Exchange Lifetime Research Articles

A Transient, Excited Species of the Autoinhibited α-State of the Bacterial Transcription Factor RfaH May Represent an Early Intermediate on the Fold-Switching Pathway.

RfaH is a two-domain transcription factor in which the C-terminal domain switches fold from an α-helical hairpin to a β-roll upon binding the ops-paused RNA polymerase. To ascertain the presence of a sparsely populated excited state that may prime the autoinhibited resting state of RfaH for binding ops-paused RNA polymerase, we carried out a series of NMR-based exchange experiments to probe for conformational exchange on the millisecond time scale. Quantitative analysis of these data reveals exchange between major ground (∼95%) and sparsely populated excited (∼5%) states with an exchange lifetime of ∼3 ms involving residues at the interface between the N-terminal and C-terminal domains formed by the β3/β4 hairpin and helix α3 of the N-terminal domain and helices α4 and α5 of the C-terminal domain. The largest 15N backbone chemical shift differences are associated with the β3/β4 hairpin, leading us to suggest that the excited state may involve a rigid body lateral displacement/rotation away from the C-terminal domain to adopt a position similar to that seen in the active RNA polymerase-bound state. Such a rigid body reorientation would result in a reduction in the interface between the N- and C-terminal domains with the possible introduction of a cavity or cavities. This hypothesis is supported by the observation that the population of the excited species and the exchange rate of interconversion between ground and excited states are reduced at a high (2.5 kbar) pressure. Mechanistic implications for fold switching of the C-terminal domain in the context of RNA polymerase binding are discussed.

Digital exchange attributes and the risk of closure

Presently, there are over 500 cryptocurrency exchanges worldwide and more than 19,700 different cryptocurrencies. Despite the fact that cryptocurrency trading is possible via private peer-to-peer transactions, more than 90% of trading occurs on organised exchanges, which provide convenience and liquidity. However, centralised cryptocurrency exchanges are regarded as high-value targets by criminals and are often victims of cyberattacks. In this paper, we investigate the risk of cryptocurrency exchange closures and develop predictive models to forecast which markets will close down and which ones will remain active using publicly available data. Our models perform well and reach a high level of classification accuracy. Exchange trading volume, the availability of public information on exchange staff, exchange lifetime, and several cybersecurity features are identified as key attributes in predicting exchange closures. Nevertheless, our models do not account for all sources of risk, e.g., potential fraud and mismanagement of client funds committed by the exchanges themselves, and market participants are encouraged to carefully consider where and how they store their digital assets.

Cryptocurrency exchanges: Predicting which markets will remain active

AbstractAbout 99% of cryptocurrency trades occur on organized exchanges with many investors subsequently keeping their digital assets in accounts with cryptocurrency markets. This generates exposure to the risk of exchange closures. We construct a database containing eight key characteristics on 238 cryptocurrency exchanges and employ machine learning techniques to predict whether a cryptocurrency market will remain active or whether it will go out of business. Both in‐sample and out‐of‐sample measures of forecasting performance are computed and ranked for four popular machine learning algorithms. Although all four models produce satisfactory classification accuracy, our best model is a random forest classifier. It reaches accuracy of 90.4% on training data and 86.1% on a test dataset. From the list of predictors, we find that exchange lifetime, transacted volume, and cyber‐security measures such as security audit, cold storage, and bug bounty programs rank high in terms of feature importance across multiple algorithms. On the other hand, whether an exchange has previously experienced a security breach does not rank highly according to its contribution to classification accuracy.

