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The interfacial interactions between methylene diphenyl di-isocyanate (MDI) and polymeric MDI (PMDI) with 316L stainless steel have been studied in order to understand the adhesion properties of polyurethane based adhesives (containing free isocyanate groups) on metal surfaces. A thin (< 5 nm) layer of MDI and PMDI was deposited on the surface of clean 316L stainless steel and then analysed by X-ray photoelectron spectroscopy (XPS) and time of flight secondary ion mass spectrometry (ToF-SIMS). By using density functional theory (DFT) methods for the interpretation of XPS data, the presence of specific interactions between the adsorbate and the substrate was established. The reaction between isocyanate and metal hydroxyl groups with the formation of urethane-like bonding with the metal was observed. The formation of hydrogen bonds between the isocyanate nitrogen and the hydroxyl groups and the formation of nitrogen-metal double bond, as consequence of the cycloaddition reaction between isocyanate and metal oxide, are also proposed.

Prior research indicates that preschool classroom quality is positively associated with children’s emergent academic skills at the end of the preschool period, but these associations appear to diminish during kindergarten (K). To consider the accumulation of classroom experiences during preschool and K, data were drawn from a sample of children (N = 1015) who participated in state-funded pre-K programs across six states and were followed into the spring of K. We examined if pre-K and K classroom quality were associated with children’s language, literacy, and mathematics skills in the spring of K after controlling for pre-K entry skills, child background demographics, and other classroom covariates. Classroom quality was assessed with the Classroom Assessment Scoring System. We found that additive cumulative effects described associations between classroom quality and children’s language and literacy outcomes. For language skills, higher-quality pre-K Instructional Support predicted better K language skills at all levels of Instructional Support quality in K, but higher-quality K Instructional Support also contributed to the prediction of better K language skills in an additive manner. For literacy skills, higher-quality pre-K Instructional Support, Emotional Support, and Classroom Management predicted better K literacy skills at all levels of K quality, but each domain of K quality also contributed to the prediction of better K literacy skills in an additive manner. In contrast, for mathematics, we found that multiplicative cumulative effects described associations between classroom quality and K mathematics skills such that the positive predictive effect of pre-K Instructional Support and Emotional Support was enhanced as the level of K quality increased in each of these domains, respectively. Moreover, sensitivity analyses revealed that higher-quality pre-K Instructional Support and Emotional Support significantly predicted better K mathematics skills for children who experienced high, but not average or low levels of K quality in these domains, respectively. Implications are discussed in relation to classroom quality alignment during pre-K and the early elementary grades.

Early literacy skills play an important role in children’s success in school. Especially important to better literacy skills may be the quality of the classroom environment (emotional support, classroom organization, and instructional support) across the early years of schooling. This study used an a priori threshold of quality approach to understanding the possible link between the number of years of better classroom quality over four years, from kindergarten through third grade, in relation to children’s literacy skills by third grade. This study examined a representative sample of 1292 children followed from birth who lived in low-wealth rural counties in the United States. These children were followed into school with classroom observations conducted each year from kindergarten through third grade and literacy related achievement measures in pre-kindergarten and third grade. Findings suggested that even after controlling for poverty related variables, the quality of the home environment, school entry literacy skills, and teacher rated literacy instruction, children who had more years of better classroom quality had higher third grade literacy scores. Additionally, we found an interaction effect, suggesting that children who entered kindergarten with lower emergent literacy skills benefited more from a greater number of years of better classroom quality in relation to reading comprehension in third grade. Thus, more years of better classroom quality may help in narrowing the gap between those who enter kindergarten with higher literacy skills and those who enter with lower literacy skills.

Venetoclax, a selective B-cell lymphoma-2 inhibitor, is a biopharmaceutics classification system class IV compound. The aim of this study was to develop a physiologically based pharmacokinetic (PBPK) model to mechanistically describe absorption and disposition of an amorphous solid dispersion formulation of venetoclax in humans. A mechanistic PBPK model was developed incorporating measured amorphous solubility, dissolution, metabolism, and plasma protein binding. A middle-out approach was used to define permeability. Model predictions of oral venetoclax pharmacokinetics were verified against clinical studies of fed and fasted healthy volunteers, and clinical drug interaction studies with strong CYP3A inhibitor (ketoconazole) and inducer (rifampicin). Model verification demonstrated accurate prediction of the observed food effect following a low-fat diet. Ratios of predicted versus observed Cmax and area under the curve of venetoclax were within 0.8- to 1.25-fold of observed ratios for strong CYP3A inhibitor and inducer interactions, indicating that the venetoclax elimination pathway was correctly specified. The verified venetoclax PBPK model is one of the first examples mechanistically capturing absorption, food effect, and exposure of an amorphous solid dispersion formulated compound. This model allows evaluation of untested drug-drug interactions, especially those primarily occurring in the intestine, and paves the way for future modeling of biopharmaceutics classification system IV compounds.

The gap in school readiness skills between children growing up in poverty and other children has become a major policy issue as increasing proportions of families are living in poverty, especially in low-wealth rural communities. The purpose of this paper was to document the degree to which depth, persistence, and timing of poverty was related to the early development of children in a representative sample of 1,292 families in two of the four poor rural regions in the United States, labeled Appalachia and the Black South. Analyses documented the emergence of the poverty gap in the child’s first 5 years of life, asking when the gap emerged and whether it continued to grow through the early childhood period. Findings indicated that families who experienced poverty during the child’s first 2-years showed substantially lower cognitive, language, executive functioning, and social skills by 2 to 3 years of age (0.5 to 1.0 SD difference) and these gaps appeared to stabilize between 3 and 5 years of age. Transitions into deep poverty during the preschool period (3- to 5-years) were also related to substantially lower scores, and to a lesser extent, transitions out of poverty were related to higher skill levels. Accounting for baseline demographic and maternal characteristics diminished the poverty gap, but did not eliminate it. The poverty gaps at 3-years in language, executive functioning, and social skills accounted for much of the poverty gaps observed at 5-years. Policy implications for early care and education programming are discussed.

