombinant B subunit. This trend was consistent for both the amounts and kinetics of the antibody induced, and priming of antigen-specific T lymphocytes. The data suggest that the innate high adjuvanticity of LT derives from the independent contribution of the nontoxic AB complex and the enzymatic activity. LTR72 optimizes the use of both properties: the enzymatic activity for which traces are enough, and the nontoxic AB complex, the effect of which is dose dependent. In fact, in dose–response experiments in mice, 20 μg of LTR72 were a stronger mucosal adjuvant than wild-type LT. This suggests that LTR72 may be an excellent candidate to be tested in clinical trials.
CD40 Ligand Is Not Essential for Induction of Type 1 Cytokine Responses or Protective Immunity after Primary or Secondary Infection With Histoplasma capsulatum
Authors: Zhou Ping , Seder Robert A.
Published: July 2002

The induction of type 1 immune responses (interleukin [IL]-12, interferon [IFN]-γ) has been shown to be important in mediating protection against many intracellular infections including Histoplasma capsulatum. Costimulatory molecules such as CD40 ligand (CD40L) have been shown to be a central regulator of type 1 responses in vivo. To study the role of CD40L in mediating protection against infection with H. capsulatum, CD40L-deficient (CD40L−/−) and CD40L+/+ mice were infected with H. capsulatum and assessed for various parameters. After a lethal challenge of H. capsulatum, CD40L−/− mice were not substantially different from CD40L+/+ mice in terms of mortality, fungal burden, or production of IFN-γ, IL-12, nitric oxide, or tumor necrosis factor α. Moreover, CD40L−/− mice treated with anti–IFN-γ or anti–IL-12 at the time of infection had accelerated mortality, providing further evidence that IL-12 and IFN-γ are produced in vivo in the absence of CD40L. In addition, CD40L−/− mice infected with a sublethal dose of H. capsulatum survived infection, whereas all mice infected with the same dose and treated with anti–IFN-γ had accelerated mortality, demonstrating that IFN-γ but not CD40L was essential for primary immunity to H. capsulatum infection. Interestingly, depletion of either CD4+ or CD8+ T cells resulted in accelerated mortality in CD40L−/− mice, suggesting a critical role for these cells in response to infection. Finally, CD40L−/− mice initially infected with a sublethal dose of H. capsulatum were protected from secondary infection with a lethal dose of H. capsulatum, demonstrating that CD40L is not required for the maintenance of memory immunity.
Genetic Regulation of Commitment to Interleukin 4 Production by a CD4+ T Cell–intrinsic Mechanism
Authors: Bix Mark , Wang Zhi-En , Thiel Bonnie , Schork Nicholas J. , Locksley Richard M.
Published: July 2002

The dysregulated expression of interleukin 4 (IL-4) can have deleterious effects on the outcome of infectious and allergic diseases. Despite this, the mechanisms by which naive T cells commit to IL-4 expression during differentiation into mature effector cells remain incompletely defined. As compared to cells from most strains of mice, activated CD4+ T cells from BALB mice show a bias towards IL-4 production and T helper 2 commitment in vitro and in vivo. Here, we show that this bias arises not from an increase in the amount of IL-4 produced per cell, but rather from an increase in the proportion of CD4+ T cells that commit to IL-4 expression. This strain-specific difference in commitment was independent of signals mediated via the IL-4 receptor and hence occurred upstream of potential autoregulatory effects of IL-4. Segregation analysis of the phenotype in an experimental backcross cohort implicated a polymorphic locus on chromosome 16. Consistent with a role in differentiation, expression of the phenotype was CD4+ T cell intrinsic and was evident as early as 16 h after the activation of naive T cells. Probabilistic gene activation is proposed as a T cell–intrinsic mechanism capable of modulating the proportion of naive T cells that commit to IL-4 production.
Induction of Fas Ligand Expression by HIV Involves the Interaction of Nef with the T Cell Receptor ζ Chain
Authors: Xu Xiao-Ning , Laffert Bernd , Screaton Gavin R. , Kraft Michael , Wolf Dietlinde , Kolanus Waldemar , Mongkolsapay Juthathip , McMichael Andrew J. , Baur Andreas S.
Published: July 2002

