THE ROLE OF LAND USE IN ENVIRONMENTAL DECISION MAKING AT THREE DOE MEGA-CLEANUP SITES FERNALD & ROCKY FLATS & MOUND

This paper explores the role that future land use decisions have played in the establishment of cost-effective cleanup objectives and the setting of environmental media cleanup levels for the three major U.S. Department of Energy (DOE) sites for which cleanup has now been successfully completed: the Rocky Flats, Mound, and Fernald Closure Sites. At each site, there are distinct consensus-building histories throughout the following four phases: (1) the facility shut-down and site investigation phase, which took place at the completion of their Cold War nuclear-material production missions; (2) the decision-making phase, whereby stakeholder and regulatory-agency consensus was achieved for the future land-use-based environmental decisions confronting the sites; (3) the remedy selection phase, whereby appropriate remedial actions were identified to achieve the future land-use-based decisions; and (4) the implementation phase, whereby the selected remedial actions for these high-profile sites were implemented and successfully closed out. At each of the three projects, there were strained relationships and distrust between the local community and the DOE as a result of site contamination and potential health effects to the workers and local residents. To engage citizens and interested stakeholder groups - particularly in the role of final land use in the decision-making process, the site management teams at each respective site developed new public-participation strategies to open stakeholder communication channels with site leadership, technical staff, and the regulatory agencies. This action proved invaluable to the success of the projects and reaching consensus on appropriate levels of cleanup. With the implementation of the cleanup remedies now complete, each of the three DOE sites have become models for future environmental-remediation projects and associated decision making

Increased Lysis of Stem Cells but Not Their Differentiated Cells by Natural Killer Cells; De-Differentiation or Reprogramming Activates NK Cells

The aims of this study are to demonstrate the increased lysis of stem cells but not their differentiated counterparts by the NK cells and to determine whether disturbance in cell differentiation is a cause for increased sensitivity to NK cell mediated cytotoxicity. Increased cytotoxicity and augmented secretion of IFN-γ were both observed when PBMCs or NK cells were co-incubated with primary UCLA oral squamous carcinoma stem cells (UCLA-OSCSCs) when compared to differentiated UCLA oral squamous carcinoma cells (UCLA-OSCCs). In addition, human embryonic stem cells (hESCs) were also lysed greatly by the NK cells. Moreover, NK cells were found to lyse human Mesenchymal Stem Cells (hMSCs), human dental pulp stem cells (hDPSCs) and human induced pluripotent stem cells (hiPSCs) significantly more than their differentiated counterparts or parental lines from which they were derived. It was also found that inhibition of differentiation or reversion of cells to a less-differentiated phenotype by blocking NFκB or targeted knock down of COX2 in monocytes significantly augmented NK cell cytotoxicity and secretion of IFN-γ. Taken together, these results suggest that stem cells are significant targets of the NK cell cytotoxicity. However, to support differentiation of a subset of tumor or healthy untransformed primary stem cells, NK cells may be required to lyse a number of stem cells and/or those which are either defective or incapable of full differentiation in order to lose their cytotoxic function and gain the ability to secrete cytokines (split anergy). Therefore, patients with cancer may benefit from repeated allogeneic NK cell transplantation for specific elimination of cancer stem cells