We explore three issues related to the practice of preventive medicine. First, how does the dearth of preventive medicine physicians on state licensure boards affect quality of medical care? Second, should a process be established to assess the training and skills of candidates for population health positions, like the "credentialing" or "privilege-granting" process used by hospitals and health systems for clinical positions? And third, how should the pervasive lack of recognition of preventive medicine as a bona fide medical specialty be addressed? In exploring these issues, we conclude that preventive medicine physicians are critical to the US health care ecosystem at every level, and to building a dominant culture of prevention. Preventive medicine physicians are actively engaged in the practice of medicine and should be party to the same licensure, credentialing, and privilege-granting procedures as all other specialties. Further, we raise a call to action to our profession to define and raise awareness of preventive medicine, participate in state licensure boards, and establish clear standards of practice for which we are uniquely trained and capable.

The positive effects of pre-kindergarten (pre-K) programming may be enhanced in later grades for children who subsequently experience high-quality educational environments in elementary school. The current study tested this hypothesis in relation to the effects of North Carolina's NC Pre-K program on child outcomes at the end of kindergarten, including language, literacy, mathematics, and working memory. Measures of elementary school quality were examined as moderators of the NC Pre-K effects, including school-wide academic proficiency and school-wide growth in academic achievement. We found no reliable effects of NC Pre-K participation for children attending elementary schools with average levels of quality. However, the positive effects of NC Pre-K participation on language and working memory skills were evident for children attending elementary schools with higher levels of academic proficiency and academic growth, respectively. No evidence of moderation was found in relation to literacy and mathematics skills.

A major developmental task for young children in the United States involves the acquisition of knowledge about the letters in the English alphabet. In the current study, we examined the growth trajectories of children's letter name knowledge (LNK) during pre-kindergarten and kindergarten. A diverse sample of 1015 children was drawn from the National Center for Early Development and Learning Multi-State Study of Pre-Kindergarten. Latent class growth analyses were used to identify three heterogeneous classes of children based on their LNK growth trajectories. Children's fall-of-pre-kindergarten language skills were associated with trajectory class membership, which in turn was associated with children's spring-of-kindergarten literacy skills. We also found that the association between children's fall-of-pre-kindergarten language skills and spring-of-kindergarten literacy skills was partially mediated by trajectory class membership. These findings point to the importance of LNK skill development as a marker variable to monitor and support children's emergent literacy development.

Our HCV research program investigated novel 2′-dihalogenated nucleoside HCV polymerase inhibitors and identified compound 1, a 5′-phosphoramidate prodrug of 2′-deoxy-2′-α-bromo-β-chloro uridine. Although 1 had a favorable in vitro activity profile in HCV replicons, oral dosing in dog resulted in low levels of the active 5′-triphosphate (TP) in liver. Metabolism studies using human hepatocytes provided a simple assay for screening alternative phosphoramidate prodrug analogs. Compounds that produced high TP concentrations in hepatocytes were tested in dog liver biopsy studies. This method identified 2-aminoisobutyric acid ethyl ester (AIBEE) phosphoramidate prodrug 14, which provided 100-fold higher TP concentrations in dog liver in comparison to 1 (4 and 24 h after 5 mg/kg oral dose).

The purpose of this study was to conduct a head-to-head comparison of different solubility-enabling formulations, and their consequent solubility–permeability interplay. The low-solubility anticancer drug etoposide was formulated in several strengths of four solubility-enabling formulations: hydroxypropyl-β-cyclodextrin, the cosolvent polyethylene glycol 400 (PEG-400), the surfactant sodium lauryl sulfate, and an amorphous solid dispersion formulation. The ability of these formulations to increase the solubility of etoposide was investigated, followed by permeability studies using the parallel artificial membrane permeability assay (PAMPA) and examination of the consequent solubility–permeability interplay. All formulations significantly increased etoposide’s apparent solubility. The cyclodextrin-, surfactant-, and cosolvent-based formulations resulted in a concomitant decreased permeability that could be modeled directly from the proportional increase in the apparent solubility. On the contrary, etoposide permeability remained constant when using the ASD formulation, irrespective of the increased apparent solubility provided by the formulation. In conclusion, supersaturation resulting from the amorphous form overcomes the solubility–permeability tradeoff associated with other formulation techniques. Accounting for the solubility–permeability interplay may allow to develop better solubility-enabling formulations, thereby maximizing the overall absorption of lipophilic orally administered drugs.

This is a pictorial essay in which we review and illustrate a variety of thoracic injuries related to blunt trauma. Non-aortic blunt thoracic trauma can be divided anatomically into injuries of the chest wall, lungs, pleura, mediastinum, and diaphragm. Some injuries involve more than one anatomic compartment, and multiple injuries commonly coexist. This article provides common imaging findings and discussion of both common and uncommon but critical thoracic injuries encountered.

Acid strength effects on alkane isomerization turnover rates and selectivities are probed using hexene isomers as reactants on bifunctional catalysts containing tungsten Keggin polyoxometalates (POM) with different central atoms and exhibiting well-defined structures amenable to reliable estimates of deprotonation energies (DPE) as rigorous descriptors of acid strength. Titrations of protons with hindered bases during catalysis and mechanistic interpretations of rate data on POM acids in terms of a common sequence of elementary steps give isomerization rate constants that decrease exponentially with increasing DPE. The sensitivity to acid strength is the same for all interconversions among isomeric hexenes because their respective transition states are similar in the amount and localized character of their cationic charges, which determine, in turn, the extent to which the ionic and covalent interactions that determine DPE are recovered upon formation of ion pairs at transition states. The ratios of rate constants for such interconversions, and thus selectivities, are independent of acid strength and their magnitude merely reflects the stability of the gaseous analogs of their respective transition states on all acids.