During HIV/SIV infection, there is widespread programmed cell death in infected and, perhaps more importantly, uninfected cells. Much of this apoptosis is mediated by Fas–Fas ligand (FasL) interactions. Previously we demonstrated in macaques that induction of FasL expression and apoptotic cell death of both CD4+ and CD8+ T cells by SIV is dependent on a functional nef gene. However, the molecular mechanism whereby HIV-1 induces the expression of FasL remained poorly understood. Here we report a direct association of HIV-1 Nef with the ζ chain of the T cell receptor (TCR) complex and the requirement of both proteins for HIV-mediated upregulation of FasL. Expression of FasL through Nef depended upon the integrity of the immunoreceptor tyrosine-based activation motifs (ITAMs) of the TCR ζ chain. Conformation for the importance of ζ for Nef-mediated signaling in T cells came from an independent finding. A single ITAM motif of ζ but not CD3ε was both required and sufficient to promote activation and binding of the Nef-associated kinase (NAK/p62). Our data imply that Nef can form a signaling complex with the TCR, which bypasses the requirement of antigen to initiate T cell activation and subsequently upregulation of FasL expression. Thus, our study may provide critical insights into the molecular mechanism whereby the HIV-1 accessory protein Nef contributes to the pathogenesis of HIV.
Regulation of FAS Ligand Expression during Activation-Induced Cell Death in T Cells by p38 Mitogen-Activated Protein Kinase and C-Jun Nh2-Terminal Kinase
Authors: Zhang Jian , Gao Jian-Xin , Salojin Kostantin , Shao Qing , Grattan Marsha , Meagher Craig , Laird Dale W. , Delovitch Terry L.
Published: July 2002

Activation-induced cell death (AICD) is a mechanism of peripheral T cell tolerance that depends upon an interaction between Fas and Fas ligand (FasL). Although c-Jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) may be involved in apoptosis in various cell types, the mode of regulation of FasL expression during AICD in T cells by these two MAPKs is incompletely understood. To investigate the regulatory roles of these two MAPKs, we analyzed the kinetics of TCR-induced p38 MAPK and JNK activity and their regulation of FasL expression and AICD. We report that both JNK and p38 MAPK regulate AICD in T cells. Our data suggest a novel model of T cell AICD in which p38 MAPK acts early to initiate FasL expression and the Fas-mediated activation of caspases. Subsequently, caspases stimulate JNK to further upregulate FasL expression. Thus, p38 MAPK and downstream JNK converge to regulate FasL expression at different times after T cell receptor stimulation to elicit maximum AICD.
A B Cell Superantigen–Induced Persistent “Hole” in the B-1 Repertoire
Authors: Silverman Gregg J. , Cary Stephen P. , Dwyer Denise C. , Luo Linda , Wagenknecht Raymond , Curtiss Virginia E.
Published: July 2002

The bacterial toxin protein A from Staphylococcus aureus (SpA) interacts with B cell antigen receptors encoded by variable region heavy chain (VH) clan III genes via a V region framework surface that has been highly conserved during the evolution of the adaptive immune system. We have investigated the consequences of exposure to this prototypic B cell superantigen, and found that treatment of neonates or adults induces a T cell–independent deletion of a large supraclonal set of susceptible B cells that includes clan III/VH S107 family–expressing lymphocytes. In studies of different SpA forms, the magnitude of the induced deletion directly correlated with the VH-specific binding affinity/avidity. Upon cessation of SpA exposure, the representation of conventional splenic (B-2 subset) lymphocytes normalized; however, we found that the VH family–restricted deficit of peritoneal B-1 cells persisted. SpA treatment also induced a persistent loss of splenic S107-μ transcripts, with a loss of certain natural antibodies and specific tolerance to phosphorylcholine immunogens that normally recruit protective antimicrobial responses dominated by the S107-expressing B-1 clone, T15. These studies illustrate how a B cell superantigen can exploit a primordial Achilles heel in the immune system, for which B-1 cells, an important source of natural antibodies and host immune responses, have special susceptibility.
Suppression of Signal Transducer and Activator of Transcription 3–Dependent B Lymphocyte Terminal Differentiation by Bcl-6
Authors: Reljic Rajko , Wagner Simon D. , Peakman Luke J. , Fearon Douglas T.
Published: July 2002

