Guest-Host Raman under Liquid Nitrogen Spectroscopy for the Acquisition of Improved Vibrational Spectra of Solids.

Guest-host Raman under liquid nitrogen spectroscopy (GHRUNS) is introduced whereby solid-state guest molecules are isolated inside cage-like host environments for the facile acquisition of their Raman spectra. This convenient method features reduced fluorescence, the analysis of populations in their ground states, and increased signal to noise ratios. Samples are also preserved through the reduction of thermal degradation and oxidation. To demonstrate the benefits of this new method, Raman spectra of the ubiquitous molecule C60 inside a cage of water ice are presented. Using this technique, a new normal mode of C60 is elucidated. The GHRUNS methodology is of interest to those seeking to acquire and characterize the vibrational spectra, structure, and properties of emissive, air-sensitive molecules.

Postexercise hypotension in central aortic pressures following walking and its relation to cardiorespiratory fitness.

BACKGROUND: Central aortic blood pressure (BP) is reduced after exercise. The aim of this study was to determine whether cardiorespiratory fitness relates to postexercise reductions in aortic BP. METHODS: Sixteen young adults completed maximal exercise testing for peak oxygen uptake (VO2). Participants walked at a slow (80 steps/min, ~47% maxHR) and fast (125 steps/min, ~65% maxHR) stepping cadence for 3000 steps on two nonconsecutive days. Before and after each walking condition, radial tonometry was used to derive aortic pressures. Measurements after walking were taken after 30 and 60 min of supine recovery. RESULTS: The change in aortic BP was similar between walking cadences. Aortic systolic BP (-2.3 mmHg, P=0.03) and pulse pressure (-3.2 mmHg, P<0.001) were significantly reduced after 60 min of recovery as compared to baseline. The reduction in aortic pulse pressure was associated with decreased forward (r=0.69, P<0.001) and backward wave pressure (r=0.70, P<0.001). Peak VO2 was not associated (P>0.05) with these changes, but was strongly associated with non-significant changes in aortic systolic BP (30min: r=-0.54, P=0.03) and diastolic BP (30 min: r=-0.64, 60 min: r=-0.77; both P<0.01) after slow walking only. CONCLUSIONS: These results indicate that cardiorespiratory fitness associates with aortic pressure reductions after walking dependent on exercise intensity.

Children's Access to Dental Care Affected by Reimbursement Rates, Dentist Density, and Dentist Participation in Medicaid.

OBJECTIVES: To assess the relation between Medicaid reimbursement rates and access to dental care services in the context of dentist density and dentist participation in Medicaid in each state. METHODS: Data were from Early and Periodic Screening, Diagnostic, and Treatment reports for 2014, Medicaid reimbursement rate in 2013, dentist density in 2014, and dentist participation in Medicaid in 2014. We assessed patterns of mediation or moderation. RESULTS: Reimbursement rates and access to dental care were directly related at the state level, but no evidence indicated that higher reimbursement rates resulted in overuse of dental services for those who had access. The relation between reimbursement rates and access to care was moderated by dentist density and dentist participation in Medicaid. We estimate that more than 1.8 million additional children would have had access to dental care if reimbursement rates were higher in states with low rates. CONCLUSIONS: Children who access the dental care system receive care, but reimbursement may significantly affect access. States with low dentist density and low dentist participation in Medicaid may be able to improve access to dental services significantly by increasing reimbursement rates.

Inconsistent reproductive isolation revealed by interactions between Catostomus fish species.

Interactions between species are central to evolution and ecology, but we do not know enough about how outcomes of interactions between species vary across geographic locations, in heterogeneous environments, or over time. Ecological dimensions of interactions between species are known to vary, but evolutionary interactions such as the establishment and maintenance of reproductive isolation are often assumed to be consistent across instances of an interaction between species. Hybridization among Catostomus fish species occurs over a large and heterogeneous geographic area and across taxa with distinct evolutionary histories, which allows us to assess consistency in species interactions. We analyzed hybridization among six Catostomus species across the Upper Colorado River basin (US mountain west) and found extreme variation in hybridization across locations. Different hybrid crosses were present in different locations, despite similar species assemblages. Within hybrid crosses, hybridization varied from only first generation hybrids to extensive hybridization with backcrossing. Variation in hybridization outcomes might result from uneven fitness of hybrids across locations, polymorphism in genetic incompatibilities, chance, unidentified historical contingencies, or some combination thereof. Our results suggest caution in assuming that one or a few instances of hybridization represent all interactions between the focal species, as species interactions vary substantially across locations.

