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Creating collaborative environments between design and the sciences has the potential to solve problems in new and creative ways through the design process, a process unfamiliar or unknown to many scientific fields. This type of collaboration has been an ongoing pursuit, with a recent instance being a cross disciplinary workshop between Schools of Industrial Design and Horticulture. This unique workshop consisted of a studio-style multidisciplinary workshop in which professors guided students to generate innovative concepts for greenhouse cooling. The focus of this particular collaboration was the creation of energy-efficient, long-term, and cost-effective solutions for greenhouse designs that allow year-round food production in both food-poor locations and temperate climates that are home to a significant portion of greenhouse farming. Opportunity for creative and novel solutions to cooling are vitally important and timely due the negative impact of climate change on food production in many at-risk and low-income regions.

Plant-derived natural products are significant resources for drug discovery and development including appreciable potentials in preventing and managing oxidative stress, making them promising candidates in cancer and other disease therapeutics. Their effects have been linked to phytochemicals such as phenolic compounds and their antioxidant activities. The abundance and complexity of these bio-constituents highlight the need for well-defined in vitro characterization and quantification of the plant extracts/preparations that can translate to in vivo effects and hopefully to clinical use. This review article seeks to provide relevant information about the applicability of cell-based assays in assessing anti-cytotoxicity of phytochemicals considering several traditional and current methods.

Saltwater intrusion (SWI) into root zone in low-lying coastal areas can affect the survival and spatial distribution of various vegetation species by altering plant communities and the wildlife habitats they support. In this study, a baseline model was developed based on FEMWATER to simulate the monthly variation of root zone salinity of a geo-typical area located at the Cape Canaveral Barrier Island Complex (CCBIC) of coastal east-central Florida (USA) in 2010. Based on the developed and calibrated baseline model, three diagnostic FEMWATER models were developed to predict the extent of SWI into root zone by modifying the boundary values representing the rising sea level based on various sea-level rise (SLR) scenarios projected for 2080. The simulation results indicated that the extent of SWI would be insignificant if SLR is either low (23.4cm) or intermediate (59.0cm), but would be significant if SLR is high (119.5cm) in that infiltration/diffusion of overtopping seawater in coastal low-lying areas can greatly increase root zone salinity level, since the sand dunes may fail to prevent the landward migration of seawater because the waves of the rising sea level can reach and pass over the crest under high (119.5cm) SLR scenario.

Eileen S Hwang,1 Brian C Stagg,1 Russell Swan,1 Carlton R Fenzl,1 Molly McFadden,2 Valliammai Muthappan,1 Luis Santiago-Caban,1 Mark D Mifflin,1 Majid Moshirfar1,3 1Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, 2Department of Internal Medicine, University of Utah, Salt Lake City, 3HDR Research Center, Hoopes Vision, Draper, UT, USA Background: The purpose of this study was to evaluate the effects of laser-assisted in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) on corneal biomechanical properties.Methods: We used the ocular response analyzer to measure corneal hysteresis (CH) and corneal resistance factor (CRF) before and after refractive surgery.Results: In all, 230 eyes underwent LASIK and 115 eyes underwent PRK without mitomycin C (MMC). Both procedures decreased CH and CRF from baseline. When MMC was used after PRK in 20 eyes, it resulted in lower corneal biomechanical properties at 3months when compared to the other procedures, but all three procedures had similar values at 12months.Conclusion: Significant but similar decreases in corneal biomechanical properties after LASIK, PRK without MMC, and PRK with MMC were noted. Keywords: corneal biomechanics, photorefractive keratectomy, laser-assisted in situ keratomileusis, corneal hysteresis, corneal resistance factor, mitomycin C

Mark D Mifflin,1 Brent S Betts,1 P Adam Frederick,2 Jason M Feuerman,3 Carlton R Fenzl,4 Majid Moshirfar,1,5 Brian Zaugg1 1Department of Ophthalmology and Visual Sciences, John A Moran Eye Center, University of Utah, Salt Lake City, UT, 2The Eye Center, Huntsville, AL, 3Eye Institute of Austin, Austin, TX, 4Eye Surgeons Associates, Bettendorf, IA, 5Hoopes Vision, Draper, UT, USA Purpose: To compare the outcome of photorefractive keratectomy (PRK) and complications in patients treated with either loteprednol etabonate 0.5% gel or prednisolone acetate 1% suspension and fluorometholone (fml) 0.1% suspension.Setting: John A Moran Eye Center, University of Utah, Salt Lake City, UT, USA.Design: Prospective, randomized, partially masked trial.Methods: PRK was performed on 261 eyes of 132 participants. Patients were randomized to a postoperative corticosteroid regimen of either loteprednol etabonate 0.5% gel (loteprednol) or prednisolone 1% acetate suspension followed by fluorometholone 0.1% suspension (prednisolone/fml). Primary outcome measures included incidence and grade of postoperative corneal haze and incidence of increased intraocular pressure of 10 mmHg above baseline, or any intraocular pressure over 21 mmHg. Secondary outcome measures included uncorrected distance visual acuity, best corrected distance visual acuity, and manifest refraction spherical equivalent.Results: The incidence of haze in the first 3 months was 2.6% (3/114 eyes) in the loteprednol group and 4.8% (7/147 eyes) in the prednisolone/fml group and was not statistically significant between groups (P=0.37). The incidence of elevated intraocular pressure was 1.8% (2/114 eyes) in the loteprednol group and 4.1% (6/147 eyes) in the prednisolone/fml group, and was not statistically significant between the groups (P=0.12). The mean 3-month postoperative logMAR uncorrected visual acuity was −0.078±0.10 and −0.075±0.09 in the loteprednol and prednisolone/fml groups, respectively (P=0.83).Conclusion: Postoperative corneal haze and elevated intraocular pressure were uncommon in both treatment arms. There was no statistically significant difference between each postoperative regimen. Refractive results were similar and excellent in both treatment arms. A tapered prophylactic regimen of loteprednol 0.5% gel is equally effective to prednisolone 1%/fml 0.1% after PRK. Keywords: PRK, corticosteroid, fluorometholone, loteprednol, lotemax, wavefront optimized

The ecosystem services afforded by coastal wetlands are threatened by climate change and other anthropogenic stressors. The Kennedy Space Center and Merritt Island National Wildlife Refuge in east central Florida offer a representative site for investigating how changes to vegetation distribution interact with management to impact coastal protection. Here, salt marshes are converting to mangroves, and mosquito impoundment structures are being modified. The resulting changes to vegetation composition and topography influence coastal protection services in wetlands. We used a model-based assessment of wave attenuation and erosion to compare vegetation (mangrove, salt marsh) and impoundment state (intact, graded). Our findings suggest that the habitat needed to attenuate 90% of wave height is significantly larger for salt marshes than mangroves. Erosion prevention was significantly higher (470%) in scenarios with mangroves than in salt marshes. Intact berms attenuated waves over shorter distances, but did not significantly reduce erosion. Differences in coastal protection were driven more by vegetation than by impoundment state. Overall, our findings reveal that mangroves provide more coastal protection services, and therefore more coastal protection value, than salt marshes in east central Florida. Other coastal regions undergoing similar habitat conversion may also benefit from increased coastal protection in the future.

