Adsorption interaction of carrier-free thallium species with gold and quartz surfaces

The adsorption interactions of thallium and its compounds with gold and quartz surfaces were investigated. Carrier-free amounts of thallium were produced in nuclear fusion reactions of alpha particles with thick gold targets. The method chosen for the studies was gas thermochromatography and varying the redox potential of the carrier gases. It was observed that thallium is extremely sensitive to trace amounts of oxygen and water, and can even be oxidized by the hydroxyl groups located on the quartz surface. The experiments on a quartz surface with O2, He, H2 gas in addition with water revealed the formation and deposition of only one thallium species – TlOH. The adsorption enthalpy was determined to be Δ HSiO2ads(TlOH) = −134 ± 5 kJ mol−1. A series of experiments using gold as stationary surface and different carrier gases resulted in the detection of two thallium species – metallic Tl (H2 as carrier gas) and TlOH (O2, O2+H2O and H2+H2O as pure carrier gas or carrier gas mixture) with Δ HAuads(Tl) = −270 ± 10 kJ mol− and Δ HAuads(TlOH) = −146 ± 3 kJ mol−1. These data demonstrate a weak interaction of TlOH with both quartz and gold surfaces. The data represent important information for the design of future experiments with the heavier homologue of Tl in group 13 of the periodic table – element 113 (E113).

Design, synthesis and biological evaluation of 5$\sp\prime$-mononucleotide prodrugs: Strategies to introduce nucleotides into cells

The neutral bis ((pivaloyloxy)methyl) (PIV$\sb2\rbrack$ derivatives of FdUMP, ddUMP, and AZTMP were synthesized as potential membrane-permeable prodrugs of FdUMP, ddUMP, and AZTMP. These compounds were designed to enter cells by passive diffusion and revert to the parent nucleotides after removal of the PIV groups by hydrolytic enzymes. These prodrugs were prepared by condensation of FUdR, ddU, and AZT with PIV$\sb2$ phosphate in the presence of triphenylphosphine and diethyl azodicarboxylate (the Mitsunobo reagent). PIV$\sb2$-FdUMP, PIV$\sb2$-ddUMP, and PIV$\sb2$-AZTMP were stable in the pH range 1.0-4.0 (t$\sb{1/2} = {>}$100 h). They were also fairly stable at pH 7.4 (t$\sb{1/2} = {>}$40 h). In 0.05 M NaOH solution, however, they were rapidly degraded (t$\sb{1/2} < 2$ min). In the presence hog liver carboxylate esterase, they were converted quantitatively to the corresponding phosphodiesters, PIV$\sb1$-FdUMP, PIV$\sb1$-ddUMP, and PIV$\sb1$-AZTMP; after 24 h incubation, only trace amounts of FdUMP, ddUMP, and AZTMP (1-5%) were observed indicating that the PIV$\sb1$ compounds were poor substrates for the enzyme. In human plasma, the PIV$\sb2$ compounds were rapidly degraded with half-lives of less than 5 min. The rate of degradation of the PIV$\sb2$ compounds in the presence of phosphodiesterase I was the same as that in buffer controls, indicating that they were not substrates for this enzyme. In the presence of phosphodiesterase I, PIV$\sb1$-FdUMP, PIV$\sb1$-ddUMP, and PIV$\sb1$-AZTMP were converted quantitatively to FdUMP, ddUMP, and AZTMP.^ PIV$\sb2$-ddUMP and PIV$\sb2$-AZTMP were effective at controlling HIV type 1 infection in MT-4 and CEM tk$\sp-$ cells in culture. Mechanistic studies demonstrated that PIV$\sb2$-ddUMP and PIV$\sb2$-AZTMP were taken up by the cells and converted to ddUTP and AZTTP, both potent inhibitors of HIV reverse transcriptase. However, a potential shortcoming of PIV$\sb2$-ddUMP and PIV$\sb2$-AZTMP as clinical therapeutic agents is that they are rapidly degraded (t$\sb{1/2}$ = approx. 4 minutes) in human plasma by carboxylate esterases. To circumvent this limitation, chemically-labile nucleotide prodrugs and liposome-encapsulated nucleotide prodrugs were investigated. In the former approach, the protective groups bis(N, N-(dimethyl)carbamoyloxymethyl) (DM$\sb2$) and bis (N-(piperidino)carbamoyloxymethyl) (DP$\sb2$) were used to synthesize DM$\sb2$-ddUMP and DP$\sb2$-ddUMP, respectively. In aqueous buffers (pH range 1.0-9.0) these compounds were degraded with half-lives of 3 to 4 h. They had similar half-lives in human plasma demonstrating that they were resistant to esterase-mediated cleavage. However, neither compound gave rise to significant concentrations of ddUMP in CEM or CEM tk$\sp-$ cells. In the liposome-encapsulated nucleotide prodrug approach, three different liposomal formulations of PIV$\sb2$-ddUMP (L-PIV$\sb2$-ddUMP) were investigated. The half-lifes of these L-PIV$\sb2$-ddUMP preparations in human plasma were 2 h compared with 4 min for the free drug. The preparations were more effective at controlling HIV-1 infection than free PIV$\sb2$-ddUMP in human T cells in culture. Collectively, these data indicate that PIV$\sb2$-FdUMP, PIV$\sb2$-ddUMP, and PIV$\sb2$-AZTMP are effective membrane-permeable prodrugs of FdUMP, ddUMP, and AZTMP. ^