The effects of heteroatom identity (Al 3+ ,G a 3+ ,F e 3+ ,o r B 3+ ), concentration and location on catalysis by MFI zeolites are examined and interpreted mechanistically using methanol dehydration rate constants and density functional theory estimates of acid strength (deprotonation energies, DPE). In doing so, we shed light on the concomitant effects of confinement and acid strength on catalytic reactivity. Rate constants (per H + from pyridine titrations during catalysis) in the first-order and zero-order kinetic regimes decreased exponentially as the DPE of MFI with different heteroatoms increased. These trends reflect a decrease in the stability of ion-pair transition states relative to the relevant precursors (H-bonded methanol and methanol dimers, respectively, for these two regimes) with decreasing acid strength and resemble those in mesoporous solid acids (e.g., polyoxometalates). Confinement effects, weaker in mesoporous solids, give larger rate constants on MFI than on POM clusters with similar DPE. Such reactivity enhancements reflect the effects of MFI voids that solvate transition states preferentially over smaller precursors via van der Waals interactions with the confining voids. Both dehydration rate constants on MFI with 0.7– 2.4 H + per unit cell volume (5.2 nm 3 ) are independent of Al or H + densities, indicating that neither H

Members of the Tequesta, a pre/proto-historic indigenous group of South Florida, cut thousands of postholes into the shallow limestone bedrock of the Metropolitan Square site, located in present-day Miami. Calcrete (limestone soil crust) formations found in and around these postholes serve as a geochemical repository attesting to various human and natural processes at the site. We present here the results of petrographic, total organic carbon (TOC), X-ray diffraction (XRD), X-ray fluorescence (XRF), and stable-isotope analysis, which were used in an attempt to relatively date posthole excavation and to identify patterns of changing site use. Ultimately, the combination of these methods yielded useful insights into paleoenvironment and proposed changes in site use, while failing to provide desired information on chronology. A combined geochemical approach such as that employed here would seem to hold potential for future study of sites located in calcareous/karstic contexts.

Veliparib (ABT-888) is largely eliminated as parent drug in human urine (70% of the dose). Renal unbound clearance exceeds glomerular filtration rate, suggesting the involvement of transporter-mediated active secretion. Clinically relevant pharmacokinetic interactions in the kidney have been associated with OAT1, OAT3, OCT2, MATE1, and MATE2K. In the present study, interactions of veliparib with these transporters were investigated. Veliparib inhibited OAT1, OAT3, OCT2, MATE1, and MATE2K with IC 50 values of 1371, 505, 3913, 69.9, and 69.5 μM, respectively. The clinical unbound maximum plasma concentration of veliparib after single oral dose of 50 mg (0.45 μM) is manyfold lower than IC 50 values for OAT1, OAT3, OCT2, MATE1, or MATE2K. These results indicate a low potential for drug–drug interaction (DDI) with OAT1/3, OCT2, or MATE1/2 K. Additional studies demonstrated that veliparib is a substrate of OCT2. In Oct1/Oct2 double-knockout mice, the plasma exposure of veliparib was increased by 1.5-fold, and the renal clearance was decreased by 1.8-fold as compared with wild-type mice, demonstrating that organic cation transporters contribute to the renal elimination in vivo. In summary, the in vitro transporter data for veliparib predicts minimal potential for an OAT1/3-, OCT2-, and MATE1/2 K-mediated DDI given the clinical exposure after single oral dose of 50 mg.

Kinetic, spectroscopic, and chemical titration data indicate that differences in monomolecular isobutane cracking and dehydrogenation and methanol dehydration turnover rates (per H+) among FAU zeolites treated thermally with steam (H-USY) and then chemically with ammonium hexafluorosilicate (CD-HUSY) predominantly reflect differences in the size and solvating properties of their supercage voids rather than differences in acid strength. The number of protons on a given sample was measured consistently by titrations with Na+, with CH3 groups via reactions of dimethyl ether, and with 2,6-di-tert-butylpyridine during methanol dehydration catalysis; these titration values were also supported by commensurate changes in acidic OH infrared band areas upon exposure to titrant molecules. The number of protons, taken as the average of the three titration methods, was significantly smaller than the number of framework Al atoms (Alf) obtained from X-ray diffraction and 27Al magic angle spinning nuclear magnetic resonance spectroscopy on H-USY (0.35 H+/Alf) and CD-HUSY (0.69 H+/Alf). These data demonstrate that the ubiquitous use of Alf sites as structural proxies for active H+ sites in zeolites can be imprecise, apparently because distorted Al structures that are not associated with acidic protons are sometimes detected as Alf sites. Monomolecular isobutane cracking and dehydrogenation rate constants, normalized non-rigorously by the number of Alf species, decreased with increasing Na+ content on both H-USY and CD-HUSY samples and became undetectable at sub-stoichiometric exchange levels (0.32 and 0.72 Na+/Alf ratios, respectively), an unexpected finding attributed incorrectly in previous studies to the presence of minority “super-acidic” sites. These rate constants, when normalized rigorously by the number of residual H+ sites were independent of Na+ content on both H-USY and CD-HUSY samples, reflecting the stoichiometric replacement of protons that are uniform in reactivity by Na+ cations. Monomolecular isobutane cracking and dehydrogenation rate constants (per H+; 763 K), however, were higher on H-USY than CD-HUSY (by a factor of 1.4). Equilibrium constants for the formation of protonated methanol dimers via adsorption of gaseous methanol onto adsorbed methanol monomers, determined from kinetic studies of methanol dehydration to dimethyl ether (433 K), were also higher on H-USY than CD-HUSY (by a factor of 2.1). These larger constants predominantly reflect stronger dispersive interactions in H-USY, consistent with its smaller supercage voids that result from the occlusion of void space by extraframework Al (Alex) residues. These findings appear to clarify enduring controversies about the mechanistic interpretation of the effects of Na+ and Alex species on the catalytic reactivity of FAU zeolites. They also illustrate the need to normalize rates by the number of active sites instead of more convenient but less accurate structural proxies for such sites.