Lymphocytes usually differentiate into effector cells within days after antigen exposure, except in germinal centers where terminal differentiation is delayed while somatic hypermutation creates high-affinity antibody mutants. Here we investigate whether arrest of terminal differentiation can be mediated by BCL-6, a transcriptional repressor that is expressed by germinal center B cells and is required for this phase of B cell development. We find that BCL-6 suppresses the differentiation of transformed and primary B cells to plasma cells by inhibiting the signal transducer and activator of transcription 3–dependent expression of the major regulator of plasma cell development, the B lymphocyte–induced maturation protein (Blimp-1). This function of BCL-6 as a repressor of B lymphocyte differentiation may also underlie the association between chromosomal translocations of its gene and B cell lymphomas.
Residual Type 1 Immunity in Patients Genetically Deficient for Interleukin 12 Receptor β1 (IL-12Rβ1)
Authors: Verhagen Claudia E. , de Boer Tjitske , Smits Hermelijn H. , Verreck Frank A.W. , Wierenga Eddy A. , Kurimoto M. , Lammas D. Anthony , Kumararatne Dinakanthe S. , Sanal Ozden , Kroon Frank P. , van Dissel Jaap T. , Sinigaglia Francesco , Ottenhoff Tom H.M.
Published: July 2002

Genetic lack of interleukin 12 receptor β1 (IL-12Rβ1) surface expression predisposes to severe infections by poorly pathogenic mycobacteria or Salmonella and causes strongly decreased, but not completely abrogated, interferon (IFN)-γ production. To study IL-12Rβ1–independent residual IFN-γ production, we have generated mycobacterium–specific T cell clones (TCCs) from IL-12Rβ1–deficient individuals. All TCCs displayed a T helper type 1 phenotype and the majority responded to IL-12 by increased IFN-γ production and proliferative responses upon activation. This response to IL-12 could be further augmented by exogenous IL-18. IL-12Rβ2 was found to be normally expressed in the absence of IL-12Rβ1, and could be upregulated by IFN-α. Expression of IL-12Rβ2 alone, however, was insufficient to induce signal transducer and activator of transcription (Stat)4 activation in response to IL-12, whereas IFN-α/IFN-αR ligation resulted in Stat4 activation in both control and IL-12Rβ1–deficient cells. IL-12 failed to upregulate cell surface expression of IL-18R, integrin α6, and IL-12Rβ2 on IL-12Rβ1–deficient cells, whereas this was normal on control cells. IL-12–induced IFN-γ production in IL-12Rβ1–deficient T cells could be inhibited by the p38 mitogen-activated protein kinase (MAP) kinase inhibitor SB203580 and the MAP kinase kinase (MEK) 1/2 inhibitor U0126, suggesting involvement of MAP kinases in this alternative, Stat4-independent, IL-12 signaling pathway.