Risk assessment and periodontal prevention in primary care.

The role of risk factors and risk assessment in the prediction of clinical periodontal outcomes, and thus in patient management, continues to be a subject of high professional interest and clinical relevance globally. Advances in our understanding of periodontal disease causality and the role of risk factors as predictors of future disease risk have led to the development of various quantitative tools to calculate risk and inform clinical decision-making. We review the conceptual basis for periodontal risk calculation and frame its potential, as well as its limitations, in the context of similar advances in medical care. Lastly, we discuss how broader health-policy changes are taking place that will probably lead to incorporation of risk-factor assessments in periodontal treatment planning and care management.

Negative ion properties of trans 2,2',6,6'-tetrafluoroazobenzene: Experiment and theory.

Chemical bonding and the electronic structure of the trans 2,2',6,6'-tetrafluoroazobenzene negative ion have been studied using collision-induced dissociation as well as photodetachment-photoelectron spectroscopy and the experimental results for different properties were compared with the corresponding values calculated using ab initio quantum chemistry methods. The trans 2,2',6,6'-tetrafluoroazobenzene anion was prepared by atmospheric pressure chemical ionization for the collision induced dissociation (CID) experiment and through thermal electron attachment in the photodetachment-photoelectron spectroscopy experiments. The adiabatic electron affinity of trans 2,2',6,6'-tetrafluoroazobenzene was measured to be 1.3 ± 0.10 eV using 355 nm, 488 nm, and 532 nm photodetachment photons and the vertical detachment energy was measured to be 1.78 ± 0.10 eV, 2.03 ± 0.10 eV, and 1.93 ± 0.10 eV, respectively. The adiabatic electron affinity was calculated employing different ab initio methods giving values in excellent agreement with experimental results. Energy resolved collision induced dissociation experiment study of the precursor anion resulted in 1.92 ± 0.15 eV bond dissociation energy for the collision process yielding [C6H3F2](-) fragment ion at 0 K. Calculations using different ab initio methods resulted in a bond dissociation energy ranging from 1.79 to 2.1 eV at 0 K. Two additional CID fragment ions that appear at higher energies, [C6H2F](-) and [C6H](-), are not results of a single bond cleavage. The occurrence of [C6H](-) is of particular interest since it is the first anion to be observed in the interstellar medium.

Business Barriers and Opportunities for Transforming to Preventive Care to Treat Early Childhood Caries.

Primary, secondary, and tertiary preventive dental services have the potential for achieving the triple aim of better health outcomes for populations, better patient experience of care, and lower per capita costs. Yet, maximization of preventive services has not occurred in dental practice nor been promoted by dental plans. While the lack of such things as diagnostic codes, caries classification systems, and validated risk assessment tools are barriers to increasing preventive care, they may not be the primary barriers that need to be addressed. The purpose of this paper was to focus on three issues: (1) the dental care business model based on a value proposition of surgical care rather than preventive care; (2) the benefit plan design that undervalues or does not cover effective primary, secondary, and tertiary preventive services; and (3) the current financial crisis in health care. It is the business model of dental practice and the benefit design of payers that are the biggest barriers that will have to change to transform dental care into a more effective and efficient means of achieving and maintaining health.

Structure and stability of phenoxide and fluorophenoxide anions investigated with infrared multiple-photon dissociation and detachment spectroscopy and tandem mass spectrometry.

