This report details the analyses and related uncertainties in measuring longitudinal-stress-density paths in indirect laser-driven ramp equation-of-state (EOS) experiments [Smith et al., Nat. Astron.
View Article and Find Full Text PDFAmphotericin B (AmB) is a potent antimicrobial agent used in clinical practice. Nevertheless, the mechanism of its aqueous instability remains not yet fully understood, especially the role that its aggregation state plays in this process. Therefore, the current study used an aqueous methanol media to evaluate the AmB instability as a function of pH-, organic solvent- and concentration-dependent ionization and aggregation.
View Article and Find Full Text PDFBistable perception refers to a broad class of dynamically alternating visual illusions that result from ambiguous images. These illusions provide a powerful method to study the mechanisms that determine how visual input is integrated over space and time. Binocular rivalry occurs when subjects view different images in each eye, and a similar experience called stimulus rivalry occurs even when the left and right images are exchanged at a fast rate.
View Article and Find Full Text PDFThe purpose of this work was to determine the degradation pathway of Amphotericin B (AmB) and its kinetics in lipid-based solutions. Mixtures of AmB in lipophilic solvent media were stored under different conditions, such as surface area, temperature, light exposure, presence of antioxidants and other co-solutes. AmB was quantified by HPLC and UV-Vis spectrometry.
View Article and Find Full Text PDFA quantitative, model-based risk assessment process was evaluated using Bayesian parameter estimation to determine the posterior distribution of the probability of a model tablet formulation's (gabapentin) ability to meet end-of-expiry stability criteria-based manufacturing controls. Experimental data was obtained from an FDA-supported, multi-year project that involved researchers at nine universities working collaboratively with industrial and governmental scientists under the leadership of the National Institute for Pharmaceutical Technology and Education (NITPE). The risk assessment process involved the development of a design space manufacturing model and shelf life stability model that shared stability-related critical quality attributes (CQAs).
View Article and Find Full Text PDFAAPS PharmSciTech
October 2018
The use of particle size distribution (PSD) similarity metrics and the development and incorporation of drug release predictions based on PSD properties into PBPK models for various drug administration routes may provide a holistic approach for evaluating the effect of PSD differences on in vitro drug release and bioavailability of disperse systems. The objectives of this study were to provide a rational approach for evaluating the utility of in vitro PSD comparators for predicting bioequivalence for subcutaneously administered test and reference drug emulsions. Two types of in vitro comparators for test and reference emulsion products were evaluated: PSD characterization comparators (overlap metrics, median, and span ratios) and release profile comparators (f and various fractional time ratios).
View Article and Find Full Text PDFPurpose: The purpose of the research described herein was to develop a kinetic model for quantifying the effects of conditional and compositional variations on non-covalent polymorphic and covalent chemical transformations of gabapentin.
Methods: Kinetic models that describe the relationship between polymorphs and degradation product in a series of sequential or parallel steps were devised based on analysis of the resultant concentration time profiles. Model parameters were estimated using non-linear regression and Bayesian methods and evaluated in terms of their quantitative relationship to compositional and conditional variations.
Gabapentin was used as a model pharmaceutical compound with susceptibility to polymorphic transformation as a function of environmental and mechanical stress. The utility of C CP/MAS NMR and XRPD as stability-indicating methods to quantify polymorphic transformation kinetics was investigated. Polymorphic Form II and III were distinguishable based on their chemical shift and distinct diffraction peak differences.
View Article and Find Full Text PDFWhen incompatible images are presented to each eye, a phenomenon known as binocular rivalry occurs in which the viewer's conscious visual perception alternates between the two images. In stimulus rivalry, similar perceptual alternations between rival images can occur even in the midst of fast image swapping between the eyes. Here, we used functional magnetic resonance imaging to directly compare brain activity underlying the two types of perceptual rivalry.
View Article and Find Full Text PDFPatient safety risk due to toxic degradation products is a potentially critical quality issue for a small group of useful drug substances. Although the pharmacokinetics of toxic drug degradation products may impact product safety, these data are frequently unavailable. The objective of this study is to incorporate the prediction capability of physiologically based pharmacokinetic (PBPK) models into a rational drug degradation product risk assessment procedure using a series of model drug degradants (substituted anilines).
View Article and Find Full Text PDFThe interaction mechanism of lipopeptide antibiotic daptomycin and polyamidoamine (PAMAM) dendrimers was studied using fluorescence spectroscopy. The fluorescence changes observed are associated with daptomycin-dendrimer interactions. The binding isotherms were constructed by plotting the fluorescence difference at 460 nm from kynurenine (Kyn-13) of daptomycin in the presence and absence of dendrimer.