Dimethyl ether (DME) homologation forms isobutane and triptane (2,2,3-trimethylbutane) with supra-equilibrium selectivities within C 4 and C 7 hydrocarbons on both mesoporous solid acids (SiO 2 –Al 2 O 3 , H 3 PW 12 O 40 /SiO 2 ) and the acid forms of various zeolites (BEA, FAU, MFI) via methylation and hydride transfer steps that favor isobutane and triptane formation because of the relative stabilities of ion-pairs at transition states for chains along the preferred growth path. The stabilities of ion-pair transition states increase as acid sites become stronger and energies for charge separation decrease and as van der Waals interactions within pores become stronger, which respectively lead to higher rates on H 3 PW 12 O 40 /SiO 2 and aluminosilicate zeolites than on amorphous SiO 2 –Al 2 O 3 . Solid acids with different strengths and abilities to solvate ion-pairs by confinement differ in selectivity because strength and solvation influence transition states for the hydride transfer, methylation, and isomerization steps to different extents. Stronger acid sites on H 3 PW 12 O 40 /SiO 2 favor isomerization and hydride transfer over methylation; they lead to higher selectivities to n -butane and non-triptane C 7 isomers than the weaker acid sites on BEA, FAU, and mesoporous SiO 2 –Al 2 O 3 . This preference for hydride transfer and isomerization on stronger acids reflects transition states with more diffuse cationic charge, which interact less effectively with conjugate anions than more localized cations at methylation transition states. The latter recover a larger fraction of the energy required to form the ion-pair, and their stabilities are less sensitive to acid strength than for diffuse cations. Large-pore zeolites (BEA, FAU) form triptane with higher selectivity than SiO 2 –Al 2 O 3 because confinement within large pores preferentially solvates the larger transition states for hydride transfer and methylation, which preserve the four-carbon backbone in triptane, over smaller transition states for alkoxide isomerization steps, which disrupt this backbone and cause growth beyond C 7 chains and subsequent facile β-scission to form isobutane. MFI forms isobutane and triptane with much lower selectivity than mesoporous acids or large-pore zeolites, because smaller pores restrict the formation of bimolecular methylation and hydride transfer transition states required for chain growth and termination steps to a greater extent than those for monomolecular alkoxide isomerization. These data and their mechanistic interpretations show that the selective formation of isobutane and triptane from C 1 precursors like DME is favored on all acids as a result of the relative stability of methylation, hydride transfer, and isomerization transition states, but to a lesser extent when small confining voids and stronger acid sites preferentially stabilize monomolecular isomerization transition states. The observed effects of acid strength and confinement on rates and selectivities reflect the more effective stabilization of all ion-pairs on stronger acids and within solvating environments, but a preference for transition states with more diffuse charge on stronger acids and for ion-pairs with the appropriate solvation within voids of molecular dimensions.

Consider the traveling salesman problem (TSP) defined on the complete graph, where the edge costs satisfy the triangle inequality. Let TOUR denote the optimal solution value for the TSP. Two well-known relaxations of the TSP are the subtour elimination problem and the 2-matching problem. If we let SUBT and 2M represent the optimal solution values for these two relaxations, then it has been conjectured that TOUR/SUBT ≤ 4 / 3 , and that 2M/SUBT ≤ 10 / 9 . In this paper, we exploit the structure of certain 1 / 2 -integer solutions for the subtour elimination problem in order to obtain low cost TSP and 2-matching solutions. In particular, we show that for cost functions for which the optimal subtour elimination solution found falls into our classes, the above two conjectures are true. Our proofs are constructive and could be implemented in polynomial time, and thus, for such cost functions, provide a 4/3 (or better) approximation algorithm for the TSP.

Delaminated materials ITQ-2, ITQ-6 and ITQ-18 are very efficient catalysts of zeolitic nature for the synthesis of diamino diphenyl methane (DADPM), the polyamine precursor in the production of MDI for polyurethanes. The exfoliation process results in excellent accessibility of their active sites to reactant molecules as well as fast desorption of products. These catalysts present higher activity and slower rates of deactivation than their corresponding zeolites. Moreover, the topology of the delaminated structure imposes a precise control of the isomer distribution, offering an additional flexibility in the synthesis of DADPM. By optimizing the process conditions it is possible to achieve final DADPM crude under industrial production specifications with ITQ-18. This catalyst represents a real chance for replacing HCl in the industrial production of DADPM., The authors thank Huntsman Polyurethanes and CICYT (MAT2006-14274-C02-01), Project Prometeo from Generalitat Valenciana, Project MULTICAT (Consolider-Ingenio 2010) and Fundacion Areces for financial support.

Rationale and Objectives Diagnostic tests are validated by comparison against a “gold standard” reference test. When the reference test is invasive or expensive, it may not be applied to all patients. This can result in biased estimates of the sensitivity and specificity of the diagnostic test. This type of bias is called “verification bias,” and is a common problem in imaging research. The purpose of our study is to estimate the prevalence of verification bias in the recent radiology literature. Materials and Methods All issues of the American Journal of Roentgenology (AJR), Academic Radiology, Radiology, and European Journal of Radiology (EJR) between November 2006 and October 2009 were reviewed for original research articles mentioning sensitivity or specificity as endpoints. Articles were read to determine whether verification bias was present and searched for author recognition of verification bias in the design. Results During 3 years, these journals published 2969 original research articles. A total of 776 articles used sensitivity or specificity as an outcome. Of these, 211 articles demonstrated potential verification bias. The fraction of articles with potential bias was respectively 36.4%, 23.4%, 29.5%, and 13.4% for AJR, Academic Radiology, Radiology, and EJR. The total fraction of papers with potential bias in which the authors acknowledged this bias was 17.1%. Conclusion Verification bias is a common and frequently unacknowledged source of error in efficacy studies of diagnostic imaging. Bias can often be eliminated by proper study design. When it cannot be eliminated, it should be estimated and acknowledged.

