Structure, expression and divergence of T-cell receptor beta-chain variable regions

Analysis of three new T-cell receptor beta-chain variable regions together with those in the literature indicates that they have both remarkable similarities and differences with those of immunoglobulin. Less than 10 V regions appear to predominate in the thymus. V beta sequences are much more heterogeneous at the amino acid level than are immunoglobulin V regions and they appear to diverge between species much more quickly, apparently the result of additional hypervariable regions. Three of these putative new hypervariable regions lie outside of the classical immunoglobulin binding site, an indication that important interactions may be occurring in these regions with polymorphic MHC determinants.     

Imaging the effects of individual zinc impurity atoms on superconductivity in Bi2Sr2CaCu2O8+delta

Although the crystal structures of the copper oxide high-temperature superconductors are complex and diverse, they all contain some crystal planes consisting of only copper and oxygen atoms in a square lattice: superconductivity is believed to originate from strongly interacting electrons in these CuO2 planes. Substituting a single impurity atom for a copper atom strongly perturbs the surrounding electronic environment and can therefore be used to probe high-temperature superconductivity at the atomic scale. This has provided the motivation for several experimental and theoretical studies. Scanning tunnelling microscopy (STM) is an ideal technique for the study of such effects at the atomic scale, as it has been used very successfully to probe individual impurity atoms in several other systems. Here we use STM to investigate the effects of individual zinc impurity atoms in the high-temperature superconductor Bi2Sr2CaCu2O8+delta. We find intense quasiparticle scattering resonances at the Zn sites, coincident with strong suppression of superconductivity within approximately 15 A of the scattering sites. Imaging of the spatial dependence of the quasiparticle density of states in the vicinity of the impurity atoms reveals the long-sought four-fold symmetric quasiparticle 'cloud' aligned with the nodes of the d-wave superconducting gap which is believed to characterize superconductivity in these materials.     

Interplay of magnetism and high-Tc superconductivity at individual Ni impurity atoms in Bi2Sr2CaCu2O8+delta.

Magnetic interactions and magnetic impurities are destructive to superconductivity in conventional superconductors. By contrast, in some unconventional macroscopic quantum systems (such as superfluid 3He and superconducting UGe2), the superconductivity (or superfluidity) is actually mediated by magnetic interactions. A magnetic mechanism has also been proposed for high-temperature superconductivity. Within this context, the fact that magnetic Ni impurity atoms have a weaker effect on superconductivity than non-magnetic Zn atoms in the high-Tc superconductors has been put forward as evidence supporting a magnetic mechanism. Here we use scanning tunnelling microscopy to determine directly the influence of individual Ni atoms on the local electronic structure of Bi2Sr2CaCu2O8+delta. At each Ni site we observe two d-wave impurity states of apparently opposite spin polarization, whose existence indicates that Ni retains a magnetic moment in the superconducting state. However, analysis of the impurity-state energies shows that quasiparticle scattering at Ni is predominantly non-magnetic. Furthermore, we show that the superconducting energy gap and correlations are unimpaired at Ni. This is in strong contrast to the effects of non-magnetic Zn impurities, which locally destroy superconductivity. These results are consistent with predictions for impurity atom phenomena derived from a magnetic mechanism.     

A radiation hybrid map of the rat genome containing 5,255 markers.

A whole-genome radiation hybrid (RH) panel was used to construct a high-resolution map of the rat genome based on microsatellite and gene markers. These include 3,019 new microsatellite markers described here for the first time and 1,714 microsatellite markers with known genetic locations, allowing comparison and integration of maps from different sources. A robust RH framework map containing 1,030 positions ordered with odds of at least 1,000:1 has been defined as a tool for mapping these markers, and for future RH mapping in the rat. More than 500 genes which have been mapped in mouse and/or human were localized with respect to the rat RH framework, allowing the construction of detailed rat-mouse and rat-human comparative maps and illustrating the power of the RH approach for comparative mapping.     

HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus

Early treatment of acute HIV-1 infection followed by treatment interruptions has shown promise for enhancing immune control of infection. A subsequent loss of control, however, allows the correlates of protective immunity to be assessed. Here we show that sudden breakthrough of plasma viraemia occurred after prolonged immune containment in an individual infected with HIV-1 at a time when 25 distinct CD8+ T-cell epitopes in the viral proteins Gag, RT, Integrase, Env, Nef, Vpr, Vif and Rev were being targeted. Sequencing of the virus in plasma and cells showed that superinfection with a second clade-B virus was coincident with the loss of immune control. This sudden increase in viraemia was associated with a decline in half of the CD8+ T-cell responses. The declining CD8+ T-cell responses were coupled with sequence changes relative to the initial virus that resulted in impaired recognition. Our data show that HIV-1 superinfection can occur in the setting of a strong and broadly directed virus-specific CD8+ T-cell response. The lack of cross-protective immunity for closely related HIV-1 strains, despite persistent recognition of multiple CD8 epitopes, has important implications for public health and vaccine development.     

Age and peritoneal fluid cellular distribution in women 20-40 years of age.

Cytologic aspiration specimens of peritoneal fluid revealed that mesothelial cell proportions were significantly reduced 19.2% in women between 26 and 35 years of age. Possibly, mesothelial cell renewal was decreased in women of the older age groups.     

Comparison of vegetation patterns resulting from bulldozing and two-way chaining on a Utah pinyon-juniper big game range

Two adjacent mechanically treated pinyon-juniper ( Pinus spp. and Juniperus spp.) big game winter range sites in central Utah were sampled in 1981 to estimate vegetational differences and tree mortality from the two treatments. One site was treated by selectively bulldozing in 1957 and the other was double chained in 1965. Both treatments significantly reduced tree and litter cover, whereas significant increases were found for native grasses and shrubs compared to a nearby untreated site. Juniper cover for the untreated site was 35.5% compared to only 1.4% for the bulldozed area and 4.1% for the two-way chained area. Browse species densities were increased by the mechanical treatments. The use of different mechanical treatments on separate smaller portions of critical areas of big game winter range would help provide: (1) for both long-term and short-term use of a critical wintering area, (2) greater overall productivity and carrying capacity, and (3) greater diversity by creating more edge effect between the differently treated and untreated areas.     

Chromatin-remodeling complex specificity and embryonic vascular development

Vascular development is a dynamic process that relies on the coordinated expression of numerous genes, but the factors that regulate gene expression during blood vessel development are not well defined. ATP-dependent chromatin-remodeling complexes are gaining attention for their specific temporal and spatial effects on gene expression during vascular development. Genetic mutations in chromatin-remodeling complex subunits are revealing roles for the complexes in vascular signaling pathways at discrete developmental time points. Phenotypic analysis of these models at various stages of vascular development will continue to expand our understanding of how chromatin remodeling impacts new blood vessel growth. Such research could also provide novel therapeutic targets for the treatment of vascular pathologies.     

The Mathematics of the Area Law: Kepler's Successful Proof in Epitome Astronomiae Copernicanae (1621)

Epitome V (1621), and consisted of matching an element of area to an element of time, where each was mathematically determined. His treatment of the area depended solely on the geometry of Euclid's Elements, involving only straight-line and circle propositions – so we have to account for his deliberate avoidance of the sophisticated conic-geometry associated with Apollonius. We show also how his proof could have been made watertight according to modern standards, using methods that lay entirely within his power. The greatest innovation, however, occurred in Kepler's fresh formulation of the measure of time. We trace this concept in relation to early astronomy and conclude that Kepler's treatment unexpectedly entailed the assumption that time varied nonuniformly; meanwhile, a geometrical measure provided the independent variable. Even more surprisingly, this approach turns out to be entirely sound when assessed in present-day terms. Kepler himself attributed the cause of the motion of a single planet around the Sun to a set of `physical' suppositions which represented his religious as well as his Copernican convictions; and we have pared to a minimum – down to four – the number he actually required to achieve this. In the Appendix we use modern mathematics to emphasize the simplicity, both geometrical and kinematical, that objectively characterizes the Sun-focused ellipse as an orbit. Meanwhile we highlight the subjective simplicity of Kepler's own techniques (most of them extremely traditional, some newly created). These two approaches complement each other to account for his success. (Received April 19, 2002) Published online April 2, 2003 Communicated by N. M. Swerdlow