Additional Modes Research Articles

Identifying fracture-controlled resonance modes for structural health monitoring: insights from Hunter Canyon Arch (Utah, USA)

Abstract. Progressive fracturing contributes to structural degradation of natural rock arches and other freestanding rock landforms. However, methods to detect structural changes arising from fracturing are limited, particularly at sites with difficult access and high cultural value, where non-invasive approaches are essential. This study aims to determine how fractures affect the dynamic properties of rock arches, focusing on resonance modes as indicators of structural health conditions. We hypothesize that damage resulting from fracture propagation may influence specific resonance modes that can be identified through ambient vibration modal analysis. We characterized the dynamic properties (i.e., resonance frequencies, damping ratios, and mode shapes) of Hunter Canyon Arch, Utah (USA), using spectral and cross-correlation analyses of data generated from an array of nodal geophones. Results revealed properties of nine resonance modes with frequencies between 1 and 12 Hz. Experimental data were then compared to numerical models with homogeneous and heterogeneous compositions, the latter implementing weak mechanical zones in areas of mapped fractures. All numerical solutions replicated the first two resonance modes of the arch, indicating these modes are insensitive to structural complexity derived from fractures. Meanwhile, heterogenous models with discrete fracture zones succeeded in matching the frequency and shape of one additional higher mode, indicating this mode is sensitive to the presence of fractures and thus most likely to respond to structural change from fracture propagation. An evolutionary crack damage model was then applied to simulate fracture propagation, confirming that only this higher mode is sensitive to structural damage resulting from fracture growth. While examination of fundamental modes is common practice in structural health monitoring studies, our results suggest that analysis of higher-order resonance modes can be more informative for characterizing fracture-driven structural damage.

The mismatch repair factor Mlh1-Pms1 uses ATP to compact and remodel DNA.

ABSTRACTIn eukaryotes, mismatch repair begins withMutS homolog (MSH) complexes, which scan newly replicated DNA for mismatches. Upon mismatch detection, MSH complexes recruit the PCNA- stimulated endonuclease Mlh1-Pms1/PMS2 (yeast/human), which nicks the DNA to allow downstream proteins to remove the mismatch. Past work has shown that although Mlh1-Pms1 is an ATPase and this activity is importantin vivo, ATP is not required to nick DNA. Our data, using yeast as a model, suggests that Mlh1-Pms1 forms oligomeric complexes that drive DNA conformational rearrangements using the protein’s ATPase activity. Experiments with non-B-form DNA structures, common in microsatellite regions, show that these structures inhibit Mlh1-Pms1’s activities, likely through impeding Mlh1-Pms1-dependent DNA conformational changes. This could explain an additional mode for instability in these regions of the genome. These findings highlight the importance of DNA compaction and topological rearrangements in Mlh1-Pms1’s function and provide insight into how mismatch repair relies on DNA structure to coordinate events.GRAPHICAL ABSTRACT

A Multimodal Social Semiotic Analysis of Typography and Layout in ‘’Alexander Master’s Novel Stuart: A Life Backwards’’

The output of multimodal texts has increased over the past 20 years due to advances in technology and culture, which has accelerated the demand for tackling multimodal additional semiotic modes for meaning making, such as typography, layout ,visual images, colour, etc. The theory of multimodality, as supposed by Kress and Van Leeuwen (2001–2006), Baldry and Thibaut (2006), is applied to a potential framework for the analysis of multimodal novels that use not only wording structure but also many semiotic modes in the formation of meaning. The social approach to multimodality, in brief, is based on Halliday's linguistic description and adhered to the multimodal assumption that "mutual propositions are employed and worked together in various modes" (Kress and Leeuwen,2002:3). Thus, Kress and Van Leeuwen (1996:39), in their book ‘’Reading Images’’ investigate the level for which the underlying theories of Halliday's framework to language are feasible and applicative to visual communicative management, and they create a visual system that mostly makes use of Halliday's principles and concepts. The study is concerned with the investigation of a multimodal analysis of the multiple elements of various modes of typographic devices, and layout design used in the selected novel. This selected text ‘’Stuart: A Life Backwards’’ is a multimodal novel since the writer Masters does not rely on linguistic verbal tools, he extends them to incorporate a variety of visual semiotic modes and graphic communicative elements that will intensify his understanding of storytelling and narrative development. The study has shown that an extension to the mode of wording formation is performed in the multimodal analysis by incorporating more multimodal tackling features of typographic principles and layout framing devices in creating an appropriate comprehensive meaning construction in Masters’ selected narration.