The effects of acid identity on CH3OH dehydration are examined here using density functional theory (DFT) estimates of acid strength (as deprotonation energies, DPE) and reaction energies, combined with rate data on Keggin polyoxometalate (POM) clusters and zeolite H-BEA. Measured first-order (kmono) and zero-order (kdimer) CH3OH dehydration rate constants depend exponentially on DPE for POM clusters; the value of kmono depends more strongly on DPE than kdimer does. The chemical significance of these rate parameters and the basis for their dependences on acid strength were established by using DFT to estimate the energies of intermediates and transition states involved in elementary steps that are consistent with measured rate equations. We conclude from this treatment that CH3OH dehydration proceeds via direct reactions of co-adsorbed CH3OH molecules for relevant solid acids and reaction conditions. Methyl cations formed at ion-pair transition states in these direct routes are solvated by H2O and CH3OH more effectively than those in alternate sequential routes involving methoxide formation and subsequent reaction with CH3OH. The stability of ion-pairs, prevalent as intermediates and transition states on solid acids, depends sensitively on DPE because of concomitant correlations between the stability of the conjugate anionic cluster and DPE. The chemical interpretation of kmono and kdimer from mechanism-based rate equations, together with thermochemical cycles of their respective transition state formations, show that similar charge distributions in the intermediate and transition state involved in kdimer cause its weaker dependence on DPE. Values of kmono involve uncharged reactants and the same ion-pair transition state as kdimer; these species sense acid strength differently and cause the larger effects of DPE on kmono. Confinement effects in H-BEA affect the value of kmono because the different sizes and number of molecules in reactants and transition states selectively stabilize the latter; however, they do not influence kdimer, for which reactants and transition states of similar size sense spatial constraints to the same extent. This combination of theory and experiment for solid acids of known structure sheds considerable light on the relative contributions from solvation, electrostatic and van der Waals interactions in stabilizing cationic transition states and provides predictive insights into the relative contributions of parallel routes based on the size and charge distributions of their relevant intermediates and transition states. These findings also demonstrate how the consequences of acid strength on measured turnover rates depend on reaction conditions and their concomitant changes in the chemical significance of the rate parameters measured. Moreover, the complementary use of experiment and theory in resolving mechanistic controversies has given predictive guidance about how rate and equilibrium constants, often inextricably combined as measured rate parameters, individually depend on acid strength based on the magnitude and spatial distributions of charges in reactants, products and transition states involved in relevant elementary steps. The unique relations between kmono, kdimer and DPE developed here for CH3OH dehydration can be applied in practice to assess the acid strength of any solid acid, many of which have unknown structures, preventing reliable calculations of their DPE by theory.

We discuss the effectiveness of integer programming for solving large instances of the independent set problem. Typical LP formulations, even strengthened by clique inequalities, yield poor bounds for this problem. We show that a strong bound can be obtained by the use of the so-called rank inequalities, which generalize the clique inequalities. For some problems the clique inequalities imply the rank inequalities, and then a strong bound is guaranteed already by the simpler formulation.

The A-matching problem generalizes matching problems by stipulating that the degree of each vertex lies in a set A"v of admissible values. If these sets have no large ''gaps'', the decision problem is in P, while the complexity of the optimization version is open. We present a polynomial time solvable 12-integral linear relaxation for this case.

Methods have been developed and compared for the analysis of a glycerol-based polyether polyol using a low-field, medium-resolution NMR spectrometer, with an operating frequency of 29 MHz for 1 H . Signal areas in the time and frequency domains were used to calculate the ethylene oxide (EO) content of individual samples. The time domain signals (free induction decay) were analysed using a new version of the direct exponential curve resolution algorithm (FID-DECRA). Direct analysis of the 1 H NMR FT spectra gave percentage EO concentrations of reasonable accuracy (average percentage error of 1.3%) and precision (average RSD of 1.8%) when compared with results derived from high-field 13 C NMR spectrometry. The direct FID-DECRA method showed a negative bias (−0.8±0.12% w/w) in the estimation of percentage EO concentration, but the precision (average RSD of 0.9%) was twice as good as that of direct spectral analysis. When the 13 C NMR analysis was used as a reference method for univariate calibration of the 1 H NMR procedures, the best accuracy (average percentage error of 0.5%) and precision (average RSD of 0.6%) were obtained using FID-DECRA, for EO concentrations in the range 14.8–15.5% w/w. An additional advantage of FID-DECRA is that the analytical procedure could be automated, which is particularly desirable for process analysis.

In this paper, we illustrate by means of examples a technique for formulating compact (i.e. polynomial-size) linear programming relaxations in place of exponential-size models requiring separation algorithms. In the same vein as a celebrated theorem by Grotschel, Lovasz and Schrijver, we state the equivalence of compact separation and compact optimization. Among the examples used to illustrate our technique, we introduce a new formulation for the traveling salesman problem, whose relaxation we show as an equivalent to the subtour elimination relaxation.

We present a unified scheme which, by combining backward differentiation formulae and variational optimisation theory, significantly extends the scope of both concepts and their application to optimisation problems wherein the constituent dynamics consist of widely disparate scales. Our approach is based on the time-integration of a series of matrix Riccati expressions which satisfy a Hamilton–Jacobi equation.

