Soft Spots Research Articles

Armouring of a Frictional Interface by Mechanical Noise

A dry frictional interface loaded in shear often displays stick–slip. The amplitude of this cycle depends on the probability that a microscopic event nucleates a rupture and on the rate at which microscopic events are triggered. The latter is determined by the distribution of soft spots, P(x), which is the density of microscopic regions that yield if the shear load is increased by some amount x. In minimal models of a frictional interface—that include disorder, inertia and long-range elasticity—we discovered an ‘armouring’ mechanism by which the interface is greatly stabilised after a large slip event: P(x) then vanishes at small argument as P(x)∼xθ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$P(x)\\sim x^\ heta $$\\end{document} (de Geus et al., Proc Natl Acad Sci USA 116(48):23977-23983, 2019. https://doi.org/10.1073/pnas.1906551116). The exponent θ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ heta $$\\end{document} is non-zero only in the presence of inertia (otherwise θ=0\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ heta =0$$\\end{document}). It was found to depend on the statistics of the disorder in the model, a phenomenon that was not explained. Here, we show that a single-particle toy model with inertia and disorder captures the existence of a non-trivial exponent θ>0\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ heta >0$$\\end{document}, which we can analytically relate to the statistics of the disorder.

Pre- and Post-Improvement Performance of a Railway Embankment Stabilized with Ductile Inclusions

Large deflections and accumulation of permanent track geometry defects at railway soft spots cause significant operational issues including increased maintenance costs, decreased train speed, and, at an extreme, derailments and track failures. Reinforcing inclusions placed between the ties are a promising rehabilitation scheme to locally stabilize the embankment and transfer the loads to deeper, more suitable soils. In this paper we report the results of a long-term monitoring program to assess the performance of ductile inclusions, known commercially as “GeoSpike® elements”, to stabilize a rapidly deteriorating railway soft spot. Observations of track bed behavior are presented for 8 months prior to installation and 15 months after installation using a combination of LIDAR, Digital Image Correlation (DIC), and ShapeAccelArrays (SAA). Through the monitoring program, it was determined that the ductile inclusions decreased the average rate of deterioration by a factor of approximately 3, which allowed the frequency of site maintenance to be decreased from three times a year to once a year.

Clustering of negative topological charges precedes plastic failure in 3D glasses.

The deformation mechanism in amorphous solids subjected to external shear remains poorly understood because of the absence of well-defined topological defects mediating the plastic deformation. The notion of soft spots has emerged as a useful tool to characterize the onset of irreversible rearrangements and plastic flow, but these entities are not clearly defined in terms of geometry and topology. In this study, we unveil the phenomenology of recently discovered, precisely defined topological defects governing the microscopic mechanical and yielding behavior of a model 3D glass under shear deformation. We identify the existence of vortex-like and antivortex-like topological defects within the 3D nonaffine displacement field. The number density of these defects exhibits a significant anticorrelation with the plastic events, with defect proliferation-annihilation cycles matching the alternation of elastic-like segments and catastrophic plastic drops, respectively. Furthermore, we observe collective annihilation of these point-like defects via plastic events, with large local topological charge fluctuations in the vicinity of regions that feature strong nonaffine displacements. We reveal that plastic yielding is driven by several large sized clusters of net negative topological charge, the massive annihilation of which triggers the onset of plastic flow. These findings suggest a geometric and topological characterization of soft spots and pave the way for the mechanistic understanding of topological defects as mediators of plastic deformation in glassy materials.

Application of Electro-Activated Dissociation Fragmentation Technique to Identifying Glucuronidation and Oxidative Metabolism Sites of Vepdegestrant by Liquid Chromatography-High Resolution Mass Spectrometry.

