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The gas-phase structures of protonated unsymmetrical 1,1-dimethylhydrazine (UDMH) and the proton-bound dimers of UDMH and hydrazine are examined by infrared multiple photon dissociation (IRMPD) action spectroscopy utilizing light generated by a free electron laser and an optical parametric oscillator laser system. To identify the structures present in the experimental studies, the measured IRMPD spectra are compared to spectra calculated at the B3LYP-GD3BJ/6-311+G(d,p) level of theory. These comparisons show that protonated UDMH binds the proton at the methylated nitrogen atom (α) with two low-lying α conformers probably being populated. For (UDMH)2H+, the proton is shared between the methylated nitrogen atoms with several low-lying α conformers likely to be populated. Higher-lying conformers of (UDMH)2H+ in which the proton is shared between α and β (unmethylated) nitrogen atoms cannot be ruled out on the basis of the IRPMD spectrum. For (N2H4)2H+, there are four low-lying conformers that all reproduce the IRMPD spectrum reasonably well. As hydrazine and UDMH see usage as fuels for rocket engines, such spectra are potentially useful as a means of remotely monitoring rocket launches, especially in cases of unsuccessful launches where environmental hazards need to be assessed. [ABSTRACT FROM AUTHOR]

The Blackfoot Reservoir volcanic field (BRVF), Idaho, USA, is a bimodal volcanic field that has hosted silicic eruptions during at least two episodes, as recently as 58 ka. Using newly collected ground and boat‐based gravity data, two large negative anomalies (−16 mGal) are modeled as shallow (<1 km) intrusions beneath a NE‐trending alignment of BRVF rhyolite domes and tuff rings. Given the trade‐off between density contrast and model volume, best‐fit gravity inversion models yield a total intrusion volume of 50−120 km3; a density contrast of −400 kg m−3 results in two intrusions, each ∼9 km ×4.5 km and about 0.5 km thick, with cumulative volume of 100 km3. A network of 340°−360° trending faults lies directly above and on the margins of the mapped gravity anomalies. Most of these faults have 5−10 m throw; one has throw up to ∼50 m. We suggest that the emplacement of shallow sill‐like intrusions produced this fault zone and also created a ENE‐trending fault set, indicating widespread ground deformation during intrusion emplacement. The intrusions and silicic domes are located 3−5 km E of a regional, 20 mGal step in gravity. We interpret this step in gravity as thickening of the Upper Precambrian to lowermost Cambrian quartzites in the Meade thrust sheet, part of the Idaho‐Wyoming Thrust Belt. Silicic volcanism in the BRVF is a classic example of volcanotectonic interaction, influenced by regional structure and creating widespread deformation. We suggest volcanic hazard assessments should consider the possibility of large‐volume silicic eruptions in the future. Plain Language Summary: On Earth, gravity anomalies occur where there are significant, subsurface, lateral density variations. We map two gravity anomalies located in the Blackfoot Reservoir volcanic field, Idaho, a site which has experienced explosive volcanic eruptions as recently as 58,000 years ago. Our numerical models of the gravity anomalies indicate that they are caused by two saucer‐shaped intrusions, magma bodies that likely fed eruptions at the surface and triggered fault displacement. Although these magma bodies have cooled, they have large volumes and the timing of the emplacements suggest that large‐volume explosive volcanic eruptions are possible in this volcanic field in the future. Key Points: Large‐amplitude gravity anomalies are mapped in a combined ground and boat‐based gravity survey in the Blackfoot Reservoir volcanic field, Idaho (BRVF), adjacent to young (1.5 Ma, 58 ka) topaz rhyolite domes and tuff rings within a Quaternary basaltic volcanic fieldBest‐fit 3D inversion of the gravity data, constrained by density contrast estimates and excess mass calculations, indicates the presence of two bodies with thick sill‐like shapes in the uppermost crust, with cumulative volume of ∼100 km3 and volume uncertainty in the range 50−120 km3Extensive volcanotectonic interaction is suggested by comparison of mapped gravity with fault distribution. The western edges of the gravity anomalies coincide with normal faults with vertical displacements that range from 5−10 m (maximum 50 m) [ABSTRACT FROM AUTHOR]

Cisplatin, (NH3)2PtCl2, has been known as a successful metal-based anticancer drug for more than half a century. Its analogue, Argplatin, arginine-linked cisplatin, (Arg)PtCl2, is being investigated because it exhibits reactivity towards DNA and RNA that differs from that of cisplatin. In order to understand the basis for its altered reactivity, the deprotonated and sodium cationized forms of Argplatin, [(Arg-H)PtCl2]− and [(Arg)PtCl2 + Na]+, are examined by infrared multiple photon dissociation (IRMPD) action spectroscopy in the IR fingerprint and hydrogen-stretching regions. Complementary electronic structure calculations are performed using density functional theory approaches to characterize the stable structures of these complexes and to predict their infrared spectra. Comparison of the theoretical IR spectra predicted for various stable conformations of these Argplatin complexes to their measured IRMPD spectra enables determination of the binding mode(s) of Arg to the Pt metal center to be identified. Arginine is found to bind to Pt in a bidentate fashion to the backbone amino nitrogen and carboxylate oxygen atoms in both the [(Arg-H)PtCl2]− and [(Arg)PtCl2 + Na]+ complexes, the NO− binding mode. The neutral side chain of Arg also interacts with the Pt center to achieve additional stabilization in the [(Arg-H)PtCl2]− complex. In contrast, Na+ binds to both chlorido ligands in the [(Arg)PtCl2 + Na]+ complex and the protonated side chain of Arg is stabilized via hydrogen-bonding interactions with the carboxylate moiety. These findings are consistent with condensed-phase results, indicating that the NO− binding mode of arginine to Pt is preserved in the electrospray ionization process even under variable pH and ionic strength. [ABSTRACT FROM AUTHOR]