Technology, automation, and their related systems, have been put in place to add efficiency and convenience to our lives, allowing modern cultures to live prosperous and “easy” lives compared to most cultures throughout history. Our lives of ease have many desirable attributes but, we have simultaneously developed a high level of dependency and a lack of resilience in the face of many common challenges. Through intentional and strategic design, our society could be nudged into a philosophical shift toward a life of resilience, independence, and greater humanness.

Seagrasses are the foundation of many coastal ecosystems and are in global decline because of anthropogenic impacts. For the Indian River Lagoon (Florida, U.S.A.), we developed competing multistate statistical models to quantify how environmental factors (surrounding land use, water depth, and time [year]) influenced the variability of seagrass state dynamics from 2003 to 2014 while accounting for time-specific detection probabilities that quantified our ability to determine seagrass state at particular locations and times. We classified seagrass states (presence or absence) at 764 points with geographic information system maps for years when seagrass maps were available and with aerial photographs when seagrass maps were not available. We used 4 categories (all conservation, mostly conservation, mostly urban, urban) to describe surrounding land use within sections of lagoonal waters, usually demarcated by land features that constricted these waters. The best models predicted that surrounding land use, depth, and year would affect transition and detection probabilities. Sections of the lagoon bordered by urban areas had the least stable seagrass beds and lowest detection probabilities, especially after a catastrophic seagrass die-off linked to an algal bloom. Sections of the lagoon bordered by conservation lands had the most stable seagrass beds, which supports watershed conservation efforts. Our results show that a multistate approach can empirically estimate state-transition probabilities as functions of environmental factors while accounting for state-dependent differences in seagrass detection probabilities as part of the overall statistical inference procedure.

A three-dimensional variable-density groundwater flow and salinity transport model is implemented using the SEAWAT code to quantify the spatial variation of water-table depth and salinity of the surficial aquifer in Merritt Island and Cape Canaveral Island in east-central Florida (USA) under steady-state 2010 hydrologic and hydrogeologic conditions. The developed model is referred to as the ‘reference’ model and calibrated against field-measured groundwater levels and a map of land use and land cover. Then, five prediction/projection models are developed based on modification of the boundary conditions of the calibrated ‘reference’ model to quantify climate change impacts under various scenarios of sea-level rise and precipitation change projected to 2050. Model results indicate that west Merritt Island will encounter lowland inundation and saltwater intrusion due to its low elevation and flat topography, while climate change impacts on Cape Canaveral Island and east Merritt Island are not significant. The SEAWAT models developed for this study are useful and effective tools for water resources management, land use planning, and climate-change adaptation decision-making in these and other low-lying coastal alluvial plains and barrier island systems.

Climate change such as altered frequency and intensity of storm surge from tropical cyclones can cause saltwater intrusion into coastal aquifers. In this study, a reference SEAWAT model and a diagnostic SEAWAT model are developed to simulate the temporal variation of surficial aquifer total dissolved solids (TDS) concentrations after the occurrence of a storm surge for exploration of the effects of storm surge on the extent of saltwater intrusion into the surficial aquifer in coastal east-central Florida (USA). It is indicated from the simulation results that: (1) rapid infiltration and diffusion of overtopping saltwater resulting from storm surge could cause a significant and rapid increase of TDS concentrations in the surficial aquifer right after the occurrence of storm surge; (2) rapid infiltration of freshwater from rainfall could reduce surficial aquifer TDS concentrations beginning from the second year after the occurrence of storm surge in that the infiltrated rainwater could generate an effective hydraulic barrier to impede further inland migration of saltwater and provide a downgradient freshwater discharge for saltwater dilution and flushing counteracting the effects of storm surge on the extent of saltwater intrusion; and (3) infiltrated rainwater might take approximately eight years to dilute and flush the overwhelming majority of infiltrated saltwater back out to the surrounding waterbodies, i.e., the coastal lagoons and the Atlantic Ocean.

Proxima Centauri has become the subject of intense study since the radial-velocity discovery by Anglada-Escud\'e et al. 2016 of a planet orbiting this nearby M-dwarf every ~ 11.2 days. If Proxima Centauri b transits its host star, independent confirmation of its existence is possible, and its mass and radius can be measured in units of the stellar host mass and radius. To date, there have been three independent claims of possible transit-like event detections in light curve observations obtained by the MOST satellite (in 2014-15), the BSST telescope in Antarctica (in 2016), and the Las Campanas Observatory (in 2016). The claimed possible detections are tentative, due in part to the variability intrinsic to the host star, and in the case of the ground-based observations, also due to the limited duration of the light curve observations. Here, we present preliminary results from an extensive photometric monitoring campaign of Proxima Centauri, using telescopes around the globe and spanning from 2006 to 2017, comprising a total of 329 observations. Considering our data that coincide directly and/or phased with the previously published tentative transit detections, we are unable to independently verify those claims. We do, however, verify the previously reported ubiquitous and complex variability of the host star. We discuss possible interpretations of the data in light of the previous claims, and we discuss future analyses of these data that could more definitively verify or refute the presence of transits associated with the radial-velocity discovered planet., Comment: Published in The Astronomical Journal, Volume 155, Number 6. 15 pages, 13 figures, and 2 tables. Updated Table 2 FOVs

This review looks at the benefits, limitations, complications, and future applications of the small-incision lenticule extraction procedure. Using the search terms small incision lenticule extraction and femtosecond lenticule extraction , we obtained data from 56 articles (omitting German and Chinese articles) from the PubMed database. Small-incision lenticule extraction has shown efficacy, predictability, and safety that are proportionate to those of laser in situ keratomileusis (LASIK), with the additional benefit that it eliminates flap creation and the attendant risks. The potential advantages of the procedure related to improved biomechanical stability, postoperative inflammation, and dry-eye symptoms have not been fully established. Small-incision lenticule extraction–treated eyes have shown a reduced degree of postoperative corneal denervation and higher-order aberrations and an accelerated rate of corneal nerve convalescence relative to LASIK. Future possibilities related to long-term cryogenic storage of extracted lenticules with eventual reimplantation or donation have been investigated with encouraging preliminary results. Financial Disclosure Drs. Reinstein and Shah are consultants to Carl Zeiss Meditec AG. No author has a financial or proprietary interest in any material or method mentioned.

