Reduction of Th1 cell activity in the peripheral circulation of patients with rheumatoid arthritis after treatment with a non-depleting humanized monoclonal antibody to CD4

Differences in early events during entry and integration of HIV-1 into peripheral blood mononuclear cells (PBMC) might contribute to the absence of AIDS-like disease in chimpanzees as compared to humans. To address this question, we first tested the in vitro susceptibility of human and chimpanzee PBMC for infection with the two HIV-1 isolates III B and RF. The results of these studies revealed that chimpanzee PBMC had a slightly lower capability to support the growth of HIV-1 as compared to human PBMC. This was accompanied by a delayed accumulation of proviral HIV-1 DNA in cultures of HIV-1-infected chimpanzee PBMC. However, no differences between cells of the two species were observed when very early events of HIV-1 infection were studied. Shortly (20 h) after infection chimpanzee and human cells harbored similar amounts of proviral HIV-1 DNA and PBMC of both species behaved comparably with respect to pre-integration latency (i.e. the ability to activate extrachromosomal HIV-1 intermediates in HIV-1 infected quiescent cells at various times after infection). These results strongly suggest that the absence of AIDS-like disease in chimpanzees cannot be correlated with defects in early events of the HIV-1 replicative cycle.     

Fuel composition and secondary organic aerosol formation: gas-turbine exhaust and alternative aviation fuels

A series of smog chamber experiments were performed to investigate the effects of fuel composition on secondary particulate matter (PM) formation from dilute exhaust from a T63 gas-turbine engine. Tests were performed at idle and cruise loads with the engine fueled on conventional military jet fuel (JP-8), Fischer-Tropsch synthetic jet fuel (FT), and a 50/50 blend of the two fuels. Emissions were sampled into a portable smog chamber and exposed to sunlight or artificial UV light to initiate photo-oxidation. Similar to previous studies, neat FT fuel and a 50/50 FT/JP-8 blend reduced the primary particulate matter emissions compared to neat JP-8. After only one hour of photo-oxidation at typical atmospheric OH levels, the secondary PM production in dilute exhaust exceeded primary PM emissions, except when operating the engine at high load on FT fuel. Therefore, accounting for secondary PM production should be considered when assessing the contribution of gas-turbine engine emissions to ambient PM levels. FT fuel substantially reduced secondary PM formation in dilute exhaust compared to neat JP-8 at both idle and cruise loads. At idle load, the secondary PM formation was reduced by a factor of 20 with the use of neat FT fuel, and a factor of 2 with the use of the blend fuel. At cruise load, the use of FT fuel resulted in no measured formation of secondary PM. In every experiment, the secondary PM was dominated by organics with minor contributions from sulfate when the engine was operated on JP-8 fuel. At both loads, FT fuel produces less secondary organic aerosol than JP-8 because of differences in the composition of the fuels and the resultant emissions. This work indicates that fuel reformulation may be a viable strategy to reduce the contribution of emissions from combustion systems to secondary organic aerosol production and ultimately ambient PM levels.     

Hafnium binary alloys from experiments and first principles

Despite the increasing importance of hafnium in numerous technological applications, experimental and computational data on its binary alloys is sparse. In particular, data is scant on those binary systems believed to be phase-separating. We performed a comprehensive study of hafnium binary systems with alkali metals, alkaline earths, transition metals and metals, using high-throughput first-principles calculations. These computations predict novel unsuspected compounds in six binary systems previously believed to be phase-separating. They also predict a few unreported compounds in additional systems and indicate that some reported compounds may actually be unstable at low temperatures. We report the results for the following systems: AgHf, AlHf, AuHf, BaHf, BeHf, BiHf, CaHf, CdHf, CoHf, CrHf, CuHf, FeHf, GaHf, HfHg, HfIn, HfIr, HfK, HfLa, HfLi, HfMg, HfMn, HfMo,HfNa, HfNb, HfNi, HfOs, HfPb, HfPd, HfPt, HfRe, HfRh, HfRu, HfSc, HfSn, HfSr, HfTa, HfTc, HfTi, HfTl, HfV, HfW, HfY, HfZn and HfZr ( = systems in which the ab initio method predicts that no compounds are stable).     

Role of the RCII-D1 protein in the reversible association of the oxygen-evolving complex proteins with the lumenal side of photosystem II

The nuclear-encoded proteins of the oxygen-evolving complex (OEC) of photosystem II are bound on the lumenal side of the thylakoid membrane and stabilize the manganese ion cluster forming the photosystem II electron donor side. The OEC proteins are released from their binding site(s) following light-induced degradation of reaction center II (RCII)-D1 protein in Chlamydomonas reinhardtii. The kinetics of OEC proteins release correlates with that of RCII-D1 protein degradation. Only a limited amount of RCII-D2 protein is degraded during the process, and no loss of the core proteins CP43 and CP47 is detected. The release of the OEC proteins is prevented when the photoinactivated RCII-D1 protein degradation is retarded by addition of 3-(3,5-dichlorophenyl)-1,1-dimethylurea or by a high PQH2/PQ ratio prevailing in membranes of the plastocyanin-deficient mutant Ac208. The released proteins are not degraded but persist in the thylakoid lumen for up to 8 h and reassociate with photosystem II when new D1 protein is synthesized in cells exposed to low light, thus allowing recovery of photosystem II function. Reassociation also occurs following D1 protein synthesis in darkness when RCII activity is only partially recovered. These results indicate that (i) the D1 protein participates in the formation of the lumenal OEC proteins binding site(s) and (ii) the photoinactivation of RCII-D1 protein does not alter the conformation of the donor side of photosystem II required for the binding of the OEC proteins.     