The design and performance of a simulated countercurrent moving bed chromatographic reactor (SCMCR) for high temperature reactions are investigated for both reversible and irreversible reactions of a single reactant. From an analysis of the solid phase and gas phase flow ratios in each of the SCMCR sections, the flow conditions necessary for optimizing the conversion and yield are obtained. Reactor performance is not evaluated from typical material balance equations, but rather by considering the separation of reactant and product waves as they flow through the sections of the SCMCR, and as the feed point is cycled under the assumption of dispersionless plug flow. The additional assumptions of linear adsorption equilibria and infinite gas–solid mass transfer rates permit the expressions for exit molar flow profiles during the initial transient period, and of the ultimate periodic steady state, to be readily obtained. Simple algebraic expressions for the production rate of the reaction product as a function of the adsorption equilibrium constants, the per pass conversion, the number of switching periods, and the molar flow rate of the reactant, are presented.

The gas-phase kinetics of the CH2ClO radical, formed by flash photolysis of Cl2 in CH3Cl/O2/N2 mixtures, was investigated at 306 K and at total pressures from 5 to 35 Torr by time-resolved mass spectrometry. Reaction of CH2ClO with O2 to form HC(O)Cl and HO2, and unimolecular dissociation to HCl and HCO were both observed. The absolute rate coefficient for reaction of CH2ClO with O2 is (2.8±1.2)×10−13 cm3 molecule−1 s−1. The unimolecular dissociation is well into the fall-off, the rate coefficient increasing from 6×102 s−1 to 4×103 s−1 between 5 and 35 Torr.

The kinetics and mechanism of the reaction of CHClFO 2 radicals with NO were studied by time-resolved mass spectrometric monitoring of the molecular ions of NO 2 and NO. The rate constant was determined to be (1.31 ± 0.20) × 10 −11 cm 3 molecule −1 s −1 at (26 ± 1)°C, and was found to be independent of pressure over the range 6–25 Torr. The CHClFO radicals formed in this reaction were found to dissociate by unimolecular CCl bond scission. The unimolecular rate coefficient for Cl atom loss was estimated to be greater than 3 × 10 3 s −1 at (26 ± 1)°C.

A mathematical model of a simulated countercurrent moving bed chromatographic reactor (SCMCR) has been developed. The model represents a multiple column reactor consisting of a series of either four or five tubular fixed beds packed with a mixture of catalyst and adsorbent, with a port that can serve either as an inlet or an outlet between each. A reversible first order reaction, A /agB, with rate coefficients and rate parameters taken from the hydrogenation of 1,3,5-trimethylbenzene is incorporated into the model. The partial differential equations governing the isothermal reactor at 463 K are solved by an adaptive finite element method with uneven grid points. Model predictions of concentration profiles in the columns, and overall reactor performance, are obtained. It is shown that reaction and separation occur simultaneously, and that the conversion of this equilibrium limited reaction is greatly increased over the 0.62 that would be the maximum obtainable in a non-separative system. Under appropriate operating conditions, the model calculations predict that high product purity streams (98–99%) and nearly unit conversions can be obtained.

This report describes an HPLC assay developed for the quantification of the enantiomers of lomefloxacin (LFLX), a quinolone antibiotic, in plasma. Following addition of racemic acebutolol (internal standard, IS), plasma samples were extracted at pH 7 with a mixture of chloroform-isopentyl alcohol-diethyl ether (71.25:3.75:25, v/v/v). The organic layer was evaporated, and LFLX and IS enantiomers in the resulting residue were derivatized with chloroform solutions of 1% triethylamine and 1% ( S )-(+)-(1-naphthyl)ethyl isocyanate, followed by 2% ethyl chloroformate (ECF) 1 min later. Ethanolamine was added 30 s after the addition of ECF. The enantiomers were separated as diastereomers on an 8 × 100 mm Radial Pak normal phase column using a mobile phase of hexane-chloroform-methanol (64.5:33:2.5, v/v/v) pumped at 2.0 ml min −1 . The IS was detected by fluorescence at 245 and 420 nm (excitation and emission, respectively) during the first 12 min, after which time the wavelengths were 280 and 470 nm for detection of LFLX. The method: (1) was sensitive and showed excellent linearity (10–1000 ng ml −1 , r 2 > 0.99) between added enantiomer concentrations and peak-area-ratio (LFLX/IS); and (2) separated LFLX and IS enantiomers within 25 min. The assay is suitable for the quantification of LFLX enantiomers in plasma samples.

A novel reactor design which simulates countercurrent reaction chromatography is described. Rapid separation of products from reactants allows high conversions in both equilibrium limited and low per pass conversion reactions. Two studies of solid catalyzed reactions are reviewed. Application of this technology to a mesitylene hydrogenation reaction shows an increase in conversion from 40% (at equilibrium, 473 K) to over 80%. A modified reactor configuration applied to the oxidative coupling of methane to ethane and ethylene shows a 12 fold increase in conversion for this low per pass conversion reaction, with yields twice that reporter in conventional reactors.

An experimental investigation of the catalytic hydrogenation of 1,3,5-trimethylbenzene to 1,3,5-trimethylcyclohexane in a simulated countercurrent moving-bed chromatographic reactor is reported. A multiple column configuration of the simulated countercurrent moving-bed chromatographic reactor has been designed and assembled. A microcomputer has been interfaced with the reactor and an analytical gas chromatograph for computer control, data acquisition and analysis. This separative reactor gives a reaction product that contains relatively small amounts of unconverted reactant, and conversions that are considerably in excess of the thermodynamic equilibrium that would be the maximum achieved in non-separative reactors. With appropriate operating conditions, a product purity of 96% and reactant conversion of 0.83 was obtained. Under the conditions of the experiment the equilibrium conversion is 0.4.