A partnership between Earth scientists and institutional stewards is helping the National Aeronautics and Space Administration (NASA) prepare for a changing climate and growing climate-related vulnerabilities. An important part of this partnership is an agency-wide Climate Adaptation Science Investigator (CASI) Workgroup. CASI has thus far initiated 1) local workshops to introduce and improve planning for climate risks, 2) analysis of climate data and projections for each NASA Center, 3) climate impact and adaptation toolsets, and 4) Center-specific research and engagement. Partnering scientists with managers aligns climate expertise with operations, leveraging research capabilities to improve decision-making and to tailor risk assessment at the local level. NASA has begun to institutionalize this ongoing process for climate risk management across the entire agency, and specific adaptation strategies are already being implemented. A case study from Kennedy Space Center illustrates the CASI and workshop process, highlighting the need to protect launch infrastructure of strategic importance to the United States, as well as critical natural habitat. Unique research capabilities and a culture of risk management at NASA may offer a pathway for other organizations facing climate risks, promoting their resilience as part of community, regional, and national strategies.

Case Presentation: A nine-year-old boy presented to the general ophthalmologist with a several weeks history of redness, photophobia and intermittent foreign body sensation in the right eye. A pigmented lesion with anterior chamber inflammation was noted on examination. B-scan ultrasound was performed and revealed no foreign body. The patient was diagnosed with anterior uveitis, which did not completely respond to treatment. The differential diagnosis was expanded to include peripheral ulcerative keratitis, phlyctenulosis, pigmented neoplasm, and corneal foreign body. Upon referral to a cornea specialist, an exam under anesthesia revealed a large foreign body consistent with a rock fragment in the peripheral cornea, which was subsequently removed without complication. Conclusion: This case highlights an atypical presentation of foreign body as well as a differential diagnosis of pigmented peripheral corneal lesions. Foreign bodies represent the most common cause of urgent ophthalmic evaluation. When evaluating lesions of the cornea, it is imperative to keep an extensive differential diagnosis, giving the potential for severe and rapid development of visually threatening complications.

Purpose: To report a case of bilateral glaucoma related to pseudophacomorphic mechanism in one eye and pupillary block in the other eye after Visian Implantable Collamer Lens (ICL; STAAR Surgical) insertion. Methods: A 44-year-old female with high myopia underwent bilateral ICL implantation of MICL12.6 after sulcus diameter measurements were performed by Pentacam. Results: Pseudophacomorphic glaucoma-related angle closure occurred due to lens oversizing in the right eye. The mechanism was relieved via ICL explantation. In the left eye, pupillary block developed in a subacute manner after closure of the Peripheral Iridotomy (PI). The attack was ameliorated by reestablishing patency of the iridotomy. Conclusions: ICL-related glaucomatous attacks may result from improper sizing as well as from placement of a single PI. Identification of the proper mechanism is vital as treatments differ significantly. In pseudo phacomorphic glaucoma, explantation is needed. In pupillary block glaucoma, treatment involves establishment of a patent PI.

Current and planned wildfire detection systems are impressive but lack both sensitivity and rapid response times. A small telescope with modern detectors and significant computing capacity in geosynchronous orbit can detect small (12 m2) fires on the surface of the earth, cover most of the western United States (under conditions of moderately clear skies) every few minutes or so, and attain very good signal-to-noise ratio against Poisson fluctuations in a second. Hence, these favorable statistical significances have initiated a study of how such a satellite could operate and reject the large number of expected systematic false alarms from a number of sources. Here we present both studies of the backgrounds in Geostationary Operational Environmental Satellites (GOES) 15 data and studies that probe the sensitivity of a fire detection satellite in geosynchronous orbit. We suggest a number of algorithms that can help reduce false alarms, and show efficacy on a few. Early detection and response would be of true value in the United States and other nations, as wildland fires continue to severely stress resource managers, policy makers, and the public, particularly in the western US. Here, we propose the framework for a geosynchronous satellite with modern imaging detectors, software, and algorithms able to detect heat from early and small fires, and yield minute-scale detection times.

Experiments have demonstrated that ocean acidification (OA) conditions projected to occur by the end of the century will slow the calcification of numerous coral species and accelerate the biological erosion of reef habitats (bioerosion). Microborers, which bore holes less than 100 mu m diameter, are one of the most pervasive agents of bioerosion and are present throughout all calcium carbonate substrates within the reef environment. The response of diverse reef functional groups to OA is known from real-world ecosystems, but to date our understanding of the relationship between ocean pH and carbonate dissolution by microborers is limited to controlled laboratory experiments. Here we examine the settlement of microborers to pure mineral calcium carbonate substrates (calcite) along a natural pH gradient at a volcanically acidified reef at Maug, Commonwealth of the Northern Mariana Islands (CNMI). Colonization of pioneer microborers was higher in the lower pH waters near the vent field. Depth of microborer penetration was highly variable both among and within sites (4.2-195.5 mu m) over the short duration of the study (3 mo.) and no clear relationship to increasing CO2 was observed. Calculated rates of biogenic dissolution, however, were highest at the two sites closer to the vent and were not significantly different from each other. These data represent the first evidence of OA-enhancement of microboring flora colonization in newly available substrates and provide further evidence that microborers, especially bioeroding chlorophytes, respond positively to low pH. The accelerated breakdown and dissolution of reef framework structures with OA will likely lead to declines in structural complexity and integrity, as well as possible loss of essential habitat.

Purpose To report outcomes in Descemet stripping automated endothelial keratoplasty (DSAEK) using donor tissue from eyes that have had previous refractive surgery and to report histopathology of the donor free cap. Methods Retrospective case series. Preoperative and postoperative data were collected on each patient, and donor information was collected. Histopathologic evaluation was carried out on donor caps to determine the stability of the laser in situ keratomileusis (LASIK) flap and smoothness of the microkeratome cut during preparation of the donor. Results DSAEK was performed on 7 eyes using donors that had undergone photorefractive keratectomy (PRK) or LASIK. One patient received PRK donor tissue, had no interface haze, and had improvement in vision. All but one patient who received LASIK donor tissue had improvement in vision, and that patient had severe graft folds noted intraoperatively that persisted. Histopathologic examination of 3 donor caps showed mild to moderate dehiscence of the LASIK flap, but the cut interface was consistent with normal donor tissue preparation histopathology. Conclusions We report the first case of DSAEK using PRK donor tissue, which was successful. Our experience with LASIK donor tissue was comparable to nonrefractive donor tissue with the exception of the persistent donor macrofolds in one patient.

