Bedrock fracture systems facilitate weathering, allowing fresh mineral surfaces to interact with corrosive waters and biota from Earth's surface, while simultaneously promoting drainage of chemically equilibrated fluids. We show that topographic perturbations to regional stress fields explain bedrock fracture distributions, as revealed by seismic velocity and electrical resistivity surveys from three landscapes. The base of the fracture-rich zone mirrors surface topography where the ratio of horizontal compressive tectonic stresses to near-surface gravitational stresses is relatively large, and it parallels the surface topography where the ratio is relatively small. Three-dimensional stress calculations predict these results, suggesting that tectonic stresses interact with topography to influence bedrock disaggregation, groundwater flow, chemical weathering, and the depth of the "critical zone" in which many biogeochemical processes occur.

The zoster vaccine induced a significant increase in VZV-CMI and VZV antibody. The magnitude and duration of the boost in VZV-CMI in vaccine recipients and the relationship of this boost to age paralleled the clinical effects of the vaccine observed during the efficacy trial. These findings support the hypothesis that boosting VZV-CMI protects older adults against herpes zoster and postherpetic neuralgia.

Higher VZV CMI at HZ onset was associated with reduced HZ severity and less postherpetic neuralgia. Higher antibody titers were associated with increased HZ severity and occurrence of postherpetic neuralgia. HZ and zoster vaccine generated comparable VZV CMI.

Observing the critical zone (CZ) below the top few meters of readily excavated soil is challenging yet crucial to understanding Earth surface processes. Near‐surface geophysical methods can overcome this challenge by imaging the CZ in three dimensions (3‐D) over hundreds of meters, thus revealing lateral heterogeneity in subsurface properties across scales relevant to understanding hillslope erosion, weathering, and biogeochemical cycling. We imaged the CZ under a soil‐mantled ridge developed in granitic terrain of the Laramie Range, Wyoming, using data from five boreholes and a 3‐D volume (970 by 600 by 80 m) of seismic velocities generated by ordinary kriging of 25 two‐dimensional seismic refraction transects. The observed CZ structure under the ridge broadly matches predictions of two recently proposed hypotheses: the uppermost surface of weathered bedrock is consistent with subsurface weathering driven by bedrock drainage and subsurface topography defining the top of unweathered protolith is consistent with fracturing predicted from topographic and regional stresses. In contrast, differences in slope aspect along the ridge are too subtle to explain observed variations in regolith structure. Our observations suggest that multiple processes, each of which may dominate at different depths, work in concert to regulate deep CZ structure.

Cell-mediated immunity appears to be critical for the prevention and control of varicella-zoster virus (VZV) infection and complications arising from zoster. Current assays of VZV-specific cell-mediated immunity are cumbersome or lack sensitivity. We have developed a gamma interferon ELISPOT assay that provides a direct measure of the number of T cells secreting a cytokine following stimulation with antigen. This assay is extremely sensitive and specific, with the ability to detect gamma interferon spot-forming cells (SFC) in the range of 10 to 1,000 SFC per million peripheral blood mononuclear cells (PBMCs). This assay has been validated by demonstrating the following: (i) the response detected is mediated almost entirely by CD4 ؉ T cells, (ii) ELISPOT responses from fresh-frozen PBMCs are equivalent to those from freshly isolated cells, (iii) frozen PBMCs can be shipped on dry ice for up to 48 h without loss of activity, (iv) frozen PBMC samples can be stored in liquid nitrogen over long periods (>22 months) without any significant change in response, and (v) the numbers of ELISPOTs counted using a computer-based imaging system are equivalent to those counted by humans but have lower variability. The ability to use frozen cells is facilitated by the use of a recombinant nuclease (Benzonase) that can prevent cell clumping when samples are thawed. Frozen PBMC samples can be cycled through multiple changes in storage between liquid nitrogen and dry ice without any change in response being detected. This facilitates collection of samples at one site and testing performed at a remote location. This VZV ELISPOT assay provides a new versatile tool for monitoring cellular immune responses either during a herpes zoster disease outbreak or following vaccination.The importance of cellular immunity in prevention and control of varicella-zoster virus (VZV) infection has been well documented (1-4, 10, 12). Components of cellular immunity for memory responses following both natural infection and vaccination have been described. This includes detection of both CD4ϩ (helper)-and CD8 ϩ (cytotoxic)-T-cell responses specific to numerous VZV antigens (7, 11, 13-19, 25, 28, 30, 33, 36-38). Lymphoproliferation assays are not quantitative and measure only CD4 T-cell responses. The limiting-dilution format responder cell frequency (RCF) assay permits some quantitation of response yet is very cumbersome. The cytotoxic-Tcell (CTL) assays can measure CD8 T-cell responses but are also quantitative only in the cumbersome format of limitingdilution analysis. Intracellular cytokine staining can be used for both CD4 and CD8 T-cell responses, but high background signals can limit detection of low-frequency responses. All of these methods utilize freshly isolated cells for optimum detection of signal. There is a need for new quantitative assays to assess these cellular immune responses both during the course of infection and after vaccination. ELISPOT assays for the detection of cytokine-producing T cells are becoming more widely adopted for t...

