Net Proton Research Articles

Lipopolysaccharide Triggers Luminal Acidification to Promote Defense Against Bacterial Infection in Vaginal Epithelium

The vaginal epithelium plays pivotal roles in host defense against pathogen invasion, contributing to the maintenance of an acidic microenvironment within the vaginal lumen through the activity of acid-base transport proteins. However, the precise defense mechanisms employed by the vaginal epithelium following bacterial infection remain incompletely understood. This study demonstrated that the bacterial lipopolysaccharide (LPS) potentiated net proton efflux by up-regulating the expression of Na+-H+ exchanger 1 (NHE1), without affecting other acid-base transport proteins in vaginal epithelial cells. Pharmacological inhibition or genetic knockdown of Toll-like receptor-4 (TLR4) and the extracellular-signal-regulated protein kinase (ERK) signaling pathway effectively counteracted the up-regulation of NHE1 and the enhanced proton efflux triggered by LPS in vaginal epithelial cells. In vivo studies revealed that LPS administration led to luminal acidification through the up-regulation of NHE1 expression in the rat vagina. Moreover, inhibition of NHE exhibited impaired defense against acute bacterial infection in the rat vagina. These findings collectively indicated the active involvement of vaginal epithelial cells in facilitating luminal acidification during acute bacterial infection, offering potential insights into the treatment of bacterial vaginosis.

Comparative functional analysis reveals differential nucleotide sensitivity between human and mouse UCP1.

Mitochondrial uncoupling protein 1 (UCP1) is a unique protein of brown adipose tissue. Upon activation by free fatty acids, UCP1 facilitates a thermogenic net proton flux across the mitochondrial inner membrane. Non-complexed purine nucleotides inhibit this fatty acid-induced activity of UCP1. The most available data have been generated from rodent model systems. In light of its role as a putative pharmacological target for treating metabolic disease, in-depth analyses of human UCP1 activity, regulation, and structural features are essential. In the present study, we established a doxycycline-regulated cell model with inducible human or murine UCP1 expression and conducted functional studies using respirometry comparing wild-type and mutant variants of human UCP1. We demonstrate that human and mouse UCP1 exhibit similar specific fatty acid-induced activity but a different inhibitory potential of purine nucleotides. Mutagenesis of non-conserved residues in human UCP1 revealed structural components in α-helix 56 and α-helix 6 crucial for uncoupling function. Comparative studies of human UCP1 with other orthologs can provide new insights into the structure-function relationship for this mitochondrial carrier and will be instrumental in searching for new activators.

Bulk medium properties of heavy-ion collisions from the beam energy scan with a multistage hydrodynamic model

I introduce a method to reconstruct full rapidity distributions of charged particle multiplicity and net proton yields, crucial for constraining the longitudinal dynamics of nuclear matter created in the beam energy scan program. Employing rapidity distributions within a multistage hydrodynamic model calibrated for Au+Au collisions at sNN=7.7–200GeV, I estimate the total energy and baryon number deposited into the collision fireball, offering insights into initial dynamics and the identification of nuclear remnants. I explore the potential of rapidity-dependent measurements in probing equations of state at finite chemical potentials. Furthermore, I compare the freeze-out parameters derived from both hydrodynamics and thermal models, highlighting that the parameters extracted via thermal models represent averaged properties across rapidities. Published by the American Physical Society 2024