Using AVL trees for fault-tolerant group key management

In this paper we describe an efficient algorithm for the management of group keys for group communication systems. Our algorithm is based on the notion of key graphs, previously used for managing keys in large Internet-protocol multicast groups. The standard protocol requires a centralized key server that has knowledge of the full key graph. Our protocol does not delegate this role to any one process. Rather, members enlist in a collaborative effort to create the group key graph. The key graph contains n keys, of which each member learns log₂n of them. We show how to balance the key graph, a result that is applicable to the centralized protocol. We also show how to optimize our distributed protocol, and provide a performance study of its capabilities. Published online: 26 October 2001     

Increased levels of circulating intercellular adhesion molecule 1 in the sera of patients with rheumatoid arthritis

OBJECTIVE: We sought to assess whether circulating levels of intercellular adhesion molecule 1 (ICAM-1) in patients with rheumatoid arthritis (RA) are elevated and correlate with clinical measures of disease activity and whether this ICAM-1 originates from the synovium. METHODS: Circulating ICAM-1 (cICAM-1) levels were determined by sandwich enzyme-linked immunosorbent assay of serum from 61 RA, 18 osteoarthritis (OA), and 11 inflammatory arthritis (IA) patients. In addition, paired serum and synovial fluid samples were collected from 17 RA, 9 OA, and 4 IA patients. The stability of cICAM-1 was assessed by overnight incubation at 37 degrees C. Finally, the potential degradative effects of synovial fluid proteases were assessed by incubation of recombinant soluble ICAM-1 with patient synovial fluid. RESULTS: RA sera contained significantly greater (P < 0.001) levels of cICAM-1 compared with RA synovial fluid and compared with sera or synovial fluid from the OA and IA patients. Circulating ICAM-1 levels were unaffected by overnight incubation at 37 degrees C and were unaffected by exposure to RA, OA, or IA synovial fluid. Serum levels of cICAM-1 demonstrated a weak, but significant (P < 0.05) correlation with the joint score and erythrocyte sedimentation rate in 25 RA patients treated with nonsteroidal antiinflammatory drugs. CONCLUSION: The greatest elevations of cICAM-1 were seen in RA patient sera. In both RA and OA, synovial fluid cICAM-1 levels were consistently lower than serum levels, suggesting that cICAM-1 did not originate in the synovium. Because the production of cICAM-1 can be increased by cytokines (e.g., interleukin-1, tumor necrosis factor alpha), elevated levels of circulating ICAM-1 in RA may be reflective of systemic exposure to elevated cytokine levels.     

Approximate Pattern Matching with the <Emphasis Type="Italic">L</Emphasis><Subscript>1</Subscript>, <Emphasis Type="Italic">L</Emphasis><Subscript>2</Subscript> and <Emphasis Type="Italic">L</Emphasis><Subscript>∞</Subscript> Metrics

Given an alphabet Σ={1,2,…,|Σ|} text string T∈Σ ⁿ and a pattern string P∈Σ ^m , for each i=1,2,…,n−m+1 define L _p (i) as the p-norm distance when the pattern is aligned below the text and starts at position i of the text. The problem of pattern matching with L _p distance is to compute L _p (i) for every i=1,2,…,n−m+1. We discuss the problem for d=1,2,∞. First, in the case of L ₁ matching (pattern matching with an L ₁ distance) we show a reduction of the string matching with mismatches problem to the L ₁ matching problem and we present an algorithm that approximates the L ₁ matching up to a factor of 1+ε, which has an O(\frac1e²nlogmlog|S|)O(\frac{1}{\varepsilon^{2}}n\log m\log|\Sigma|) run time. Then, the L ₂ matching problem (pattern matching with an L ₂ distance) is solved with a simple O(nlog m) time algorithm. Finally, we provide an algorithm that approximates the L _∞ matching up to a factor of 1+ε with a run time of O(\frac1enlogmlog|S|)O(\frac{1}{\varepsilon}n\log m\log|\Sigma|) . We also generalize the problem of String Matching with mismatches to have weighted mismatches and present an O(nlog ⁴ m) algorithm that approximates the results of this problem up to a factor of O(log m) in the case that the weight function is a metric.     

Curvature-based perceptual singularities and texture saliency with early vision mechanisms

Recent work has shown that salient perceptual singularities occur in visual textures even in the absence of feature gradients. In smoothly varying orientation-defined textures, these striking non-smooth percepts can be predicted from two texture curvatures, one tangential and one normal [Proc. Natl. Acad. Sci. USA103, 15704 (2006)]. We address the issue of detecting these perceptual singularities in a biologically plausible manner and present three different models to compute the tangential and normal curvatures using early cortical mechanisms. The first model relies on the response summation of similarly scaled even-symmetric simple cells at different positions by utilizing intercolumnar interactions in the primary visual cortex (V1). The second model is based on intracolumnar interactions in a two-layer mechanism of simple cells having the same orientation tuning but significantly different scales. Our third model uses a three-layer circuit in which both even-symmetric and odd-symmetric receptive fields (RFs) are used to compute all possible directional derivatives of the dominant orientation, from which the tangential and normal curvatures at each spatial position are selected using nonlinear shunting inhibition. We show experimental results of all three models, we outline an extension to oriented textures with multiple dominant orientations at each point, and we discuss how our results may be relevant to the processing of general textures.