Drug metabolite identification is an integrated part of drug metabolism and pharmacokinetics studies in drug discovery and development. Definitive identification of metabolic modification sides of test compounds such as screening metabolic soft spots and supporting metabolite synthesis are often required. Currently, liquid chromatography-high resolution mass spectrometry is the dominant analytical platform for metabolite identification. However, the interpretation of product ion spectra generated by commonly used collision-induced disassociation (CID) and higher-energy collisional dissociation (HCD) often fails to identify locations of metabolic modifications, especially glucuronidation. Recently, a ZenoTOF 7600 mass spectrometer equipped with electron-activated dissociation (EAD-HRMS) was introduced. The primary objective of this study was to apply EAD-HRMS to identify metabolism sites of vepdegestrant (ARV-471), a model compound that consists of multiple functional groups. ARV-471 was incubated in dog liver microsomes and 12 phase I metabolites and glucuronides were detected. EAD generated unique product ions via orthogonal fragmentation, which allowed for accurately determining the metabolism sites of ARV-471, including phenol glucuronidation, piperazine N-dealkylation, glutarimide hydrolysis, piperidine oxidation, and piperidine lactam formation. In contrast, CID and HCD spectral interpretation failed to identify modification sites of three O-glucuronides and three phase I metabolites. The results demonstrated that EAD has significant advantages over CID and HCD in definitive structural elucidation of glucuronides and phase I metabolites although the utility of EAD-HRMS in identifying various types of drug metabolites remains to be further evaluated. SIGNIFICANCE STATEMENT: Definitive identification of metabolic modification sites by liquid chromatography-high resolution mass spectrometry is highly needed in drug metabolism research, such as screening metabolic soft spots and supporting metabolite synthesis. However, commonly used collision-induced dissociation (CID) and higher-energy collisional dissociation (HCD) fragmentation techniques often fail to provide critical information for definitive structural elucidation. In this study, the electron-activated dissociation (EAD) was applied to identifying glucuronidation and oxidative metabolism sites of vepdegestrant, which generated significantly better results than CID and HCD.

Rapid and Definitive Identification of Cyclic Peptide Soft Spots by Isotope-Labeled Reductive Dimethylation and Mass Spectrometry Fragmentation.

Cyclic peptides are an emerging therapeutic modality over the past few decades. To identify drug candidates with sufficient proteolytic stability for oral administration, it is critical to pinpoint the amide bond hydrolysis sites, or soft spots, to better understand their metabolism and provide guidance on further structure optimization. However, the unambiguous characterization of cyclic peptide soft spots remains a significant challenge during early stage discovery studies, as amide bond hydrolysis forms a linearized isobaric sequence with the addition of a water molecule, regardless of the amide hydrolysis location. In this study, an innovative strategy was developed to enable the rapid and definitive identification of cyclic peptide soft spots by isotope-labeled reductive dimethylation and mass spectrometry fragmentation. The dimethylated immonium ion with enhanced MS signal at a distinctive m/z in MS/MS fragmentation spectra reveals the N-terminal amino acid on a linearized peptide sequence definitively and, thus, significantly simplifies the soft spot identification workflow. This approach has been evaluated to demonstrate the potential of isotope-labeled dimethylation to be a powerful analytical tool in cyclic peptide drug discovery and development.

A method of particleboard surface defect detection and recognition based on deep learning

ABSTRACT Particleboard is a material for furniture and other wooden industrial products, directly impacting the service life of the final product. In this study, an innovative dual-attention mechanism, the Dense Connection Idea (DC-DACB), which combines Ganomaly and ResNet networks to detect and identify surface defects on particleboards was proposed. The model demonstrates superior performance in fine-grained direction. Evaluation metrics including precision, recall, average F1Score, and mAP are employed. Comparative analysis with Faster-RCNN and Yolo v5 baseline models reveals a 2.4% and 2.2% improvement in mAP for particleboard surface-defect detection. Moreover, the model exhibits excellent accuracy (93.1%) in recognizing five common defect types: shaving, scratches, chalk marks, soft spots, and adhesive spots. Comparative analysis with SE-Net, SA-Net, the original CBAM, and self-attention further supports its effectiveness in particleboard surface-defect detection. The integration of artificial-intelligence detection technology enables the timely detection of production process issues, reduces wood resource waste, and benefit the production of the enterprise.

Chemical Catalysis Guides Structural Identification for the Major In Vivo Metabolite of the BET Inhibitor JQ1.

