Activity of microemulsion-based nanoparticles at the human bio-nano interface: concentration-dependent effects on thrombosis and hemolysis in whole blood

Background: Although microemulsion-based nanoparticles (MEs) may be useful for drug delivery or scavenging, these benefits must be balanced against potential nanotoxicological effects in biological tissue (bio-nano interface). We investigated the actions of assembled MEs and their individual components at the bio-nano interface of thrombosis and hemolysis in human blood. Methods: Oil-in-water MEs were synthesized using ethylbutyrate, sodium caprylate, and pluronic F-68 (ME4) or F-127 (ME6) in 0.9% NaCl_w/v. The effects of MEs or components on thrombosis were determined using thrombo-elastography, platelet contractile force, clot elastic modulus, and platelet counting. For hemolysis, ME or components were incubated with erythrocytes, centrifuged, and washed for measurement of free hemoglobin by spectroscopy. Results and conclusions: The mean particle diameters (polydispersity index) for ME6 and ME4 were 23.6 ± 2.5 nm (0.362) and 14.0 ± 1.0 nm (0.008), respectively. MEs (0, 0.03, 0.3, 3 mM) markedly reduced the thromboelastograph maximal amplitude in a concentration-dependent manner (49.0 ± 4.2, 39.0 ± 5.6, 15.0 ± 8.7, 3.8 ± 1.3 mm, respectively), an effect highly correlated (r2 = 0.94) with similar changes caused by pluronic surfactants (48.7 ± 10.9, 30.7 ± 15.8, 20.0 ± 11.3, 2.0 ± 0.5) alone. Neither oil nor sodium caprylate alone affected the thromboelastograph. The clot contractile force was reduced by ME (27.3 ± 11.1–6.7 ± 3.4 kdynes/cm², P = 0.02, n = 5) whereas the platelet population not affected (175 ± 28–182 ± 23 10⁶/ml, P = 0.12, n = 6). This data suggests that MEs reduced platelet activity due to associated pluronic surfactants, but caused minimal changes in protein function necessary for coagulation. Although pharmacological concentrations of sodium caprylate caused hemolysis (EC₅₀ = 213 mM), MEs and pluronic surfactants did not disrupt erythrocytes. Knowledge of nanoparticle activity and potential associated nanotoxicity at this bio-nano interface enables rational ME design for in vivo applications.     

Ti(III)-Mediated reductions of N-hydroxy imidazoles to 1-protio-2,4(5)-disubstituted derivatives

N-hydroxy imidazoles are converted $\text{via}$ TiCl₃ in MeOH/H₂O to N-protio derivatives, useful precursors of chiral amino acids.     

The hydroazocine route to highly functionalized pyrrolizidines

Studies of the preparation of 1,8-dihydroazocines and transannular cyclization of hydroazocines to produce functionalized pyrrolizidines are described. Results are presented which demonstrate that unsymmetrically substituted acetylenes bearing at least one electron withdrawing groups undergo efficient cycloaddition to 1 - β - styryl - 1,2 - dihydropyridine producing in a regio-selective fashion 3,4 - disubstituted - 1,8 - dihydroazocines. The dihydroazocines generated in this manner can be converted to 1 - formyl - Δ^4,5 - epoxyazocines which undergo interesting rearrangement reactions to form pyrrolizidines when subjected to methoxide deformylation followed by acid treatment. In addition, 1,6,7,8 - tetrahydroazocines can be converted to pyrrolizidines under bromination conditions. The intriguing chemical process which occur under the conditions outlined above are described.     

Hospital profit planning under Medicare reimbursement.

The federal Medicare regulations reimburse hospitals on a pro rata share of the hospital's cost. Hence, to meet its financial requirements, a hospital is forced to shift more of the financial burdens onto its private patients. This procedure has contributed to double digit inflation in hospital prices and to proposed federal regulation to control the rate of increase in hospital revenues. In this regulatory environment, we develop nonlinear programming pricing and cost allocation models to aid hospital administrators in meeting their profit maximizing and profit satisfying goals. The model enables administrators to explore tactical issues such as: (i) studying the relationship between a voluntary or legislated cap on a hospital's total revenues and the hospital's profitability, (ii) identifying those departments within the hospital that are the most attractive candidates for cost reduction or cost containment efforts, and (iii) isolating those services that should be singled out by the hospital manager for renegotiation of the prospective or "customary and reasonable" cap. Finally the modeling approach is helpful in explaining the departmental cross subsidies observed in practice, and can be of aid to federal administrators in assessing the impacts of proposed changes in the Medicare reimbursement formula.     