Collectively, these results indicate that IL-12 acts as a partial agonist in the absence of IL-12Rβ1. Moreover, the results reveal the presence of a novel IL-12Rβ1/Stat4–independent pathway of IL-12 responsiveness in activated human T cells involving MAP kinases. This pathway is likely to play a role in the residual type 1 immunity in IL-12Rβ1 deficiency.
CD8+ T Cell Tolerance to a Tumor-associated Antigen Is Maintained at the Level of Expansion Rather than Effector Function
Authors: Öhlén Claes , Kalos Michael , Cheng Laurence E. , Shur Aaron C. , Hong Doley J. , Carson Bryan D. , Kokot Niels C.T. , Lerner Cara G. , Sather Blythe D. , Huseby Eric S. , Greenberg Philip D.
Published: July 2002

CD8+ T cell tolerance to self-proteins prevents autoimmunity but represents an obstacle to generating T cell responses to tumor-associated antigens. We have made a T cell receptor (TCR) transgenic mouse specific for a tumor antigen and crossed TCR-TG mice to transgenic mice expressing the tumor antigen in hepatocytes (gag-TG). TCRxgag mice showed no signs of autoimmunity despite persistence of high avidity transgenic CD8+ T cells in the periphery. Peripheral CD8+ T cells expressed phenotypic markers consistent with antigen encounter in vivo and had upregulated the antiapoptotic molecule Bcl-2. TCRxgag cells failed to proliferate in response to antigen but demonstrated cytolytic activity and the ability to produce interferon γ. This split tolerance was accompanied by inhibition of Ca2+ flux, ERK1/2, and Jun kinasephosphorylation, and a block in both interleukin 2 production and response to exogenous interleukin 2. The data suggest that proliferation and expression of specific effector functions characteristic of reactive cells are not necessarily linked in CD8+ T cell tolerance.
A one-box-shift morphism between Specht modules
Authors: Künzer Matthias
Published: July 2002

We give a formula for a morphism between Specht modules over

(

Z

/

m
)

S

n

(\mathbf {Z}/m)\mathcal {S}_n

, where

n
≥
1

n\geq 1

, and where the partition indexing the target Specht module arises from that indexing the source Specht module by a downwards shift of one box,

m
m

being the box shift length. Our morphism can be reinterpreted integrally as an extension of order

m
m

of the corresponding Specht lattices.
A “regular” pentagonal tiling of the plane
Authors: Bowers Philip , Stephenson Kenneth
Published: July 2002

The paper introduces conformal tilings, wherein tiles have specified conformal shapes. The principal example involves conformally regular pentagons which tile the plane in a pattern generated by a subdivision rule. Combinatorial symmetries imply rigid conformal symmetries, which in turn illustrate a new type of tiling self-similarity. In parallel with the conformal tilings, the paper develops discrete tilings based on circle packings. These faithfully reflect the key features of the theory and provide the tiling illustrations of the paper. Moreover, it is shown that under refinement the discrete tiles converge to their true conformal shapes, shapes for which no other approximation techniques are known. The paper concludes with some further examples which may contribute to the study of tilings and shinglings being carried forward by Cannon, Floyd, and Parry.
Ceramic Capillaries for Use in Microarray Fabrication
Authors: George Reed A. , Woolley John Patrick , Spellman Paul T.
Published: July 2002

We have used ceramic capillary tips generally used in the microelectronics industry for the production of DNA microarrays. The ceramic tips improve the morphology of microarray elements, allow higher element density, and increase printing tip life over the customary slotted stainless-steel pins. Ceramic tips are less expensive than steel pins and allow printing from 1536-well sample source plates. In this work, we describe experiments that establish printing performance of the ceramic tips and hybridization experiments that show that DNA hybridization is unaffected by the choice of tip material.
Nonstationary noise characteristics of the helical scan and its impact on image quality and artifacts
Authors: Hsieh Jiang
Published: July 2002

Helical computed tomography has replaced the conventional step‐and‐shoot CT in many clinical applications. Because of its clinical importance, a number of comparative studies have been performed to evaluate its performance parameters, such as the noise and the slice sensitivity profile. In this paper, the nonstationary noise characteristics of helical images are carefully examined. Their impact on the low contrast detectability and three‐dimensional (3‐D) image artifacts is assessed. An analytical equation is derived to relate the interactions between various helical reconstruction schemes and the fan‐beam filtered backprojection algorithm. We demonstrate that for many popular helical weights, the noise variation within the field of view of the reconstruction is close to a factor of 3. Several approaches to overcome the undesired characteristics are proposed.
Radioactivity teaching: Environmental consequences of the radiological accident in Goiânia (Brazil)
Authors: Anjos R. M. , Facure A. , Lima E. L. N. , Gomes P. R. S. , Santos M. S. , Brage J. A. P. , Okuno E. , Yoshimura E. M. , Umisedo N. K.
Published: July 2002