The bromodomain inhibitor (+)-JQ1 is a highly validated chemical probe; however, it exhibits poor in vivo pharmacokinetics. To guide efforts toward improving its pharmacological properties, we identified the (+)-JQ1 primary metabolite using chemical catalysis methods. Treatment of (+)-JQ1 with tetrabutylammonium decatungstate under photochemical conditions resulted in selective formation of an aldehyde at the 2-position of the thiophene ring [(+)-JQ1-CHO], which was further reduced to the 2-hydroxymethyl analog [(+)-JQ1-OH]. Comparative LC/MS analysis of (+)-JQ1-OH to the product obtained from liver microsomes suggested (+)-JQ1-OH as the major metabolite of (+)-JQ1. The 2-thienyl position was then substituted to generate a trideuterated (-CD3, (+)-JQ1-D) analog having half-lives that were 1.8- and 2.8-fold longer in mouse and human liver microsomes, respectively. This result unambiguously confirmed (+)-JQ1-OH as the major metabolite of (+)-JQ1. These studies demonstrate an efficient process for studying drug metabolism and identifying the metabolic soft spots of bioactive compounds.

Toxic metabolites and metabolic soft spots of celastrol based on glutathione metabolic capture and high-resolution mass spectrometry

ABSTRACT Background Celastrol is known as one of the most medicinally valuable compounds. However, the pharmaceutical application of celastrol is significantly limited due to high toxicity, while there are few reports on the mechanism of toxicity. Methods This study searched for possible toxic metabolites through phase I in vitro metabolism and glutathione capture experiments. Then in vivo metabolism experiments in mice and rats were conducted to look for metabolites in vivo. Finally, mice in vivo toxicity experiment was conducted to verify the toxicity of different doses of celastrol to mice. Results In the in vivo and in vitro metabolism experiments, we found 7 phase I metabolites in vitro, 9 glutathione conjugation metabolites in vitro, and 20 metabolites in vivo. The metabolic soft points of celastrol could be the quinone methyl structure at C3-OH and C6. In vivo toxicity experiments show that celastrol causes weight loss, diarrhea, gastrointestinal tract and liver inflammation in mice. Conclusions This study analyzed the metabolites and possible metabolic soft spots of celastrol, and its hepatotoxicity and gastrointestinal toxicity were demonstrated through in vivo studies for the first time. The results might provide an important basis for potential structural modification to increase the druggability of celastrol.

Structure-based optimization of indoline-containing compounds as second generation inhibitors of NF-κB-inducing kinase (NIK)

Overactivation of NIK led to increased transcriptional activity of NF-κB2, which was associated with human metabolic diseases, immunological disorders, and cancer. Therefore, NIK inhibitors were pursued as a potential treatment of NIK-driven human diseases. The first generation of NIK inhibitors features propargylic alcohol moieties, which were metabolic soft spots that led to the discovery of a second generation of NIK inhibitors without a propargylic alcohol. In this study, a series of compounds were designed, synthesized, and evaluated as novel NIK inhibitors using a NIK kinase assay. To evaluate selectivity profiles of these inhibitors, the most potent compound 50 was tested over COT and other two panels of 31 kinases. In addition, 50 inhibited NIK-driven upregulation of CCL5 gene in primary hepatocytes and showed low cytotoxicity against normal kidney cells HEK-293. These attributes make 50 a promising candidate for future optimization aimed to increase potency and selectivity against NIK and NF-κB2 pathway.