Flash photolysis with time-resolved mass spectrometry was used to study the reactions of CF 3 O 2 and CF 3 O radicals with NO in the pressure range 2–30 Torr at 293 ± 1 K. The CF 3 O 2 (reactant) and NO 2 (product) signals were simultaneously monitored. The reaction rate constant from either the reactant or the product signal was determined to be (1.57 ± 0.31) × 10 −11 cm 3 molecule −1 s −1 and was found to be independent of pressure in the range 2–30 Torr. Modeling of a secondary reaction between CF 3 O and NO was done by monitoring NO decay rates and the reaction rate constant was determined to be (4.72 ± 0.30) × 10 −11 cm 3 molecule −1 s −1 .

The oxidative coupling reaction of methane (OCM) is a potential industrial reaction for the efficient production of ethylene. Replacement of current technologies requires significant product yield improvements. A novel experimental reactor, the simulated countercurrent moving-bed chromatographic reactor (SCMCR), has reported OCM yields which exceed conventional reactors [ Tonkovich et al. , 1993, Science 262 , 221 ; Tonkovich and Carr, 1995, Chem. Engng Sci. (in press) ]. An understanding of the SCMCR operation is aided by concurrent mathematical modeling. The model mimics the experimental reactor configuration and operation. Four sections are used in the SCMCR, each containing one reaction column and two separation columns connected in series. The feed is switched from section to section at a rate less than a single section breakthrough time, and a make-up feed is used after the first cycle. Reaction occurs in the first column and is followed by rapid product and reactant separation in the ensuing section columns. The model does not incorporate the realistic and complex kinetics arising from the OCM, rather a simplified reaction term is used to qualitatively gain insight into the operation of the SCMCR. The effects of the feed switching time and the make-up feed rate are investigated. The reactant conversion has a maximum at intermediate values of both parameters. This agrees with experimental trends, where the methane conversion and the C 2 yield are also maximized at similar intermediate values of the switching time.

The simulated countercurrent moving-bed chromatographic reactor (SCMCR) is applied to the oxidative coupling reaction of methane (OCM). A four-section experimental apparatus, each section containing a reaction column and two separation columns, is used to quickly separate the reactants and products using the principles of simulated countercurrent flow. Rapid product separation inhibits side reactions. Microreactor trials with a samarium oxide catalyst give yields between 2% and 10%. Yields as high as 50% are observed with the same catalyst and run conditions in the SCMCR. The effects of temperature, feed switching time, and methane to oxygen feed ratio have been investigated. The reactor, while not fully optimized, does give promise as an alternative production method for ethylene.

The simulated countercurrent moving bed chromatographic reactor (SCMCR) is a device for carrying out chemical reaction and separation simultaneously in a fixed bed. This is a novel reactor type in which separation takes place at the site of chemical reaction to improve product purities and conversions beyond those prescribed by thermodynamic equilibrium. The simulated countercurrent system mimics the behavior of a countercurrent moving bed by periodically changing feed and product locations sequentially along a fixed bed. The present investigations endeavor to determine to what extent the moving bed reactor advantages of high product purity and favorable equilibrium shifts are retained in SCMCR operations. An equilibrium stage model of the SCMCR consisting of a single fixed bed having series of inlets and outlets along its length is considered. The mass balance equations are discretized to give an equilibrium plate model. Predictions of the concentration profiles in the column(s) are obtained for the 1,3,5-trimethylbenzene hydrogenation reaction at 463 K. It is shown that reaction and separation can be achieved simultaneously and that the yield of the reversible reaction can be improved greatly. Under appropriate operating conditions, the model calculations predict high-purity product streams and nearly complete conversion of a reaction which would otherwise be limited by equilibrium to 62%.

A sensitive high-performance liquid chromatographic assay was developed for the determination of tocainide enantiomers in plasma. Following extraction of tocainide from plasma, the enantiomers were derivatized with S-(+)-1-(1-naphthyl)ethylisocyanate. The resulting diastereomers were separated and quantified using normal-phase chromatography with fluorescence detection set at 220/345 nm (excitation/emission). The peaks, resolved with a resolution factor greater than 1.5, were free from interference. Linearity was established over the concentration range 0.25-10.0 mg/l for each enantiomer in plasma (r2 greater than 0.998). The inter-assay variability was less than 10% at all concentrations examined. The method can be used to determine the pharmacokinetics of tocainide enantiomers in man.

Winter flounder, Pseudopleuronectes americanus, from Boston Harbor near the Deer Island sewage outfall and from a nearby reference population near Plymouth Beach, Massachusetts, USA, were collected on several occasions and analysed for a variety of biochemical variables and histopathological conditions. A number of biochemical variables including hepatic and pectoral fin ascorbic acid concentrations, hepatic glycogen and lipid levels, plasma glucose concentrations, brain serotonin and norepinephrine concentrations, and the concentration and ratio of various free amino acids in muscle tissue were significantly different between the two populations. The apparent apoptotic hepatic lesions were found in the majority of the winter flounder collected from Boston Harbor and were rarely observed in animals from the reference site. Low tissue concentrations of ascorbic acid and hepatic glycogen were found to have significant statistical associations with the presence and degree of severity of these hepatic lesions.

The simulated countercurrent moving bed chromatographic reactor (SCMCR) is a device for carrying out chemical reaction and separation simultaneously in a fixed bed. It mimics the behavior of a countercurrent moving bed, in which a stream of solids flows countercurrent to an inert fluid and past a stationary reactant inlet, by periodically changing feed locations sequentially along a fixed bed. True countercurrent motion is thus replaced by a periodic motion, while overcoming the problems of solids handling and attrition inherent in moving bed operations, as well as avoiding the flow channeling that would be attendant with scaleup to large column diameters. The present investigations seek to determine to what extent the moving bed reactor advantages of high product purity and favorable equilibrium shifts are retained in SCMCR operations. Two configurations of the SCMCR, a single fixed bed having a series of inlets and outlets along its length, and a series of columns with an inlet or outlet between each, are considered. Model calculations predict that both configurations give high purity product streams and nearly unit conversions of the equilibrium limited reaction.