Enhanced broadband quantum efficiency in LWIR T2SL detectors with guided-mode resonance structure.

Type-II superlattice (T2SL) detectors are emerging as key technologies for next-generation long-wavelength infrared (LWIR) applications, particularly in the 8-14 µm range, offering advantages in space exploration, medical imaging, and defense. A major challenge in improving quantum efficiency (QE) lies in achieving sufficient light absorption without increasing the active layer (AL) thickness, which can elevate dark current and complicate manufacturing. Traditional methods, such as thickening the absorber, are limited by the short carrier lifetime in T2SLs, necessitating alternative solutions. In this study, we introduced a guided-mode resonance (GMR) structure into T2SL LWIR detectors to enhance QE while maintaining a thin AL for efficient carrier collection. The GMR structure was fabricated by introducing a grating array on the surface of the detector and an Au mirror beneath the absorber. This configuration enhanced light trapping, which introduced additional resonance modes. The optimized grating design, with a 5 µm period and a fill factor of 0.6, significantly increased absorption, as predicted by finite-difference time-domain (FDTD) simulations and confirmed experimentally. The GMR-enhanced T2SL detector demonstrated a 2.58-fold improvement in QE over conventional LWIR detectors and a 1.33-fold increase compared to Fabry-Pérot (FP) resonance-based detectors in the 6-11 µm range. Despite exhibiting an almost identical dark current density, the GMR LWIR detector demonstrated superior performance, featuring a broader cut-off wavelength of 9.3 µm and higher QE compared to FP LWIR detectors.

Altered brain-ventricle coupling modes over Alzheimer's disease progression detected with fMRI.

The origins of resting-state functional MRI (rsfMRI) signal fluctuations remain debated. Recent evidence shows coupling between global cortical rsfMRI signals and cerebrospinal fluid inflow in the fourth ventricle, increasing during sleep and decreasing with Alzheimer's disease (AD) progression, potentially reflecting brain clearance mechanisms. However, the existence of more complex brain-ventricle coupling modes and their relationship to cognitive decline remains unexplored. Analyzing 599 minimally-preprocessed rsfMRI scans from 163 elderly participants across the AD spectrum, we identified distinct brain-ventricle coupling modes that differentiate across groups and correlate with cognitive scores. Beyond the known anti-phase coupling between global brain signals and ventricles -more frequent in cognitively normal controls- we discovered additional modes where specific brain areas temporarily align with ventricle signals. At the cortical level, these modes form canonical resting-state networks, such as the Default Mode Network, which occurs less in AD or the Frontoparietal Network, which correlates positively with memory scores. The direct link between ventricle and brain signals challenges the common practice of removing CSF components from rsfMRI analyses and questions the origin of cortical signal fluctuations forming functional networks, which may reflect region-specific fluid inflow patterns. These findings provide new insights into the relationship between brain clearance mechanisms and network dysfunction in neurodegenerative diseases.

Edible Mushrooms: a Nutrient-Rich Ingredient for Healthier Food Products - A Review.