Golden Boy

Golden Boy Lily Meyer (bio) The tomato sat in a bowl of its own on the counter. "Look at him," my dad crowed. "Golden Boy." Golden Boy was fat and streaky, with rich orange veins running down his red sides. His stem gave off the faint, bitter smell of sun-cooked dirt. He had no wormholes, no soft spots, not one pucker or bruise. The chipmunks hadn't touched him. He was misshapen, but most heirlooms are. "Nice tomato," I said. "Nice?" Dad scooped Golden Boy from the bowl, cradling him to his chest. My dad's knuckles were swollen with arthritis. When I last saw him, eighteen months ago, his joints had recently started aching. Now his whole body seemed stooped. "Naomi thinks you're nice," he told the tomato. "Not perfect. Not blue-ribbon quality. Nice." "Blue ribbon?" I asked, dropping my backpack on the spotless, sandless kitchen floor. The marble countertop gleamed. Copper pots sparkled over the range. I smelled bleach and lemons, and I wondered who did the cleaning. Surely my father hadn't learned, at sixty-eight, to dust and scrub. [End Page 219] He lifted his chin. "What's wrong with a blue ribbon?" "Nothing." I kept my voice light. "Are you entering an ag show?" The answer, I knew, was no, though my father could clean up at the Truro Fair. He gardens with the zeal he once reserved for finance. In addition to heirloom tomatoes—Striped Caverns, Black Russians, Great Whites—he grows zucchini, pattypan squash, and both Japanese and Italian eggplants. He has blackberries and blueberries, which he protects from marauding birds with reflective tape and netting, and a brambly patch of raspberries that stay sour and greenish until the end of July. He has a peach tree and a stunted Braeburn apple that was here when he bought the house in 2001. He grows the Simon & Garfunkel herbs, plus basil, chives, cilantro, and some ailing lemongrass. All this, within fifty feet of the front door. The property extends further, but my father, these days, does not. He stroked Golden Boy, looking hurt. Out the window, a whale-watching boat cut a neat line across Cape Cod Bay, and I felt a brief and total longing to be on it. To be anywhere but my father's gigantic beach house, once my favorite place on Earth. In penance, I said, "It's a perfect tomato." "Thank you." "Do we get to eat it?" "Your brother brought a beautiful burrata from the city. I was thinking caprese for lunch." My brother was on the back deck, snoring gently. A water glass sweated next to his lounger. His legs were profoundly tan. Rather than wake him, I leaned on the railing and compared the view to the one I remembered. In five years, not much had changed. The bay rolled and glittered before me. Seabirds hunted overhead, and squirrels and chipmunks rustled in the scrub pines. The neighbors' wind chimes rang in the distance. The breeze carried all the right beach smells: hot driftwood, dried seaweed, dead fish. [End Page 220] I heard Caleb stirring. "Naomi?" As I turned, he clambered upright. "Nome! You came!" "You asked me to." He wrapped his arms around me, then picked me up—my giant baby brother—to whirl me in the air. "I did." He set me down, grinning, and I relaxed into his side. Already I felt less sorry to be here. Under even the worst circumstances, time with Caleb was a treat. I reached up to ruffle the remains of his Wall Street-short curls. Four years in banking had stripped him of scruffiness, though he retained the white goal-collision scar on his forehead and the spray of blackheads on the bridge of his nose. The sun beamed down on his white smile. At twenty-six, he was thoroughly handsome. Jewish-looking, even more than Dad or me. "How was the trip?" he asked. "Fine. Easy." I was lying, but not completely. The travel itself—a three-hour flight from Kansas City, then a two-hour drive down the arm of Cape Cod—had been smooth. Fast, even, for a summer Saturday. I...

Synthesis and biological evaluation of N-(3-fluorobenzyl)-4-(1-(methyl-d3)-1H-indazol-5-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-amine as a novel, potent ALK5 receptor inhibitor

Specific inhibition of ALK5 provides a novel method for controlling the development of cancers and fibrotic diseases. In this work, a novel series of N-(3-fluorobenzyl)-4-(1-(methyl-d3)-1H-indazol-5-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-amine (11), a potential clinical candidate, was synthesized by strategic incorporation of deuterium at potential metabolic soft spots and identified as ALK5 inhibitors. This compound has a low potential for CYP-mediated drug-drug interactions as a CYP450 inhibitor (IC50 = >10 μM) and showed potent inhibitory effects in cellular assay (IC50 = 3.5 ± 0.4 nM). The pharmacokinetic evaluation of 11 in mice demonstrated moderate clearance (29.0 mL/min/kg) and also revealed high oral bioavailability in mice (F = 67.6%).

Discovery of Proline-Based p300/CBP Inhibitors Using DNA-Encoded Library Technology in Combination with High-Throughput Screening.