View Article and Find Full Text PDFThe aggregation behavior and critical aggregation concentration (CAC) values of daptomycin in aqueous solutions were evaluated under the external factors of pH, temperature, daptomycin concentration, and calcium ions concentration by using the complementary characterization techniques, fluorescence, dynamic and static light scattering, and nuclear magnetic resonance (NMR) spectroscopy. On the basis of the intrinsic fluorescence resonance energy transfer of daptomycin, the CAC values were identified by an upward inflection of the fluorescence emission from Kyn-13 at 460 nm. The pH-dependent CAC values were determined to be 0.
View Article and Find Full Text PDFA QCD analysis is reported of ATLAS data on inclusive W(±) and Z boson production in pp collisions at the LHC, jointly with ep deep-inelastic scattering data from HERA. The ATLAS data exhibit sensitivity to the light quark sea composition and magnitude at Bjorken x∼0.01.
View Article and Find Full Text PDFA search is reported for the pair production of a new quark b' with at least one b' decaying to a Z boson and a bottom quark. The data, corresponding to 2.0 fb(-1) of integrated luminosity, were collected from pp collisions at √s = 7 TeV with the ATLAS detector at the CERN Large Hadron Collider.
View Article and Find Full Text PDFA search is presented for production of a heavy up-type quark (t') together with its antiparticle, assuming subsequent decay to a W boson and a b quark, t't[over ¯]'→W(+)bW(-)b[over ¯]. The search is based on 1.04 fb(-1) of proton-proton collisions at √[s]=7 TeV collected by the ATLAS detector at the CERN Large Hadron Collider.
View Article and Find Full Text PDFA search for the decay of a light Higgs boson (120-140 GeV) to a pair of weakly interacting, long-lived particles in 1.94 fb(-1) of proton-proton collisions at sqrt[s] = 7 TeV recorded in 2011 by the ATLAS detector is presented. The search strategy requires that both long-lived particles decay inside the muon spectrometer.
View Article and Find Full Text PDFA search is presented for gluinos decaying via the supersymmetric partner of the top quark using events with two same-sign leptons, jets, and missing transverse momentum. The analysis is performed with 2.05 fb(-1) of integrated luminosity from pp collisions at sqrt[s]=7 TeV collected by the ATLAS detector at the LHC.
View Article and Find Full Text PDFA measurement of spin correlation in tt[over ¯] production is reported using data collected with the ATLAS detector at the LHC, corresponding to an integrated luminosity of 2.1 fb(-1). Candidate events are selected in the dilepton topology with large missing transverse energy and at least two jets.
View Article and Find Full Text PDFThis Letter describes a model-independent search for the production of new resonant states in photon+jet events in 2.11 fb(-1) of proton-proton collisions at √s=7 TeV. We compare the photon+jet mass distribution to a background model derived from data and find consistency with the background-only hypothesis.
View Article and Find Full Text PDFThis Letter presents a search for tb resonances in 1.04 fb(-1) of LHC proton-proton collision data collected by the ATLAS detector at a center-of-mass energy of 7 TeV. Events with a lepton, missing transverse momentum, and two jets are selected and the invariant mass of the corresponding final state is reconstructed.
View Article and Find Full Text PDFThis Letter presents a search for pair production of heavy down-type quarks decaying via b' → Wt in the lepton + jets channel, as b'b' → W- tW+ t → bbW+ W- W+ W- → l± νbbqqqqqq. In addition to requiring exactly one lepton, large missing transverse momentum, and at least six jets, the invariant mass of nearby jet pairs is used to identify high transverse momentum W bosons. In data corresponding to an integrated luminosity of 1.
View Article and Find Full Text PDFThe results of a search for pair production of the scalar partners of bottom quarks in 2.05 fb(-1) of pp collisions at sqrt[s]=7 TeV using the ATLAS experiment are reported. Scalar bottom quarks are searched for in events with large missing transverse momentum and two jets in the final state, where both jets are identified as originating from a bottom quark.
View Article and Find Full Text PDFThe χ(b)(nP) quarkonium states are produced in proton-proton collisions at the Large Hadron Collider at sqrt[s] = 7 TeV and recorded by the ATLAS detector. Using a data sample corresponding to an integrated luminosity of 4.4 fb(-1), these states are reconstructed through their radiative decays to Υ(1S,2S) with Υ → μ+ μ-.
View Article and Find Full Text PDFA search for the standard model Higgs boson is performed in the diphoton decay channel. The data used correspond to an integrated luminosity of 4.9 fb(-1) collected with the ATLAS detector at the Large Hadron Collider in proton-proton collisions at a center-of-mass energy of √s=7 TeV.
View Article and Find Full Text PDFA search for the Higgs boson has been performed in the H→WW(*)→ℓ(+)νℓ(-)ν[over ¯] channel (ℓ=e/μ) with an integrated luminosity of 2.05 fb(-1) of pp collisions at √s=7 TeV collected with the ATLAS detector at the Large Hadron Collider. No significant excess of events over the expected background is observed and limits on the Higgs boson production cross section are derived for a Higgs boson mass in the range 110 GeV