Ionizing radiation and its effects on human beings, radiation protection, and radiological accident prevention are topics usually not included in the physics courses at the Brazilian universities. As a consequence, high school teachers are not able to enlighten their students when radiological or nuclear accidents occur. This paper presents a teaching program on ionizing radiation physics, to be applied to undergraduate physics students and to physics high school teachers. It is based on the environmental consequences of the 1987 radiological accident in Goiânia. This program was applied to two undergraduate physics students, in 1999, at the Universidade Federal Fluminense, Brazil. Results of the gamma ray spectrometry measurements of samples collected in Goiânia by the students are presented.
A generalized Westervelt equation for nonlinear medical ultrasound
Authors: Taraldsen G.
Published: July 2002

A model equation is derived for nonlinear medical ultrasound. Unlike the existing models, which use spatial coordinates, material coordinates are used and hence a model for a heterogeneous medium is able to be derived. The equation is a generalization of the Westervelt equation, and includes the nonlinearity, relaxation, and heterogeneity of soft tissue. The validity of the generalized Westervelt equation as a model equation for a Piola–Kirchoff acoustic pressure and as an equation for the acoustic pressure is discussed. In the second case it turns out that the model follows from two geometric approximations which are valid when the radius of curvature of the phase fronts is much larger than the particle displacements. The model is exact for plane waves and includes arbitrary nonlinearity in the stress–strain relation.
A new method for measuring in situ concrete elastic constants using horizontally polarized conical transducers
Authors: Wu T.-T. , Fang J.-S.
Published: July 2002

This paper presents a result on the measurements of longitudinal and Rayleigh wave velocities in a concrete plate using horizontally polarized conical transducers. The characteristics of horizontally polarized surface responses due to a point source applied at a half-space and a plate are analyzed and discussed. The analyses show that the horizontal component of a skimming longitudinal wavefront due to a point source is much larger than its vertical component. This suggests the utilization of a horizontal component of a surface response to detect the skimming longitudinal wavefront. In addition, theoretical analysis shows that by using the horizontal component to determine the Rayleigh wave velocity, the source-to-receiver distance can be reduced significantly. Homemade horizontally polarized conical transducers were fabricated to demonstrate the feasibility of the present method on measuring the dynamic concrete elastic constants. Experimental results on the measurements of the horizontal component of a surface response due to a point impact were in good agreement with the theoretical prediction. In conclusion, it is noted that, based on this proposed method, concrete dynamic elastic constants can be determined through a single transient elastic wave experiment.
Analysis of engine noise for application in predictive maintenance
Authors: Meegan G. Douglas , Nelson H. Roice , Barlett Martin L. , Wilson Gary R.
Published: July 2002

The analysis of radiated sound and vibrational signatures of engines may be useful for monitoring an engine’s performance and assessing the need for maintenance. Measurements of the vibrational signatures and exhaust noise produced by normal engines and engines with known faults will be presented along with a corresponding model for engine exhaust noise. The results of power spectral and higher-order spectral processing of the engine noise will be compared and their usefulness as a means of detecting faulty engine operation will be discussed. [Work supported by the Office of Naval Research, Contract No. N00014-96-1-0298-7.]
Observations of cnoidal internal waves and their effect on acoustic propagation in shallow water
Authors: Rubenstein David
Published: July 2002