In Ukrainian

The paper discusses the results of saponite research from the Tashkiv deposit of Ukraine. X-ray structural analysis proved the necessity of preliminary cleaning of saponites from mineral impurities. The study of the morphology, nanoprofile and topography of the surface of saponite by the methods of SEM-microscopy and Atomic Force Microscopy revealed that the mineral is represented by aggregates of nano- and microparticles of a pyramidal shape. Its characteristic feature is the heterogeneity of isomorphic substitutions of ions in the tetrahedral and octahedral sheets of the structural elementary package. According to X-ray fluorescence analysis, saponite contains a significant amount of Fe3+, which isomorphically replaces magnesium Mg2+ and, accordingly, is located mastly in the octahedral sheet of the structural package with a charge from +0.37 to +0.35. The number and mechanism of isomorphic substitutions determine the presence of a total negative charge of the crystal lattice (from –0.38 to –0.3), the value of which ensures intensive interaction with water molecules of the interpacket space with the formation of surface OH groups. Accordingly, both acidic and alkaline Lewis and Brønsted centers are present on the surface with a predominance of acidic ones, so the acidity function is 5.82, and the point of zero proton charge is pH = 5.5. During dispersion in water, a part of the alkaline centers of the side surface are transformed into Brønsted acid centers as a result of their protonation, which causes an increase in the pH of the dispersion medium to pH = 8–8.6. Accordingly, the isoionic state is reached at pH = 7.5. The difference in pH values characterizing the isoionic state of the surface and the point of zero net proton charge (PZNPC) indicates the presence of weak acid-alkaline centers on the surface. The study of the adsorption of acid-alkaline dyes showed the adsorption of alkaline (pK = 1¸3) and acid (pK = 7¸14) dyes on saponites. The latter is significantly reduced due to the preliminary hydration of the solid surface - mainly the lateral edges of the particles. Acidic dyes are not adsorbed from a dispersion medium with pH < 5.5 (PZNPC), and basic dyes are adsorbed at pH > 5,5( PZNPC).

Surfaces of Atmospheric Droplet Models Probed with Synchrotron XPS on a Liquid Microjet.

ConspectusThe atmosphere is a key part of the earth system comprising myriad chemical species in all basic forms of matter. Ubiquitous nano- and microscopic aerosol particles and cloud droplets suspended in the air play crucial roles in earth's climate and the formation of air pollution. Surfaces are a prominent part of aerosols and droplets, due to the high surface area to bulk volume ratios, but very little is known about their specific properties. Many atmospheric compounds are surface-active, leading to enhanced surface concentrations in aqueous solutions. Their distribution between the surface and bulk may determine heterogeneous chemistry and many other properties of aerosol and cloud droplets, but has not been directly observed.We used X-ray photoelectron spectroscopy (XPS) to obtain direct molecular-level information on the surface composition and structure of aqueous solutions of surface-active organics as model systems for atmospheric aerosol and cloud droplets. XPS is a vacuum-based technique enabled for volatile aqueous organic samples by the application of a high-speed liquid microjet. In combination with brilliant synchrotron X-rays, the chemical specificity of XPS allows distinction between elements in different chemical states and positions within molecular structures. We used core-level C 1s and N 1s signals to identify the alkyl and hydrophilic groups of atmospheric carboxylic acids, alkyl-amines, and their conjugate acids and bases. From this, we infer changes in the orientation of surface-adsorbed species and quantify their relative abundances in the surface. XPS-derived surface enrichments of the organics follow trends expected from their surface activities and we observed a preferential orientation at the surface with the hydrophobic alkyl chains pointing increasingly outward from the solution at higher concentrations. This provides a first direct experimental observation of well-established concepts of surface adsorption and confirms the soundness of the method.We mapped relative abundances of conjugate acid-base pairs in the aqueous solution surfaces from the respective intensities of distinctive XPS signals. For each pair, the protonation equilibrium was significantly shifted toward the neutral form in the surface, compared to the bulk solution, across the full pH range. This represents an apparent shift of the pKa in the surface, which may be toward either higher or lower pH, depending on whether the acid or base form of the pair is the neutral species. The surface shifts are broadly consistent with the relative differences in surface enrichment of the individual acid and base conjugates in binary aqueous solutions, with additional contributions from nonideal interactions in the surface. In aqueous mixtures of surface-active carboxylate anions with ammonium salts at near-neutral pH, we found that the conjugate carboxylic acids were further strongly enhanced. This occurs as the coadsorption of weakly basic carboxylate anions and weakly acidic ammonium cations forms ion-pair surface layers with strongly enhanced local abundances, increasing the probability of net proton transfer according to Le Chatelier's principle. The effect is stronger when the evaporation of ammonia from the surface further contributes to irreversibly perturb the protonation equilibrium, leaving a surplus of carboxylic acid. These surface-specific effects may profoundly influence atmospheric chemistry mediated by aqueous aerosols and cloud droplets but are currently not taken into account in atmospheric models.