A reduction in progenitor cell populations that help preserve vascular continuity and induce vascularization may accentuate endothelial cell apoptosis and dysfunction, ultimately contributing to organ failure and increased cardiovascular disease in chronic kidney disease (CKD). We hypothesized that CD45+ myeloid and CD34+ hematopoietic circulating progenitor cell (CPC) subpopulations would be reduced, peripheral blood mononuclear cell (PBMNC) colony-forming units (CFU) would be impaired, and flow-mediated dilation (FMD) would be impaired in patients with moderate-to-severe CKD as compared with healthy controls. Eleven moderate-to-severe CKD patients (mean estimated glomerular filtration rate [eGFR]: 36 ± 5) and 14 healthy controls were studied; blood was drawn and FMD was assessed by brachial artery FMD. CPCs were quantified via flow cytometry, and isolated PBMNCs were cultured for the colony-forming assay. CKD patients had significantly impaired FMD; lower CD34+, CD34+/KDR+, CD34+/CD45− and CD34+/KDR+/CD45− hematopoietic CPCs; lower CD45+, CD45+/KDR+, CD34+/CD45+ and CD34+/KDR+/CD45+ myeloid CPCs; and impaired CFUs as compared with healthy controls. Regression analysis revealed that CD34+, CD34+/KDR+ and CD34+/CD45− hematopoietic CPCs were associated positively with eGFR and negatively with blood urea nitrogen and serum creatinine. The CD45+/KDR+ myeloid CPCs also were associated positively with eGFR and negatively with serum creatinine. CD34+ hematopoietic CPCs and CD45+/KDR+ as well as CD34+/CD45+ myeloid CPCs were associated positively with FMD. In conclusion, myeloid and hematopoietic CPCs are reduced and associated with renal function as well as FMD in CKD. Therefore, reductions in CPCs may be a potential mechanism by which vascular integrity is compromised, increasing cardiovascular disease risk and contributing to renal disease progression in CKD.

Thalidomide (Figure 1) was derived from alpha-phnthaloylisoglutamine, a derivative of glutamic acid1 by Chemie Grünenthal GmbH, a West German Company in 1954. Thalidomide has a low level of toxicity and no LD50 could be established. Indeed, high doses of thalidomide did not cause respiratory or cardiac failure, suggesting that accidental death or suicide with this compound was highly unlikely. As a matter of fact, 17 patients, including small children and one suicide attempt, survived ingestion of excessive amounts of thalidomide. In 1957, thalidomide was approved for commercial use in West Germany as a sedative and sold under the brand name Kevadon. About this time, the anti-emetic (anti-nausea) activity was discovered and the drug was prescribed to counteract morning sickness in pregnant women. Unfortunately, the teratological effects of thalidomide were not revealed through studies in rodents and approximately 12,000 children were born deformed before thalidomide was banned for clinical use in March 1962 by the Canadian Food and Drug Directorate2. In 1998, thalidomide was approved to treat erythema nodosum leprosum, a painful inflammatory dermatologic reaction of leprosy. In 2006, the FDA approved thalidomide under the brand name Thalomid (Celgene Corp) for treatment of newly diagnosed multiple myeloma As a result of these approvals, the interest in thalidomide as a chemotherapeutic agent for other cancers, including prostate cancer (Figure 2), has emerged.

An approach using a combination of well known circuit principles, is used to convert the impedance matrix - determined for three phase, single lamination/phase busway - to industry specified 'average' impedance values as specified by the National Electrical Manufacturers Association ( NEMA). This paper details how this approach can be used to predict 'average' busway impedance with reasonable accuracy, and therefore help to reduce the number of physical tests and related costs in the design process. Four cases are provided for validation purposes. The results show good correlation with published data.

Chemokines and corresponding receptor interactions have been shown to be involved in prostate cancer (PCa) progression and organ-specific metastasis. We have recently shown that PCa cell lines and primary prostate tumors express CXCR5, which correlates with PCa grade. In this study, we present the first evidence that CXCL13, the only ligand for CXCR5, and IL-6 were significantly elevated in PCa patient serum compared to serum from subjects with benign prostatic hyperplasia (BPH), or high-grade prostatic intraepithelial neoplasia (HGPIN) as well as normal healthy donors (NHD). Serum CXCL13 levels significantly (p < 0.0001) correlated with serum prostate-specific antigen (PSA), whereas serum IL-6 levels significantly (p < 0.0003) correlated with CXCL13 serum levels. CXCL13 was found to be a better predictor of PCa than PSA. In addition, CXCL13 was highly expressed by human bone marrow endothelial (HBME) cells and osteoblasts (OBs), but not osteoclasts (OCs), following treatment with physiologically relevant levels of interleukin-6 (IL-6). We further demonstrate that CXCL13, produced by IL-6-treated HBME cells, was able to induce PCa cell invasion in a CXCR5-dependent manner. CXCL13-mediated PCa cell αvβ3-integrin clustering and adhesion to HBME cells was abrogated by CXCR5 blockade. These results demonstrate that the CXCL13-CXCR5 axis is significantly associated with PCa progression.

By analogy, the study of metastasis is like a group of blind people studying an elephant. Each describes the pachyderm based on the part (s)he touches, but none comprehends the whole elephant because his/her exposure is limited. Likewise, the complexity of metastasis can only be appreciated when one

We present statistical details for estimating an in vitro 50% inhibitory concentration (IC 50 ), based on several models for continuous response data fit to bone-marrow endothelial cell lines replicated in vehicle and at several dose increments. Nonlinear models are fit via maximum likelihood assuming normal errors, and primary attention is given to exponential, Gompertz, and scaled logistic dose–response curves that admit increasing or decreasing monotonic and sigmoidal patterns. Careful consideration is given to dose axis scaling, comparative model fit via mean squared error and graphical assessment, analogues to weighted least squares analysis to address heterogeneity of variance across doses, and potential hormetic effects. Standard error estimation is discussed in detail, highlighting the advantage of reparameterizing dose–response models directly in terms of IC 50 . Specific results for two cell lines are provided, along with a sample commercial software-based program for implementing a selection of the methods discussed.