The FReedom from Ischemic Events-New Dimensions for Survival (FRIENDS) registry: design of a prospective cohort study of patients with advanced peripheral artery disease.

BACKGROUND Advanced lower extremity peripheral artery disease (PAD), whether presenting as acute limb ischemia (ALI) or chronic critical limb ischemia (CLI), is associated with high rates of cardiovascular ischemic events, amputation, and death. Past research has focused on strategies of revascularization, but few data are available that prospectively evaluate the impact of key process of care factors (spanning pre-admission, acute hospitalization, and post-discharge) that might contribute to improving short and long-term health outcomes. METHODS/DESIGN The FRIENDS registry is designed to prospectively evaluate a range of patient and health system care delivery factors that might serve as future targets for efforts to improve limb and systemic outcomes for patients with ALI or CLI. This hypothesis-driven registry was designed to evaluate the contributions of: (i) pre-hospital limb ischemia symptom duration, (ii) use of leg revascularization strategies, and (iii) use of risk-reduction pharmacotherapies, as pre-specified factors that may affect amputation-free survival. Sequential patients would be included at an index "vascular specialist-defined" ALI or CLI episode, and patients excluded only for non-vascular etiologies of limb threat. Data including baseline demographics, functional status, co-morbidities, pre-hospital time segments, and use of medical therapies; hospital-based use of revascularization strategies, time segments, and pharmacotherapies; and rates of systemic ischemic events (e.g., myocardial infarction, stroke, hospitalization, and death) and limb ischemic events (e.g., hospitalization for revascularization or amputation) will be recorded during a minimum of one year follow-up. DISCUSSION The FRIENDS registry is designed to evaluate the potential impact of key factors that may contribute to adverse outcomes for patients with ALI or CLI. Definition of new "health system-based" therapeutic targets could then become the focus of future interventional clinical trials for individuals with advanced PAD.

High-density large-scale field emitter arrays for x-ray free electron laser cathodes

High brightness electron sources are of great importance for the operation of the hard X-ray free electron lasers. Field emission cathodes based on the double-gate metallic field emitter arrays (FEAs) can potentially offer higher brightness than the currently used ones. We report on the successful application of electron beam lithography for fabrication of the large-scale single-gate as well as double-gate FEAs. We demonstrate operational high-density single-gate FEAs with sub-micron pitch and total number of tips up to 106 as well as large-scale double-gate FEAs with large collimation gate apertures. The details of design, fabrication procedure and successful measurements of the emission current from the single- and double-gate cathodes are presented.

Pododermatitis in Captive and Free-Ranging Greater Flamingos (Phoenicopterus roseus)

Pododermatitis is frequent in captive flamingos worldwide, but little is known about the associated histopathologic lesions. Involvement of a papillomavirus or herpesvirus has been suspected. Histopathologic evaluation and viral assessment of biopsies from 19 live and 10 dead captive greater flamingos were performed. Selected samples were further examined by transmission electron microscopy and immunohistochemistry. Feet from 10 dead free-ranging greater flamingos were also evaluated. The histologic appearance of lesions of flamingos of increasing age was interpreted as the progression of pododermatitis. Mild histologic lesions were seen in a 3-week-old flamingo chick with no macroscopic lesions, and these were characterized by Micrococcus-like bacteria in the stratum corneum associated with exocytosis of heterophils. The inflammation associated with these bacteria may lead to further histologic changes: irregular columnar proliferations, papillary squirting, and dyskeratosis. In more chronic lesions, hydropic degeneration of keratinocytes, epidermal hyperplasia, and dyskeratosis were seen at the epidermis, as well as proliferation of new blood vessels and increased intercellular matrix in the dermis. Papillomavirus DNA was not identified in any of the samples, while herpesvirus DNA was seen only in a few cases; therefore, these viruses were not thought to be the cause of the lesions. Poor skin health through suboptimal husbandry may weaken the epidermal barrier and predispose the skin to invasion of Micrococcus-like bacteria. Histologic lesions were identified in very young flamingos with no macroscopic lesions; this is likely to be an early stage lesion that may progress to macroscopic lesions.