The influence of phosphorus availability on rice root traits driving iron plaque formation and dissolution, and implications for phosphorus uptake

Background and aimsIron (Fe) plaque which normally coats rice roots has a strong affinity for phosphorus (P), with a debated effect on plant P uptake. Furthermore, plant responses to P availability shape the rhizospheric environment, possibly affecting the rates of Fe plaque formation and dissolution. The role of Fe plaque to serve as a sink or source of available P may depend on root traits, themselves influenced by P availability. However, the underlying mechanism regulating these interactions remains unclear. In this study, we investigated the effects of P availability on root traits, Fe plaque dynamics and their implications for P uptake and rice plant growth.MethodsPlants were hydroponically grown for 60 days under P-sufficiency or P-deficiency, with or without Fe plaque. Root traits, rhizosphere acidification, and the rates of Fe plaque formation and dissolution were investigated and linked to differences in rice P content and growth.ResultsP-deficient conditions stimulated root development and promoted Fe plaque formation on the root surface compared to P-sufficient conditions. However, P limited plants exhibited a faster Fe plaque dissolution, along with increased net proton exudation. After 60 d, P-deficient plants showed higher P uptake in the presence of Fe plaque, whereas the opposite was observed in P-sufficient plants, where Fe plaque limited plant P uptake.ConclusionsThe role of Fe plaque in regulating P uptake highly depends on the dynamic nature of this Fe pool that is strictly linked to P availability and regulated by plant responses to P deficiency.

Non-Electroneutrality Generated by Bacteriorhodopsin-Incorporated Membranes Enhances the Conductivity of a Gelatin Memory Device.

We have previously demonstrated the potential of gelatin films as a memory device, offering a novel approach for writing, reading, and erasing through the manipulation of gelatin structure and bound water content. Here, we discovered that incorporating a bacteriorhodopsin (BR)-lipid membrane into the gelatin devices can further increase the electron conductivity of the polypeptide-bound water network and the ON/OFF ratio of the device by two folds. Our photocurrent measurements show that the BR incorporated in the membrane sandwiched in a gelatin device can generate a net proton flow from the counter side to the deposited side of the membrane. This leads to the establishment of non-electroneutrality on the gelatin films adjacent to the BR-incorporated membrane. Our Raman spectroscopy results show that BR proton pumping in the ON state gelatin device increases the bound water presence and promotes polypeptide unwinding compared to devices without BR. These findings suggest that the non-electroneutrality induced by BR proton pumping can increase the extent of polypeptide unwinding within the gelatin matrix, consequently trapping more bound water within the gelatin-bound water network. The resulting rise in hydrogen bonds could expand electron transfer routes, thereby enhancing the electron conductivity of the memory device in the ON state.

Proton-Coupled Electron Transfer at the Surface of Polyoxovanadate-Alkoxide Clusters.