The vertebrate fauna from the Ohio Shale formation is a key element to our understanding of aspinothoracid arthrodires. Many of the original descriptions for taxa from this important fauna are based on incomplete material or lack phylogenetic analyses. An ongoing study already has provided redescriptions of a number of these taxa based on a wealth of new material recovered from the Interstate 71 Paleontological Salvage Project. Continuing work centers on remaining problematic taxa from the Ohio Shale. Further analysis of this fauna will provide important information for phylogenetic studies and our understanding of the complex history of the Upper Devonian.

Dinichthyidae has historically been a repository for a number of large pachyosteomorph arthrodires with questionsraised on several occasions concerning the validity of this family. A cladistic analysis of dinichthyid arthrodires results in a revision of basal pachyosteomorph arthrodires. We amend the families Dinichthyidae, Dunkleosteidae, and Panxiosteidae with Dinichthys (Dinichthyidae, in part), Hadrosteus, Heintzichthys, Gorgonichthys , and Holdenius assigned to Aspinothoracidi. Dunkleosteus is rediagnosed and united with Eastmanosteus, Golshanichthys, Hussakofia , and Westralichthys in Dunkleosteidae. Janiosteus , and possibly Plourdosteus are united in Panxiosteidae as sister group to Dunkleosteidae. Finally, we refer Kiangyousteus , formerly a dinichthyid arthrodire, to Pachyosteomorphi incertae sedis .

FIGURE 1. Intraoperative photograph showing apical left ventricular papillary fibroelastoma. A 66-year-old man with a history of smoking was seen for increasing shortness of breath. A chest radiograph demonstrated a right lower lobe mass. Chest computed tomography confirmed the presence of a 2.7-cm lung lesion suggestive of neoplasm. Preoperative cardiac clearance included echocardiography. Transthoracic echocardiography demonstrated a 1-cm mass in the apex of the left ventricle. No other cardiac pathology was noted. Removal of the mass was accomplished through a left ventriculotomy with cardiopulmonary bypass by means of an Embol-X aortic cannula (Embol-X, Inc, Mountain View, Calif). The intraoperative finding was that of a friable tumor embedded within the apical endocardium and myocardium (Figure 1). Pathologic findings included a 1-cm friable tumor with histologic features consistent with papillary fibroelastoma. The heparin-coated mesh filter of the Embol-X cannula captured a 1-mm tumor fragment. The patient had an uneventful recovery and was discharged at 6 postoperative days. Papillary fibroelastomas account for 8% of all cardiac tumors, with 85% involving the cardiac valves. An apical left ventricular location is a rare finding. The main indication for removal is the risk of embolic complications, particularly stroke. Removal is surgical.

Sclerosing stromal tumor is an uncommon ovarian neoplasm that has only recently been defined and distinguished from fibrothecoma. This case report describes a 17-year-old patient who presented with a large sclerosing stromal tumor and a smaller mature teratoma in the left ovary. Eighteen months later, an immature teratoma was discovered in the contralateral ovary and microscopic spread outside the ovary was documented at staging laparotomy. Mature and immature teratomas have been observed in opposite ovaries in a small number of patients. However, sclerosing stromal tumor, in over 60 published cases, has not been associated with other forms of ovarian neoplasia. Gonadal stromal differentiation, in fact, has not been convincingly demonstrated in teratomas. The observations in this case, therefore, appear to be unique.

With the exception of müllerian-like glandular inclusions in women, reports of nonendometriotic benign glandular inclusions in abdominal lymph nodes are uncommon. We report the case of a 50-year-old woman with an apparently unique, non-müllerian, benign cystic epithelial choristoma in a celiac lymph node found incidentally at cholecystectomy. This case further expands the spectrum of benign lesions that must be differentiated from metastatic adenocarcinoma. Possible histogenesis is discussed.

A method is described for the determination of hydrogen in solid samples. The sample is heated under vacuum after which the evolved gases are separated by gas chromatography with a helium ionization detector. The system is calibrated by injecting known amounts of hydrogen, as determined manometrically. The method, which is rapid and reliable, was checked for a variety of lunar soils; the limit of detection is about 10 ng of hydrogen.

Energy removed from highly vibrationally excited polyatomic molecules by polyatomic collision partners decreases with increasing number of atoms in the hot molecule. The trend is qualitatively predicted by two quasi-statistical models of energy transfer, and calculations of energy removal by the transitional modes model gives agreement with experiment.

Neanthes virens (Sars) were exposed to acute lethal and chronic sublethal concentrations of pentachlorophenol (PCP) in the laboratory. Coelomic fluid glucose and osmolality and tissue ascorbic acid and glycogen were monitored in order to assess the time-course response of this polychaete to pollutant stress. Glycemic responses and alterations in tissue ascorbic acid and glycogen levels were observed to be dose and time-dependent. During the acute lethal exposure (720 μg/I initially), a hypoglycemic response was evident during the first 8 h of exposure. At a less severe but still lethal exposure concentration (365 μg/I initially), a significant hyperglycemic response was observed after 21 h. The coelomic fluid glucose levels decreased gradually during the 4-day exposure as glycogen reserves were depleted. During the chronic (ca. 2-mth) exposure to 100 μg PCP/1. no unusual glycemic responses were observed. Glycogen reserves remained constant during the first month of exposure but were significantly depleted after 2 mth. Ascorbic acid levels became elevated in PCP-exposed worms after I wk in both parapodial tissue and posterior segments. This tendency continued throughout the exposure period and the difference between the exposed and control values was statistically significant at the termination of the experiment. An uptake and depuration experiment with14C-PCP was also conducted. Polychaetes exposed to 100 μg/l14C-PCP for 2 wk accumulated ca. 280 times the ambient exposure concentration on a wet weight basis. After 2 wk of depuration the mean PCP body burden of depurated animals had decreased by 29%.