Palladium complexes of bidentate pyridine N‐heterocyclic carbenes: Optical resolution,antimicrobial and cytotoxicity studies

A series of bidentate pyridine‐functionalized palladium N‐heterocyclic carbene (Pd NHC) complexes with various wingtip substituents (R = methyl, phenyl and tert‐butyl) have been synthesized and evaluated for their potential biomedical applications as antimicrobials and antiproliferative drug candidates. The obtained Pd NHC complexes were applied in a standard broth microdilution assay for determination of their antimicrobial activities against thirteen strains of pathogenic microorganisms. In addition to that, cytotoxic activities of the Pd NHC complexes were also evaluated against three human cancer cell lines, namely breast (MCF‐7), colon (HCT116) and oral (H103) cancer cells, using a standard MTT assay. Upon coordination to palladium, the Pd NHC complexes show significant antimicrobial activities with minimum inhibitory concentrations in the micromolar range, and they are cytotoxic to the tested carcinomas with IC₅₀ ranging from 13 to 38 μM. Evidences for influence of both wingtip substituents and optical isomerism on the biological activities of the complexes have been found.     

A Framework for Comparative Evaluation of Dosimetric Methods to Triage a Large Population Following a Radiological Event

BACKGROUND: To prepare for a possible major radiation disaster involving large numbers of potentially exposed people, it is important to be able to rapidly and accurately triage people for treatment or not, factoring in the likely conditions and available resources. To date, planners have had to create guidelines for triage based on methods for estimating dose that are clinically available and which use evidence extrapolated from unrelated conditions. Current guidelines consequently focus on measuring clinical symptoms (e.g., time-to-vomiting), which may not be subject to the same verification of standard methods and validation processes required for governmental approval processes of new and modified procedures. Biodosimeters under development have not yet been formally approved for this use. Neither set of methods has been tested in settings involving large-scale populations at risk for exposure. OBJECTIVE: To propose a framework for comparative evaluation of methods for such triage and to evaluate biodosimetric methods that are currently recommended and new methods as they are developed. METHODS: We adapt the NIH model of scientific evaluations and sciences needed for effective translational research to apply to biodosimetry for triaging very large populations following a radiation event. We detail criteria for translating basic science about dosimetry into effective multi-stage triage of large populations and illustrate it by analyzing 3 current guidelines and 3 advanced methods for biodosimetry. CONCLUSIONS: This framework for evaluating dosimetry in large populations is a useful technique to compare the strengths and weaknesses of different dosimetry methods. It can help policy-makers and planners not only to compare the methods' strengths and weaknesses for their intended use but also to develop an integrated approach to maximize their effectiveness. It also reveals weaknesses in methods that would benefit from further research and evaluation.     

A computational study of x-ray emission from high-Z x-ray sources on the National Ignition Facility laser

We have begun to use 350–500 kJ of 1/3-micron laser light from the National Ignition Facility (NIF) laser to create millimeter-scale, bright multi-keV x-ray sources. In the first set of shots we achieved 15%–18% x-ray conversion efficiency into Xe M-shell (∼1.5–2.5 keV), Ar K-shell (∼3 keV) and Xe L-shell (∼4–5.5 keV) emission (Fournier et al., Phys. Plasmas 17, 082701, 2010), in good agreement with the emission modeled using a 2D radiation-hydrodynamics code incorporating a modern Detailed Configuration Accounting atomic model in non-LTE (Colvin et al., Phys. Plasmas, 17, 073111, 2010). In this paper we first briefly review details of the computational model and comparisons of the simulations with the Ar/Xe NIF data. We then discuss a computational study showing sensitivity of the x-ray emission to various beam illumination details (beam configuration, pointing, peak power, pulse shape, etc.) and target parameters (size, initial density, etc.), and finally make some predictions of how the x-ray conversion efficiency expected from NIF shots scales with atomic number of the emitting plasma.     