ConspectusProton-coupled electron transfer (PCET) is a fundamental process involved in all areas of chemistry, with relevance to biological transformations, catalysis, and emergent energy storage and conversion technologies. Early observations of PCET were reported by Meyer and co-workers in 1981 while investigating the proton dependence of reduction of a molecular ruthenium oxo complex. Since that time, this conceptual framework has grown to encompass an enormous scope of charge transfer and compensation reactions. In this Account, we will discuss ongoing efforts in the Matson Laboratory to understand the fundamental thermodynamics and kinetics of PCET processes at the surface of a series of Lindqvist-type polyoxovanadate clusters. This project aims to provide atomistic resolution of net H atom uptake and transfer at the surfaces of transition-metal oxide materials.First, we discuss our efforts aimed at understanding PCET at metal oxide surfaces using the Lindqvist-type polyoxovanadate-alkoxide (POV-alkoxide) cluster [nBu4N]2[V6O13(TRIOLNO2)2]. These clusters reversibly bind H atom equivalents at bridging oxide sites, mirroring the proposed uptake and release of e-/H+ pairs at transition-metal oxide surfaces. Summarized results include the measurement of bond dissociation free energies of surface hydroxide moieties (BDFE(O-H)) as well as mechanistic analyses that verify concerted proton electron transfer as the operative pathway for PCET at the surface of POV-alkoxide clusters.Next, we discuss net proton and H atom uptake at the surface of reduced variants of the Lindqvist-type POV-alkoxide cluster, [V6O7(OR)12]n (R = Me, Et; n = -2, -1, 0, + 1). In the case of these low-valent POV-alkoxide clusters, nucleophilic bridging sites are kinetically inhibited by functionalization of the cluster surface with organic ligands. This molecular modification enables site-selectivity in proton and H atom uptake to terminal oxide sites. The impact of reaction site and cluster electronics on reaction driving force of PCET is explored, with core electron density playing a critical role in dictating thermodynamics of H atom uptake and transfer. Additional work described here contrasts the kinetics of PCET at terminal oxide sites to the reactivity observed at bridging oxides in POV-alkoxide clusters.Overall, this Account summarizes our foundational knowledge regarding the assessment of PCET reactivity at the surfaces of molecular metal oxides. Drawing analogies between POV-alkoxide clusters and nanoscopic metal oxide materials provide design principles for the advancement of materials applications with atomic precision. These complexes are additionally highlighted as tunable redox mediators in their own right; our studies demonstrate how cluster surface reactivities can be optimized by modifying electronic structure and surface functionalities.

Iron toxicity downregulates root-proton efflux and decreases zinc accumulation in cassava

Iron (Fe) plays a pivotal role in biogeochemical cycling in the soil-plant-human continuum; however, much research has focused on Fe deficiency with limited knowledge about Fe toxicity impacts on micronutrient (e.g., zinc: Zn) accumulation in cassava, an important staple tuber food in the Tropics. A sand-hydroponic-hybrid technique was undertaken for 60 days to investigate the effects of variable Fe concentrations (0.1–500 μmol Fe L−1) on the root-proton and root-organic acid release, rhizosphere Fe solubility, and levels of cassava nutrient accumulation. The results showed that high Fe concentrations (50–500 μmol Fe L−1) significantly decreased the root (0.34–0.51 g dry weight) biomass compared to the control (0.82–0.83 g dry weight). The Fe concentrations significantly regulated the net proton release from the roots by upregulating (25–45 μmol L−1 h−1 g−1 fresh weight root) and downregulating (1.8–7.1 μmol L−1 h−1 g−1 fresh weight root) the net proton efflux at low (1.0 μmol Fe L−1) and high Fe concentrations (500 μmol Fe L−1), respectively. Succinic acid was the sole organic acid observed and only in the Fe-sensitive cultivar. The water-extractable Fe in the rhizosphere sand (average 3.37 mg kg−1) was lower than in the bulk sand (average 5.31 mg kg−1), indicating that net proton efflux controlled rhizosphere Fe solubility. The high Fe concentrations significantly decreased Zn accumulation (20–29 mg Zn kg−1) but increased phosphorus (P) accumulation (2.7–3.4 g P kg−1) in the roots compared to the control (48–59 mg Zn kg−1 and 2.0–2.3 g P kg−1, respectively), implying that Fe toxicity could be responsible for the undernourished Zn content in the tuber. This study suggested the importance of alleviating Fe toxicity in soil-plant systems to mitigate cassava root Zn deficiency, which is relevant to human Zn malnutrition in countries consuming cassava as the main staple diet.

Transformation From NHx to NOy Deposition Aggravated China's Forest Soil Acidification

AbstractElevated nitrogen (N) deposition and changes in reduced or oxidized component contribution greatly affect soil acidification. China has experienced a significant transformation of N deposition components from NHx to NOy over the past 40 years, but the effects of component transformation on soil acidification are poorly understood. Therefore, long‐term monitoring data and literature on N deposition, combined with the results of isotope experiments, were used to explore the contributions of different N forms on soil acidification in China's forests. Here, all processes related to NHx and NOy, including the transformation to NH4+ and NO3− and subsequent N cycling in the soil, were considered. We found that N‐induced soil acidification in 80% area of China’s forests was dominated by NHx deposition, and the other areas (South China) were dominated by NOy deposition in 2010s. From 1980 to 2019, the average contribution of NHx was higher than that of NOy but the latter contribution continued to increase. Meanwhile, the results showed that soil acidification increased with the decrease of the ratio of NHx to NOy (RNHx/NOy), which is mainly because NOy is more easily leached in the form of NO3− than that of NHx under the influence of different plant preferences and soil retention rates, resulting in a higher net proton production of NOy. Our research has powerful implications for policymaking, provides a theoretical basis for formulating different N reduction policies in different regions, and points out that the synergistic effect of RNHx/NOy changes should be considered to alleviate soil acidification.

