Active Transport of Peptides Across the Intact Human Tympanic Membrane.

We previously identified peptides that are actively transported across the intact tympanic membrane (TM) of rats with infected middle ears. To assess the possibility that this transport would also occur across the human TM, we first developed and validated an assay to evaluate transport in vitro using fragments of the TM. Using this assay, we demonstrated the ability of phage bearing a TM-transiting peptide to cross freshly dissected TM fragments from infected rats or from uninfected rats, guinea pigs and rabbits. We then evaluated transport across fragments of the human TM that were discarded during otologic surgery. Human trans-TM transport was similar to that seen in the animal species. Finally, we found that free peptide, unconnected to phage, was transported across the TM at a rate comparable to that seen for peptide-bearing phage. These studies provide evidence supporting the concept of peptide-mediated drug delivery across the intact TM and into the middle ears of patients

Evidence for chemical equilibration at RHIC

This contribution focuses on the results of statistical model calculations at RHIC energies, including recently available experimental data. Previous calculations of particle yield ratios showed good agreement with measurements at SPS and lower energies, suggesting that the composite system possesses a high degree of chemical equilibrium at freeze-out. The effect of feeddown contamination on the model parameters is discussed, and the sensitivity of individual ratios to the model parameters ($T$, $\mu_B$) is illustrated.Comment: Talk presented at Strange Quarks in Matter 2001, Frankfurt, September 24-29, 2001. Proceedings to be published by J. Phys. G. 8 pages with 4 figure

Analysis of the Human Mucosal Response to Cholera Reveals Sustained Activation of Innate Immune Signaling Pathways

To better understand the innate immune response to Vibrio cholerae infection, we tracked gene expression in the duodenal mucosa of 11 Bangladeshi adults with cholera, using biopsy specimens obtained immediately after rehydration and 30 and 180 days later. We identified differentially expressed genes and performed an analysis to predict differentially regulated pathways and upstream regulators. During acute cholera, there was a broad increase in the expression of genes associated with innate immunity, including activation of the NF-kappaB, mitogen-activated protein kinase (MAPK), and Toll-like receptor (TLR)-mediated signaling pathways, which, unexpectedly, persisted even 30 days after infection. Focusing on early differences in gene expression, we identified 37 genes that were differentially expressed on days 2 and 30 across the 11 participants. These genes included the endosomal Toll-like receptor gene TLR8, which was expressed in lamina propria cells. Underscoring a potential role for endosomal TLR-mediated signaling in vivo, our pathway analysis found that interferon regulatory factor 7 and beta 1 and alpha 2 interferons were among the top upstream regulators activated during cholera. Among the innate immune effectors, we found that the gene for DUOX2, an NADPH oxidase involved in the maintenance of intestinal homeostasis, was upregulated in intestinal epithelial cells during cholera. Notably, the observed increases in DUOX2 and TLR8 expression were also modeled in vitro when Caco-2 or THP-1 cells, respectively, were stimulated with live V. cholerae but not with heat-killed organisms or cholera toxin alone. These previously unidentified features of the innate immune response to V. cholerae extend our understanding of the mucosal immune signaling pathways and effectors activated in vivo following cholera

Analysis of the Human Mucosal Response to Cholera Reveals Sustained Activation of Innate Immune Signaling Pathways

To better understand the innate immune response to Vibrio cholerae infection, we tracked gene expression in the duodenal mucosa of 11 Bangladeshi adults with cholera, using biopsy specimens obtained immediately after rehydration and 30 and 180 days later. We identified differentially expressed genes and performed an analysis to predict differentially regulated pathways and upstream regulators. During acute cholera, there was a broad increase in the expression of genes associated with innate immunity, including activation of the NF-kappaB, mitogen-activated protein kinase (MAPK), and Toll-like receptor (TLR)-mediated signaling pathways, which, unexpectedly, persisted even 30 days after infection. Focusing on early differences in gene expression, we identified 37 genes that were differentially expressed on days 2 and 30 across the 11 participants. These genes included the endosomal Toll-like receptor gene TLR8, which was expressed in lamina propria cells. Underscoring a potential role for endosomal TLR-mediated signaling in vivo, our pathway analysis found that interferon regulatory factor 7 and beta 1 and alpha 2 interferons were among the top upstream regulators activated during cholera. Among the innate immune effectors, we found that the gene for DUOX2, an NADPH oxidase involved in the maintenance of intestinal homeostasis, was upregulated in intestinal epithelial cells during cholera. Notably, the observed increases in DUOX2 and TLR8 expression were also modeled in vitro when Caco-2 or THP-1 cells, respectively, were stimulated with live V. cholerae but not with heat-killed organisms or cholera toxin alone. These previously unidentified features of the innate immune response to V. cholerae extend our understanding of the mucosal immune signaling pathways and effectors activated in vivo following cholera