Statistical study of “trunk-like” heavy ion structures in the inner magnetosphere

We present a statistical study of “trunk-like” structures observed in He⁺ and O⁺ in the inner magnetosphere. The main characteristic of these structures is that the energy of the peak flux decreases earthward. Using observations from the Helium Oxygen Proton Electron (HOPE) instrument onboard Van Allen Probe A, we identify the trunks observed from November 2012 to June 2019 and obtain the universal time, <italic>L</italic> shell, magnetic local time (MLT), and energy information of each trunk’s root and tip. We then investigate the behavior of trunks in terms of their frequency of occurrence, temporal evolution, spatial and energy distribution, and trunk dependence on different geomagnetic indices. We find that (1) the trunks are always located at <italic>L</italic> = 1.5−4.0 and have a preferential location mainly concentrated at MLT = 18−24, (2) the sector within MLT = 14−16 is a forbidden zone without trunk roots, and (3) the energy of He⁺ trunks is the largest near dusk and gradually decreases in the counterclockwise direction, whereas the energy of O⁺ trunks is relatively evenly distributed with MLT and <italic>L</italic>. The differences between He⁺ and O⁺ trunks are probably due to the different charge exchange and Coulomb collision lifetime. The dependence on different geomagnetic indices indicates that the trunk structures occur more frequently during relatively quiet periods.

Ligand modulation of the conformational dynamics of the A2A adenosine receptor revealed by single-molecule fluorescence

G protein-coupled receptors (GPCRs) are the largest class of transmembrane proteins, making them an important target for therapeutics. Activation of these receptors is modulated by orthosteric ligands, which stabilize one or several states within a complex conformational ensemble. The intra- and inter-state dynamics, however, is not well documented. Here, we used single-molecule fluorescence to measure ligand-modulated conformational dynamics of the adenosine A2A receptor (A2AR) on nanosecond to millisecond timescales. Experiments were performed on detergent-purified A2R in either the ligand-free (apo) state, or when bound to an inverse, partial or full agonist ligand. Single-molecule Förster resonance energy transfer (smFRET) was performed on detergent-solubilized A2AR to resolve active and inactive states via the separation between transmembrane (TM) helices 4 and 6. The ligand-dependent changes of the smFRET distributions are consistent with conformational selection and with inter-state exchange lifetimes ≥ 3 ms. Local conformational dynamics around residue 2296.31 on TM6 was measured using fluorescence correlation spectroscopy (FCS), which captures dynamic quenching due to photoinduced electron transfer (PET) between a covalently-attached dye and proximal aromatic residues. Global analysis of PET-FCS data revealed fast (150–350 ns), intermediate (50–60 μs) and slow (200–300 μs) conformational dynamics in A2AR, with lifetimes and amplitudes modulated by ligands and a G-protein mimetic (mini-Gs). Most notably, the agonist binding and the coupling to mini-Gs accelerates and increases the relative contribution of the sub-microsecond phase. Molecular dynamics simulations identified three tyrosine residues (Y112, Y2887.53, and Y2907.55) as being responsible for the dynamic quenching observed by PET-FCS and revealed associated helical motions around residue 2296.31 on TM6. This study provides a quantitative description of conformational dynamics in A2AR and supports the idea that ligands bias not only GPCR conformations but also the dynamics within and between distinct conformational states of the receptor.

Enhanced performance of dye-sensitized solar cell-based g-C3N4/Ag3PO4 hybrid composites as novel electrodes fabricated by facial hydrothermal approach

In this work, holey g-C3N4 nanosheet wrapped Ag3PO4 composite was prepared by facile hydrothermal method. The structural, morphological, optical and elemental composition of the samples were analyzed by X-ray diffraction, Scanning electron microscope, Transmission electron microscope, Raman, UV–Vis diffuse reflectance spectra, Photoluminescence, N2 adsorption–desorption and X-ray photoelectron spectra, respectively. Systematic investigation indicated that phosphorus was effectively doped into the g-C3N4 framework, which increases the BET surface area, expands the visible light response region, and elevates the separation efficiency of electron–hole pairs. Sandwich type DSSC was fabricated and studied the studied the J–V characteristics. The results suggest that the optimal composite electrode (APG-50) with Ag3PO4/g-C3N4 ratio of 3:1 showed high photo-conversion efficiency (9.71%) than compared with bare g-C3N4 (1.89%) and Ag3PO4 (2.52%) electrodes, respectively. Besides, the EIS comes about illustrate that the APG-50 test appears tall electron exchange proficiency and lifetime. The progressed instrument of the proposed materials was moreover examined in detail.