The gas-phase infrared multiple-photon dissociation and detachment (IRMPD) vibrational action spectra of the unsubstituted phenoxide anion and a series of fluorine- and trifluoromethyl-substituted phenoxide anions in the spectral region between 600 and 1800 cm(-1) are presented along with density functional theory (DFT) harmonic vibrational frequency calculations to establish the characteristic vibrations of the phenoxide functionality. The fluorophenoxide anions studied include the conjugate bases of o-, m-, and p-fluorophenol (C6H4FO(-)) as well as o-, m-, and p-α,α,α-trifluorocresol (CF3C6H4O(-)). The influence of the substituent on the characteristic vibrational frequencies is interpreted in terms of inductive and resonance shifts. In addition to the dissociation induced by infrared multiple-photon excitation, the electron detachment is also shown to play an important role in the decomposition of the unsubstituted phenoxide. It is demonstrated that the amount of electron detachment relative to dissociation is strongly mitigated by fluorination, and interpretations aided by DFT energy calculations suggest this is primarily due to the increased availability of low-energy dissociation pathways in the substituted phenoxides. Collision-induced dissociation (CID) mass spectrometry of the parent ions is used to estimate relative energies of the dissociation processes, and particular fragmentation motifs are elucidated. In particular, overall HF and CO losses provide facile decomposition pathways, yielding interesting fragment ions such as C6H(-) or C3H2FO(-) from the CF3C6H4O(-) parent anions.

Laser multiphoton ionization of tetrakis(dimethylamino)ethylene.

The tetrakis(dimethylamino)ethylene (TDAE) molecule possesses the lowest known molecular ionization potential (<5.4 eV) and exhibits an intense Rydberg series between the first and second ionization limit (∼14 eV). The ionization of TDAE using multiphoton ionization photoelectron spectroscopy was carried out using laser light at a variety of wavelengths with a hemispherical energy analyzer. Interestingly, photoelectron signal due to direct two-photon ionization was not seen, rather ionization from a fluorescent charge-transfer state located ∼2.5 eV below the ionization limit was evident and in general agreement with a previous study. In addition, a second intense peak exists corresponding to thermal energy electrons. Measurements of the angular distribution for the electrons due to photoionization from the intermediate state are peaked along the electric field vector of the laser and the thermal electrons direction is independent of this angle. From this, we propose that the thermal peak is most likely due to thermionic emission initiated through excitation of a known long-lived Rydberg state at ∼6.5 eV. Alternately, we speculate that excitation leading to thermionic emission could result from a "collective" excitation mechanism.

Synthesis, characterization, and reversible hydrogen sorption study of sodium-doped fullerene.

Herein is presented a novel, straightforward route to the synthesis of an alkali metal-doped fullerene as well as a detailed account of its reversible and enhanced hydrogen sorption properties in comparison to pure C60. This work demonstrates that a reaction of sodium hydride with fullerene (C60) results in the formation of a sodium-doped fullerene capable of reversible hydrogen sorption via a chemisorption mechanism. This material not only demonstrated reversible hydrogen storage over several cycles, it also showed the ability to reabsorb over three times the amount of hydrogen (relative to the hydrogen content of NaH) under optimized conditions. The sodium-doped fullerene was hydrogenated on a pressure composition temperature (PCT) instrument at 275 °C while under 100 bar of hydrogen pressure. The hydrogen desorption behavior of this sodium-doped fullerene hydride was observed over a temperature range up to 375 °C on the PCT and up to 550 °C on the thermogravimetric analysis (TGA). Powder x-ray diffraction verifies the identity of this material as being Na6C60. Characterization of this material by thermal decomposition analysis (e.g. PCT and TGA methods), as well as FT-IR and mass spectrometry, indicates that the hydrogen sorption activity of this material is due to the reversible formation of a hydrogenated fullerene (fullerane). However, the reversible formation of fullerane was found to be greatly enhanced by the presence of sodium. It was also demonstrated that the addition of a catalytic amount of titanium (via TiO2 or Ti(OBu)4) further enhances the hydrogen sorption process of the sodium-doped fullerene material.

Negative ions of p-nitroaniline: photodetachment, collisions, and ab initio calculations.