New Constraints on the 18F(p,alpha) 15O Rate in Novae from the (d,p) Reaction

The degree to which the (p,gamma) and (p,alpha) reactions destroy 18F at temperatures 1-4x10^8 K is important for understanding the synthesis of nuclei in nova explosions and for using the long-lived radionuclide 18F, a target of gamma-ray astronomy, as a diagnostic of nova mechanisms. The reactions are dominated by low-lying proton resonances near the 18F+p threshold (E_x=6.411 MeV in 19Ne). To gain further information about these resonances, we have used a radioactive 18F beam from the Holifield Radioactive Ion Beam Facility to selectively populate corresponding mirror states in 19F via the inverse d(18F,p)19F neutron transfer reaction. Neutron spectroscopic factors were measured for states in 19F in the excitation energy range 0-9 MeV. Widths for corresponding proton resonances in 19Ne were calculated using a Woods-Saxon potential. The results imply significantly lower 18F(p,gamma)19Ne and 18F(p,alpha)15O reaction rates than reported previously, thereby increasing the prospect of observing the 511-keV annihilation radiation associated with the decay of 18F in the ashes ejected from novae.Comment: Error involving sum rule was corrected. Proton widths were recalculated using a Woods-Saxon potential. Both low-lying resonances (8- and 38-keV) are now included in the rate band. 12 pages, 4 figures, 1 table. Submitted to Phys. Rev.

Electronic health records in outpatient clinics: Perspectives of third year medical students

Abstract Background United States academic medical centers are increasingly incorporating electronic health records (EHR) into teaching settings. We report third year medical students' attitudes towards clinical learning using the electronic health record in ambulatory primary care clinics. Methods In academic year 2005–06, 60 third year students were invited to complete a questionnaire after finishing the required Ambulatory Medicine/Family Medicine clerkship. The authors elicited themes for the questionnaire by asking a focus group of third year students how using the EHR had impacted their learning. Five themes emerged: organization of information, access to online resources, prompts from the EHR, personal performance (charting and presenting), and communication with patients and preceptors. The authors added a sixth theme: impact on student and patient follow-up. The authors created a 21-item questionnaire, based on these themes that used a 5-point Likert scale from "Strongly Agree" to "Strongly Disagree". The authors emailed an electronic survey link to each consenting student immediately following their clerkship experience in Ambulatory Medicine/Family Medicine. Results 33 of 53 consenting students (62%) returned completed questionnaires. Most students liked the EHR's ability to organize information, with 70% of students responding that essential information was easier to find electronically. Only 36% and 33% of students reported accessing online patient information or clinical guidelines more often when using the EHR than when using paper charts. Most students (72%) reported asking more history questions due to EHR prompts, and 39% ordered more clinical preventive services. Most students (69%) reported that the EHR improved their documentation. 39% of students responded that they received more feedback on their EHR notes compared to paper chart notes. Only 64% of students were satisfied with the doctor-patient communication with the EHR, and 48% stated they spent less time looking at the patient. Conclusion Third year medical students reported generally positive attitudes towards using the EHR in the ambulatory setting. They reported receiving more feedback on their electronic charts than on paper charts. However, students reported significant concerns about the potential impact of the EHR on their ability to conduct the doctor-patient encounter.Peer Reviewe

Export of a Toxoplasma gondii Rhoptry Neck Protein Complex at the Host Cell Membrane to Form the Moving Junction during Invasion

One of the most conserved features of the invasion process in Apicomplexa parasites is the formation of a moving junction (MJ) between the apex of the parasite and the host cell membrane that moves along the parasite and serves as support to propel it inside the host cell. The MJ was, up to a recent period, completely unknown at the molecular level. Recently, proteins originated from two distinct post-Golgi specialised secretory organelles, the micronemes (for AMA1) and the neck of the rhoptries (for RON2/RON4/RON5 proteins), have been shown to form a complex. AMA1 and RON4 in particular, have been localised to the MJ during invasion. Using biochemical approaches, we have identified RON8 as an additional member of the complex. We also demonstrated that all RON proteins are present at the MJ during invasion. Using metabolic labelling and immunoprecipitation, we showed that RON2 and AMA1 were able to interact in the absence of the other members. We also discovered that all MJ proteins are subjected to proteolytic maturation during trafficking to their respective organelles and that they could associate as non-mature forms in vitro. Finally, whereas AMA1 has previously been shown to be inserted into the parasite membrane upon secretion, we demonstrated, using differential permeabilization and loading of RON-specific antibodies into the host cell, that the RON complex is targeted to the host cell membrane, where RON4/5/8 remain associated with the cytoplasmic face. Globally, these results point toward a model of MJ organization where the parasite would be secreting and inserting interacting components on either side of the MJ, both at the host and at its own plasma membranes