The nature of impairments of memory in patients with end-stage renal disease (ESRD)

Possible impairments of memory in end-stage renal disease (ESRD) were investigated in two experiments. In Experiment 1, in which stimulus words were presented visually, participants were tested on conceptual or perceptual memory tasks, with retrieval being either explicit or implicit. Compared with healthy controls, ESRD patients were impaired when memory required conceptual but not when it required perceptual processing, regardless of whether retrieval was explicit or implicit. An impairment of conceptual implicit memory (priming) in the ESRD group represented a previously unreported deficit compared to healthy aging. There were no significant differences between pre- and immediate post-dialysis memory performance in ESRD patients on any of the tasks. In Experiment 2, in which presentation was auditory, patients again performed worse than controls on an explicit conceptual memory task. We conclude that the type of processing required by the task (conceptual vs. perceptual) is more important than the type of retrieval (explicit vs. implicit) in memory failures in ESRD patients, perhaps because temporal brain regions are more susceptible to the effects of the illness than are posterior regions

Magnetic White Dwarfs from the SDSS II. The Second and Third Data Releases

Fifty-two magnetic white dwarfs have been identified in spectroscopic observations from the Sloan Digital Sky Survey (SDSS) obtained between mid-2002 and the end of 2004, including Data Releases 2 and 3. Though not as numerous nor as diverse as the discoveries from the first Data Release, the collection exhibits polar field strengths ranging from 1.5MG to ~1000MG, and includes two new unusual atomic DQA examples, a molecular DQ, and five stars that show hydrogen in fields above 500MG. The highest-field example, SDSSJ2346+3853, may be the most strongly magnetic white dwarf yet discovered. Analysis of the photometric data indicates that the magnetic sample spans the same temperature range as for nonmagnetic white dwarfs from the SDSS, and support is found for previous claims that magnetic white dwarfs tend to have larger masses than their nonmagnetic counterparts. A glaring exception to this trend is the apparently low-gravity object SDSSJ0933+1022, which may have a history involving a close binary companion.Comment: 20 pages, 4 figures Accepted for publication in the Astronomical Journa

Eo-1 Hyperion Measures Canopy Drought Stress In Amazonia

The central, south and southeast portions of the Amazon Basin experience a period of decreased cloud cover and precipitation from June through November. There are likely important effects of seasonal and interannual rainfall variation on forest leaf area index, canopy water stress, productivity and regional carbon cycling in the Amazon. While both ground and spaceborne studies of precipitation continue to improve, there has been almost no progress made in observing forest canopy responses to rainfall variability in the humid tropics. This shortfall stems from the large stature of the vegetation and great spatial extent of tropical forests, both of which strongly impede field studies of forest responses to water availability. Those few studies employing satellite measures of canopy responses to seasonal and interannual drought (e.g., Bohlman et al. 1998, Asner et al. 2000) have been limited by the spectral resolution and sampling available from Landsat and AVHRR sensors. We report on a study combining the first landscape-level, managed drought experiment in Amazon tropical forest with the first spaceborne imaging spectrometer observations of this experimental area. Using extensive field data on rainfall inputs, soil water content, and both leaf and canopy responses, we test the hypothesis that spectroscopic signatures unique to hyperspectral observations can be used to quantify relative differences in canopy stress resulting from water availability