Cryptocurrency Exchanges: Predicting Which Markets Will Remain Active

About 99 percent of cryptocurrency trades occur on organised exchanges and many investors subsequently keep their digital assets in accounts with cryptocurrency markets. This generates exposure to the risk of exchange closures. We construct a database containing eight key characteristics on 238 cryptocurrency exchanges and employ machine learning techniques to predict whether a cryptocurrency market will remain active or whether it will go out of business. Both in-sample and out-of-sample measures of forecasting performance are computed and ranked for four popular machine learning algorithms. While all four models produce satisfactory classification accuracy, our best model is a random forest classifier. It reaches accuracy of 90.4 percent on training data and 86.1 percent on test data. From the list of predictors we find that exchange lifetime, transacted volume and cyber security measures such as security audit, cold storage and bug bounty programs rank high in terms of feature importance across multiple algorithms. On the other hand, whether an exchange has previously experienced a security breach does not rank highly according to its contribution to classification accuracy.

Ring Current Decay During Geomagnetic Storm Recovery Phase: Comparison Between RBSP Observations and Theoretical Modeling

AbstractRing current decay during storm recovery phase may be affected by different loss processes. In this study, we have investigated the lifetimes of ring current ions (H+ and O+) of energies from 1 keV to several hundred keV at L shell from 3 to 6 during the storm recovery phase through a statistical survey. The observational data of 48 geomagnetic storms from March 2013 to May 2019 are collected based on Van Allen Probe observations. We find that (1) the observed lifetimes of H+ and O+ in general increase with L shell and (2) the lifetimes of H+ is short than that of O+ when E &lt; ∼50 keV while the situation is reversed when E &gt; ∼50 keV. In addition, we have made use of the charge exchange theory, combined with previous experimental results on the charge exchange cross section and two distribution models of neutral hydrogen atoms in the exosphere, so as to directly estimate the ring current ions decay caused by charge exchange mechanism only. Through the comparison between the model predictions of charge exchange lifetime and the observed lifetimes, we find that (3) the observed lifetimes are in general consistent with model results, which confirms that charge exchange is a dominant loss mechanism of ring current ions during storm recovery phase.

Conditions on marginals and copula of component lifetimes for signature representation of system lifetime

The signature of a system is a probability vector that depends only on the system structure. Under the classic IID (independent and identically distributed) assumption on the component lifetimes, the system lifetime distribution is the convex combination of consecutive component failure times, and the signature coordinates constitute the mixture coefficients. In this case the signature representations are very useful in determining the system lifetime distributions and for stochastic comparisons of them. This first representation was obtained in 1985 by Samaniego. Then it was extended to the more general case of exchangeable component lifetimes. In 2011 Marichal, Mathonet and Waldhauser presented necessary and sufficient conditions assuring the Samaniego representation. There were expressed in terms of distributional properties of families of auxiliary indicator random vectors parametrized by positive numbers. In the paper we obtain other necessary and sufficient conditions represented in terms of the marginal distributions of component lifetimes and the dependence copula of them. Moreover, we study symmetry conditions for the equality of structural and probabilistic signatures.

Relaxometric studies of erythrocyte suspensions infected by Plasmodium falciparum: a tool for staging infection and testing anti-malarial drugs.