Ionic liquids (ILs) exhibit unique properties that have led to their development and widespread use for a variety of applications. Development efforts have generally focused on achieving desired macroscopic properties via tuning of the IL through variation of the cations and anions. Both the macroscopic and microscopic properties of an IL influence its tunability and thus feasibility of use for selected applications. Works geared toward a microscopic understanding of the nature and strength of the intrinsic cation--anion interactions of ILs have been limited to date. Specifically, the intrinsic strength of the cation--anion interactions in ILs is largely unknown. In previous work, we employed threshold collision-induced dissociation (TCID) approaches supported and enhanced by electronic structure calculations to determine the bond dissociation energies (BDEs) and characterize the nature of the cation--anion interactions in a series of four 2 : 1 clusters of 1-alkyl-3-methylimidazolium cations with the hexafluorophosphate anion, [2Cnmim:PF6]+. To examine the effects of the 1-alkyl chain on the structure and energetics of binding, the cation was varied over the series: 1-ethyl-3-methylimidazolium, [C2mim]+, 1-butyl-3-methylimidazolium, [C4mim]+, 1-hexyl-3-methylimidazolium, [C6mim]+, and 1-octyl- 3-methylimidazolium, [C8mim]+. The variation in the strength of binding among these [2Cnmim:PF6]+ clusters was found to be similar in magnitude to the average experimental uncertainty in the measurements. To definitively establish an absolute order of binding among these [2Cnmim:PF6]+ clusters, we extend this work again using TCID and electronic structure theory approaches to include competitive binding studies of three mixed 2 : 1 clusters of 1-alkyl-3-methylimidazolium cations and the hexafluorophosphate anion, [Cn-2mim:PF6:Cnmim]+ for n = 4, 6, and 8. The absolute BDEs of these mixed [Cn-2mim:PF6:Cnmim]+ clusters as well as the absolute difference in the strength of the intrinsic binding interactions as a function of the cation are determined with significantly improved precision. By combining the thermochemical results of the previous independent and present competitive measurements, the BDEs of the [2Cnmim:PF6]+ clusters are both more accurately and more precisely determined. Comparisons are made to results for the analogous [2Cnmim:BF4]+ and [Cn-2mim:BF4:Cnmim]+ clusters previously examined to elucidate the effects of the [PF6]- and [BF4]- anions on the binding. [ABSTRACT FROM AUTHOR]

Imidazolium-based cations and the hexafluorophosphate anion are among the most commonly used ionic liquids (ILs). Yet, the nature and strength of the intrinsic cation–anion interactions, and how they influence the macroscopic properties of these ILs are still not well understood. Threshold collision-induced dissociation is utilized to determine the bond dissociation energies (BDEs) of the 2 : 1 clusters of 1-alkyl-3-methylimidazolium cations and the hexafluorophosphate anion, [2Cnmim:PF6]+. The cation, [Cnmim]+, is varied across the series, 1-ethyl-3-methylimidazolium [C2mim]+, 1-butyl-3-methylimidazolium [C4mim]+, 1-hexyl-3-methylimidazolium [C6mim]+, 1-octyl-3-methylimidazolium [C8mim]+, to examine the structural and energetic effects of the size of the 1-alkyl substituent of the cation on the binding to [PF6]−. Complementary electronic structure methods are employed for the [Cnmim]+ cations, (Cnmim:PF6) ion pairs, and [2Cnmim:PF6]+ clusters to elucidate details of the cation–anion interactions and their impact on structure and energetics. Multiple levels of theory are benchmarked with the measured BDEs including B3LYP, B3LYP-GD3BJ, and M06-2X each with the 6-311+G(d,p) basis set for geometry optimizations and frequency analyses and the 6-311+G(2d,2p) basis set for energetic determinations. The modest structural variation among the [Cnmim]+ cations produces only minor structural changes and variation in the measured BDEs of the [2Cnmim:PF6]+ clusters. Present results are compared to those previously reported for the analogous 1-alkyl-3-methylimidazolium tetrafluoroborate IL clusters to compare the effects of these anions on the nature and strength of the intrinsic binding interactions. [ABSTRACT FROM AUTHOR]

The article focuses on products liability Multidistrict litigations (MDLs) including In re Abilify Products Liability Litigation and In re 3M Products Liability Litigation. Topics include deficiency disputes that the parties are unable to resolve themselves may be brought to the court for resolution, and the parties use a litigation database called MDL Centrality® for centralized litigation management and support.

