On the interactions between molecules in an off-resonant laser beam:Evaluating the response to energy migration and optically induced pair forces

Electronically excited molecules interact with their neighbors differently from their ground-state counterparts. Any migration of the excitation between molecules can modify intermolecular forces, reflecting changes to a local potential energy landscape. It emerges that throughput off-resonant radiation can also produce significant additional effects. The context for the present analysis of the mechanisms is a range of chemical and physical processes that fundamentally depend on intermolecular interactions resulting from second and fourth-order electric-dipole couplings. The most familiar are static dipole-dipole interactions, resonance energy transfer (both second-order interactions), and dispersion forces (fourth order). For neighboring molecules subjected to off-resonant light, additional forms of intermolecular interaction arise in the fourth order, including radiation-induced energy transfer and optical binding. Here, in a quantum electrodynamical formulation, these phenomena are cast in a unified description that establishes their inter-relationship and connectivity at a fundamental level. Theory is then developed for systems in which the interplay of these forms of interaction can be readily identified and analyzed in terms of dynamical behavior. The results are potentially significant in Förster measurements of conformational change and in the operation of microelectromechanical and nanoelectromechanical devices. © 2009 American Institute of Physics

A molecular theory for two-photon and three-photon fluorescence polarization

In the analysis of molecular structure and local order in heterogeneous samples, multiphoton excitation of fluorescence affords chemically specific information and high-resolution imaging. This report presents the results of an investigation that secures a detailed theoretical representation of the fluorescence polarization produced by one-, two-, and three-photon excitations, with orientational averaging procedures being deployed to deliver the fully disordered limits. The equations determining multiphoton fluorescence response prove to be expressible in a relatively simple, generic form, and graphs exhibit the functional form of the multiphoton fluorescence polarization. Amongst other features, the results lead to the identification of a condition under which the fluorescence produced through the concerted absorption of any number of photons becomes completely unpolarized. It is also shown that the angular variation of fluorescence intensities is reliable indicator of orientational disorder

Bioactivation of Trimethoprim to Protein-Reactive Metabolites in Human Liver Microsomes

The formation of drug-protein adducts via metabolic activation and covalent binding may stimulate an immune response or may result in direct cell toxicity. Protein covalent binding is a potentially pivotal step in the development of idiosyncratic adverse drug reactions (IADRs). Trimethoprim (TMP)-sulfamethoxazole (SMX) is a combination antibiotic that commonly causes IADRs. Recent data suggest that the contribution of the TMP component of TMP-SMX to IADRs may be underappreciated. We previously demonstrated that TMP is bioactivated to chemically reactive intermediates that can be trapped in vitro by N-acetyl cysteine (NAC), and we have detected TMP-NAC adducts (i.e., mercapturic acids) in the urine of patients taking TMP-SMX. However, the occurrence and extent of TMP covalent binding to proteins was unknown. To determine the ability of TMP to form protein adducts, we incubated [14C]TMP with human liver microsomes in the presence and absence of NADPH. We observed protein covalent binding that was NADPH dependent and increased with incubation time and concentration of both protein and TMP. The estimated covalent binding was 0.8 nmol Eq TMP/mg protein, which is comparable to the level of covalent binding for several other drugs that have been associated with covalent binding–induced toxicity and/or IADRs. NAC and selective inhibitors of CYP2B6 and CYP3A4 significantly reduced TMP covalent binding. These results demonstrate for the first time that TMP bioactivation can lead directly to protein adduct formation, suggesting that TMP has been overlooked as a potential contributor of TMP-SMX IADRs

Zinc for the prevention or treatment of acute viral respiratory tract infections in adults : a rapid systematic review and meta-analysis of randomised controlled trials

Objective To evaluate the benefits and risks of zinc formulations compared with controls for prevention or treatment of acute viral respiratory tract infections (RTIs) in adults. Method Seventeen English and Chinese databases were searched in April/May 2020 for randomised controlled trials (RCTs), and from April/May 2020 to August 2020 for SARS-CoV-2 RCTs. Cochrane rapid review methods were applied. Quality appraisals used the Risk of Bias 2.0 and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Results Twenty-eight RCTs with 5446 participants were identified. None were specific to SARS-CoV-2. Compared with placebo, oral or intranasal zinc prevented 5 RTIs per 100 person-months (95% CI 1 to 8, numbers needed to treat (NNT)=20, moderate-certainty/quality). Sublingual zinc did not prevent clinical colds following human rhinovirus inoculations (relative risk, RR 0.96, 95% CI 0.77 to 1.21, moderate-certainty/quality). On average, symptoms resolved 2 days earlier with sublingual or intranasal zinc compared with placebo (95% CI 0.61 to 3.50, very low-certainty/quality) and 19 more adults per 100 were likely to remain symptomatic on day 7 without zinc (95% CI 2 to 38, NNT=5, low-certainty/quality). There were clinically significant reductions in day 3 symptom severity scores (mean difference, MD-1.20 points, 95% CI-0.66 to-1.74, low-certainty/quality), but not average daily symptom severity scores (standardised MD-0.15, 95% CI-0.43 to 0.13, low-certainty/quality). Non-serious adverse events (AEs) (eg, nausea, mouth/nasal irritation) were higher (RR 1.41, 95% CI 1.17 to 1.69, NNHarm=7, moderate-certainty/quality). Compared with active controls, there were no differences in illness duration or AEs (low-certainty/quality). No serious AEs were reported in the 25 RCTs that monitored them (low-certainty/quality). Conclusions In adult populations unlikely to be zinc deficient, there was some evidence suggesting zinc might prevent RTIs symptoms and shorten duration. Non-serious AEs may limit tolerability for some. The comparative efficacy/effectiveness of different zinc formulations and doses were unclear. The GRADE-certainty/quality of the evidence was limited by a high risk of bias, small sample sizes and/or heterogeneity. Further research, including SARS-CoV-2 clinical trials is warranted