An unbiased cDNA expression phage library derived from bone-marrow endothelial cells was used to identify novel surface adhesion molecules that might participate in metastasis. Herein we report that reticulocalbin 1 (RCN1) is a cell surface-associated protein on both endothelial (EC) and prostate cancer (PCa) cell lines. RCN1 is an H/KDEL protein with six EF-hand, calcium-binding motifs, found in the endoplasmic reticulum. Our data indicate that RCN1 also is expressed on the cell surface of several endothelial cell lines, including human dermal microvascular endothelial cells (HDMVECs), bone marrow endothelial cells (BMEC), and transformed human bone marrow endothelial cells (TrHBMEC). While RCN1 protein levels were highest in lysates from HDMVEC, this difference was not statistically significant compared BMEC and TrHBMEC. Given preferential adhesion of PCa to bone-marrow EC, these data suggest that RCN1 is unlikely to account for the preferential metastasis of PCa to bone. In addition, there was not a statistically significant difference in total RCN1 protein expression among the PCa cell lines. RCN1 also was expressed on the surface of several PCa cell lines, including those of the LNCaP human PCa progression model and the highly metastatic PC-3 cell line. Interestingly, RCN1 expression on the cell surface was upregulated by tumor necrosis factor alpha treatment of bone-marrow endothelial cells. Taken together, we show cell surface localization of RCN1 that has not been described previously for either PCa or BMEC and that the surface expression on BMEC is regulated by pro-inflammatory TNF-alpha.

Background The Rho GTPases comprise one of the eight subfamilies of the Ras superfamily of monomeric GTP-binding proteins and are involved in cytoskeletal organization. Previously, using a dominant negative construct, we demonstrated a role for RhoC GTPase in conferring invasive capabilities to PC-3 human prostate cancer cells. Further, we demonstrated that inactivation of RhoC led to morphological changes commensurate with epithelial to mesenchymal transition (EMT) and was accompanied by increased random, linear motility and decreased directed migration and invasion. EMT was related positively to sustained expression and activity of Rac GTPase. In the current study we analyze the individual roles of RhoA, RhoC and Rac1 GTPases in PC-3 cell directed migration, invasion and tumor cell diapedesis across a human bone marrow endothelial cell layer in vitro. Results Use of specific shRNA directed against RhoA, RhoC or Rac1 GTPases demonstrated a role for each protein in maintaining cell morphology. Furthermore, we demonstrate that RhoC expression and activation is required for directed migration and invasion, while Rac1 expression and activation is required for tumor cell diapedesis. Inhibition of RhoA expression produced a slight increase in invasion and tumor cell diapedesis. Conclusions Individual Rho GTPases are required for critical aspects of migration, invasion and tumor cell diapedesis. These data suggest that coordinated activation of individual Rho proteins is required for cells to successfully complete the extravasation process; a key step in distant metastasis.

The issue of certificate revocation in mobile ad hoc networks (MANETs) where there are no on-line access to trusted authorities, is a challenging problem. In wired network environments, when certificates are to be revoked, certificate authorities (CAs) add the information regarding the certificates in question to certificate revocation lists (CRLs) and post the CRLs on accessible repositories or distribute them to relevant entities. In purely ad hoc networks, there are typically no access to centralized repositories or trusted authorities; therefore the conventional method of certificate revocation is not applicable. In this paper, we present a decentralized certificate revocation scheme that allows the nodes within a MANET to revoke the certificates of malicious entities. The scheme is fully contained and it does not rely on inputs from centralized or external entities.

In order for cancer cells to successfully colonize a metastatic site, they must detach from the primary tumor using extracellular matrix-degrading proteases, intravasate and survive in the circulation, evade the immune response, and extravasate the vasculature to invade the target tissue parenchyma, where metastatic foci are established. Though many of the steps of metastasis are widely studied, the precise cellular interactions and molecular alterations associated with extravasation are unknown, and further study is needed to elucidate the mechanisms inherent to this process. Studies of leukocytes localized to inflamed tissue during the immune response may be used to elucidate the process of cancer extravasation, since leukocyte diapedesis through the vasculature involves critical adhesive interactions with endothelial cells, and both leukocytes and cancer cells express similar surface receptors capable of binding endothelial adhesion molecules. Thus, leukocyte extravasation during the inflammatory response has provided a model for transendothelial migration (TEM) of cancer cells. Leukocyte extravasation is characterized by a process whereby rolling mediated by cytokine-activated endothelial selectins is followed by firmer adhesions with beta1 and beta2 integrin subunits to an activated endothelium and subsequent diapedesis, which most likely involves activation of Rho GTPases, regulators of cytoskeletal rearrangements and motility. It is controversial whether such selectin-mediated rolling is necessary for TEM of cancer cells. However, it has been established that similar stable adhesions between tumor and endothelial cells precede cancer cell transmigration through the endothelium. Additionally, there is support for the preferential attachment of tumor cells to the endothelium and, accordingly, site-specific metastasis of cancer cells. Rho GTPases are critical to TEM of cancer cells as well, and some progress has been made in understanding the specific roles of the Rho GTPase family, though much is still unknown. As the mechanisms of cancer TEM are elucidated, new approaches to study and target metastasis may be utilized and developed.

Seagrasses are the foundation of many coastal ecosystems and are in global decline because of anthropogenic impacts. For the Indian River Lagoon (Florida, U.S.A.), we developed competing multistate statistical models to quantify how environmental factors (surrounding land use, water depth, and time [year]) influenced the variability of seagrass state dynamics from 2003 to 2014 while accounting for time-specific detection probabilities that quantified our ability to determine seagrass state at particular locations and times. We classified seagrass states (presence or absence) at 764 points with geographic information system maps for years when seagrass maps were available and with aerial photographs when seagrass maps were not available. We used 4 categories (all conservation, mostly conservation, mostly urban, urban) to describe surrounding land use within sections of lagoonal waters, usually demarcated by land features that constricted these waters. The best models predicted that surrounding land use, depth, and year would affect transition and detection probabilities. Sections of the lagoon bordered by urban areas had the least stable seagrass beds and lowest detection probabilities, especially after a catastrophic seagrass die-off linked to an algal bloom. Sections of the lagoon bordered by conservation lands had the most stable seagrass beds, which supports watershed conservation efforts. Our results show that a multistate approach can empirically estimate state-transition probabilities as functions of environmental factors while accounting for state-dependent differences in seagrass detection probabilities as part of the overall statistical inference procedure.