Description: In June 2019, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) approved an update of the joint clinical practice guideline for rehabilitation after stroke. This synopsis summarizes the key recommendations from this guideline.Methods: In February 2018, the VA/DoD Evidence-Based Practice Work Group convened a joint VA/DoD guideline development effort that included clinical stakeholders and stroke survivors and conformed to the National Academy of Medicine (formerly the Institute of Medicine) tenets for trustworthy clinical practice guidelines. The guideline panel identified key questions, systematically searched and evaluated the literature, and developed 2 algorithms and 42 key recommendations using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Stroke survivors and their family members were invited to share their perspectives to further inform guideline development.Recommendations: The guideline recommendations provide evidence-based guidance for the rehabilitation care of patients after stroke. The recommendations are applicable to health care providers in both primary care and rehabilitation. Key features of the guideline are recommendations in 6 areas: timing and approach; motor therapy; dysphagia; cognitive, speech, and sensory therapy; mental health therapy; and other functions, such as returning to work and driving. [ABSTRACT FROM AUTHOR]

Nucleobases serve as ideal targets where drugs bind and exert their anticancer activities. Cisplatin (cisPt) preferentially coordinates to 2′-deoxyguanosine (dGuo) residues within DNA. The dGuo adducts that are formed alter the DNA structure, contributing to inhibition of function and ultimately cancer cell death. Despite its success as an anticancer drug, cisPt has a number of drawbacks that reduce its efficacy, including repair of adducts and drug resistance. Some approaches to overcome this problem involve development of compounds that coordinate to other purine nucleobases, including those found in RNA. In this work, amino acid-linked platinum(II) (AAPt) compounds of alanine and ornithine (AlaPt and OrnPt, respectively) were studied. Their reactivity preferences for DNA and RNA purine nucleosides (i.e., 2′-deoxyadenosine (dAdo), adenosine (Ado), dGuo, and guanosine (Guo)) were determined. The chosen compounds form predominantly monofunctional adducts by reacting at the N1, N3, or N7 positions of purine nucleobases. In addition, features of AAPt compounds that impact the glycosidic bond stability of Ado residues were explored. The glycosidic bond cleavage is activated differentially for AlaPt-Ado and OrnPt-Ado isomers. Formation of unique adducts at non-canonical residues and subsequent destabilization of the glycosidic bonds are important features that could circumvent platinum-based drug resistance. [ABSTRACT FROM AUTHOR]

Summary: Objective: Fibroblast growth factor 21 (FGF21), a primarily hepatic hormone with pleotropic metabolic effects, is regulated by fructose in humans. Recent work has established that 75 g of oral fructose robustly stimulates FGF21 levels in humans with peak levels occurring 2 h following ingestion; this has been termed an oral fructose tolerance test (OFTT). It is unknown whether prolonged high‐fructose consumption influences the FGF21 response to acute fructose or whether biological sex influences FGF21–fructose dynamics. Methods: Thirty‐nine healthy adults underwent baseline OFTT following an overnight fast. For the high‐fructose exposure protocol, 20 subjects ingested 75 g of fructose daily for 14 ± 3 d, followed by repeat OFTT. For the control group, an OFTT was repeated following 14 ± 3 d of ad lib diet. For all subjects, FGF21 levels, glucose, insulin, non‐esterified fatty acids and triglyceride levels were measured at baseline and 2 h following OFTT. All subjects maintained 3‐d food logs prior to OFTT testing. Results: Women demonstrated significantly higher baseline and peak stimulated total and intact FGF21 levels compared with men both before and after high‐fructose exposure. Baseline total and intact FGF21 levels decreased following ongoing fructose exposure, maintaining a stable ratio. This decrease was sex specific, with only women demonstrating decreased baseline FGF21 levels. There were no changes in metabolic or anthropometric parameters following the high‐fructose exposure. Conclusions: Daily ingestion of 75 g of fructose for 2 weeks results in a sex‐specific decrease in baseline FGF21 levels without change in body weight or biochemical evidence of metabolic injury. There were also sex‐specific differences in peak fructose‐stimulated FGF21 levels, which do not change with high‐fructose consumption. The role of FGF21 in the development of metabolic disease caused by fructose consumption may differ based on biological sex. Future long‐term studies should consider sex differences in FGF21–fructose dynamics. [ABSTRACT FROM AUTHOR]

Complexes of 18-crown-6 ether (18C6) with four protonated amino acids (AAs) are examined using infrared multiple photon dissociation (IRMPD) action spectroscopy utilizing light generated by the infrared free electron laser at the Centre Laser Infrarouge d’Orsay (CLIO). The AAs examined in this work include glycine (Gly) and the three basic AAs: histidine (His), lysine (Lys), and arginine (Arg). To identify the (AA)H+(18C6) conformations present in the experimental studies, the measured IRMPD spectra are compared to spectra calculated at the B3LYP/6-311+G(d,p) level of theory. Relative energies of various conformers and isomers are provided by single point energy calculations carried out at the B3LYP, B3P86, M06, and MP2(full) levels using the 6-311+G(2p,2d) basis set. The comparisons between the IRMPD and theoretical IR spectra indicate that 18C6 binds to Gly and His via the protonated backbone amino group, whereas protonated Lys prefers binding via the protonated side-chain amino group. Results for Arg are less definitive with strong evidence for binding to the protonated guanidino side chain (the calculated ground conformer at most levels of theory), but contributions from backbone binding to a zwitterionic structure are likely. [ABSTRACT FROM AUTHOR]