Malaria is a global health problem with the most malignant form caused by Plasmodium falciparum (P. falciparum). Parasite maturation in red blood cells (RBCs) is accompanied by changes including the formation of paramagnetic hemozoin (HZ) nanocrystals, and increased metabolism and variation in membrane lipid composition. Herein, MR relaxometry (MRR) was applied to investigate water exchange across RBCs' membrane and HZ formation in parasitized RBCs. Transverse water protons relaxation rate constants (R2 = 1/T2 ) were measured for assessing HZ formation in P. falciparum-parasitized human RBCs. Moreover, water exchange lifetimes across the RBC membrane (τi ) were assessed by measuring longitudinal relaxation rate constants (R1 = 1/T1 ) at 21.5 MHz in the presence of a gadolinium complex dissolved in the suspension medium. τi increased after invasion of parasites (ring stage, mean τi / = 1.234 ± 0.022) and decreased during maturation to late trophozoite (mean τi / = 0.960 ± 0.075) and schizont stages (mean τi / = 1.019 ± 0.065). The HZ accumulation in advanced stages was revealed by T2 -shortening. The curves reporting R2 (1/T2 ) vs. magnetic field showed different slopes for non-parasitized RBCs (npRBCs) and parasitized RBCs (pRBCs), namely 0.003 ± 0.001 for npRBCs, 0.009 ± 0.002, 0.028 ± 0.004 and 0.055 ± 0.002 for pRBCs at ring-, early trophozoite-, and late trophozoite stage, respectively. Antimalarial molecules dihydroartemisinin and chloroquine elicited measurable changes in parasitized RBCs, namely dihydroartemisinin modified τi , whereas the interference of chloroquine with HZ formation was detectable by a significant T2 increase. MRR can be considered a useful tool for reporting on P. falciparum blood stages and for screening potential antimalarial molecules.

New insight into the organization of myelin water using deuterium NMR.

Myelin water is commonly characterized by its short proton T2 relaxation time, suggesting strong association with the polar head groups of the bilayer constituents. Deuterium NMR of water in ordered structures exhibits splittings as a result of quadrupolar interactions that are observable using the double-quantum filter. The purpose of the current study was to identify and characterize the water populations. The 2 H double-quantum-filtered spectroscopic experiments were conducted at 62MHz (9.4 T) on a sample of reconstituted myelin from ovine spinal cord after exchange of native water with D2 O. Signals passing the double-quantum filter were attributed to 2 water pools: 1 consisting of a doublet of 650-Hz splitting, and a second unsplit signal. Similar signals were observed in the sciatic and optic nerves and in the spinal cord. Further, data suggest that diffusion of water molecules in these 2 pools (Dapp ≤5×10-7 cm2 /s) is either hindered or restricted. An estimate of exchange lifetime of 10-15ms between water pertaining to the single peak and that of the split peaks suggests exchange occurs in a slow-intermediate rate regime. Further distinction between the 2 pools was obtained from T1 measurements. Deuterons belonging to the doublet resonance were found to have short T1 , estimated to be on the order of 10-20ms, whereas those corresponding to the single peak were close to that of bulk D2 O. The results suggest that myelin extract water consists of 2 hindered populations with distinct degrees of anisotropic motion that can be studied by 2 H double-quantum-filtered NMR.

Relations between ageing and dependence for exchangeable lifetimes with an extension for the IFRA/DFRA property

AbstractWe first review an approach that had been developed in the past years to introduce concepts of “bivariate ageing” for exchangeable lifetimes and to analyze mutual relations among stochastic dependence, univariate ageing, and bivariate ageing.A specific feature of such an approach dwells on the concept of semi-copula and in the extension, from copulas to semi-copulas, of properties of stochastic dependence. In this perspective, we aim to discuss some intricate aspects of conceptual character and to provide the readers with pertinent remarks from a Bayesian Statistics standpoint. In particular we will discuss the role of extensions of dependence properties. “Archimedean” models have an important role in the present framework.In the second part of the paper, the definitions of Kendall distribution and of Kendall equivalence classes will be extended to semi-copulas and related properties will be analyzed. On such a basis, we will consider the notion of “Pseudo-Archimedean” models and extend to them the analysis of the relations between the ageing notions of IFRA/DFRA-type and the dependence concepts of PKD/NKD.