PURPOSE: To review refractive regression and current therapeutic options for patients who have residual refractive error after LASIK. METHODS: An extensive literature search using PubMed was performed for terms such as “LASIK,” “PRK,” “enhancement,” “overcorrection,” “undercorrection,” “re-lift,” “mini-flap,” and related terms. RESULTS: The presence of residual refractive error following LASIK is a challenging situation. After excluding anatomical causes (eg, ocular surface disease, cataract, and macular pathology) and intraoperative flap complications, evaluation of the residual stromal bed must be performed. Depending on the length of time since primary LASIK, procedures such as flap re-lift, flap re-cut, and surface ablation may be performed. CONCLUSIONS: Residual refractive errors can be seen after LASIK surgery and may benefit from an enhancement procedure. Different options are available for enhancement, each requiring proper evaluation and an analytical approach to make the procedure safe and effective. [ J Refract Surg . 2017;33(2):116–127.]

Readmissions are an increasing area of focus for quality improvement initiatives. Widely variable estimates exist on preventability and impact of multipronged readmission interventions. Given the rotating nature of attending physicians in academic centers, physicians often are unaware of readmissions. We present a before-and-after (uncontrolled) trial evaluating timely feedback of readmissions to hospitalist physicians.A daily list of patients (inpatient, observation, procedure, or emergency department) who are registered as receiving care within University of North Carolina hospitals was filtered to include only inpatients within the last 30 days and cared for by a faculty member from the hospital medicine program, and readmissions were tracked. A hospitalist physician performed an in-depth review of readmissions using a readmission diagnostic worksheet developed by the Institute for Healthcare Improvement STate Action on Avoidable Rehospitalizations Initiative. Physicians were surveyed on their perception of readmissions in general and their preventability. Outcomes of interest were 30-day readmission rates, physician perspectives and estimates of preventability, patient factors from the STate Action on Avoidable Rehospitalizations tool, and length of stay.Compared with the previous 18 months, the readmission rate was reduced modestly during the 6 months of our intervention (12% to 10%, t test + 0.071). The average length of stay increased from 4.73 days during the prior 18 months to 5.01 for the 4 months since the intervention (t test 0.1). Based on the attending physician survey, 13% of attending physicians believed that fewer than 10% of readmissions were preventable; this increased to 30% after 6 months of timely notification and chart reviews. At baseline, the top three contributors to readmissions were believed to be patient understanding, medication nonadherence, and substance abuse/addiction. After 6 months of the intervention, the top three contributors were believed to be substance abuse/addiction, medication nonadherence, and lack of primary care.Our intervention of real-time feedback regarding readmissions and enforced chart review led to a modest reduction in readmission rates without significant changes in length of stay. Physicians continued to believe that a readmission event was multifactorial and largely not preventable. Real-time notification did increase physician involvement in prevention initiatives, in particular with high-use patients.

Neck pain presents a tremendous physical and financial burden. This study compared the efficacy of the complementary and alternative medical treatments of integrative muscular movement technique (IMMT) and Swedish massage on neck pain in women of occupation age, the largest demographic group with neck pain.A total of 38 women were assigned to IMMT (n=28) or Swedish massage (n=10) in a blinded manner. Both groups received eight 30-minute treatments over 4 weeks. Cervical range of motion (ROM) in flexion, extension, sidebending, and rotation was measured before and after treatment. Each patient's pain was assessed by using an analogue pain scale of 0-10.Compared with the Swedish massage group, patients receiving IMMT experienced a significant increase in ROM in cervical flexion (p0.001), extension (p0.001), sidebending (p0.05), and rotation (p0.001). Absolute change in pain for IMMT was -1.75 units compared with -0.3 units for Swedish massage (p0.05).Patients receiving the IMMT demonstrated significantly improved cervical ROM in every movement measured compared with Swedish massage. Inclusion of the IMMT in a treatment regimen for chronic neck pain may lead to decreased pain and increased cervical ROM. These positive effects of the IMMT intervention may have a role in enhancing functional outcomes in patients with neck pain.

BACKGROUND. Stromal cell-derived factor-1 (SDF-1 or CXCL12) and CXCR4 are key elements in the metastasis of prostate cancer cells to bone—but the mechanisms as to how it localizes to the marrow remains unclear. METHODS. Prostate cancer cell lines were stimulated with SDF-1 and evaluated for alterations in the expression of adhesion molecules using microarrays, FACs, and Western blotting to identify avb3 receptors. Cell–cell adhesion and invasion assays were used to verify that activation of the receptor is responsive to SDF-1. RESULTS. We demonstrate that SDF-1 transiently regulates the number and affinity of avb3 receptors by prostate cancer cells to enhance their metastatic behavior by increasing adhesiveness and invasiveness. SDF-1 transiently increased the expression of b3 receptor subunit and increased its phosphorylation in metastatic but not nonmetastatic cells. CONCLUSIONS. The transition from a locally invasive phenotype to a metastatic phenotype may be primed by the elevated expression of avb3 receptors. Activation and increased expression of avb3 within SDF-1-rich organs may participate in metastatic localization. Prostate

To report a case of bilateral glaucoma related to pseudophacomorphic mechanism in one eye and pupillary block in the other eye after Visian Implantable Collamer Lens (ICL, STAAR Surgical) insertion.A 44 year-old female with high myopia underwent bilateral ICL implantation of MICL12.6 after sulcus diameter measurements were performed by Pentacam.Pseudophacomorphic glaucoma-related angle closure occurred due to lens oversizing in the right eye. The mechanism was relieved via ICL explantation. In the left eye, pupillary block developed in a subacute manner after closure of the peripheral iridotomy (PI). The attack was ameliorated by reestablishing patency of the iridotomy.ICL-related glaucomatous attacks may result from improper sizing as well as from placement of a single PI. Identification of the proper mechanism is vital as treatments differ significantly. In pseudophacomorphic glaucoma, explantation is needed. In pupillary block glaucoma, treatment involves establishment of a patent PI.

Declining rates of tuberculosis (TB) in the United States has resulted in a low prevalence of the disease among patients placed on respiratory isolation. The purpose of this study is to systematically review decision rules to predict the patient's risk for active pulmonary TB at the time of admission to the hospital.We searched MEDLINE (1975 to 2003) supplemented by reference tracking. We included studies that reported the sensitivity and specificity of clinical variables for predicting pulmonary TB, used Mycobacterium TB culture as the reference standard, and included at least 50 patients.Two reviewers independently assessed study quality and abstracted data regarding the sensitivity and specificity of the prediction rules.Nine studies met inclusion criteria. These studies included 2,194 participants. Most studies found that the presence of TB risk factors, chronic symptoms, positive tuberculin skin test (TST), fever, and upper lobe abnormalities on chest radiograph were associated with TB. Positive TST and a chest radiograph consistent with TB were the predictors showing the strongest association with TB (odds ratio: 5.7 to 13.2 and 2.9 to 31.7, respectively). The sensitivity of the prediction rules for identifying patients with active pulmonary TB varied from 81% to 100%; specificity ranged from 19% to 84%.Our analysis suggests that clinicians can use prediction rules to identify patients with very low risk of infection among those suspected for TB on admission to the hospital, and thus reduce isolation of patients without TB.