E1A binding protein (p300) and CREB binding protein (CBP) are two highly homologous and multidomain histone acetyltransferases. These two proteins are involved in many cellular processes by acting as coactivators of a large number of transcription factors. Dysregulation of p300/CBP has been found in a variety of cancers and other diseases, and inhibition has been shown to decrease Myc expression. Herein, we report the identification of a series of highly potent, proline-based small-molecule p300/CBP histone acetyltransferase (HAT) inhibitors using DNA-encoded library technology in combination with high-throughput screening. The strategy of reducing ChromlogD and fluorination of metabolic soft spots was explored to improve the pharmacokinetic properties of potent p300 inhibitors. Fluorination of both cyclobutyl and proline rings of 22 led to not only reduced clearance but also improved cMyc cellular potency.

Influences on Quantitative Nitriding Layer Thickness Measurements using Model-Based Photothermal Radiometry

Abstract In nitriding furnaces, the nitriding result is currently only controlled indirectly via the nitriding potential based on gas sensors. Detrimental properties such as soft spots, insufficient compound layer thickness or strongly porous zones, which might result from reduced surface reactivity, are thus only detected post-process. Therefore, in-process measurements of the layer formation promise a real benefit for energy efficiency and process quality enhancement. Photothermal radiometry is a promising contactless method for layer inspection that so far showed qualitative correlations of the photothermal phase signal with material parameters and layer thicknesses. In this article, thickness and thermal conductivity of the compound layer are quantitatively determined by using a physical signal model for a least-squares approximation of in-process measured photothermal phase signals. In addition, the influence of roughness and surface curvature is investigated, with the model-based photothermal layer thickness measurement showing robustness to different surface conditions and allowing quantification of the layer thickness with uncertainties < 1 μm even during in-process measurement inside an industrial nitriding furnace.

Selective deuteration of bupropion slows epimerization and reduces metabolism

Strategically replacing hydrogen with deuterium at sites of metabolism in small molecule drugs can significantly alter clearance and potentially enhance clinical safety. Bupropion is an antidepressant and smoking cessation medication with the potential to cause seizures. We hypothesized that incorporating deuterium at specific sites in bupropion may greatly reduce epimerization, potentially slow metabolism, and reduce the formation of toxic metabolites, namely hydroxybupropion which has been associated with bupropion’s toxicity. Four deuterated analogues were synthesized incorporating deuterium at sites of metabolism and epimerization with the aim of altering the metabolic profile of bupropion. Spectroscopic binding and metabolism studies with bupropion and R-or S-d4 and R-or S-d10 analogs were performed with recombinant CYP2B6, human liver microsomes, and human hepatocytes. Results demonstrate that deuterated bupropion analogues exhibited 20–25% decrease in racemization and displayed a significant decrease in the formation of CYP2B6-mediated R,R - or S,S-hydroxybupropion with recombinant protein and human liver microsomes. In primary human hepatocytes, metabolism of deuterated analogs to R,R - and S,S-hydroxybupropion and threo- and erythro-hydrobupropion was significantly less than R/S-d0 bupropion. Selective deuterium substitution at metabolic soft spots in bupropion has the potential to provide a drug with a simplified pharmacokinetic profile, reduced toxicity and improved tolerability in patients.

Designer antiviral takes aim at one of influenza’s soft spots

Designer antiviral takes aim at one of influenza’s soft spots

Metabolite Identification of HIV-1 Capsid Modulators PF74 and 11L in Human Liver Microsomes.

