Determinants of human immunodeficiency virus type 1 envelope glycoprotein activation by soluble CD4 and monoclonal antibodies

Infection by some human immunodeficiency virus type 1 (HIV-1) isolates is enhanced by the binding of subneutralizing concentrations of soluble receptor, soluble CD4 (sCD4), or monoclonal antibodies directed against the viral envelope glycoproteins. In this work, we studied the abilities of different antibodies to mediate activation of the envelope glycoproteins of a primary HIV-1 isolate, YU2, and identified the regions of gp120 envelope glycoprotein contributing to activation. Binding of antibodies to a variety of epitopes on gp120, including the CD4 binding site, the third variable (V3) loop, and CD4-induced epitopes, enhanced the entry of viruses containing YU2 envelope glycoproteins. Fab fragments of antibodies directed against either the CD4 binding site or V3 loop also activated YU2 virus infection. The activation phenotype was conferred on the envelope glycoproteins of a laboratory-adapted HIV-1 isolate (HXBc2) by replacing the gp120 V3 loop or V1/V2 and V3 loops with those of the YU2 virus. Infection by the YU2 virus in the presence of activating antibodies remained inhibitable by macrophage inhibitory protein 1beta, indicating dependence on the CCR5 coreceptor on the target cells. Thus, antibody enhancement of YU2 entry involves neither Fc receptor binding nor envelope glycoprotein cross-linking, is determined by the same variable loops that dictate enhancement by sCD4, and probably proceeds by a process fundamentally similar to the receptor-activated virus entry pathway.     

Inhibition of L- and P-selectin by a rationally synthesized novel core 2-like branched structure containing GalNAc-Lewisx and Neu5Acalpha2-3Galbeta1-3GalNAc sequences

The selectins interact in important normal and pathological situations with certain sialylated, fucosylated glycoconjugate ligands containing sialyl Lewisx(Neu5Acalpha2-3Galbeta1-4(Fucalpha1-3)GlcN Ac). Much effort has gone into the synthesis of sialylated and sulfated Lewisxanalogs as competitive ligands for the selectins. Since the natural selectin ligands GlyCAM-1 and PSGL-1 carry sialyl Lewisxas part of a branched Core 2 O-linked structure, we recently synthesized Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-6(SE-3Galbeta1++ +-3)GalNAc1alphaOMe and found it to be a moderately superior ligand for L and P-selectin (Koenig et al. , Glycobiology 7, 79-93, 1997). Other studies have shown that sulfate esters can replace sialic acid in some selectin ligands (Yeun et al. , Biochemistry, 31, 9126-9131, 1992; Imai et al. , Nature, 361, 555, 1993). Based upon these observations, we hypothesized that Neu5Acalpha2-3Galbeta1-3GalNAc might have the capability of interacting with L- and P-selectin. To examine this hypothesis, we synthesized Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-6(Neu5Acalpha2++ +-3Galbeta1-3)-GalNAc alpha1-OB, which was found to be 2- to 3-fold better than sialyl Lexfor P and L selectin, respectively. We also report the synthesis of an unusual structure GalNAcbeta1-4(Fucalpha1- 3)GlcNAcbeta1-OMe (GalNAc-Lewisx-O-methyl glycoside), which also proved to be a better inhibitor of L- and P-selectin than sialyl Lewisx-OMe. Combining this with our knowledge of Core 2 branched structures, we have synthesized a molecule that is 5- to 6-fold better at inhibiting L- and P-selectin than sialyl Lewisx-OMe, By contrast to unbranched structures, substitution of a sulfate ester group for a sialic acid residue in such a molecule resulted in a considerable loss of inhibition ability. Thus, the combination of a sialic acid residue on the primary (beta1-3) arm, and a modified Lexunit on the branched (beta1-6) arm on an O-linked Core 2 structure generated a monovalent synthetic oliogosaccharide inhibitor superior to SLexfor both L- and P-selectin.     

A finite element analysis of factors influencing total hip dislocation

A previously validated three-dimensional finite element model was used to study how several total hip component design and surgical placement variables contribute to resisting the propensity for posterior dislocation in the case of leg crossing in an erectly seated position. The computational formulation incorporated treatments of polyethylene material nonlinearity and large displacement sliding contact. The primary outcome measures were the peak intrinsic moment developed to resist dislocation, and the ranges of motion before neck on lip impingement and before frank dislocation. Modifications of the acetabular linear design (chamfer bevel angle, lip breadth, head center inset) involved trading off improved peak resisting moment for compromised range of motion and vice versa. Increases of head size led to substantial improvements in peak resisting moment, but if the head to neck diameter ratio was held constant, had almost no influence on the component range of motion. For the leg crossing event studied, increased component anteversion, and even more so increased tilt (less net abduction), achieved improvements in range of motion and in peak resisting moment, but these changes imply diminished resistance to anterior dislocation from extension and adduction motion inputs.     