The second year of method development work was conducted on the ADTI-WP1 (Humidity Cell) and the ADTI-WP2 (Leaching Column) standard test methods. The performance of the leaching column method was superior to the humidity cell method. In making improvements to the leaching column method, variations in column diameter and water-handling/gas-handling procedures were evaluated. Two commercial laboratories and a university research lab participated in the study. Relative percent differences between duplicate samples and relative standard deviations between laboratories were evaluated. Surface area measurements, using BET methods, were conducted on each of 8 particle size classes, before and after weathering tests on 4 different lithologic samples. Observed alkalinity concentrations were consistent with the elevated PCO2 and approached saturation with respect to calcite for calcareous rocks. The maximum concentrations of acidity (33,700 mg/L), sulfates (37,404 mg/L) and iron (9,120 mg/L) for the high-sulfur coal refuse sample were consistent with the maximum concentrations observed in the field. The measured surface areas of the shale samples were significantly higher than the sandstone, limestone and coal- refuse samples. However, the surface area measurements post-weathering were not significantly different from the pre-weathering measurements for most rock samples and most particle size classes.

Microvessel density is a prognostic factor for many cancers, including prostate. For this reason, several studies and therapeutic approaches that target the tumor microvasculature have been attempted. Thalidomide has long been recognized as an antiangiogenic molecule. Recently, this drug has regained favor as an anticancer agent and is in clinical trial for multiple myeloma and prostate cancer, among others. This article will briefly review the proposed mechanisms of action for thalidomide, discuss why these activities are of therapeutic value in diseases currently undergoing clinical trials, and summarize the current status of clinical trials for prostate cancer. The focus will be predominantly on the relationship of thalidomide to angiogenesis, as well as on the future and potential value of thalidomide-inspired structural derivatives.

BACKGROUND Prostate carcinoma (PC) frequently metastasizes to bone, where it causes significant morbidity and mortality. Stromal elements in the primary and metastatic target organs are important mediators of tumor cell intravasation, chemoattraction, adhesion to target organ microvascular endothelium, extravasation, and growth at the metastatic site. METHODS The role of stromal factors in bone metastasis was determined with a cyclic DNA microarray comparison of a bone-derived cell PC cell line with a soft tissue-derived cell PC cell line and by evaluating the effects of selected stromal components on PC cell chemotaxis, cell adhesion to human bone marrow endothelium (HBME), and PC cell growth. RESULTS The authors demonstrate that PC cells express protease-activated receptor 1 (PAR1; thrombin receptor), and its expression is up-regulated in PC compared with normal prostate tissue. In addition, this overexpression was very pronounced in bone-derived PC cell lines (VCaP and PC-3) compared with soft tissue PC cell lines (DUCaP, DU145, and LNCaP). The authors report that bone stromal factors, including stromal cell-derived factor 1 (SDF-1) and collagen Type I peptides, are chemoattractants for PC cells, and they demonstrate that some of these factors (e.g., extracellular matrix components, transforming growth factor β, bone morphogenic proteins [BMPs], and SDF-1) significantly alter PC-HBME interaction in vitro. Finally, stromal factors, such as BMPs, can regulate the proliferation of PC cells in vitro. CONCLUSIONS Soluble and insoluble elements of the stroma are involved in multiple steps of PC metastasis to bone. The authors hypothesize that PAR1 may play a central role in prostate tumorigenesis. Cancer 2003;97(3 Suppl):739–47. © 2003 American Cancer Society. DOI 10.1002/cncr.11181

This paper presents an objective and subjective verification of a high-resolution configuration of the Regional Atmospheric Modeling System (RAMS) over east-central Florida during the 1999 and 2000 summer months. Centered on the Cape Canaveral Air Force Station (CCAFS), the innermost nested grid of RAMS has a horizontal grid spacing of 1.25 km, thereby providing forecasts capable of modeling finescale phenomena such as ocean and river breezes, and convection. The RAMS is run operationally at CCAFS within the Eastern Range Dispersion Assessment System (ERDAS), in order to provide emergency response guidance during space operations. ERDAS uses RAMS wind and temperature fields for input into ERDAS diffusion algorithms; therefore, the accuracy of dispersion predictions is highly dependent on the accuracy of RAMS forecasts. The most substantial error in RAMS over east-central Florida is a surface-based cold temperature bias, primarily during the daylight hours. At the Shuttle Landing Facility, the RAMS point error statistics are not substantially different than the National Centers for Environment Prediction Eta Model; however, an objective evaluation consisting of only point error statistics cannot adequately determine the added value of a high-resolution model configuration. Thus, results from a subjective evaluation of the RAMS forecast sea breeze and thunderstorm initiation on the 1.25-km grid are also presented. According to the subjective verification of the Florida east coast sea breeze, the RAMS categorical and skill scores exceeded that of the Eta Model predictions in most instances. The RAMS skill scores in predicting thunderstorm initiation are much lower than the sea-breeze evaluation scores, likely resulting from the lack of a sophisticated data assimilation scheme in the current operational configuration.

Androgen independence and bone metastasis are lethal complications in patients with advanced prostate cancer. Presently, there is no cure for patients with androgen-independent prostate cancer. In order to develop more effective therapies for this disease, the molecular events involved in the development of androgen independence and bone metastasis must be elucidated and then targeted by therapeutic agents. Several studies presented at a recent conference on prostate cancer sponsored by the American Association for Cancer Research (AACR) provided evidence that prostate cancer metastasis to bone is mediated by the prostate cancer cell expression of molecules that allow the cells to invade, grow in and stimulate cells in the bone microenvironment resulting in an osteoblastic reaction. Androgen independence was reportedly mediated by an increased expression of survival genes following androgen ablation therapies and several molecular mechanisms involved in genetic instability. Treatment strategies are being designed to target some of the molecular events involved in androgen independence and bone metastasis. Targeting these molecular events with combinational therapies will hopefully delay the progression to androgen independence in patients with early stage disease, suppress the growth of androgen-independent cells in patients with advanced disease and enhance the chemosensitivity of androgen-independent cells.