Evidence for the feasibility of transmembrane proton gradient regulating oxytetracycline extracellular biodegradation mediated by biosynthesized palladium nanoparticles

Extracellular biodegradation is a promising technology for removing antibiotics and repressing the spread of resistance genes, but the strategy is limited by the low extracellular electron transfer (EET) efficiency of microorganisms. In this work, biogenic Pd0 nanoparticles (bio-Pd0) were introduced in cells in situ to enhance oxytetracycline (OTC) extracellular degradation and the effects of transmembrane proton gradient (TPG) on EET and energy metabolism mediated by bio-Pd0 were investigated. The results indicated that the intracellular OTC concentration gradually decreased with increase in pH due to the simultaneous decreases of OTC adsorption and TPG-dependent OTC uptake. On the contrary, the efficiency of OTC biodegradation mediated by bio-Pd0@B. megaterium showed a pH-dependent increase. The negligible intracellular OTC degradation, the high dependence of OTC biodegradation on respiration chain and the results on enzyme activity and respiratory chain inhibition experiments showed that NADH-dependent (rather than FADH2-dependent) EET process mediated by substrate-level phosphorylation modulated OTC biodegradation due to high energy storage and proton translocation capacity. Moreover, the results showed that altering TPG is an efficient approach to improve EET efficiency, which can be attributed to the increased NADH generation by the TCA cycle, enhanced transmembrane electron output efficiency (as evidenced by increased intracellular electron transfer system (IETS) activity, the negative shift of onset potential, and enhanced one-electron transfer through bound flavin) and stimulation of substrate-level phosphorylation energy metabolism catalyzed by succinic thiokinase (STH) under low TPG conditions. The results of structural equation model that OTC biodegradation was directly and positively modulated by the net outward proton flux as well as STH activity, and indirectly regulated by TPG through NADH level and IETS activity confirmed the previous findings. This study provides a new perspective for engineering microbial EET and application of bioelectrochemistry processes in bioremediation.

Impact of hadronic interactions and conservation laws on cumulants of conserved charges in a dynamical model

Understanding the phase diagram of QCD by measuring fluctuations of conserved charges in heavy-ion collision is one of the main goals of the beam energy scan program at the BNL Relativistic Heavy Ion Collider (RHIC). Within this work, we calculate the role of hadronic interactions and momentum cuts on cumulants of conserved charges up to fourth order in a system in equilibrium within a hadronic transport approach (smash). In our model the net baryon, net charge, and net strangeness are perfectly conserved on an event-by-event basis and the cumulants are calculated as a function of subvolume sizes and compared to analytic expectations. We find a modification of the kurtosis due to charge annihilation processes in systems with simplified degrees of freedom. Furthermore the result of the full smash hadron gas for the net baryon and net proton number fluctuations is presented for systems with zero and finite values of baryon chemical potential. Additionally we find that due to dynamical correlations the cumulants of the net baryon number cannot easily be recovered from the net protons. Finally the influence of deuteron cluster formation on the net proton and net baryon fluctuations in a simplified system is shown. This analysis is important to better understand the relation between measurements of fluctuations in heavy-ion collisions and theoretical calculations which are often performed in a grand canonical ensemble.