Packets of cnoidal internal waves were observed during a shallow-water experiment in the Gulf of Mexico. They lasted about 3 h and were always observed at the same time of day, clearly in response to tidal forcing. The cnoidal waves had 2–10 m amplitudes, narrow frequency bandwidths with central frequencies of about 9 cph, wavelengths of about 435 m, and they propagated in the along-slope direction. Data from a set of three thermistor arrays were processed to obtain directional wave spectra. These spectra establish the strong directionality of the cnoidal wave packets. The background ‘‘continuum’’ spectrum is resolved into a small set of discrete, strongly directional components. Observations of low-frequency acoustic propagation along several baselines showed fluctuations induced by cnoidal waves. These effects were simulated using a time-step PE approach. A mode-coupling resonance with the internal wave field results in elevated acoustic variability along a set of discrete spokes, emanating from the acoustic source. While acoustic variability tends to increase with range and with internal wave amplitude, tangential and radial correlation scales do not show a systematic dependence. Other implications of relative directionality between internal wave and acoustic propagation are discussed.
Acoustic travel time and intensity fluctuations measured in the SWARM95 experiment
Authors: Headrick Robert H. , Lynch James F. , Orr Marshall , Pasewark Bruce , Wolf Steve , Badiey Mohsen , Chiu Ching-Sang , Apel John
Published: July 2002

During the summer of 1995, a multidisciplinary, multilaboratory experiment entitled ‘‘SWARM’’ (shallow-water acoustics in a random medium) was conducted on the continental shelf off New Jersey. The purpose of this experiment was to examine the effects of internal waves, both linear and nonlinear, upon acoustic transmissions in the 10 to 1000-Hz range. Towards this goal, numerous oceanographic sensors were deployed along a fixed across shelf track, together with a fixed acoustic transmission range. Shipborne acoustic sources also allowed out of plane (along shelf) studies. Results will be presented of recent data analyses showing the nature of the measured acoustic travel time and intensity fluctuations, and how they correlate to environmental forcing, particularly by internal waves and the shelfbreak front. [Work supported by ONR.]
Various approaches to estimating natural frequencies of automobile cab cavities from a boundary-element model
Authors: Kondapalli Prasanna , Birkett Craig
Published: July 2002

The boundary-element method has gained wide acceptance as an acoustic analysis tool in the automobile industry. The methodology for extracting eigenvalues of acoustic cavities of complex shapes by the boundary element method is not yet well established. The finite-element method is widely used for eigenvalue analysis, but it is very expensive and time consuming to build a finite-element mesh solely for this purpose. Two ways for estimating the natural frequencies of a cab cavity from its boundary element model are discussed in this paper. One approach is derived from the experimental technique for determining cavity modes. An acoustic (point) source(s) placed inside the cab is used to excite the various cavity modes by doing a frequency sweep in the range of interest. The response is measured at suitable locations and the identified peaks in the frequency response function give an estimate of the cavity modes. By examining the sound pressure level plots on the boundary, the type of mode is identified. The second approach makes use of an automatic mesh generator which automatically meshes the interior cavity by tetra elements from a boundary element model. Then, a finite-element eigenvalue analysis is carried out to determine the cavity modes. Both of the above approaches require significantly less time than constructing a finite-element model. Numerical examples of a rectangular box and a simple car model are considered, and results obtained from a regular finite-element model, tetra finite-element model, and a boundary-element model are compared. [See NOISE-CON Proceedings for full paper.]
Analysis of periodic acoustic problems with double-sided impedance condition
Authors: Raveendra S. T. , Konno B.
Published: July 2002