Evolutions of equatorial ring current ions during a magnetic storm

In this paper, we present evolutions of the phase space density (PSD) spectra of ring current (RC) ions based on observations made by Van Allen Probe B during a geomagnetic storm on 23–24 August 2016. By analyzing PSD spectra ratios from the initial phase to the main phase of the storm, we find that during the main phase, RC ions with low magnetic moment μ values can penetrate deeper into the magnetosphere than can those with high μ values, and that the μ range of PSD enhancement meets the relationship: S(O+) >S(He+) >S(H+). Based on simultaneously observed ULF waves, theoretical calculation suggests that the radial transport of RC ions into the deep inner magnetosphere is caused by drift-bounce resonance interactions, and the efficiency of these resonance interactions satisfies the relationship: η(O+) > η(He+) > η(H+), leading to the differences in μ range of PSD enhancement for different RC ions. In the recovery phase, the observed decay rates for different RC ions meet the relationship: R(O+) > R(He+) > R(H+), in accordance with previous theoretical calculations, i.e., the charge exchange lifetime of O+ is shorter than those of H+ and He+.

Molecular Mobility Suppression of Ibuprofen-Rich Amorphous Nanodroplets by HPMC Revealed by NMR Relaxometry and Its Significance with Respect to Crystallization Inhibition

In the present study, the molecular state of drug-rich amorphous nanodroplets was evaluated using NMR techniques to reveal the mechanism underlying the crystallization inhibition of drug-rich amorphous nanodroplets by a polymer. Ibuprofen (IBP) with a low glass transition temperature was used for direct characterization of drug-rich amorphous nanodroplets. Highly supersaturated IBP formed IBP-rich amorphous nanodroplets through phase separation from aqueous solution. Increasing the concentration of hypromellose (HPMC) in the aqueous solution contributed to the inhibition of IBP crystallization and maintenance of supersaturation at IBP amorphous solubility. Solution 1H NMR measurements of IBP supersaturated solution containing IBP-rich amorphous nanodroplets clearly showed two kinds of 1H peaks derived from the dissolved IBP in bulk water phase and phase-separated IBP in IBP-rich amorphous nanodroplets. NMR spectral analysis indicated that HPMC did not affect the chemical environment and mobility of the dissolved IBP. However, 1H spin-spin relaxation time measurements clarified that the dissolved IBP in the bulk water phase was exchanged with the IBP-rich amorphous nanodroplets with an exchange lifetime of more than 10 ms. Moreover, the 1H peaks of HPMC partially disappeared due to the formation of IBP-rich amorphous nanodroplets, suggesting that a part of HPMC distributed into the IBP-rich amorphous nanodroplets from the bulk water phase. The incorporation of HPMC significantly changed the chemical environment of the phase-separated IBP in the IBP-rich amorphous nanodroplets and strongly suppressed molecular mobility. The resulting molecular mobility suppression effectively inhibited IBP crystallization from the IBP-rich amorphous nanodroplets. Thus, direct investigation of drug-rich amorphous nanodroplets using NMR can be a promising approach for selecting appropriate pharmaceutical excipients to suppress drug crystallization in supersaturated drug solutions.

Exchange saturation transfer and associated NMR techniques for studies of protein interactions involving high-molecular-weight systems.

A brief overview of theoretical and experimental aspects of the Dark state Exchange Saturation Transfer (DEST) and lifetime line broadening ([Formula: see text]) NMR methodologies is presented from a physico-chemical perspective. We describe how the field-dependence of [Formula: see text] can be used for determining the exchange regime on the transverse spin relaxation time-scale. Some limitations of DEST/[Formula: see text] methodology in applications to molecular systems with intermediate molecular weights are discussed, and the means of overcoming these limitations via the use of closely related exchange NMR techniques is presented. Finally, several applications of DEST/[Formula: see text] methodology are described from a methodological viewpoint, with an emphasis on providing examples of how kinetic and relaxation parameters of exchange can be reliably extracted from the experimental data in each particular case.