Biochanin A and prunetin improve epithelial barrier function in intestinal CaCo-2 cells via downregulation of ERK, NF-κB, and tyrosine phosphorylation

The single-layered gut epithelium represents the primary line of defense against environmental stressors; thereby monolayer integrity and tightness are essentially required to maintain gut health and function. To date only a few plant-derived phytochemicals have been described as affecting intestinal barrier function. We investigated the impact of 28 secondary plant compounds on the barrier function of intestinal epithelial CaCo-2/TC-7 cells via transepithelial electrical resistance (TEER) measurements. Apart from genistein, the compounds that had the biggest effect in the TEER measurements were biochanin A and prunetin. These isoflavones improved barrier tightness by 36 and 60%, respectively, compared to the untreated control. Furthermore, both isoflavones significantly attenuated TNFα-dependent barrier disruption, thereby maintaining a high barrier resistance comparable to nonstressed cells. In docking analyses exploring the putative interaction with the tyrosine kinase EGFR, these novel modulators of barrier tightness showed very similar values compared to the known tyrosine kinase inhibitor genistein. Both biochanin A and prunetin were also identified as potent reducers of NF-κB and ERK activation, zonula occludens 1 tyrosine phosphorylation, and metalloproteinase-mediated shedding activity, which may account for the barrier-improving ability of these isoflavones.

Exploring the validity and reliability of a questionnaire for evaluating virtual patient design with a special emphasis on fostering clinical reasoning

Background: Virtual patients (VPs) are increasingly used to train clinical reasoning. So far, no validated evaluation instruments for VP design are available. Aims: We examined the validity of an instrument for assessing the perception of VP design by learners. Methods: Three sources of validity evidence were examined: (i) Content was examined based on theory of clinical reasoning and an international VP expert team. (ii) The response process was explored in think-aloud pilot studies with medical students and in content analyses of free text questions accompanying each item of the instrument. (iii) Internal structure was assessed by exploratory factor analysis (EFA) and inter-rater reliability by generalizability analysis. Results: Content analysis was reasonably supported by the theoretical foundation and the VP expert team. The think-aloud studies and analysis of free text comments supported the validity of the instrument. In the EFA, using 2547 student evaluations of a total of 78 VPs, a three-factor model showed a reasonable fit with the data. At least 200 student responses are needed to obtain a reliable evaluation of a VP on all three factors. Conclusion: The instrument has the potential to provide valid information about VP design, provided that many responses per VP are available.

Is ego depletion associated with increased distractibility? Results from a basketball free throw task

Objectives: It has been repeatedly demonstrated that athletes in a state of ego depletion do not perform up to their capabilities in high pressure situations. We assume that momentarily available self-control strength determines whether individuals in high pressure situations can resist distracting stimuli. Design/method: In the present study, we applied a between-subjects design, as 31 experienced basketball players were randomly assigned to a depletion group or a non-depletion group. Participants performed 30 free throws while listening to statements representing worrisome thoughts (as frequently experienced in high pressure situations) over stereo headphones. Participants were instructed to block out these distracting audio messages and focus on the free throws. We postulated that depleted participants would be more likely to be distracted. They were also assumed to perform worse in the free throw task. Results: The results supported our assumption as depleted participants paid more attention to the distracting stimuli. In addition, they displayed worse performance in the free throw task. Conclusions: These results indicate that sufficient levels of self-control strength can serve as a buffer against distracting stimuli under pressure.