Summary: Objective: Fructose consumption is a risk factor for metabolic disease. We recently demonstrated that fibroblast growth factor 21 (FGF21), a metabolic hormone involved in lipid and glucose metabolism, is acutely stimulated in humans by 75 g oral fructose, with peak levels occurring 2 h after consumption. This study reports on the dose dependency and reproducibility of the FGF21 response to fructose. Methods: Lean, healthy adults drank either five different doses of fructose dissolved in water, each separated by 2 weeks, or the same dose on three occasions, each separated by 1 week. Results: Fibroblast growth factor 21 levels peaked at 2 h in a dose‐dependent manner. No significant increase in FGF21 was seen after consumption of 10 g fructose, while robust increases were seen after drinking solutions containing 30, 50 and 75 g. At 2 h, the minimal fold change of FGF21 was highest following a 75 g fructose drink, and all subjects demonstrated at least a doubling of FGF21 levels following consumption of this dose. Conclusions: The increase in FGF21 following an oral fructose challenge is dose dependent, with levels peaking at 2 h independent of dose. The FGF21 response to 75 g fructose is also highly reproducible within individuals. Clinical Implications: By demonstrating that the FGF21 response to fructose is dose dependent and reproducible, this study deepens current understanding of FGF21 fructose dynamics and physiology in humans. This is an important area of clinical interest given associations between fructose intake and a wide variety of metabolic derangements. [ABSTRACT FROM AUTHOR]

Presents information on a study which investigated the switching behavior of ferroelectric capacitors experiencing arbitrary time-dependent electric fields and arbitrary initial conditions. Methods; Results; Discussion.

Studies the device modeling of ferroelectric capacitors. Applications of ferroelectric capacitors; Ferroelectric capacitor module; Use of model as a physical diagnostic tool.

Monowai is a submarine volcanic center in the Kermadec Arc, Southwest Pacific Ocean. In the past, activity at the volcano had been intermittently observed in the form of fallout at the sea surface, discolored water, changes in seafloor topography, and T phase seismicity, but there is no continuous record for more recent years. In this study, we investigated 3.5 years of recordings at a hydrophone array of the International Monitoring System, located near Juan Fernández Islands, for long‐range underwater sound waves from Monowai. Results from direction‐of‐arrival calculations and density‐based spatial clustering indicate that 82 discrete episodes of activity occurred between July 2003 and March 2004 and from April 2014 to January 2017. Volcanic episodes are typically spaced days to weeks apart, range from hours to days in length, and amount to a cumulative sum of 137 days of arrivals in total, making Monowai one of the most active submarine arc volcanoes on Earth. The resolution of the hydrophone recordings surpasses broadband network data by at least 1 order of magnitude, identifying seismic events as low as 2.2 mb in the Kermadec Arc region. Further observations suggest volcanic activity at a location approximately 400 km north of Monowai in the Tonga Arc and at Healy or Brothers volcano in the southern Kermadec Arc. Our findings are consistent with previous studies and highlight the exceptional capabilities of the International Monitoring System network for the scientific study of active volcanism in the global ocean. Key Points: Volcanic activity at Monowai is detected by an IMS hydrophone array at Juan Fernández Islands, Southeast Pacific OceanEighty‐two discrete episodes of activity have been identified in a 3.5‐year recordMonowai is one of the most active submarine arc volcanoes currently known [ABSTRACT FROM AUTHOR]

The gas-phase conformations of the protonated forms of thymidine-5′-monophosphate and uridine-5′-monophosphate, [pdThd+H]+ and [pUrd+H]+, are investigated by infrared multiple photon dissociation (IRMPD) action spectroscopy and electronic structure calculations. The IRMPD action spectra of [pdThd+H]+ and [pUrd+H]+ are measured over the IR fingerprint and hydrogen-stretching regions using the FELIX free electron laser and an OPO/OPA laser system. Low-energy conformations of [pdThd+H]+ and [pUrd+H]+ and their relative stabilities are computed at the MP2(full)/6-311+G(2d,2p)//B3LYP/6-311+G(d,p) and B3LYP/6-311+G(2d,2p)//B3LYP/6-311+G(d,p) levels of theory. Comparisons of the measured IRMPD action spectra and B3LYP/6-311+G(d,p) linear IR spectra computed for the low-energy conformers indicate that the dominant conformers of [pdThd+H]+ and [pUrd+H]+ populated in the experiments are protonated at the phosphate oxo oxygen atom, with a syn nucleobase orientation that is stabilized by strong P=OH+…O2 and P–OH…O4′ hydrogen-bonding interactions, and C2′-endo sugar puckering. Minor abundance of conformers protonated at the O2 carbonyl of the nucleobase residue may also contribute for [pdThd+H]+, but do not appear to be important for [pUrd+H]+. Comparisons to previous IRMPD spectroscopy investigations of the protonated forms of thymidine and uridine, [dThd+H]+ and [Urd+H]+, and the deprotonated forms of pdThd and pUrd, [pdThd−H]− and [pUrd−H]−, provide insight into the effects of the phosphate moiety and protonation on the conformational features of the nucleobase and sugar moieties. Most interestingly, the thymine and uracil nucleobases remain in their canonical forms for [pdThd+H]+ and [pUrd+H]+, unlike [dThd+H]+ and [Urd+H]+, where protonation occurs on the nucleobases and induces tautomerization of the thymine and uracil residues. [ABSTRACT FROM AUTHOR]