Real-Time High Resolution 3D Imaging of the Lyme Disease Spirochete Adhering to and Escaping from the Vasculature of a Living Host

Pathogenic spirochetes are bacteria that cause a number of emerging and re-emerging diseases worldwide, including syphilis, leptospirosis, relapsing fever, and Lyme borreliosis. They navigate efficiently through dense extracellular matrix and cross the blood–brain barrier by unknown mechanisms. Due to their slender morphology, spirochetes are difficult to visualize by standard light microscopy, impeding studies of their behavior in situ. We engineered a fluorescent infectious strain of Borrelia burgdorferi, the Lyme disease pathogen, which expressed green fluorescent protein (GFP). Real-time 3D and 4D quantitative analysis of fluorescent spirochete dissemination from the microvasculature of living mice at high resolution revealed that dissemination was a multi-stage process that included transient tethering-type associations, short-term dragging interactions, and stationary adhesion. Stationary adhesions and extravasating spirochetes were most commonly observed at endothelial junctions, and translational motility of spirochetes appeared to play an integral role in transendothelial migration. To our knowledge, this is the first report of high resolution 3D and 4D visualization of dissemination of a bacterial pathogen in a living mammalian host, and provides the first direct insight into spirochete dissemination in vivo

Antigen-expressing immunostimulatory liposomes as a genetically programmable synthetic vaccine

Liposomes are versatile (sub)micron-sized membrane vesicles that can be used for a variety of applications, including drug delivery and in vivo imaging but they also represent excellent models for artificial membranes or cells. Several studies have demonstrated that in vitro transcription and translation can take place inside liposomes to obtain compartmentalized production of functional proteins within the liposomes (Kita et al. in Chembiochem 9(15):2403–2410, 2008; Moritani et al.in FEBS J, 2010; Kuruma et al. in Methods Mol Biol 607:161–171, 2010; Murtas et al. in Biochem Biophys Res Commun 363(1):12–17, 2007; Sunami et al. in Anal Biochem 357(1):128–136, 2006; Ishikawa et al. in FEBS Lett 576(3):387–390, 2004; Oberholzer et al. in Biochem Biophys Res Commun 261(2):238–241, 1999). Such a minimal artificial cell-based model is ideal for synthetic biology based applications. In this study, we propose the use of liposomes as artificial microbes for vaccination. These artificial microbes can be genetically programmed to produce specific antigens at will. To show proof-of-concept for this artificial cell-based platform, a bacterial in vitro transcription and translation system together with a gene construct encoding the model antigen β-galactosidase were entrapped inside multilamellar liposomes. Vaccination studies in mice showed that such antigen-expressing immunostimulatory liposomes (AnExILs) elicited higher specific humoral immune responses against the produced antigen (β-galactosidase) than control vaccines (i.e. AnExILs without genetic input, liposomal β-galactosidase or pDNA encoding β-galactosidase). In conclusion, AnExILs present a new platform for DNA-based vaccines which combines antigen production, adjuvanticity and delivery in one system and which offer several advantages over existing vaccine formulations

Neutron single particle strengths from the (d,p) reaction on F18

The F19 nucleus has been studied extensively. However, there have been no comprehensive experimental studies of F18+n single-particle components in F19, and no measure of neutron vacancies in the F18 ground state, as such experiments require a (radioactive) F18 target or beam. We have used the H2(F18,p)F19 reaction to selectively populate states in F19 that are of F18+n character. The 108.5-MeV radioactive F18+9 beam was provided by the Holifield Radioactive Ion Beam Facility at Oak Ridge National Laboratory. Proton-recoil coincidence data were taken for both α-decaying and particle-stable final states. Angular distributions and spectroscopic factors were measured for nine proton groups, corresponding to 13 states in F19. The results are compared to shell model calculations

Atomic resolution insight into host cell recognition by Toxoplasma gondii.

Accepted versio