Objective-To evaluate the expression of biomarkers of implantation, Glycodelin A (GdA), Osteopontin (OPN), Lysophosphatidic acid receptor 3 (LPA3), and HOXA10, in eutopic endometrium of women with and without endometriosis.Design-Prospective observational study. Setting-Clinical Research Center.Patient(s)-Twenty-four women with endometriosis and 23 healthy volunteers of similar age. Intervention(s)-Secretory phase endometrial biopsy.Main Outcome Measure(s)-Expression of immunohistochemical staining intensity and localization of GdA, OPN, LPA3 and HOXA10 in eutopic endometrium. Result(s)-EndometrialGdA expression was significantly reduced in patients after cycle day 22. The endometrium from women with endometriosis also showed decreased expression of OPN in the late secretory phase and LPA3 and HOXA10 expression in the mid-and late secretory phases. Conclusion(s)-The decreased expression of these four biomarkers of implantation may indicate impaired endometrial receptivity in endometriosis patients, providing one explanation for the subfertility observed even in women with few pelvic implants. As many of these markers are progesterone-dependent, these findings suggest the possibility of reduced endometrial progesterone action in this population.

To determine if measuring skeletal status at the calcaneus is a potentially valuable technique for diagnosing osteoporosis, we examined five calcaneal assessment techniques in 53 young normal women and 108 postmenopausal women with osteoporosis and compared these measurements to dual-energy X-ray absorptiometry (DEXA) at the calcaneus, hip, and spine. The five instruments, including single-energy X-ray absorptiometry (SEXA) and four quantitative ultrasound (QUS) instruments, were evaluated for precision, ability to discriminate osteoporotic from young normal subjects, and correlation to the other instruments. The coefficient of variation (%CV) for instrument, positioning, interobserver, and short-term precision of the five calcaneal instruments ranged from 1.34 -7.76%, 1.63-7.00%, 1.84 -9.44%, and 1.99 -7.04%, respectively. The %CVs for positioning, interobserver, and short-term precision were similar for calcaneal DEXA, calcaneal SEXA, and stiffness (as measured by Achilles). The %CVs for instrument precision were similar between calcaneal DEXA and SEXA. The ability of the five calcaneal instruments to discriminate osteoporotic from young normal subjects was similar based on the analysis of area under the receiver operating characteristic curves (range 0.88 -0.93) and equivalent to DEXA of the calcaneus and hip (0.88 -0.93). The correlations between the measurements of five calcaneal instruments were strong (0.80 r 0.91, p < 0.001). These data suggest that although the precision is variable, the calcaneal QUS and SEXA instruments can discriminate between osteoporotic patients and young normal controls and appear to be a useful technique for assessment of osteoporosis. (J Bone Miner Res 1997;12:1303-1313)

An effective vaccine for HIV is likely to require induction of T-cell-mediated immune responses, and the interferon-gamma (IFNgamma) enzyme-linked immunospot (ELISPOT) assay has become the most commonly used assay for measuring these responses in vaccine trials. We optimized and validated the HIV ELISPOT assay using an empirical method to establish positivity criteria that results in a < or =1% false-positive rate. Using this assay, we detected a broad range of HIV-specific ELISPOT responses to peptide pools of overlapping 20mers, 15mers, or 9mers in study volunteers receiving DNA- or adenovirus vector-based HIV vaccines and in HIV-seropositive donors. We found that 15mers generally had higher response magnitudes than 20mers and lower false-positive rates than 9mers. These studies show that our validated ELISPOT assay using 15mer peptide pools and the positivity criteria of > or =55 spots per 10(6) cells and > or =4-fold over mock (negative control) is a sensitive and specific assay for the detection of HIV vaccine-induced cell-mediated immunity.