ZnO Synthesized Using Bipolar Electrochemistry: Structure and Activity.

The photoactive materials broadly applied in catalysis and energy conversion are generally composed of metal oxides. Among these oxides, ZnO showed a promising photocatalytic activity; however, traditional synthetic routes generated by-products and large amounts of secondary waste. Herein, we report the use of bipolar electrochemistry to generate ZnO nanoparticles using deionized water and a zinc metal to conform to green chemistry practices. TEM imaging demonstrated that the sizes of the bipolar-made ZnO particles were smaller than the commercial sample. The presence of structural defects in ZnO was correlated with the chemical shifts analyzed by X-ray photoelectron spectroscopy (XPS) and by different concentrations of O2− ions in stoichiometric and defected lattice. Further, the diffuse reflectance UV–Vis studies demonstrated a blue-shift in the reflectance spectrum for the bipolar-made oxide. This was also an indication of defects in the ZnO lattice, which related to the formation of shallow levels in the bandgap of the material. The structural and morphological differences influenced the photocatalytic characteristics, revealing a higher photocurrent for the bipolar-made ZnO when compared to the reference sample. This was further manifested in lower total resistivity for all anodes made from the non-stoichiometric ZnO, and also in their shorter diffusion length for charge exchange and electron lifetimes.

TiO2 Nanoparticles Catalyze Oxidation of Huntingtin Exon 1-Derived Peptides Impeding Aggregation: A Quantitative NMR Study of Binding and Kinetics.

Polyglutamine expansion within the N-terminal region of the huntingtin protein results in the formation of intracellular aggregates responsible for Huntington's disease, a fatal neurodegenerative condition. The interaction between TiO2 nanoparticles and huntingtin peptides comprising the N-terminal amphiphilic domain without (httNT) or with (httNTQ10) a ten-residue C-terminal polyglutamine tract, is investigated by NMR spectroscopy. TiO2 nanoparticles decrease aggregation of httNTQ10 by catalyzing the oxidation of Met7 to a sulfoxide, resulting in an aggregation-incompetent peptide. The oxidation agent is hydrogen peroxide generated on the surface of the TiO2 nanoparticles either by UV irradiation or at low steady-state levels in the dark. The binding kinetics of nonaggregating httNT to TiO2 nanoparticles is characterized by quantitative analysis of 15N dark state exchange saturation transfer and lifetime line broadening NMR data. Binding involves a sparsely populated intermediate that experiences hindered rotational diffusion relative to the free state. Catalysis of methionine oxidation within the N-terminal domain of the huntingtin protein may potentially provide a strategy for delaying the onset of Huntington's disease.

A lifetime of pulmonary gas exchange.

Pulmonary gas exchange is the primary function of the lung, and during my lifetime, its measurement has passed through many stages. When I was born, many physiologists still believed that the lung secreted oxygen. When I was a medical student, the only way we had to recognize defective gas exchange was whether the patient was cyanosed. The advent of the oximeter soon showed that this sign could be very misleading. A breakthrough was the introduction of blood gas electrodes that could measure the PO 2, PCO 2, and pH of a small sample of arterial blood. It was soon recognized that the commonest cause of hypoxemia was ventilation‐perfusion inequality, and that this could also be responsible for CO 2 retention. In the early days, the understanding of the mechanisms of pulmonary gas exchange relied on graphical analysis because the oxygen and carbon dioxide dissociation curves are nonlinear and interdependent which precluded algebraic methods. However, with the introduction of digital computing, problems that had hitherto been impossible to tackle became amenable to study. A key advance was the development of the Multiple Inert Gas Elimination Technique. Now, noninvasive methods for measuring gas exchange show promise, and the whole subject continues to develop.