The structures of parent anion, M(-), and deprotonated molecule, [M-H](-), anions of the highly polar p-nitroaniline (pNA) molecule are studied experimentally and theoretically. Photoelectron spectroscopy (PES) of the parent anion is employed to estimate the adiabatic electron affinity (EAa = 0.75 ± 0.1 eV) and vertical detachment energy (VDE = 1.1 eV). These measured energies are in good agreement with computed values of 0.73 eV for the EAa and the range of 0.85 to 1.0 eV for the VDE at the EOM-CCSD∕Aug-cc-pVTZ level. Collision induced dissociation (CID) of deprotonated pNA, [pNA - H](-), with argon yielded [pNA - H - NO](-) (i.e., rearrangement to give loss of NO) with a threshold energy of 2.36 eV. Calculations of the energy difference between [pNA - H](-) and [pNA - H - NO](-) give 1.64 eV, allowing an estimate of a 0.72 eV activation barrier for the rearrangement reaction. Direct dissociation of [pNA - H](-) yielding NO2(-) occurs at a threshold energy of 3.80 eV, in good agreement with theory (between 3.39 eV and 4.30 eV). As a result of the exceedingly large dipole moment for pNA (6.2 Debye measured in acetone), we predict two dipole-bound states, one at ~110 meV and an excited state at 2 meV. No dipole-bound states are observed in the photodetachment experiments due the pronounced mixing between states with dipole-bound and valence character similar to what has been observed in other nitro systems. For the same reason, dipole-bound states are expected to provide highly efficient "doorway states" for the formation of the pNA(-) valence anion, and these states should be observable as resonances in the reverse process, that is, in the photodetachment spectrum of pNA(-) near the photodetachment threshold.

Stability of gas-phase tartaric acid anions investigated by quantum chemistry, mass spectrometry, and infrared spectroscopy.

In an effort to understand the chemical factors that stabilize dianions, experimental and theoretical studies on the stability of the tartrate dianion were performed. Quantum chemical calculations at the coupled cluster level reveal only a metastable state with a possible decomposition pathway (O(2)C-CH(OH)-CH(OH)-CO(2))(2-) → (O(2)C-CH(OH)-CH(OH))(•-) + CO(2) + e(-) explaining the observed gas-phase instability of this dianion. Further theoretical data were collected for the bare dianion, this molecule complexed to water, sodium, and a proton, in both the meso and l forms as well as for the uncomplexed radical anion and neutral diradical. The calculations suggest that the l-tartrate dianion is more thermodynamically stable than the dianion of the meso stereoisomer and that either dianion can be further stabilized by association with a separate species that can help to balance the charge of the molecular complex. Mass spectrometry was then used to measure the energy needed to initiate collisionally induced dissociation of the racemic tartrate dianion and for the proton and sodium adducts of both the racemic and meso form of this molecule. Infrared action spectra of the dianion stereoisomers complexed with sodium were also acquired to determine the influence of the metal ion on the vibrations of the dianions and validate the computationally predicted structures. These experimental data support the theoretical conclusions and highlight the instability of the bare tartrate dianion. From the experimental work, it could also be concluded that the pathway leading to dissociation is under kinetic control because the sodium adduct of the racemic stereoisomer dissociated at lower collisional energy, although it was calculated to be more stable, and that decomposition proceeded via C-C bond dissociation as computationally predicted. Taken together, these data provide insight into the gas-phase stability of the tartrate dianion and highlight the role of adducts in stabilizing this species.

Synthesis and characterization of a lithium-doped fullerane (Li(x)-C60-H(y)) for reversible hydrogen storage.

Herein, we present a lithium-doped fullerane (Li(x)-C(60)-H(y)) that is capable of reversibly storing hydrogen through chemisorption at elevated temperatures and pressures. This system is unique in that hydrogen is closely associated with lithium and carbon upon rehydrogenation of the material and that the weight percent of H(2) stored in the material is intimately linked to the stoichiometric ratio of Li:C(60) in the material. Characterization of the material (IR, Raman, UV-vis, XRD, LDI-TOF-MS, and NMR) indicates that a lithium-doped fullerane is formed upon rehydrogenation in which the active hydrogen storage material is similar to a hydrogenated fullerene. Under optimized conditions, a lithium-doped fullerane with a Li:C(60) mole ratio of 6:1 can reversibly desorb up to 5 wt % H(2) with an onset temperature of ~270 °C, which is significantly less than the desorption temperature of hydrogenated fullerenes (C(60)H(x)) and pure lithium hydride (decomposition temperature 500-600 and 670 °C respectively). However, our Li(x)-C(60)-H(y) system does not suffer from the same drawbacks as typical hydrogenated fullerenes (high desorption T and release of hydrocarbons) because the fullerene cage remains mostly intact and is only slightly modified during multiple hydrogen desorption/absorption cycles. We also observed a reversible phase transition of C(60) in the material from face-centered cubic to body-centered cubic at high levels of hydrogenation.