P-022: THERAPEUTIC EFFECTS OF GBT1118 ON SKELETAL MUSCLE ENERGETICS AND FUNCTION IN SICKLE CELL MICE

Purpose: Sickle cell disease (SCD) is an hemoglobinopathy ultimately resulting red blood cells sickling. SCD patients suffer from anemia, arterial oxyhemoglobin desaturation, hematologic and hemodynamic abnormalities, all of which disrupt oxygen supply and can reduce exercise capacity and quality of life. Strenuous exercise in SCD patients may induce hemolysis, an early lactate accumulation, an intracellular acidosis, all of which are potential triggering factors for sickling and vaso-occlusive crises. GBT1118 is a HbS polymerization inhibitor which can increase hemoglobin affinity for oxygen and the corresponding supply to tissues. On that basis, we hypothesized that GBT1118 could dampen skeletal muscle energetics and function. Materials and methods: Skeletal muscle energetics and function of sixteen Townes mice (2 ± 0.5 month-old) were assessed in response to a standardized Rest-Stimulation(1Hz)-Recovery protocol before and after an 8-week period (8WP). Investigations were conducted using a setup designed to be operational inside a 7T horizontal MRI scanner (PharmaScan-Bruker). The setup allows (i) magnetic resonance imaging, (ii) muscle force measurements and (iii) 31P-magnetic resonance spectroscopy. Assessments conducted before and after the 8WP were identified with number 1 (SCDGBT1) and two (SCDGBT2). Ten mice received a chronic supplementation of GBT1118 (4g/kg in chow) during the 8WP (SCDGBT), whereas six mice had access to not supplemented chow (SCDCON). Results: The specific peak force (sPf) measured at the beginning of stimulation significantly increased over the 8WP (SCDCON2 +68%, p < 0.05). This increased initial sPf was also present in SCDGBT2 as compared to SCDGBT1 (+ 30%, p < 0.05). Over the entire stimulation session, the overall specific [TM1] force production (sTFP) significantly increased over the 8WP (SCDCON2 +32%, p < 0.05, Figure 1). The increased sTFP was also present in SCDGBT2 as compared to SCDGBT1 (+ 25 %, p < 0.05). However, the sTFP-normalized pHi reduction and sTFP-normalized phosphocreatine (PCr) breakdown significantly decreased in SCDGBT2 as compared to SCDGBT1 (p < 0.05, Table 1). Conclusion: In the control condition, the 8-week period was accompanied by a significant increase in specific total force production. Such an increase has been previously reported from 3 to 10 weeks of age (+ 33%). Overall, the increased specific total force production we reported was related to time and cannot be accounted for by GBT supplementation. In SCDGBT, the expected increased force production related to time was associated to a reduced acidosis and PCr breakdown which were not found in the control condition. For a given amount of force, SCDGBT mice muscle would experience a lower net proton accumulation and a reduced net PCr consumption. This reduction of both acidosis and PCr consumption could illustrate a diminished cost of contraction in response to GBT1118 supplementation which could be related to an improved contractile efficiency as previously described in humans. SCD mice treated with GBT1118 exhibit a reduced acidosis for a given force. Given that acidosis is a potential triggering factor of sickling, GBT would protect SCD muscle against the consequences of sickling. One could speculate that SCD patients receiving GBT1118 might be able to perform exercise with a reduced exposure to sickling.Specific total force production in SCDCON and SCDGBT before and after the 8-week period. Each point represents a single measurement and lines are linking consecutive points. p-values are mentioned on the top of the figure.Metabolic indices in SCDCON and SCDGBT before and after the 8-week period. The authors do not declare any conflict of interest

Longitudinal dynamics and particle production in relativistic nuclear collisions

This work presents a three-dimensional dynamical initialization model for relativistic heavy-ion collisions, implementing local energy-momentum conservation and baryon charge fluctuations at string junctions. Constraining parameters using experimental data from p+p collisions at various collision energies, the model provides a very good description of the charged hadron and net proton rapidity distributions in Au+Au collisions from 7.7 to 200 GeV and Pb+Pb collisions at 8.77 and 17.3 GeV. We demonstrate the importance of fluctuations of baryon densities to string junctions for describing net-proton distributions at collision energies of 62.4 and 200 GeV. Including this improved baryon stopping description along with the requirement of strangeness neutrality also yields a good description of identified particle yields as functions of the collision energy above 7.7 GeV. We further study asymmetric p+Al and (p, d, $^3$He)+Au collisions at the top RHIC energy and p+Pb, Xe+Xe, and Pb+Pb collisions at LHC energies. We identify the produced particle rapidity distributions in asymmetric collision systems as particularly useful for constraining models of the early-time longitudinal dynamics.