Optoelectronic Dichotomy of Mixed Halide CH3NH3Pb(Br1–xClx)3 Single Crystals: Surface versus Bulk Photoluminescence

In this work, the spatially dependent recombination kinetics of mixed-halide hybrid perovskite CH3NH3Pb(Br1- xCl x)3 (0 ≤ x ≤ 0.19) single crystals are investigated using time-resolved photoluminescence spectroscopy with one- and two-photon femtosecond laser excitation. The introduction of chloride by substituting a fraction of the bromide leads to a decreased lattice constant compared to pure bromide perovskite ( x = 0) and a higher concentration of surface defects. The measured kinetics under one-photon excitation (1PE) shows that increasing the chloride addition quenches the photoluminescence (PL) lifetimes, due to substitution-induced surface defects. In stark contrast, upon 2PE, the PL lifetimes measured deeper in the bulk become longer with increasing chloride addition, until the halide substitution reaches the critical concentration of ∼19%. At x = 19% Cl concentration, a significant reversal of this behavior is observed indicating a change in crystal structure beyond the continuous trends observed at lower percentages of halide substitution ( x ≤ 11%). The observed opposing trends, based on 1PE versus 2PE, highlight a dichotomy between extrinsic (surface) and intrinsic (bulk) effects of chloride substitution on the carrier dynamics in lead bromide perovskites. We discuss the physical relation between halide exchange and bulk carrier lifetimes in CH3NH3PbBr3 in terms of the Rashba effect. We propose that the latter is suppressed at the surface due to disorder in the alignment of the MA and that it increases in the bulk with Cl concentration because of the reduction in lattice parameters, which compresses the space available for the MA orientational degrees of freedom.

Decorrelating Kinetic and Relaxation Parameters in Exchange Saturation Transfer NMR: A Case Study of N-Terminal Huntingtin Peptides Binding to Unilamellar Lipid Vesicles.

Dark state exchange saturation transfer (DEST) and lifetime line-broadening (Δ R2, the difference in the measured transverse relaxation rates for the observable species in the presence and absence of exchange with a species characterized by very large intrinsic transverse relaxation rates) have proven to be powerful NMR tools for studying exchange phenomena between a NMR visible species and a high-molecular weight, "dark", NMR invisible state. However, in the exchange regime, where the transverse spin relaxation rates in the bound state ( R2bound) are smaller than the strength of the DEST saturation radio frequency field, typically corresponding to systems below ∼6 MDa, the combination of DEST and Δ R2 data, while sufficient to define the apparent association rate constant, cannot unambiguously determine the population of the bound state pB and R2bound values independently. We show that the latter exchange and relaxation parameters can be decorrelated by the measurement of the maximal value of the contribution of the fast-relaxing magnetization component to the total NMR signal, Cfastmax, an observable that is directly proportional to pB. When integrated into the analysis of DEST/Δ R2 data, Cfastmax provides an indispensable source of information for quantitative studies of exchange involving high-molecular-weight dark states. We demonstrate the utility of this approach by investigating the binding kinetics of two huntingtin exon-1-derived peptides to small unilamellar lipid vesicles (SUV), ∼ 31 nm in diameter and 4.3 MDa in molecular weight. The interaction of the N-terminal amphiphilic domain of huntingtin exon-1 with membrane surfaces promotes polyglutamine-mediated aggregation and, as such, is thought to play a role in the etiology of Huntington's disease, an autosomal dominant fatal neurodegenerative condition. The first peptide comprises the 16-residue N-terminal amphiphilic domain (httNT) alone, while the second contains an additional seven residue polyglutamine tract at the C-terminus (httNTQ7). At a peptide-to-lipid molar ratio of 1:4, the population of peptide bound to the SUV surface is substantial, ∼ 7-8%, while exchange between the free and SUV-bound peptide is slow on the relaxation time-scale ( kex ∼ 200 s-1). The last two C-terminal residues of httNT and the last 9 of httNTQ7 remain flexible in the SUV-bound form due to transient detachment from the lipid surface that occurs on a time-scale several-fold faster than binding.