Uridine (Urd) is one of the naturally occurring pyrimidine nucleosides of RNA. 2′-Deoxyuridine (dUrd) is a naturally occurring modified form of Urd, but is not one of the canonical DNA nucleosides. In order to understand the effects of sodium cationization on the conformations and energetics of Urd and dUrd, infrared multiple photon dissociation (IRMPD) action spectroscopy experiments and density functional theory (DFT) calculations are performed. By comparing the calculated IR spectra of [Urd+Na]+ and [dUrd+Na]+ with the measured IRMPD spectra, the stable low-energy conformers populated in the experiments are determined. Anti oriented bidentate O2 and O2′ binding conformers of [Urd+Na]+ are the dominant conformers populated in the experiments, whereas syn oriented tridentate O2, O4′, and O5′ binding conformers of [dUrd+Na]+ are dominantly populated in the experiments. The 2′-hydroxyl substituent of Urd stabilizes the anti oriented O2 binding conformers of [Urd+Na]+. Significant differences between the measured IRMPD and calculated IR spectra for complexes of [Urd+Na]+ and [dUrd+Na]+ involving minor tautomeric forms of the nucleobase make it obvious that none are populated in the experiments. Survival yield analyses based on energy-resolved collision-induced dissociation (ER-CID) experiments suggest that the relative stabilities of protonated and sodium cationized Urd and dUrd follow the order: [dUrd+H]+ ＜ [Urd+H]+ ＜ [dUrd+Na]+ ＜ [Urd+Na]+. The 2′-deoxy modification is found to weaken the glycosidic bond of dUrd versus that of Urd for the sodium cationized uridine nucleosides. [ABSTRACT FROM AUTHOR]

Objective: To assess the cost-effectiveness of radiofrequency catheter ablation (RFCA) compared with anti-arrhythmic drug (AAD) therapy for the treatment of atrial fibrillation (AF) from the perspective of the UK NHS. Design: Bayesian evidence synthesis and decision analytical model. Methods: A systematic review and meta-analysis was conducted and Bayesian statistical methods used to synthesise the effectiveness evidence from randomised control trials. A decision analytical model was developed to assess the costs and consequences associated with the primary outcome of the trials over a lifetime time horizon. Main Outcome Measure: Costs from a health service perspective and outcomes measured as quality-adjusted life years (QALYs). Results: The incremental cost-effectiveness ratio of RFCA varied between pound7763 and pound7910 for each additional QALY according to baseline risk of stroke, with a probability of being cost-effective from 0.98 to 0.99 for a cost-effectiveness threshold of pound20 000. Results were sensitive to the duration of quality of life benefits from treatment. Conclusions: RFCA is potentially cost-effective for the treatment of paroxysmal AF in patients' predominantly refractory to AAD therapy provided the quality-of-life benefits from treatment are maintained for more than 5 years. These findings remain subject to limitations in the existing evidence regarding the nature of life benefits and the prognostic importance of restoring normal sinus rhythm conferred using RFCA. [ABSTRACT FROM AUTHOR]

The gas-phase conformations of protonated uridine, [Urd+H]+, and its 2′-deoxy form, protonated 2′-deoxyuridine, [dUrd+H]+, have been examined in detail previously by infrared multiple photon dissociation action spectroscopy techniques. Both 2,4-dihydroxy tautomers and O4 protonated conformers of [Urd+H]+ and [dUrd+H]+ were found to coexist in the experiments with the 2,4-dihydroxy tautomers dominating the population. In the present study, the kinetic energy dependence of the collision-induced dissociation behavior of [Urd+H]+ and [dUrd+H]+ are examined using a guided ion beam tandem mass spectrometer to probe the mechanisms and energetics for activated dissociation of these protonated nucleosides. The primary dissociation pathways observed involve N-glycosidic bond cleavage leading to competitive elimination of protonated or neutral uracil. The potential energy surfaces (PESs) for these N-glycosidic bond cleavage pathways are mapped out via electronic structure calculations for the mixture of 2,4-dihydroxy tautomers and O4 protonated conformers of [Urd+H]+ and [dUrd+H]+ populated in the experiments. The calculated activation energies (AEs) and heats of reaction (ΔHrxns) for N-glycosidic bond cleavage at both the B3LYP and MP2(full) levels of theory are compared to the measured values. The agreement between experiment and theory indicates that B3LYP provides better estimates of the energetics of the species along the PESs for N-glycosidic bond cleavage than MP2, and that the 2,4-dihydroxy tautomers, which are stabilized by strong hydrogen-bonding interactions, predominantly influence the observed threshold dissociation behavior of [Urd+H]+ and [dUrd+H]+. [ABSTRACT FROM AUTHOR]