Edible mushrooms are found to be foods with high nutritional content, which have been shown to be more widely used ingredients in cooking in traditional dishes. This article explores the rising trend in the use of edible mushrooms in new formulations of functional foods, taking advantage of their properties and benefits in human health. The use of mushrooms as an ingredient in new or modified food formulations is driven by solid evidence of their nutritional content and bioactivity. Mushrooms stand out for their high biological value and high bioavailability protein content, as well as dietary fiber that promotes improved digestive health. Other micronutrients present are B vitamins and minerals such as selenium, phosphorus and potassium. Mushroom flour has been the prevalent mode of addition to food formulations. This type of format aims to preserve and concentrate the nutritional content of mushrooms and has achieved nutritional enrichment of products. The use of this food has also been explored to improve technological qualities in food development, so it is intended to position itself as a natural additive. This review synthesizes data on the nutritional composition, bioactive properties, and physicochemical attributes of mushrooms, emphasizing their multifaceted contributions to modern food formulations. It advocates for further research to optimize mushroom application in diverse food products and to address practical challenges for seamless integration.

Light-Mediated Radical Addition to Azomethine Compounds: Novel Reactivity and Activation Modes.

Azomethines is a class of compounds, which have traditionally served as electrophilic substrates, but their reactions with radicals have long been limited. Photocatalysis provided ample opportunities for promoting these reactions, with wide variety of reagents serving as precursors of radicals. Besides regular addition mode at the azomethine fragment, the oxidative pathway, in which the C=N bond remains in the product, has become possible by proper selection of redox catalyst. This review summarizes new developments in this rapidly developing field over the past five years. New concepts on activation of the C=N bond towards radical attack are discussed.

Real-Time Quantification of Molecular-Level Dynamic Behaviors Underpinning Shear Thinning in End-Linked Associative Polymer Networks.

Shear thinning of associative polymers is tied to bond breakage under deformation and retraction of dangling chains, as predicted by transient network theories. However, an in-depth understanding of the molecular mechanisms is limited by our ability to measure the molecular states of the polymers during deformation. Herein, utilizing a custom-built rheo-fluorescence setup, bond dissociation in model end-linked associative polymers is quantified in real time with nonlinear shear deformation based on a fluorescence quench transition when phenanthroline ligands bind with Ni2+. All of the networks exhibit shear thinning, and the dangling chain fraction increases with the shear rate. However, the number of broken bonds is smaller than that predicted by transient network theories, indicating additional relaxation modes or topological inhomogeneities in the networks. Through tuning counteranion chemistry, networks with similar relaxation times but varying dissociation and association rate constants (kd and ka) of Ni2+-phenanthroline cross-links are developed. Decreasing ka contributes to more dangling chain formation, while the effect of kd is less pronounced. Following force-accelerated bond dissociation of bridging chains, the dangling ends in networks with higher ka tend to reassociate to form elastically inactive loops, while the dangling chains are preserved in networks with lower ka. This indicates the critical role of bond reassociation kinetics in dictating shear-induced topological interchange of different chain configurations. Besides reaction kinetics, decreasing network junction functionality results in less shear thinning and broken bonds, originating from the lower amount of bond breakage required to flow and the higher tendency of the dissociated bonds to reform bridging chains.

Analysis of genetic association between exon polymorphisms of ADH4 and ADH7 and risky drinking behavior of alcoholic liver disease