PF74 and 11L, as potent modulators of the HIV-1 capsid protein, have been demonstrated to act at both early and late stages in the HIV-1 life cycle. However, their clearance is high in human liver microsomes (HLMs). The main goal of this study was to clarify the metabolism of PF74 and 11L in HLMs, and provide guidance for future structural optimization. To accomplish this, the phase-I metabolites of PF74 and 11L, resulting from in vitro incubation with HLMs, were investigated via ultra-performance liquid chromatography–ultraviolet–high-resolution mass spectrometry (UPLC–UV–HRMS). The results show that 17 phase-I metabolites were putatively annotated for PF74, whereas 16 phase-I metabolites were found for 11L. The main metabolic pathways of PF74 in HLMs were oxidation and demethylation, and the secondary metabolic pathway was hydrolysis; thus, the di-oxidation and demethylation products (M7, M9, M11, and M14) were found to be major metabolites of PF74 in HLMs. In comparison, the main metabolic pathways of 11L in HLMs were oxidation, demethylation, dehydrogenation, and oxidative deamination, with M6′, M11′, M15′, and M16′ as the main metabolites. We suggest that the indole ring and N-methyl group of PF74, and the aniline group, benzene ring R1′, N-methyl, and methoxy group of 11L, were the main metabolic soft spots. Therefore, our research illuminates structural optimization options in seeking improved HIV-1 CA modulators.

A Gendered Counter‐archive: Mining and Resistance in Morocco

ABSTRACTIn August 2011, thousands of villagers climbed Mount Alebban in Imider, southeast Morocco. They shut off the valve diverting water from the mountain's reservoir to a neighbouring silver mine. The villagers’ encampment on the mount lasted for eight years, withstanding state violence, prison sentences and political containment. Although Imider was considered a political protest camp, this article explores it through the notion of counter‐archive, defining the counter‐archive as a collective record keeping of disruption. The Imider camp is a counter‐archive in the sense that it enabled unauthorized stories to surface and radical politics to emerge. As a counter‐archive, it revealed the hidden links between politics and profit, extraction and dispossession, and life and death. As a forbidden space, the camp engaged in a quotidian performance of collective modes of living that resisted erasure through artwork, gendered spatial arrangements, storytelling and record making. The goal of the article is twofold: to illustrate the everyday making of this counter‐archive by analysing the modes of disruptive engagement of the villagers with the mine, and the new communities they have generated; and to show the soft spots of radical politics and its vulnerability in the context of neoliberal governance.

The improvement of the plasticity of a Zr – Ni – Al bulk metallic glass by static quenching

A method of static quenching has been put forward to prepare the Zr-based bulk metallic glass (BMG) in this work. Compared with the traditional method of copper mold suction casting, the compressive plasticity of Zr60Ni25Al15 BMG can be improved from nearly 0 to 6.5% through the method of static quenching. An underlying reason of the improved plasticity has been clarified as that the cooling rate of static quenching is larger than that of copper mold suction casting, and there are more soft spots in the static quenching sample than suction casting. The corresponding mechanism has also been discussed.

An Unexpected Deuterium-Induced Metabolic Switch in Doxophylline.

Precision deuteration has become part of the medicinal chemist’s toolbox, but its usefulness can be undermined by unpredictable metabolic switch effects. Herein we report the deuteration of doxophylline, a drug used in the treatment of asthma and COPD that undergoes extensive oxidative metabolism. Labeling of the main metabolic soft spots triggered an unexpected multidirectional metabolic switch that, while not improving the pharmacokinetic parameters, changed the metabolic scenario and, in turn, the pharmacodynamic features in two murine models of lung injury.

Cooperative effects driving the multi-periodic dynamics of cyclically sheared amorphous solids

When subject to cyclic forcing, amorphous solids can reach periodic, repetitive states, where the system behaves plastically, but the particles return to their initial positions after one or more forcing cycles, where the latter response is called multi-periodic. It is known that plasticity in amorphous materials is mediated by local rearrangements called "soft spots" or "shear transformation zones." Experiments and simulations indicate that soft spots can be modeled as hysteretic two-state entities interacting via quadrupolar displacement fields generated when they switch states and that these interactions can give rise to multi-periodic behavior. However, how interactions facilitate multi-periodicity is unknown. Here, we show, using a model of random interacting two-state systems and molecular dynamics simulations, that multi-periodicity arises from oscillations in the magnitudes of the switching field of soft spots, which cause soft spots to be active during some forcing cycles and idle during others. We demonstrate that these oscillations result from cooperative effects facilitated by the frustrated interactions between the soft spots. The presence of such mechanisms has implications for manipulating memory in frustrated hysteretic systems.