Our previous gas-phase infrared multiple photon dissociation action spectroscopy study of protonated 2′-deoxyadenosine and adenosine, [dAdo+H]+ and [Ado+H]+, found that both N3 and N1 protonated conformers are populated with the N3 protonated ground-state conformers predominant in the experiments. Therefore, N-glycosidic bond dissociation mechanisms of N3 and N1 protonated [dAdo+H]+ and [Ado+H]+ and the associated quantitative thermochemical values are investigated here using both experimental and theoretical approaches. Threshold collision-induced dissociation (TCID) of [dAdo+H]+ and [Ado+H]+ with Xe is studied using guided ion beam tandem mass spectrometry techniques. For both systems, N-glycosidic bond cleavage reactions are observed as the major dissociation pathways resulting in production of protonated adenine or elimination of neutral adenine. Electronic structure calculations are performed at the B3LYP/6-311+G(d,p) level of theory to probe the potential energy surfaces (PESs) for N-glycosidic bond cleavage of [dAdo+H]+ and [Ado+H]+. Relative energetics of the reactants, transition states, intermediates and products along the PESs for N-glycosidic bond cleavage are determined at the B3LYP/6-311+G(2d,2p), B3LYP-GD3BJ/6-311+G(2d,2p), and MP2(full)/6-311+G(2d,2p) levels of theory. The predicted N-glycosidic bond dissociation mechanisms for the N3 and N1 protonated species differ. Base rotation of the adenine residue enables formation of a strong N3H+…O5′ hydrogen-bonding interaction that stabilizes the N3 protonated species and its glycosidic bond. Comparison between experiment and theory indicates that the N3 protonated species determine the threshold energies, as excellent agreement between the measured and B3LYP computed activation energies (AEs) and reaction enthalpies (ΔHrxns) for N-glycosidic bond cleavage of the N3 protonated species is found. [ABSTRACT FROM AUTHOR]

Infrared multiple photon dissociation (IRMPD) action spectra of the protonated forms of 2′-deoxyguanosine-5′-monophosphate and guanosine-5′-monophosphate, [pdGuo+H]+ and [pGuo+H]+, are measured over the IR fingerprint and hydrogen-stretching regions using the FELIX free electron laser and an OPO/OPA laser system. Electronic structure calculations are performed to generate low-energy conformations of [pdGuo+H]+ and [pGuo+H]+ and determine their relative stabilities at the B3LYP/6-311+G(2d,2p)//B3LYP/6-311+G(d,p) and MP2(full)/6-311+G(2d,2p)//B3LYP/6-311+G(d,p) levels of theory. Comparative analyses of the measured IRMPD action spectra and B3LYP/6-311+G(d,p) linear IR spectra computed for the low-energy conformers are performed to determine the most favorable site of protonation and the conformers present in the experiments. These comparisons and the computed energetics find that N7 protonation is considerably preferred over O6 and N3, and the N7 protonated ground-state conformers of [pdGuo+H]+ and [pGuo+H]+ are populated in the experiments. The 2′-hydroxyl substituent does not significantly impact the stable low-energy conformers of [pdGuo+H]+vs. those of [pGuo+H]+. The effect of the 2′-hydroxyl substituent is primarily reflected in the relative intensities of the measured IRMPD bands, as the IRMPD profiles of [pdGuo+H]+ and [pGuo+H]+ are quite similar. Comparisons to previous IRMPD spectroscopy investigations of the protonated forms of the guanine nucleosides, [dGuo+H]+ and [Guo+H]+, and deprotonated forms of the guanine nucleotides, [pdGuo–H]− and [pGuo–H]−, provide insight into the effects of the phosphate moiety and protonation on the conformational features of the nucleobase and sugar moieties. Protonation is found to induce base rotation of the guanine residue to an anti orientation vs. the syn orientation found for the deprotonated forms of the guanine nucleotides. [ABSTRACT FROM AUTHOR]

This paper presents an experiment in which participants were asked to identify freeway diverge locations under different work zone settings. A total of 130 participants were shown computer rendered images of freeway diverges and tasked with identifying the diverge location by clicking on the image with a mouse. The evaluation method employed the participant's response time as one of the important surrogate safety measures, along with the response accuracy and the types of errors observed. The results show that response times are closely correlated with other measures in indicating participant performance, although some differences exist. Specifically, work zone delineation methods that show greater numbers of correct responses also tended to feature shorter response times. However, the use of correct response time reveals nuanced differences among channelizing devices that otherwise would not be recognized if the participant responses were only analyzed for accuracy. This was particularly true for a proposed linear channeling device where accuracy and response time demonstrated a wider divergence. Using a framework that simultaneously assessed response accuracy, error types, and response times, portable concrete barriers were found to be the most effective in assisting drivers with locating the freeway diverge in work zones. In contrast, drums were found least effective. The proposed linear channelizing device showed mixed results among the performance measures. The study method and results show the potential importance and relevance of response time as a possible surrogate safety measure in a comprehensive evaluation of innovative traffic control devices. The inclusion of response times not only reinforces, but also adds finer detail to methods that often only focus on response accuracy. [ABSTRACT FROM AUTHOR]

The article discusses how risk assessment, behavior modification and prosocial support can be used to lowering recidivism of federal offenders in the U.S. Topics discussed include federal sentencing policy; goal of sentencing to recognize the need of protection of the public from further crimes by a defendant; and monitoring compliance with the terms and conditions of an offender's supervision.