To analyze the correlation of ADH4 exon rs1126671 and ADH7 exon rs971074 polymorphisms with risky drinking behaviors and alcoholic liver disease. The patients with alcoholic liver disease diagnosed in the Gastroenterology Department of the People's Hospital of Hechi from November 2021 to June 2022, including 52 cases of alcoholic liver disease with positive risky drinking behaviors, 103 cases of non-alcoholic liver disease with positive risky drinking behaviors of the same gender and age, and 105 healthy subjects with no risky drinking behaviors as control groups were retrospectively analyzed. The serum total protein and albumin are detected by immunoturbidimetry and globulin is calculated by the difference method; the serum total bilirubin and direct bilirubin are detected by the nitrite oxidation method and indirect bilirubin is calculated by the difference method; alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase and γ-glutamyl transferase are detected by the substrate method. The results revealed that all 52 patients with alcoholic liver disease were male. The non-parametric independent sample Kruskal-Wallis test was adopted to analyze the baseline of twelve liver functions among the alcoholic liver disease group, the risky drinking behavior group and the healthy control group, and it was found there was statistical significance in ten major liver function indicators in the difference comparison among the three groups like serum total protein (g/L) 65.0 (60.1, 71.4), 73.4 (70.3, 76.3), 72.4 (69.2, 76.2) (H=37.130, P<0.001); albumin (g/L) 36.1 (28.6, 42.9), 47.2 (45.0, 49.2), 47.5 (45.9, 49.5) (H=14.503, P=0.001); direct bilirubin (μmol/L) 10.1 (35.6, 34.0.1), 3.8 (3.1, 5.45), 4.2 (2.9, 6.0) (H=26.608, P<0.001); alkaline phosphatase (U/L) 106.0 (71.0, 164.0), 68.0 (57.5, 82.0), 70.0 (59.0, 87.0) (H=27.904, P<0.001); albumin to globulin 1.34 (0.91, 1.88), 1.82 (1.65, 2.00), 1.89 (1.68, 2.07) (H=11.047, P=0.004); direct bilirubin to indirect bilirubin 0.91 (0.69, 1.91), 0.41 (0.35, 0.54), 0.42 (0.34, 0.54) (H=19.478, P<0.001); serum total bilirubin (μmol/L) 23.9 (13.7, 51.0), 13.8 (10.2, 17.9), 13.0 (10.1, 17.4) (H=18.375, P<0.001); aspartate aminotransferase (U/L) 74.0 (39.0, 122.0), 22.0 (19.0, 28.0), 23.0 (19.0, 30.0) (H=76.365, P<0.001); alanine aminotransferase (U/L) 37.0 (25.0, 55.0), 23.0 (17.0, 30.0), 24.0 (17.0, 33.8) (H=57.041, P<0.001); γ-glutamyl transferase (U/L) 135.0 (45.0, 364.0), 33.0 (23.5, 49.5), 32.0 (19.0, 49.0) (H=82.558, P<0.001); however, there were no statistical significance in the pairwise comparisons between risky drinking and healthy groups. The two loci of ADH4 and ADH7 were in genetic linkage equilibrium. In the three groups of samples, the ADH4 gene rs1126671 locus was comprised primarily of the CC homozygous genotype, and there was no TT genotype. The ADH7 gene rs971074 genotype had statistical difference in the comparison of the three groups (χ2=9.370, P<0.05). Compared with the CC genotype, the CT genotype had no statistical difference in the pairwise comparison between the risky drinking behavior group and alcoholic liver disease group, and the healthy group and alcoholic liver disease group. There was a statistical difference in that between the healthy group and the risky drinking behavior group (χ2=6.372, P=0.012). The analysis display of mode of inheritance between RD group and HA group was statistically significant in the difference of the superdominance inheritance mode (OR=2.92, 95%CI:1.22-6.98; P=0.012), the dominant inheritance mode (OR=2.90, 95%CI:1.26-6.64; P=0.008), the co-dominant inheritance mode (OR=2.96, 95%CI:1.24-7.08; P=0.032) and the additive mode (OR=2.46, 95%CI:1.16-5.22; P=0.013). In general, the CT genotype of ADH7 gene rs971074 is a risk factor for positive risky drinking behavior, and the ADH family may still increase the susceptibility of people with a potential alcoholic liver disease protection background through the correlation between ADH7 and risky drinking behavior.

Study of influence of additive wire-arc manufacturing modes on microstructure of AA7075 alloy

Study of influence of additive wire-arc manufacturing modes on microstructure of AA7075 alloy

The Behavior of Elbow Elements at Pure Bending Applications Compared to Beam and Shell Element Models