Bayesian dual threshold design with Dirichlet distribution: An alternative way to frequentist multi-stage phase II designs in oncology

Many phase II clinical studies in oncology use two-stage frequentist design such as Simon's optimal design. However, they have a common logistical problem regarding the patient accrual at the interim. Strictly speaking, patient accrual at the end of the first stage may have to be suspended until all patients have events, success or failure. For example, when the study endpoint is six-month progression free survival, patient accrual has to be stopped until all outcomes from stage I is observed. However, study investigators may have concern when accrual is suspended after the first stage due to the loss of accrual momentum during this hiatus. We propose a two-stage phase II design that resolves the patient accrual problem due to an interim analysis, and it can be used as an alternative way to frequentist two-stage phase II studies in oncology. ^

Behavioral journalism newsletters to increase employee participation in a free worksite wellness center

Background. Providing an worksite fitness center for employees is an effective setting to increase an adult’s levels of physical activity, demonstrably reducing health care costs and elevating employee productivity. Increasing compliance and adherence among employees to consistently utilize an onsite facility remains a challenge.^ Purpose. To illustrate if two electronic behavioral journalism newsletters can increase employee participation in a free worksite wellness center.^ Design. A randomized control trial was implemented. ^ Setting. A large petroleum-producing corporation located in Houston, Texas Subjects.70 full or part time employees that had checked into visited the wellness center during September, October, and November 2009. ^ Intervention. Two behavioral journalism newsletters were created based on authentic community member role model interviews. Newsletters were distributed to intervention group participants via company email. Intervention and control group participant’s visits to the wellness center were monitored via a key card check in system at the facility for two weeks following the newsletter intervention.^ Analysis. Count variable statistics were used to identify rate differences between the intervention and control group wellness center visits. A binomial test for equality of proportions was used to identify differences between participants that had at least one visit to the wellness center compared with those with none.^ Results. Both intervention and control groups had a baseline of zero wellness center visits. The control group had a mean visit rate 0.441 and the intervention group had 0.857. A 0.416, almost one half more visits were found among the intervention group.^ Conclusion. This study indicates that behavioral journalism newsletters featuring a role model from within the worksite population can be a cost effective communication method to improve participation in an onsite wellness center. ^

Breast cancer risk with aromatase inhibition and phytoestrogen-free diet

In this thesis a mouse model was used to examine the effect of pubertal estrogen inhibition and a phytoestrogen-free diet on the development of mammary glands. The study question was does treatment with aromatase inhibitor during puberty increase susceptibility to breast cancer among cohorts that consumed a diet free of phytoestrogens. The study design consisted of a cohort of mice treated with aromatase inhibitor, letrozole, during puberty and a vehicular group that was used as a control. Both groups were fed a diet free of phytoestrogens from the time of weaning until sacrifice during adulthood. The study aimed to assess mammary gland development in terms of breast cancer risk. The methods employed in this research included morphological and histological analysis of mammary glands, as well as estradiol, RNA and protein analysis. The main finding of the study was that mice exposed to aromatase inhibitor during puberty developed mammary glands with specific characteristics suggestive of vulnerability to oncogenesis such as increased lateral branching, increased number of glands, increase ductal hyperplasia, and diminished expression of TGFβ and p27 protein levels. The conclusions suggest that puberty is a critical period in which the mammary gland is susceptible to environmental threats that may result in deleterious epigenetic effects leading to an increased breast cancer risk in adulthood. This study has several public health implications; the most significant is that environmental threats during puberty may result in adverse mammary gland development and that phytoestrogen sources in the diet are necessary for normal maturation of the mammary glands.^

Seagrass and associated benthic community data derived from field surveys at Low Isles, Great Barrier Reef, conducted July-August, 1997

The distribution of seagrass and associated benthic communities on the reef and lagoon of Low Isles, Great Barrier Reef, was mapped between the 29 July and 29 August 1997. For this survey, observers walked or free-dived at survey points positioned approximately 50 m apart along a series of transects. Visual estimates of above-ground seagrass biomass and % cover of each benthos and substrate type were recorded at each survey point. A differential handheld global positioning system (GPS) was used to locate each survey point (accuracy ±3m). A total of 349 benthic survey points were examined. To assist with mapping meadow/habitat type boundaries, an additional 177 field points were assessed and a georeferenced 1:12,000 aerial photograph (26th August 1997) was used as a secondary source of information. Bathymetric data (elevation below Mean Sea Level) measured at each point assessed and from Ellison (1997) supplemented information used to determine boundaries, particularly in the subtidal lagoon. 127.8 ±29.6 hectares was mapped. Seagrass and associated benthic community data was derived by haphazardly placing 3 quadrats (0.25m**2) at each survey point. Seagrass above ground biomass (standing crop, grams dry weight (g DW m**-2)) was determined within each quadrat using a non-destructive visual estimates of biomass technique and the seagrass species present identified. In addition, the cover of all benthos was measured within each of the 3 quadrats using a systematic 5 point method. For each quadrat, frequency of occurrence for each benthic category was converted to a percentage of the total number of points (5 per quadrat). Data are presented as the average of the 3 quadrats at each point. Polygons of discrete seagrass meadow/habitat type boundaries were created using the on-screen digitising functions of ArcGIS (ESRI Inc.), differentiated on the basis of colour, texture, and the geomorphic and geographical context. The resulting seagrass and benthic cover data of each survey point and for each seagrass meadow/habitat type was linked to GPS coordinates, saved as an ArcMap point and polygon shapefile, respectively, and projected to Universal Transverse Mercator WGS84 Zone 55 South.