Antigenic and genomic diversity of human rotavirus VP4 in two consecutive epidemic seasons in Mexico

In the present investigation we characterized the antigenic diversity of the VP4 and VP7 proteins in 309 and 261 human rotavirus strains isolated during two consecutive epidemic seasons, respectively, in three different regions of Mexico. G3 was found to be the prevalent VP7 serotype during the first year, being superseded by serotype G1 strains during the second season. To antigenically characterize the VP4 protein of the strains isolated, we used five neutralizing monoclonal antibodies (MAbs) which showed specificity for VP4 serotypes P1A, P1B, and P2 in earlier studies. Eight different patterns of reactivity with these MAbs were found, and the prevalence of three of these patterns varied from one season to the next. The P genotype of a subset of 52 samples was determined by PCR. Among the strains characterized as genotype P[4] and P[8] there were three and five different VP4 MAb reactivity patterns, respectively, indicating that the diversity of neutralization epitopes in VP4 is greater than that previously appreciated by the genomic typing methods.     

Family socialization and the IQ test performance of traditionally and transracially adopted Black children.

Compared mean IQ test performance and response styles to cognitive demands of the Wechsler Intelligence Scale for Children (WISC) among 23 Black children (aged 7–10 yrs) who had been adopted by middle-class White families (i.e., transracially adopted) and 23 age-matched Black children who had been adopted by middle-class Black families (i.e., traditionally adopted). Findings indicate that while the traditionally adopted Ss received normal IQ scores, transracially adopted Ss showed nearly 1 standard deviation Full-Scale Scoring advantage over them. A multiple analysis of variance (MANOVA) indicated significant differences in the styles of responding to test demands demonstrated by the 2 groups of Ss, which were conceptualized as contributors to the difference in average test score observed between them. Multivariate analysis of the helping behaviors adopted mothers exhibited when helping their children solve a difficult cognitive task revealed significant differences between Black and White mothers, which were conceptualized as culturally determined. White adopted mothers tended to release tension by joking, grinning, and laughing, while Black adoptive mothers more often released tension in less positive ways such as scowling, coughing, and frowning. White adoptive mothers were more likely than Black adoptive mothers to provide positive evaluations of their children's problem solving efforts. It is concluded that the ethnicity of the rearing environment exerts a significant influence on children's styles of responding to standardized intelligence tests and on their test achievement. (38 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Influence of potential on the friction and wear of mild steel in a model aqueous lubricant

An electrochemical cell has been designed, based on a Cameron-Plint friction machine, which enables measurement of friction and wear under conditions of controlled potential. For mild steel in a pH 9 aqueous solution of sodium octanoate, varying the potential of the steel over the range –1 to + 1 V vs SHE produced three distinct friction-wear regimes: high friction/low wear, low friction/high wear, and low friction/low wear. These regimes were ascribed to potential dependent changes in the coverage and stability of a lubricating octanoate film on the surface of the steel. Increasing the contact stress amplified the effect of potential on wear, and confirmed that the surface film retained its lubricity at contact stresses capable of causing plastic deformation of the steel.     

Preliminary report of the activity of docetaxel in advanced or recurrent squamous cell cancer of the cervix

Eighteen patients with squamous cell cancer of the cervix were treated with i.v. docetaxel 100 mg/m2 over 1 h every 21 days. No patient received prior chemotherapy, except as a radiation sensitizer. Median age was 42 years (range 30-58) and Zubrod performance status was 1 (0-2). Ten (59%) patients had prior surgery and 11 (65%) had prior radiation therapy. Sixteen patients were evaluable for response. Two patients had a partial response (13%; 95% CI 0-32%) and eight (50%; 95% CI 23-77%) had stable disease. Dose reduction to 75 mg/m2 was required in 10 patients and to 55 mg/m2 in one patient. Granulocytopenia was the major hematopoietic toxicity (31% grade 3 and 44% grade 4). Docetaxel is active in patients with squamous cell cancer of the cervix and may be tolerable at this dose schedule.     

Theory and application of radiation boundary operators

A succinct unified review is provided of the theory of radiation boundary operators. With the recent introduction of the on-surface radiation condition (OSRC) method and the continued growth of finite-difference and finite-element techniques for modeling electromagnetic wave scattering problems, the understanding and use of radiation boundary operators has become increasingly important. Results are presented to illustrate the application of radiation boundary operators in both these areas. Recent OSRC results include analysis of the scattering behavior of both electrically small and large cylinders, a reactively loaded acoustic sphere, and a simple reentrant duct. Radiation boundary operator results include the demonstration of the effectiveness of higher-order operators in truncating finite-difference time-domain grids     

Dynamic animation: Interaction and control

The use of the dynamics equations of motion offers a means of constraining animated motion to physical reality.Dynamic simulation treats objects as masses acting under the influence of forces and torques. Motion is derived by solving the dynamics equations of motion, rather than being exactly specified by an animator. Though dynamic simulation can create complex motion with less user input than strictlykinematic (Position-based) methods, it is also computationally expensive and difficult to control. The equations of motion are, in themselves, not difficult to program, but adding constraints for controlled motion is complex. The control issues are now being further explored. These include: low-level control issues such as collision response, elasticity, friction, joint limits, damping, and general motion constraints; user-interface issues such as interface design, menu options, and integration into a general animation system; and high-level control issues such as the automatic generation of coordinated, goal-directed motion. This paper concentrates on the first two of these areas, and describes an animation system,Kaya, developed to explore them.This work was supported by National Science Foundation grant number CCR-8606519