Abstract This paper studies the response of ELBOW31 and ELBOW31B element types under pure bending conditions, using shell and beam element models for benchmarking. Various model lengths are evaluated, showing that a model length of six pipe diameters exhibits a hardening effect when total strain exceeds 3.5%, though a strain up to 1% is deemed sufficient for pipeline design. The study examines the effects of ovality modes and boundary conditions such as NOWARP and NOOVAL on the bending response. ELBOW31 with one or two ovality modes yields accurate results, while additional ovality modes or zero ovality mode can lead to overprediction of the elastic bending moment capacity. The introduction of the NOWARP condition enhances the accuracy of the ELBOW31 model, while the NOOVAL condition alone produces unrealistic results. The simplified ELBOW31B model shows good agreement with the ELBOW31-NOWARP model but similarly overpredicts the bending moment when zero ovality mode is used. The study also finds that Poisson's ratio and model length have no significant impact on the bending response when no restrictions are applied. Additional analyses, as presented in Appendices A and B, highlight the importance of D/t ratios in pipeline performance. A D/t ratio of 20 offers a stiffer response with reduced ovalization, while a D/t ratio of 50 results in greater flexibility and increased ovalization. These findings provide valuable insights for the selection of element types, boundary conditions, and D/t ratios in robust pipeline design.

Fixing detailed balance in ancilla-based dissipative state engineering

Dissipative state engineering is a general term for a protocol which prepares the ground state of a complex many-body Hamiltonian using engineered dissipation or engineered environments. Recently, it was shown that a version of this protocol, where the engineered environment consists of one or more dissipative qubit ancillas tuned to be resonant with the low-energy transitions of a many-body system, resulted in the combined system evolving to reasonable approximation to the ground state. This potentially broadens the applicability of the method beyond nonfrustrated systems, to which it was previously restricted. Here we argue that this approach has an intrinsic limitation because the ancillas, seen as an effective bath by the system in the weak-coupling limit, do not give the detailed balance expected for a true zero-temperature environment. Our argument is based on the study of a similar approach employing linear coupling to bosonic ancillas. We explore overcoming this limitation using a recently developed open quantum systems technique called pseudomodes. With a simple example model of a one-dimensional quantum Ising chain, we show that detailed balance can be fixed, and a more accurate estimation of the ground state obtained, at the cost of two additional unphysical dissipative modes and the extrapolation error of implementing those modes in physical systems. Published by the American Physical Society 2024

The mode of subunit addition regulates the processive elongation of actin filaments by formin.

Formins play crucial roles in actin polymerization by nucleating filaments and regulating their elongation. Formins bind the barbed ends of filaments via their dimeric FH2 domains, which step processively onto incoming actin subunits during elongation. Actin monomers can bind formin-bound barbed ends directly or undergo diffusion-mediated delivery through interactions with formin FH1 domains and profilin. Despite its fundamental importance, a clear mechanism governing processive FH2 stepping has remained elusive. In this study, we systematically characterized the polymerization behavior of the S. cerevisiae formin Bni1p using in vitro reconstitution assays and stochastic simulations. We found that Bni1p assembles populations of filaments with lengths that depend nonlinearly on the rate of elongation. This processive behavior is dictated by a variable probability of dissociation that depends on the reaction conditions. Bni1p dissociates from barbed ends with a basal off-rate, which enables prolonged filament assembly over the course of a long lifetime at the barbed end. A bias towards FH1-mediated delivery as the dominant mechanism for polymerization curtails elongation by shortening the lifetime of the formin at the filament end. This facilitates the assembly of populations of filaments with similar average lengths, even when polymerization proceeds at different rates. Our results suggest a central role for formin FH1 domains in regulating processivity. The specific effects of FH1 domains on processivity are variable and likely tailored to the physiological function of each formin.

Numerical Investigation of Piezoelectric Energy Harvesting From a Multi-Mode T-Shaped Structure