Aqueous fullerene aggregates (nC60) generate minimal reactive oxygen species and are of low toxicity in fish: a revision of previous reports.

This review aims to clarify inconsistencies in previous reports regarding the potential for aqueous aggregates of fullerenes (nC60) to generate reactive oxygen species (ROS) and cause toxicity in fish. Methods for evaluation of ROS production and toxicity of aqueous nC60 have evolved over time and limitations in initial studies have led to unintentional erroneous reports of nC60 ROS generation and toxicity. Some of these reports continue to lead to misconceptions of the environmental effects of C60. Critical review of the evidence (2007-2011) indicates that aqueous nC60 have minimal potential to produce ROS and that oxidative stress in fish is not induced by environmentally relevant exposure to nC60. Future studies should acknowledge that current evidence indicates low toxicity of nC60 and refrain from citing articles that attribute toxicity in fish to nC60 based on methods shown to be compromised by experimental artifacts. Despite low toxicity of nC60 in fish, an emerging environmental issue is that nC60 can affect environmental fate, transport, and bioavailability of co-contaminants in aquatic environments in a similar manner to that observed for other anthropogenic particulates (e.g., microplastics).

The association between nC60 and 17α-ethinylestradiol (EE2) decreases EE2 bioavailability in zebrafish and alters nanoaggregate characteristics.

Manufactured nanoparticles (NPs) released into surface waters will associate with other substances and these interactions may affect environmental fate and bioavailability of NPs and the associated substances. We investigated the association between aqueous aggregates of C(60) (nC(60)) and synthetic estrogen, 17α-ethinylestradiol (EE2), and considered nC(60) physicochemistry and EE2 bioavailability (by measuring vitellogenin (vtg1A/B) gene expression) in zebrafish. Bioavailability of EE2 was reduced with increasing concentration of nC(60) (P < 0.05), and bioavailability of EE2 decreased further after aging 28 d with nC(60). Reduction in EE2 bioavailability was correlated with computed surface area of nC(60), and reduced bioavailability of EE2 upon aging was consistent with absorption of EE2 within nC(60) aggregates. Size and zeta potential of nC(60) particles were affected by EE2 (1 µg/L) and also by aging (28 d) in aqueous phase. Results indicate that nC(60) can reduce bioavailability of some substances and influence environmental fate and transport of associated substances.

No bioavailability of 17α-ethinylestradiol when associated with nC60 aggregates during dietary exposure in adult male zebrafish (Danio rerio).

The C(60) fullerene is a manufactured carbon nanoparticle (CNP) that could pose a risk to humans and other organisms after release into the environment. In surface waters, C(60) is likely to be present as aggregates of nC(60) and these aggregates can associate with other substances that are toxic. Our goal was to evaluate the association of a model contaminant [17α-ethinylestradiol (EE2)] with nC(60) and determine bioavailability of EE2 after accumulation by a filter feeding organism [Brine shrimp (BS) Artemia sp.] and subsequent dietary exposure in zebrafish. Aqueous suspensions of nC(60) were prepared (600 mg C(60)/900 mL, 6-month water stirred method) with/without EE2 (1 µg/L) and BS were exposed to these preparations. Accumulation of nC(60) in gut of BS was assessed by light microscopy, and C(60) were extracted from BS and concentration analyzed by HPLC. Adult male zebrafish were fed (5d) live BS according to the following treatments: BS (control); BS containing nC(60); BS containing nC(60)+EE2; or BS containing EE2. Liver was excised from exposed fish and total RNA was extracted for assessment of vitellogenin gene (vtg1A/B) expression. The vtg1A/B was highly up-regulated in fish exposed to BS containing EE2, but expression of vtg1A/B did not differ from controls in other treatments. The EE2 associated with nC(60) did not become bioavailable in zebrafish during passage through the intestinal tract of zebrafish. Results have implications on the effect of nC(60) on the bioavailability of co-contaminants in organisms during dietary exposure.