Limits of thermalization in relativistic heavy ion collisions

The goal of collider programs of high energy heavy-ion collisions is to produce a form of matter that can test non-perturbative aspects of Quantum Chromodynamics (QCD), the theory of strong interactions. One of the primary predictions from a computational approach to this quantum field theory is the existence of distinct thermodynamic states of QCD, particularly a state of deconfined quarks and gluons. An important step in establishing changes of state of QCD matter is to demonstrate that femto-scale system created in the laboratory can attain thermodynamic equilibrium. We present such a demonstration by checking that event-to-event fluctuations of several different conserved quantities have a consistent treatment in a grand canonical ensemble through a common temperature and chemical potentials. A key component of this work is that we used cumulants of up to third order in the net proton number, charge, and strangeness. We found a clear indication that the femto-scale fireball is thermalized when the collision energy in the centre of mass, sNN, is high enough. Also, the use of higher order cumulants, within the framework of grand canonical ensemble, reveals for the first time that the fireballs created at lower sNN are not in thermodynamic equilibrium. This opens the door to further studies of the approach to equilibrium, and the effects that a critical point in the phase diagram of QCD could have on such phenomena.

Quantifying charge state heterogeneity for proteins with multiple ionizable residues

Ionizable residues can release and take up protons and this has an influence on protein structure and function. The extent of protonation is linked to the overall pH of the solution and the local environments of ionizable residues. Binding or unbinding of a single proton generates a distinct charge microstate defined by a specific pattern of charges. Accordingly, the overall partition function is a sum over all charge microstates and Boltzmann weights of all conformations associated with each of the charge microstates. This ensemble-of-ensembles description recast as a q-canonical ensemble allows us to analyze and interpret potentiometric titrations that provide information regarding net charge as a function of pH. In the q-canonical ensemble, charge microstates are grouped into mesostates where each mesostate is a collection of microstates of the same net charge. Here, we show that leveraging the structure of the q-canonical ensemble allows us to decouple contributions of net proton binding and release from proton arrangement and conformational considerations. Through application of the q-canonical formalism to analyze potentiometric measurements of net charge in proteins with repetitive patterns of Lys and Glu residues, we determine the underlying mesostate pKa values and, more importantly, we estimate relative mesostate populations as a function of pH. This is a strength of using the q-canonical approach that cannot be replicated using purely site-specific analyses. Overall, our work shows how measurements of charge equilibria, decoupled from measurements of conformational equilibria, and analyzed using the framework of the q-canonical ensemble, provide protein-specific quantitative descriptions of pH-dependent populations of mesostates. This method is of direct relevance for measuring and understanding how different charge states contribute to conformational, binding, and phase equilibria of proteins.

Particlization of an interacting hadron resonance gas with global conservation laws for event-by-event fluctuations in heavy-ion collisions

We revisit the problem of particlization of a QCD fluid into hadrons and resonances at the end of the fluid dynamical stage in relativistic heavy-ion collisions in a context of fluctuation measurements. The existing methods sample an ideal hadron resonance gas, therefore, they do not capture the non-Poissonian nature of the grand-canonical fluctuations, expected due to QCD dynamics such as the chiral transition or QCD critical point. We address the issue by partitioning the particlization hypersurface into locally grand-canonical fireballs populating the space-time rapidity axis that are constrained by global conservation laws. The procedure allows to quantify the effect of global conservation laws, volume fluctuations, thermal smearing and resonance decays on fluctuation measurements in various rapidity acceptances, and can be used in fluid dynamical simulations of heavy-ion collisions. As a first application, we study event-by-event fluctuations in heavy-ion collisions at the LHC using an excluded volume hadron resonance gas model matched to lattice QCD susceptibilities, with a focus on (pseudo)rapidity acceptance dependence of net baryon, net proton, and net charge cumulants. We point out large differences between net proton and net baryon cumulant ratios that make direct comparisons between the two unjustified. We observe that the existing experimental data on net-charge fluctuations at the LHC shows a strong suppression relative to a hadronic description.