A meta-study of relationships between fluvial channel-body stacking pattern and aggradation rate: implications for sequence stratigraphy

A quantitative comparison of 20 literature case studies of fluvial sedimentary successions tests common assumptions made in published models of alluvial architecture concerning (1) inverse proportionality between channel-deposit density and floodplain aggradation rates, and (2) resulting characteristics of channel-body geometries and connectedness. Our results do not support the relationships predicted by established stratigraphy models: the data suggest that channel-body density, geometry, and stacking pattern are not reliable diagnostic indicators of rates of accommodation creation. Hence, these architectural characteristics alone do not permit the definition of accommodation-based “systems tracts” and “settings”, and this calls into question current sequence stratigraphic practice in application to fluvial successions

Nicotinamide Phosphoribosyltransferase Attenuates Methotrexate Response in Juvenile Idiopathic Arthritis and In Vitro

Variability in response to methotrexate (MTX) in the treatment of juvenile idiopathic arthritis (JIA) remains unpredictable and poorly understood. Based on previous studies implicating an interaction between nicotinamide phosphoribosyltransferase (NAMPT) expression and MTX therapy in inflammatory arthritis, we hypothesized that increased NAMPT expression would be associated with reduced therapeutic response to MTX in patients with JIA. A significant association was found between increased plasma concentrations of NAMPT and reduced therapeutic response in patients with JIA treated with MTX. Inhibition of NAMPT in cell culture by either siRNA-based gene silencing or pharmacological inhibition with FK-866 was found to result in a fourfold increase in the pharmacological activity of MTX. Collectively, these findings provide evidence that NAMPT inhibits the pharmacological activity of MTX and may represent a predictive biomarker of response, as well as a therapeutic target, in the treatment of JIA with MTX

Basin analysis using seismic interpretation as tools to examine the extent of a basin ore 'play'

Stratiform and stratabound base metal ores typically form in sedimentary basins during the overall rifting process with mineralising fluids transported along the growing normal faults. Understanding the detailed structural evolution, i.e. the timing, the growth and the extent of the faults, and the distribution and thickness of the syn-faulting sedimentary packages, is critical for focusing exploration efforts. In this paper, we describe how seismic interpretation and basin analysis techniques can help to do this. We assess the potential for Pb-Zn mineralisation within the Northumberland Trough, northern England, in the context of the wider Early Carboniferous basin evolution and the associated base metal ores. Through structural interpretation of seismic reflection data, we consider the detailed evolution of the fault geometries and sedimentation in time and space, to show the extent and distribution of the Early Carboniferous faulting and growth packages at depth in the study area. We conclude that basin evolution and structural framework in northern England is very similar to that associated with the significant Pb-Zn mineralisation in Ireland. We suggest a refined model for the Carboniferous evolution of this part of the basin. The study demonstrates how the techniques of basin analysis can be a used in ore exploration to establish whether the basic structural and sedimentary framework exists to enable mineralisation. In addition to assessing the general potential of base metal mineralisation, a more precise identification of potentially suitable areas for further investigation can be made. The seismic data and basin analysis approach used in this paper and exemplified through the Northumberland case should be directly applicable to any basin ore 'play' associated with rifting and/or sedimentation. The added, significant advantage of this method is the ability to assess the 3D fault geometries, including fault linkage and growth in space and time, and the associated sedimentation - an unachievable outcome if relying solely on other geophysical and geological data traditionally used in regional ore exploration

Identification of electrofacies on the basis of well logging to determine sedimentation environment of horizon JK[2] in Em-Egovskoe field (Western Siberia)

Well logging results are one of the ways to study the buried terrigenous rocks genesis. To ensure the most objective characterization of the rock and identification of electrofacies it is necessary to use a complex geological and geophysical survey. The comprehensive investigations of environmental conditions based on well logging have been performed for the horizon JK[2] of Tumenskoe formation in Em-Egovskoe area, Krasnoleninskoe field (Western Siberia). The defined electrofacies were compared with the results of earlier conducted granulometric and mineralogical analyses. The totality of research provided for a conclusion that the investigated sediments of horizon JK2 had been formed within the destructive tidal delta. Thus, objective facies prediction can only be ensured by analyzing core and well logging data comprehensively