Anti-inflammatory properties of a novel N-phenyl pyridinone inhibitor of p38 mitogen-activated protein kinase: preclinical-to-clinical translation.

Signal transduction through the p38 mitogen-activated protein (MAP) kinase pathway is central to the transcriptional and translational control of cytokine and inflammatory mediator production. p38 MAP kinase inhibition hence constitutes a promising therapeutic strategy for treatment of chronic inflammatory diseases, based upon its potential to inhibit key pathways driving the inflammatory and destructive processes in these debilitating diseases. The present study describes the pharmacological properties of the N-phenyl pyridinone p38 MAP kinase inhibitor benzamide [3- [3-bromo-4-[(2,4-difluorophenyl)methoxy]-6-methyl-2- oxo-1(2H)-pyridinyl]-N,4-dimethyl-, (-)-(9CI); PH-797804]. PH-797804 is an ATP-competitive, readily reversible inhibitor of the alpha isoform of human p38 MAP kinase, exhibiting a K(i) = 5.8 nM. In human monocyte and synovial fibroblast cell systems, PH-797804 blocks inflammation-induced production of cytokines and proinflammatory mediators, such as prostaglandin E(2), at concentrations that parallel inhibition of cell-associated p38 MAP kinase. After oral dosing, PH-797804 effectively inhibits acute inflammatory responses induced by systemically administered endotoxin in both rat and cynomolgus monkeys. Furthermore, PH-797804 demonstrates robust anti-inflammatory activity in chronic disease models, significantly reducing both joint inflammation and associated bone loss in streptococcal cell wall-induced arthritis in rats and mouse collagen-induced arthritis. Finally, PH-797804 reduced tumor necrosis factor-alpha and interleukin-6 production in clinical studies after endotoxin administration in a dose-dependent manner, paralleling inhibition of the target enzyme. Low-nanomolar biochemical enzyme inhibition potency correlated with p38 MAP kinase inhibition in human cells and in vivo studies. In addition, a direct correspondence between p38 MAP kinase inhibition and anti-inflammatory activity was observed with PH-797804, thus providing confidence in dose projections for further human studies in chronic inflammatory disease.

SD0006: a potent, selective and orally available inhibitor of p38 kinase.

SD0006 is a diarylpyrazole that was prepared as an inhibitor of p38 kinase-alpha (p38alpha). In vitro, SD0006 was selective for p38alpha kinase over 50 other kinases screened (including p38gamma and p38delta with modest selectivity over p38beta). Crystal structures with p38alpha show binding at the ATP site with additional residue interactions outside the ATP pocket unique to p38alpha that can confer advantages over other ATP competitive inhibitors. Direct correlation between inhibition of p38alpha activity and that of lipopolysaccharide-stimulated TNFalpha release was established in cellular models and in vivo, including a phase 1 clinical trial. Potency (IC(50)) for inhibiting tumor necrosis factor-alpha (TNFalpha) release, in vitro and in vivo, was <200 nmol/l. In vivo, SD0006 was effective in the rat streptococcal-cell-wall-induced arthritis model, with dramatic protective effects on paw joint integrity and bone density as shown by radiographic analysis. In the murine collagen-induced arthritis model, equivalence was demonstrated to anti-TNFalpha treatment. SD0006 also demonstrated good oral anti-inflammatory efficacy with excellent cross-species correlation between the rat, cynomolgus monkey, and human. SD0006 suppressed expression of multiple proinflammatory proteins at both the transcriptional and translational levels. These properties suggest SD0006 could provide broader therapeutic efficacy than cytokine-targeted monotherapeutics.