The modeling of unequal impedance on either side of a vibrating structure is important in many engineering applications. Although the boundary element method is well suited for the analysis of periodic acoustic problems, the modeling of the double-sided impedance condition is not possible in the conventional boundary-element method. In particular, the indirect boundary-element method allows the simultaneous modeling of acoustic domains separated by thin vibrating structures. Thus a facility to model the double-sided impedance condition is very useful in the solution of realistic engineering problems using the indirect boundary-element method. The indirect boundary-element method models the jump of the acoustic pressure and the acoustic velocity between the two sides of the vibrating surface. The impedance relationship that relates the acoustic pressure to the velocity is not reducible to a single relationship between the jump of pressure and velocity. Since the relationship is expressed by two equations, the solution of the equations requires the generation of two sets of integral equations at the impedance surface. The application of this newly developed formulation for the solution of the double-sided impedance condition will be demonstrated by solving a number of example problems. An additional feature of this development is that this formulation can be used to eliminate the irregular frequencies that are associated with the solution of periodic exterior acoustic problems using the boundary element method. The application of this formulation for the elimination of irregular frequencies will also be demonstrated through example problems. [See NOISE-CON Proceedings for full paper.]
Specifying design noise levels for occupied spaces and units of equipment
Authors: Moiseev Neil
Published: July 2002

Acousticians and mechanical engineers specify design noise levels for occupied spaces and systems components (units of equipment). While it is widely accepted that occupied spaces should have a ‘‘balanced’’ noise spectrum, individual units of mechanical, electrical, plumbing, and other building systems equipment do not. Of the three commonly used systems of rating interior noise—noise criteria, room criteria, and noise criteria–balanced curves—only noise criteria lends itself to specifying a maximum noise level for equipment. How can the need for a ‘‘balanced’’ noise environment for people be reconciled with the fact that radiated noise from a fan-powered variable air volume box is predominately in the 125- and 250-Hz octave bands with little sound energy at 1000 Hz and higher? A discussion of the need for a clear standard that is easily understandable to specifiers, clients, manufacturers, and users is undertaken, with suggestions of how to resolve the differing needs of these interacting communities. [See NOISE-CON Proceedings for full paper.]
Room noise criteria—A status report
Authors: Pei Hsien-sheng (Jason) , Peppin Richard J.
Published: July 2002

After more than 20 years of effort, American National Standard ‘‘Criteria for Evaluating Room Noise’’ ANSI S12.2-1995 was released. ANSI S12.2 is not a good standard because it offers two different possibilities to evaluate the acceptability of the sound in an occupied space with the potential for large differences in the cost of conformance and insufficient guidance to a user on how to choose between them. As members of both the ASHRAE TC2.6 and ASA S12/WG18 committees responsible for the preparation of the ANSI S12.2 standard the authors see the need for inter-society partnership to resolve the conflict. Two panel discussion sessions (ASA Boston Chapter meeting on 21 November 1995; and NOISE-CON96 Conference on 30 September 1996); one technical session (NOISE-CON96 ‘‘Room Noise Criteria—The Next 25 Years’’) and the response from the acoustical and engineering community have served to show that there are enough data to develop a road map for consensus. After the NOISE-CON96 sessions, many attendants have asked for a report. A report entitled ‘‘Room Noise Criteria—The Next 25 Years’’ was generated, which documents the findings of these sessions. This paper is a brief summary of the said report. [See NOISE-CON Proceedings for full paper.]
The impact of Rayleigh’s ‘‘The Theory of Sound’’ on the British development of the theory of electromagnetic radiation
Authors: Marston Philip L.
Published: July 2002

At the time of Maxwell’s death in 1879, British physicists had not yet formulated models for the generation of electromagnetic waves. A recent history of British electromagnetic theory of that period [B. J. Hunt, The Maxwellians (Cornell U. P., Ithaca, 1991)] notes the influence Rayleigh’s text on sound had on the calculation of the power radiated by an oscillating magnetic dipole, which G. F. FitzGerald published in 1883. Examination of a series of FitzGerald’s papers on sources of electromagnetic waves for the years 1879, 1880, 1882, and 1883 confirms Hunt’s observations. Specifically, FitzGerald credits Rayleigh’s text for the inspiration to consider traveling-wave solutions, the key to his eventual success, instead of his earlier standing-wave solution. This anecdote, and others to be noted from that period, illustrate the influence of acoustics in helping to resolve difficulties in cases in which the electromagnetic theory was poorly understood. These may be of interest to today’s students and teachers.