Synthesis of amorphous aliphatic polyester‐ether homo‐ and copolymers by radical polymerization of ketene acetals

Radical ring‐opening polymerization has been efficiently used to copolymerize 2‐methylene‐1,3,6‐trioxocane (MTC) and 2‐methylene‐1,3‐dioxepane (MDO). The cyclic ketene acetal MTC was first synthesized and homopolymerized at different temperatures using either 2,2‐azobisisobutyronitrile or dicumyl peroxide as initiator. The polymerization mechanism was not temperature‐dependent, and the polymerization proceeded with 100% ring‐opening at all the temperatures evaluated. The structures of MTC and PMTC were verified by ¹H‐nuclear magnetic resonance (NMR) and ¹³C‐NMR spectroscopies. A number‐average molecular weight of 6500 was obtained after 2 days at 70 °C in bulk, which was somewhat higher than the theoretical molecular weight. A significant amount of branching was detected from the high polydispersity index as well as the glass‐transition temperatures. The polyester‐ether was then successfully obtained by copolymerization of MTC with MDO. Different feed ratios and temperatures were used to map the reaction, and the copolymers were characterized by NMR, size exclusion chromatography, and differential scanning calorimetry. The amount of MTC within the polymer was independent of the feed ratio and always higher than the amount of MDO. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Bio‐safe synthesis of linear and branched PLLA

The catalytic activities of Bi(III) acetate (Bi(OAc)₃) and of creatinine towards the ring‐opening polymerization of L ‐lactide have been compared with those of a stannous (II) ethylhexanoate ((SnOct)₂)‐based system and with those of a system catalyzed by enzymes. All four were suitable catalysts for the synthesis of high and moderate molecular weight poly(L ‐lactide)s and the differences in reactivity and efficiency have been studied. Linear and branched poly(L ‐lactide)s were synthesized using these bio‐safe initiators together with ethylene glycol, pentaerythritol, and myoinositol as coinitiators. The polymerizations were performed in bulk at 120 and 140 °C and different reactivities and molecular weights were achieved by adding different amounts of coinitiators. A molecular weight of 105,900 g/mol was achieved with 99% conversion in 5 h at 120 °C with a Bi(OAc)₃‐based system. This system was comparable to Sn(Oct)₂ at 140 °C. The reactivity of creatinine is lower than that of Bi(OAc)₃ but higher compared with enzymes lipase PS (Pseudomonas fluorescens). A ratio of Sn(Oct)₂M_o/I_o 10,000:1 was needed to achieve a polymer with a reasonable low amount of tin residue in the precipitated polymer, and a system catalyzed by creatinine at 140 °C has a higher conversion rate than such a system. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1214–1219, 2010     

5-Aminolevulinic Acid-induced Protoporphyrin IX Levels in Tissue of Human Malignant Brain Tumors

Protoporphyrin IX (PpIX) produced from exogenous, orally administered 5-aminolevulinic acid (ALA) displays high tumor-selective uptake and is being successfully employed for fluorescence-guided resection (FGR) of human malignant gliomas. Furthermore, the phototoxicity of PpIX can be utilized for photodynamic therapy (PDT) of brain tumors, which has been shown previously. Here, the absolute PpIX concentration in human brain tissue was investigated following oral ALA administration (20 mg kg⁻¹ b.w.). An extraction procedure was used to quantify PpIX in macroscopic tissue samples, weighing 0.013–0.214 g, obtained during FGR. The PpIX concentration was significantly higher in vital grade IV tumors (5.8 ± 4.8 μm , mean ± SD, range 0–28.2 μm , n = 8) as compared with grade III tumors (0.2 ± 0.4 μm , mean ± SD, range 0–0.9 μm , n = 4). There was also a large heterogeneity within grade IV tumors with PpIX displaying significantly lower levels in infiltration zones and necrotic regions as compared with vital tumor parts. The average PpIX concentration in vital grade IV tumor parts was in the range previously shown sufficient for PDT-induced tissue damage following irradiation. However, the feasibility of PDT for grade III brain tumors and for grade IV brain tumors displaying mainly necrotic tissue areas without solid tumor parts needs to be further investigated.     

An analytical model for reverse automotive production planning and pricing

Automotive shredders need a reverse production planning strategy that includes determining at what price to purchase vehicle hulks from different sources. In this paper, we formulate the automotive reverse production planning and pricing problem in a nonlinear programming model, develop an approximate supply function for hulks when adjacent shredders price independently, and compare two hulk pricing strategies in three trends for ferrous metal and hulk prices: constant, increasing and decreasing. The case study results indicate that adjusting purchase price based on hulk composition in coordination with planning for purchasing, storing and processing can increase net revenue by 7–15%.