A previous study from our laboratory suggested that prostate cancer metastasis to bone may be mediated, in part, by preferential adhesion to human bone marrow endothelial (HBME) cells. Tumor cell adhesion to endothelial cells may be modulated by the effect of cytokines on cell adhesion molecules (CAMs). Tumor necrosis factor-alpha (TNF-alpha) regulates VCAM expression on the endothelium and this effect is enhanced by dihydrotestosterone (DHT). Transforming growth factor-beta (TGF-beta) stimulates the expression of alpha2beta1 integrin on PC-3 cells. The current study investigated the effects of the above cytokines and DHT (singularly and in various combinations) upon HBME and prostate cancer cell expression of VCAM, alpha2 integrin subunit, and beta1 integrin subunit by flow cytometry. We also monitored the effects of the above treatments on PC-3 cell adhesion to HBME monolayers. The data demonstrate that none of the treatments significantly altered the expression of selected CAMs on HBME cell and neoplastic prostate cell lines. The treatment of HBME monolayers with various combinations of cytokines and DHT prior to performing adhesion assays with PC-3 demonstrates that treatments containing TGF-beta reduced PC-3 cell adhesion to HBME monolayers by 32% or greater (P < 0.05). The reduction in PC-3 cell adhesion to TGF-beta-treated HBME monolayers was dose dependent. Interestingly, LNCaP cells but not PC-3 cells treated with TGF-beta had a reduced ability to adhere to untreated HBME monolayers. These results suggest that TGF-beta may reduce tumor cell adhesion to bone marrow microvascular endothelium, in vivo. The biological significance of this observation is discussed.

Integrin αvβ3 is involved in varied cell biological activities, including angiogenesis, cell adhesion, and migration on several extracellular matrix components. Although αvβ3 is not typically expressed in epithelial cells, it is expressed in macrophages, activated leukocytes, cytokine-stimulated endothelial cells, osteoclasts, and certain invasive tumors. Interestingly, the adhesion and migration of breast cancer cells on bone matrix are mediated, in part, by αvβ3. Similar to breast cancer cells, prostate cancer cells preferentially metastasize to the bone. The biological events that mediate this metastatic pattern of prostate cancer are not well defined. This review discusses the role αvβ3 plays in prostate cancer progression, with specific emphasis on bone metastasis and on αvβ3 signaling in prostate cancer cells. The data suggest that αvβ3, in part, facilitates prostate cancer metastasis to bone by mediating prostate cancer cell adhesion to and migration on osteopontin and vitronectin, which are common proteins in the bone microenvironment. These biological events require the activation of focal adhesion kinase and the subsequent activation of PI-3 kinase/Akt signaling pathway.

Society needs information about how vegetation communities in coastal regions will be impacted by hydrologic changes associated with climate change, particularly sea level rise. Due to anthropogenic influences which have significantly decreased natural coastal vegetation communities, it is important for us to understand how remaining natural communities will respond to sea level rise. The Cape Canaveral Barrier Island complex (CCBIC) on the east central coast of Florida is within one of the most biologically diverse estuarine systems in North America and has the largest number of threatened and endangered species on federal property in the contiguous United States. The high level of biodiversity is susceptible to sea level rise. Our objective was to model how vegetation communities along a gradient ranging from hydric to upland xeric on CCBIC will respond to three sea level rise scenarios (0.2 m, 0.4 m, and 1.2 m). We used a probabilistic model of the current relationship between elevation and vegetation community to determine the impact sea level rise would have on these communities. Our model correctly predicted the current proportions of vegetation communities on CCBIC based on elevation. Under all sea level rise scenarios the model predicted decreases in mesic and xeric communities, with the greatest losses occurring in the most xeric communities. Increases in total area of salt marsh were predicted with a 0.2 and 0.4 m rise in sea level. With a 1.2 m rise in sea level approximately half of CCBIC’s land area was predicted to transition to open water. On the remaining land, the proportions of most of the vegetation communities were predicted to remain similar to that of current proportions, but there was a decrease in proportion of the most xeric community (oak scrub) and an increase in the most hydric community (salt marsh). Our approach provides a first approximation of the impacts of sea level rise on terrestrial vegetation communities, including important xeric upland communities, as a foundation for management decisions and future modeling.

The majority of men with progressive prostate cancer develop metastases with the skeleton being the most prevalent metastatic site. Unlike many other tumors that metastasize to bone and form osteolytic lesions, prostate carcinomas form osteoblastic lesions. However, histological evaluation of these lesions reveals the presence of underlying osteoclastic activity. These lesions are painful, resulting in diminished quality of life of the patient. There is emerging evidence that prostate carcinomas establish and thrive in the skeleton due to cross-talk between the bone microenvironment and tumor cells. Bone provides chemotactic factors, adhesion factors, and growth factors that allow the prostate carcinoma cells to target and proliferate in the skeleton. The prostate carcinoma cells reciprocate through production of osteoblastic and osteolytic factors that modulate bone remodeling. The prostate carcinoma-induced osteolysis promotes release of the many growth factors within the bone extracellular matrix thus further enhancing the progression of the metastases. This review focuses on the interaction between the bone and the prostate carcinoma cells that allow for development and progression of prostate carcinoma skeletal metastases.

Binding and transport of polymeric Igs (pIgA and IgM) across epithelia is mediated by the polymeric Ig receptor (pIgR), which is expressed on the basolateral surface of secretory epithelial cells. Although an Fc receptor for IgA (FcαR) has been identified on myeloid cells and some cultured mesangial cells, the expression of an FcαR on epithelial cells has not been described. In this study, binding of IgA to a human epithelial line, HT-29/19A, with features of differentiated colonic epithelial cells, was examined. Radiolabeled monomeric IgA (mIgA) showed a dose-dependent, saturable, and cation-independent binding to confluent monolayers of HT-29/19A cells. Excess of unlabeled mIgA, but not IgG or IgM, competed for the mIgA binding, indicating that the binding was IgA isotype-specific and was not mediated by the pIgR. The lack of competition by asialoorosomucoid and the lack of requirement for divalent cations excluded the possibility that IgA binding to HT-29/19A cells was due to the asialoglycoprotein receptor or β-1,4-galactosyltransferase, previously described on HT-29 cells. Moreover, the FcαR (CD89) protein and message were undetectable in HT-29/19A cells. FACS analysis of IgA binding demonstrated two discrete populations of HT-29/19 cells, which bound different amounts of mIgA. IgA binding to other colon carcinoma cell lines was also demonstrated by FACS analysis, suggesting that an IgA receptor, distinct from the pIgR, asialoglycoprotein receptor, galactosyltransferase, and CD89 is constitutively expressed on cultured human enterocytes. The function of this novel IgA receptor in mucosal immunity remains to be elucidated.