Switching between Proton Vacancy and Excess Proton Transfer Pathways in the Reaction between 7-Hydroxyquinoline and Formate.

Bifunctional or amphoteric photoacids simultaneously present donor (acidic) and acceptor (basic) properties making them useful tools to analyze proton transfer reactions. In protic solvents, the proton exchange between the acid and the base is controlled by the acidity or basicity strength and typically occurs on two different pathways known as protolysis and hydrolysis. We report here how the addition of a formate base will alter the relative importance of the possible reaction pathways of the bifunctional photoacid 7-hydroxyquinoline (7HQ), which has been recently understood to predominantly involve a hydroxide/methoxide transport mechanism between the basic proton-accepting quinoline nitrogen site toward the proton-donating OH group with a time constant of 360 ps in deuterated methanol (CD3OD). We follow the reaction dynamics by probing the IR-active marker modes of the different charged forms of photoexcited 7HQ, and of formic acid (HCOOD) in CD3OD solution. A comparison of the transient IR spectra as a function of formate concentration, and classical molecular dynamics simulations enables us to identify distinct contributions of “tight” (meaning “contact”) and “loose” (i.e., “solvent-separated”) 7HQ–formate reaction pairs in our data. Our results suggest that depending on the orientation of the OH group with respect to the quinoline aromatic ring system, the presence of the formate molecule in a proton relay pathway facilitates a net proton transfer from the proton-donating OH group of 7HQ-N* via the methanol/formate bridge toward the quinoline N site.

Relativistic nuclear collisions: Establishing a non-critical baseline for fluctuation measurements

We study the influence of global baryon number conservation on the non-critical baseline of net baryon cumulants in heavy-ion collisions in a given acceptance, accounting for the asymmetry between the mean-numbers of baryons and antibaryons. We derive the probability distribution of net baryon number in a restricted phase space from the canonical partition function that incorporates exact conservation of baryon number in the full system. Furthermore, we provide tools to compute cumulants of any order from the generating function of uncorrelated baryons constrained by exact baryon number conservation. The results are applied to quantify the non-critical baseline for cumulants of net proton number fluctuations obtained in heavy-ion collisions by the STAR collaboration at different RHIC energies and by the ALICE collaboration at the LHC. Furthermore, volume fluctuations are added by a Monte Carlo procedure based on the centrality dependence of charged particle production as measured experimentally. Compared to the predictions based on the hadron resonance gas model or Skellam distribution a clear suppression of fluctuations is observed due to exact baryon-number conservation. The suppression increases with the order of the cumulant and towards lower collision energies. Predictions for net proton cumulants up to the eight order in heavy-ion collisions are given for experimentally accessible collision energies.

Experimental Data Contributing to the Elusive Surface Charge of Inert Materials in Contact with Aqueous Media

We studied the charging of inert surfaces (polytetrafluoroethylene, i.e., PTFE; graphite; graphene; and hydrophobic silica) using classical colloid chemistry approaches. Potentiometric titrations showed that these surfaces acquired less charge from proton-related reactions than oxide minerals. The data from batch-type titrations for PTFE powder did not show an effect of ionic strength, which was also in contrast with results for classical colloids. In agreement with classical colloids, the electrokinetic results for inert surfaces showed the typical salt level dependence. In some cases, the point of zero net proton charge as determined from mass and tentatively from acid–base titration differed from isoelectric points, which has also been previously observed, for example by Chibowski and co-workers for ice electrolyte interfaces. Finally, we found no evidence for surface contaminations of our PTFE particles before and after immersion in aqueous solutions. Only in the presence of NaCl-containing solutions did cryo-XPS detect oxygen from water. We believe that our low isoelectric points for PTFE were not due to impurities. Moreover, the measured buffering at pH 3 could not be explained by sub-micromolar concentrations of contaminants. The most comprehensive explanation for the various sets of data is that hydroxide ion accumulation occurred at the interfaces between inert surfaces and aqueous solutions.