Did the least developed countries benefit from duty-free quota-free access to the Japanese market?

Countries classified as least developed countries (LDCs) were granted duty-free quota-free (DFQF) access to the Japanese market. This study examines the impact of that access and finds that, in general, it did not benefit the LDCs. The construction of concordance tables for Japan's 9 digit tariff line codes enables analysis at the tariff line level, which overcomes a possible aggregation bias. The exogenous nature of DFQF access mitigates the endogeneity problem. Various estimation models, including the triple difference estimator, show that in general the LDCs did not benefit from DFQF access to the Japanese market. The total value of imports from LDCs has been increasing, but the imports granted both zero tariffs and substantial preference margins over non-LDC countries were not successful. These findings suggest that for LDCs the tariff barrier is a relatively small obstacle: Trade is affected more strongly by other factors, such as infrastructure, nontariff barriers, geographic distance, and cultural differences.

Optimization of a label-free biosensor vertically characterized based on a periodic lattice of high aspect ratio SU-8 nano-pillars with a simplified 2D theoretical model

We have recently demonstrated a biosensor based on a lattice of SU8 pillars on a 1 μm SiO2/Si wafer by measuring vertically reflectivity as a function of wavelength. The biodetection has been proven with the combination of Bovine Serum Albumin (BSA) protein and its antibody (antiBSA). A BSA layer is attached to the pillars; the biorecognition of antiBSA involves a shift in the reflectivity curve, related with the concentration of antiBSA. A detection limit in the order of 2 ng/ml is achieved for a rhombic lattice of pillars with a lattice parameter (a) of 800 nm, a height (h) of 420 nm and a diameter(d) of 200 nm. These results correlate with calculations using 3D-finite difference time domain method. A 2D simplified model is proposed, consisting of a multilayer model where the pillars are turned into a 420 nm layer with an effective refractive index obtained by using Beam Propagation Method (BPM) algorithm. Results provided by this model are in good correlation with experimental data, reaching a reduction in time from one day to 15 minutes, giving a fast but accurate tool to optimize the design and maximizing sensitivity, and allows analyzing the influence of different variables (diameter, height and lattice parameter). Sensitivity is obtained for a variety of configurations, reaching a limit of detection under 1 ng/ml. Optimum design is not only chosen because of its sensitivity but also its feasibility, both from fabrication (limited by aspect ratio and proximity of the pillars) and fluidic point of view. (© 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Freeform Fresnel RXI-RR Köhler design with spectrum-splitting for photovoltaics

The development of a novel optical design for the high concentration photovoltaics (HPCV) nonimaging concentrator (>500x) that utilizes a built-in spectrum splitting concept is presented. The primary optical element (POE) is a flat Fresnel lens and the secondary optical element (SOE) is a free-form RXI-type concentrator with a band-pass filter embedded in it. The POE and SOE perform Köhler integration to produce light homogenization on the receiver. The system uses a combination of a commercial concentration GaInP/GaInAs/Ge 3J cell and a concentration Back-PointContact (BPC) silicon cell for efficient spectral utilization, and an external confinement technique for recovering the 3J cell’s reflection. A design target of an “equivalent” cell efficiency ~46% is predicted using commercial 39% 3J and 26% Si cells. A projected CPV module efficiency of greater than 38% is achievable at a concentration level greater than 500X with a wide acceptance angle of ±1º. A first proof-of concept receiver prototype has been manufactured using a simpler optical architecture (with a lower concentration, ~100x and lower simulated added efficiency), and experimental measurements have shown up to 39.8% 4J receiver efficiency using a 3J cell with a peak efficiency of 36.9%