The Watson–Crick structure of DNA is among the most well-known molecular structures of our time. However, alternative base-pairing motifs are also known to occur, often depending on base sequence, pH, or the presence of cations. Pairing of cytosine (C) bases induced by the sharing of a single proton (C–H+–C) may give rise to the so-called i-motif, which occurs primarily in expanded trinucleotide repeats and the telomeric region of DNA, particularly at low pH. At physiological pH, silver cations were recently found to stabilize C dimers in a C–Ag+–C structure analogous to the hemiprotonated C-dimer. Here we use infrared ion spectroscopy in combination with density functional theory calculations at the B3LYP/6-311G+(2df,2p) level to show that copper in the 1+ oxidation state induces an analogous formation of C–Cu+–C structures. In contrast to protons and these transition metal ions, alkali metal ions induce a different dimer structure, where each ligand coordinates the alkali metal ion in a bidentate fashion in which the N3 and O2 atoms of both cytosine ligands coordinate to the metal ion, sacrificing hydrogen-bonding interactions between the ligands for improved chelation of the metal cation. [ABSTRACT FROM AUTHOR]

The article offers information on the clinical practice guidelines of the scientific organization International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) in addressing the importance of ultrasound assessment in twin pregnancy. Topics discussed include the twin-to-twin transfusion syndrome (TTTS), how to determine chorionicity/amnionicity in twin pregnancy, and the management of fetal growth restriction (FGR).

Experimental and theoretical investigations suggest that hydrolysis of N-glycosidic bonds generally involves a concerted SN2 or a stepwise SN1 mechanism. While theoretical investigations have provided estimates for the intrinsic activation energies associated with N-glycosidic bond cleavage reactions, experimental measurements to validate the theoretical studies remain elusive. Here we report experimental investigations for N-glycosidic bond cleavage of the protonated guanine nucleosides, [dGuo+H]+ and [Guo+H]+, using threshold collision-induced dissociation (TCID) techniques. Two major dissociation pathways involving N-glycosidic bond cleavage, resulting in production of protonated guanine or the elimination of neutral guanine are observed in competition for both [dGuo+H]+ and [Guo+H]+. The detailed mechanistic pathways for the N-glycosidic bond cleavage reactions observed are mapped via electronic structure calculations. Excellent agreement between the measured and B3LYP calculated activation energies and reaction enthalpies for N-glycosidic bond cleavage of [dGuo+H]+ and [Guo+H]+ in the gas phase is found indicating that these dissociation pathways involve stepwise E1 mechanisms in analogy to the SN1 mechanisms that occur in the condensed phase. In contrast, MP2 is found to significantly overestimate the activation energies and slightly overestimate the reaction enthalpies. The 2′-hydroxyl substituent is found to stabilize the N-glycosidic bond such that [Guo+H]+ requires ∼25 kJ mol−1 more than [dGuo+H]+ to activate the glycosidic bond. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the study was to identify differences in infant outcomes, virological efficacy, and preterm delivery (PTD) outcome between women exposed to lopinavir/ritonavir (LPV/r) and those exposed to atazanavir/ritonavir (ATV/r). Methods: A retrospective case note review was carried out. The case notes of 493 women who conceived while on LPV/r or ATV/r or initiated LPV/r or ATV/r during pregnancy and who delivered between 1 September 2007 and 30 August 2012 were reviewed. Data collected included demographics, antiretroviral use, HIV markers, and pregnancy and infant outcomes. Infant outcomes, virological efficacies and PTD rates for LPV/r and ATV/r were compared. Results: A total of 306 women received LPV/r (82 conceiving while on the drug and 224 commencing it post-conception) and 187 received ATV/r (96 conceiving while on the drug and 91 commencing it post-conception). Comparing the two protease inhibitors (PIs), viral suppression rates were similar and, in women starting antiretroviral therapy (ART) post-conception, the median times to first undetectable HIV viral load were not significantly different (P = 0.64). PTD rates did not differ by therapy overall (ATV/r, 13%; LPV/r, 14%) or when considering the timing of first exposure (conceiving on ART, P = 0.81; commencing ART in pregnancy, P = 0.08). Poor fetal outcomes were very uncommon. There were two transmissions, giving a mother-to-child transmission (MTCT) rate of 0.4% (95% confidence interval 0.05-1.5%). Conclusions: Both ART regimens were well tolerated and successful in preventing MTCT. No significant differences in tolerability or in pregnancy or infant outcomes were observed, which supports the provision of a choice of PI in pregnancy. [ABSTRACT FROM AUTHOR]