In this work, energy harvesting from a proposed three-mode T-shaped structure, composed of a vertical beam, two horizontal beams, a center mass, and tip masses, is investigated to expand the frequency bandwidth for energy harvesting, without compromising the power density due to the additional mass of the structure, as is the case with most multi-mode harvesters. The aim is to cleverly use and position the additional mass to help induce higher and more uniform strain levels throughout the piezoelectric patch, leading to greater power generation to help counteract the added mass. A numerical model was developed to analyze the structure, to obtain voltage and power frequency responses, taking into effect the load resistance modeling and the accurate evaluation of resonance peaks by estimating each mode damping ratio. The validity of the model was confirmed by comparisons with previous experiments involving other structures, which demonstrated strong agreement. The excitation load was strategically applied to induce maximum displacement of the center and tip masses relative to the fixed ends in each mode. The outcomes reveal that the T-shaped configuration exhibits the capacity to generate higher maximum strain and a more uniform strain distribution across the piezoelectric patch when compared to previous L-shaped and traditional cantilever harvesters' designs. These characteristics yielded a power density higher than that of the L-shaped structure by approximately 70% with only around 20% addition in structure mass. Additionally, the multi-mode T-shaped structure boasts a significantly broader harvesting bandwidth due to the additional mode, without compromising power density, as was the case with L-shaped structures. Furthermore, the positioning of the tip mass was systematically altered to assess its impact on the frequency bandwidth and power output of the horizontal and vertical beams in the three bending modes, demonstrating great robustness and tuning capabilities.

Nanoscale dynamics of Dynamin 1 helices reveals squeeze-twist deformation mode critical for membrane fission

Dynamin 1 (Dyn1) GTPase, a principal driver of membrane fission during synaptic endocytosis, self-assembles into short mechanoactive helices cleaving the necks of endocytic vesicles. While structural information about Dyn1 helix is abundant, little is known about the nanoscale dynamics of the helical scaffolding at the moment of fission, complicating mechanistic understanding of Dyn1 action. To address the role of the helix dynamics in fission, we used High-Speed Atomic Force Microscopy (HS-AFM) and fluorescence microscopy to track and compare the spatiotemporal characteristics of the helices formed by wild-type Dyn1 and its K44A mutant impaired in GTP hydrolysis on minimal lipid membrane templates. In the absence of nucleotide, membrane-bound WTDyn1 and K44ADyn1 self-assembled into tubular protein scaffolding of similar diameter encaging the lipid bilayer. In both cases, the GTP addition caused scaffold constriction coupled with formation of 20 to 30 nm nanogaps in the protein coverage. While both proteins reached scaffold diameters characteristic for membrane superconstriction causing fission, the fission was detected only with WTDyn1. We associated the fission activity with the dynamic evolution of the nanogaps: K44ADyn1 gaps were static, while WTDyn1 gaps actively evolved via repetitive nonaxisymmetric constriction-bending deformations caused by localized GTP hydrolysis. Modeling of the deformations implicated filament twist as an additional deformation mode which combines with superconstriction to facilitate membrane fission. Our results thus show that the dynamics of the Dyn1 helical scaffold goes beyond radial constriction and involves nonaxisymmetric deformations, where filament twist emerges as a critical driver of membrane fission.

A DFT Study on the NHC-Catalyzed Reaction of Enals with Aminoacrylates: Mechanism, Regioselectivity, and Stereoselectivity.

DFT (M06-2X) calculations were used to study the NHC-catalyzed [3 + 3] cycloaddition of enals with aminoacrylates. The catalytic cycle begins with the binding of the NHC to enal. Subsequent intramolecular proton transfer generates the Breslow intermediate. This intermediate undergoes an oxidative reaction, leading to the formation of an acyl azolium intermediate, which further reacts with the other substrate aminoacrylate via a new C-C bond formation. This step determines the stereoselectivity of the current reaction, and re-face addition mode leading to the formation of the intermediate with an S-configuration is predominant. Afterward, sequential protonation, deprotonation, and cyclization form the six-membered cyclic intermediate, which upon elimination of the NHC affords the final cycloaddition product dihydropyridinone. The computed enantiomeric excess (99.1% ee) is in very good agreement with the experimentally reported value (99% ee). The origin of enantioselectivity is traced to the stronger LP···π interactions between the acyl azolium intermediate and aminoacrylate in the favored S-congurational transition state.