Chapter 8 Estimating production frontier shifts: An application of DEA to technology assessment

Evaluating the separate impacts of factors which affect the productive efficiency of organizations is difficult. This is because the impact of a factor is often contingent on other organizational, managerial or environmental characteristics. Standard econometric methods are limited in their ability to discriminate between efficient and inefficient units, and often impose considerable structure in parametrically specified functional forms. We show how a nonparametric data envelopment approach can be employed to focus on the best that can be achieved, with and without the key characteristic of interest. We illustrate the approach with real data from the service sector requiring the evaluation of the impact of a new information technology. The analytical technique estimates the annual savings in materials cost for an average store using the information technology to be over $4,000 (2.04% of materials cost), well in excess of the amortized annual cost for its installation. Establishing the separation in the production frontier in different regions, we show that the information technology had a substantially larger impact for the bigger stores. The savings were about 80% greater in the larger volume stores than in the smaller volume operations, an important consideration in setting the priorities for installation. The illustration underscores the flexibility of DEA in detecting different impacts of a new technology in different environments.     

Multiplexing fiber bragg grating sensors

Bragg reflection gratings and out-coupling taps for sensors can be written holographically within the core of many commercial fibers available today. The gratings appear to be permanent and have been tested to temperatures in excess of 500°C. Quasi-distributed temperature, strain, pressure, chemical, and interferometric sensors can be made with the wavelength selective, reflection gratings, and taps. The fiber gratings, and the different types of sensors they can make, conveniently lend themselves to (wavelength-division multiplexing) WDM, (time-division multiplexing) TDM, and (frequency-division multiplexing) FDM types of multiplexing schemes. Instrumentation to detect the multiple sensors and measure their spectral shift for localized and quasi-distributed sensing is currently under development.     

Instructions to authors

In a cylindrical-beam plasma system with ω_pe < ω_ce, large-amplitude (W/nT ～ 1) bursts of spatially localized (length ～λ/2) electron plasma waves are observed to be correlated with accelerated background electrons and an increase in the luminosity of the plasma.     

Detection of chemical warfare simulants by phosphorylation of a coumarin oximate

The detection of chemical warfare simulants is attained by the PET mechanism that gives an "off-on" fluorescent response with a half-life of approximately 50 ms upon phosphorylation of a reactive oximate functionality; the X-ray crystal structure of the oximate was also obtained and is discussed.     

On the kinetic and thermodynamic reactivity of lithium di(alkyl)amidozincate bases in directed ortho metalation

Sequential reaction of HTMP (= 2,2,6,6-tetramethylpiperidine) with nBuLi and Et2Zn affords unsolvated polymer chains of EtZn(micro-Et)(micro-TMP)Li 6. The scope of this reagent in directed ortho metalation (DoM) chemistry has been tested by its reaction with N,N-diisopropylnaphthamide in THF to give EtZn(micro-C10H6C(O)NiPr2-2)2Li.2THF 7. Data reveal that 6 has undergone reaction with 2 equiv of aromatic tertiary amide and imply that it exhibits dual alkyl/amido basicity. DFT calculations reveal that direct alkyl basicity is kinetically disfavored and instead point to a stepwise mechanism whereby 6 acts as an amido base, liberating HTMP during the first DoM event. Re-coordination of the amine at lithium then incurs the elimination of EtH. Reaction of the resulting alkyl(amido)(arylamido)zincate with a second equivalent of N,N-diisopropylnaphthamide eliminates HTMP and affords 7. Both DoM steps involve the exhibition of amido basicity and each reveals a low kinetic barrier to reaction. Understanding of this reaction sequence is tested by treating 6 with N,N-diisopropylbenzamide in THF. On the basis of theory and experiment, the presence of THF solvent (in place of stronger Lewis bases) combined with the use of a sterically less congested aromatic amide is expected to encourage threefold, stepwise reaction. Isolation and characterization of the resulting tripodal zincate Zn(micro-C6H4C(O)NiPr2-2)3Li.THF 8 bears this out and suggests a significant new level of control in zincate-induced DoM chemistry through the combination of experiment and DFT studies.