The gas-phase conformations of protonated uridine, [Urd+H]+, and its modified form, protonated 2′-deoxyuridine, [dUrd+H]+, generated by electrospray ionization are investigated using infrared multiple photon dissociation (IRMPD) action spectroscopy techniques. IRMPD action spectra of [Urd+H]+ and [dUrd+H]+ are measured over the IR fingerprint and hydrogen-stretching regions. [Urd+H]+ and [dUrd+H]+ exhibit very similar IRMPD spectral profiles. However, the IRMPD yields of [Urd+H]+ exceed those of [dUrd+H]+ in both the IR fingerprint and hydrogen-stretching regions. The measured spectra are compared to the linear IR spectra predicted for the stable low-energy structures of these species computed at the B3LYP/6-311+G(d,p) level of theory to determine the tautomeric conformations populated by electrospray ionization. Both B3LYP and MP2 methods find O4 and O2 protonated canonical as well as 2,4-dihydroxy tautomers among the stable low-energy structures of [Urd+H]+ and [dUrd+H]+. Comparison between the measured IRMPD and calculated linear IR spectra suggests that these species exist in their ring-closed forms and that both 2,4-dihydroxy tautomers as well as O4 protonated canonical conformers coexist in the population generated by electrospray ionization for both [Urd+H]+ and [dUrd+H]+. The 2′-deoxy modification of [dUrd+H]+ reduces the variety of 2,4-dihydroxy tautomers populated in the experiments vs. those of [Urd+H]+. [ABSTRACT FROM AUTHOR]

The use of mechanical rock grinding to remove rock pinnacles and outcroppings, considered to be navigation hazards in the Mississippi River, was evaluated as a less damaging alternative when compared to the more conventional use of drilling and blasting. The project area contains the federally endangered pallid sturgeon ( Scaphirhynchus albus) and there was concern that intense sound pressure levels ( SPLs) could impact the species. SPLs were measured during production rock grinding ( January 2012, just north of Thebes, Illinois) and compared to those values with SPLs known to cause fish mortality, hearing damage, temporary hearing threshold shifts ( TTS), and stress. The source SPLs' maxima for each time block analyzed ranged from 160-172 d B (re 1 μPa @ 1 m) at frequencies ranging from 100-1250 Hz (1/3-octave band). The highest source SPL maximum recorded for the sound recording session was 172 dB (re 1 μPa @ 1 m) at 1250 Hz. These SPL levels at 1 m from the grinder were well below levels responsible for mortality or noise induced hearing damage. The impact zone for stress (increases in cortisol) was calculated to be within a 9 m radius of the grinder, while the impact zone for TTS was calculated to be within 31 m of the grinder. Considering the small impact zones and continuous noise production during grinding, there is a strong possibility that sturgeon would either avoid or move out of the impact zone. [ABSTRACT FROM AUTHOR]

We describe the demographics and treatment outcomes of a HIV-infected cohort from Croydon University Hospital, London, UK. We showed that the Croydon Cohort had good viral load suppression (98.6% with viral load < 100 copies/ml and 99.0% with viral load < 200 copies/ml) despite being a potentially challenging cohort in a deprived area of London. The viral load outcomes are better than the Public Health England data from 2014 and the latest British HIV Association audit using data from 2009. [ABSTRACT FROM AUTHOR]

We describe the demographics and treatment outcomes of a HIV-infected cohort from Croydon University Hospital, London, UK. We showed that the Croydon Cohort had good viral load suppression (98.6% with viral load < 100 copies/ml and 99.0% with viral load < 200 copies/ml) despite being a potentially challenging cohort in a deprived area of London. The viral load outcomes are better than the Public Health England data from 2014 and the latest British HIV Association audit using data from 2009. [ABSTRACT FROM AUTHOR]

Binding of metal cations to the nucleobases can influence base pairing, base stacking and nucleobase tautomerism. Gas-phase condensation of dc discharge generated alkali metal cations and thermally vaporized cytosine (DC/FT) has been found to produce kinetically trapped excited tautomeric conformations of the M+(cytosine) complexes, which influences the threshold collision-induced dissociation (TCID) behavior. In order to elucidate the effects of the size of alkali metal cation on the strength of binding to the canonical form of cytosine, the binding affinities of Na+ and K+ to cytosine are re-examined here, and studies are extended to include Rb+ and Cs+ again using TCID techniques. The M+(cytosine) complexes are generated in an electrospray ionization source, which has been shown to produce ground-state tautomeric conformations of M+(cytosine). The energy-dependent cross sections are interpreted to yield bond dissociation energies (BDEs) using an analysis that includes consideration of unimolecular decay rates, the kinetic and internal energy distributions of the reactants, and multiple M+(cytosine)–Xe collisions. Revised BDEs for the Na+(cytosine) and K+(cytosine) complexes exceed those previously measured by 31.9 and 25.5 kJ mol−1, respectively, consistent with the hypothesis proposed by Yang and Rodgers that excited tautomeric conformations are accessed when the complexes are generated by DC/FT ionization. Experimentally measured BDEs are compared to theoretical values calculated at the B3LYP and MP2(full) levels of theory using the 6-311+G(2d,2p)_HW* and def2-TZVPPD basis sets. The B3LYP/def2-TZVPPD level of theory is found to provide the best agreement with the measured BDEs, suggesting that this level of theory can be employed to provide reliable energetics for similar metal–ligand systems. [ABSTRACT FROM AUTHOR]