Green's Function Approach for Late‐Time Tail and Echoes in Damour–Solodukhin Type Wormholes

ABSTRACTThis study elaborates on two distinctive features in Damour–Solodukhin wormhole's waveforms: late‐time tails and echoes. As a well‐known black hole mimicker, these characteristics are crucial in differentiating wormholes from classical black holes. They emerge in the final phases of quasinormal oscillations and arise from specific structures in the Green's function. The late‐time tail results from branch cut contributions, indicating a need to refine our interpretation of spacetime geometry. The echoes originate from additional quasinormal modes, similar to scenarios with metric discontinuities. These observations suggest that late‐time wave behavior could be a unique signature of wormholes. Furthermore, the study hints at a possible interaction between late‐time tails and echoes in the waveform's evolution.

All-optical quality control of indenene intercalation into graphene/SiC

Intercalating two-dimensional quantum materials beneath a sheet of graphene provides effective environmental protection and facilitates ex situ device fabrication. However, developing a functional device requires rapid, large-scale screening methods to evaluate the quality of the intercalant, which to date can be monitored only by slow, ultra-high vacuum-based surface science techniques. In this study, we utilize ex situ Raman micro-spectroscopy to optically and nondestructively identify the quantum spin Hall insulator indenene, a monolayer of indium sandwiched between a SiC(0001) substrate and a single sheet of graphene. Color modulation combined with indenene's distinctive low-frequency Raman fingerprint enables rapid assessment of its homogeneity and crystalline quality. Density functional perturbation theory indicates that this Raman signature originates mainly from indenene's shear and breathing modes, while additional higher order modes are tentatively attributed to defect-assisted and two-phonon Raman processes.

Naltrexone blocks alcohol-induced effects on kappa-opioid receptors in the plasma membrane

Naltrexone (NTX), a homolog of the opiate antidote naloxone, is an orally active long-acting general opioid receptor antagonist used in the treatment of opiate dependence. NTX is also found to relieve craving for alcohol and is one of few FDA-approved medications for treatment of alcohol use disorder (AUD). While it was early on established that NTX acts by blocking the binding of endogenous opioid peptide ligands released by alcohol, experimental evidence emerged that could not be fully accounted for by this explanation alone, suggesting that NTX may have additional modes of action. Mu- and kappa-opioid receptors (MOP and KOP, respectively) are structurally related G-protein-coupled receptors (GPCRs), but they are anatomically differently distributed and functionally distinct, often mediating opposite responses, with MOP typically promoting euphoria and reward, while KOP is associated with dysphoria and aversive states. While the actions of NTX on MOP are extensively characterized, the interactions with KOP are not. Here, we used sensitive fluorescence-based methods with single-molecule sensitivity to study in live cells the influence of alcohol (ethanol, EtOH) on KOP and the interaction between KOP and NTX. Our data show that alcohol, at relevant concentrations (10–40 mM), alters KOP interactions with the lipid environment in the plasma membrane. The counteracting effects of NTX are exerted by both its canonical action on KOP and its hitherto unrevealed effects on the lateral dynamics and organization of lipids in the plasma membrane. The KOP-specific antagonist LY2444296, in clinical trial for major depressive disorder (MDD), blocks KOP but does not show the full action profile of NTX. The therapeutic effect of NTX treatment in AUD may in part be due to direct actions on KOP and in part due to its effect on the surrounding lipid environment.

Boson-Peak-Like Anomaly Induced by Dipole Disordered States in (CH_{3}NH_{3})_{4}InCl_{7}.

Boson peaks are observed in glassy materials due to atom, spin, and strain disordered states that provide additional vibration modes at low temperatures. However, Boson peaks have not been observed in pure dipole disordered systems without structural disorder. Here, we report the observation of a Boson-peak-like hump in specific heat near 7K in organic-inorganic hybrid crystal MA_{4}InCl_{7}(MA=CH_{3}NH_{3}). The energy barrier for unbonded Cl anions migration is extremely low, allowing that the migration persists down to low temperatures. The migration and the subsequent relaxation process induce a random change in its dipole, leading to the dipole disorder states. Our results show that MA_{4}InCl_{7} can be regarded as a dipole glass that can give rise to the Boson peak as well.