Dissociation Patterns Research Articles

Dissociable Default Mode Network Connectivity Patterns Underlie Distinct Symptoms in Psychosis Risk.

The Clinical High Risk (CHR) stage of psychosis is characterized by subthreshold symptoms of schizophrenia including negative symptoms, dysphoric mood, and functional deterioration. Hyperconnectivity of the default-mode network (DMN) has been observed in early schizophrenia, but the extent to which hyperconnectivity is present in CHR, and the extent to which such hyperconnectivity may underlie transdiagnostic symptoms, is not clear. As part of the Shanghai At-Risk for Psychosis (SHARP) program, resting-state fMRI data were collected from 251 young adults (158 CHR and 93 controls, M = 18.72, SD = 4.68, 129 male). We examined functional connectivity of the DMN by performing a whole-brain seed-to-voxel analysis with the MPFC as the seed. Symptom severity across a number of dimensions, including negative symptoms, positive symptoms, and affective symptoms were assessed. Compared to controls, CHRs exhibited significantly greater functional connectivity (p < 0.001 uncorrected) between the MPFC and 1) other DMN nodes including the posterior cingulate cortex (PCC), and 2) auditory cortices (superior and middle temporal gyri, STG/MTG). Furthermore, these two patterns of hyperconnectivity were differentially associated with distinct symptom clusters. Within CHR, MPFC-PCC connectivity was significantly correlated with anxiety (r= 0.23, p=0.006), while MPFC-STG/MTG connectivity was significantly correlated with negative symptom severity (r=0.26, p=0.001). Secondary analyses using item-level symptom scores confirmed a similar dissociation. These results demonstrate that two dissociable patterns of DMN hyperconnectivity found in the CHR stage may underlie distinct dimensions of symptomatology.

Formation of Paraldehyde (C6H12O3) in Interstellar Analog Ices of Acetaldehyde Exposed to Ionizing Radiation.

Acetaldehyde (CH3CHO) plays a crucial role in the synthesis of prebiotic molecules such as amino acids, sugars, and sugar-related compounds, and in the progress of chain reaction polymerization in deep space. Here, we report the first formation of the cyclic acetaldehyde trimer - paraldehyde (C6H12O3) - in low-temperature interstellar analog ices exposed to energetic irradiation as proxies of galactic cosmic rays (GCRs). Utilizing vacuum ultraviolet photoionization reflectron time-of-flight mass spectrometry and isotopic substitution experiments, paraldehyde was identified in the gas phase during the temperature-programmed desorption of the irradiated acetaldehyde ices based on the calculated adiabatic ionization energies and isomer-specific dissociative fragmentation patterns upon photoionization. As acetaldehyde is ubiquitous throughout the interstellar medium and has been tentatively identified in interstellar ices, paraldehyde could have formed in acetaldehyde-containing ices in a cold molecular cloud and is an excellent candidate for gas-phase observation in star-forming regions via radio telescopes. The identification of paraldehyde in the gas phase from the processed acetaldehyde ices advances our understanding of how complex organic molecules can be synthesized through polymerization reactions in extraterrestrial ices exposed to GCRs.

Time reference in French-speaking people with fluent and non-fluent aphasia (part II): a cluster analysis

ABSTRACT Background Tense production is often impaired in people with aphasia (PWA). Interestingly, the literature suggests that not all tenses are affected in the same way, although the pattern of dissociation is still debated in the literature. The heterogeneity of tense production deficits in PWA might partly explain this lack of consensus in the literature. While this heterogeneity has been demonstrated by descriptive statistics or double dissociations in several studies, no study has used cluster analyses to highlight the main patterns of tense dissociation. Furthermore, the factors underlying this heterogeneity have been little explored. Aims Our study aimed to use cluster analyses on tense production performance to (1) identify the main patterns of dissociation between tenses in PWA and (2) explore the clinical (aphasia type and severity) and cognitive (executive disorders and temporality) factors that may underlie these patterns. Methods & procedures Twenty-one French-speaking participants with fluent and non-fluent aphasia completed a verb inflection production task, as well as language and cognitive tests. Cluster analyses were performed on the differences in performance between the tenses on the verb inflection production task. Generalized linear mixed models and nonparametric statistics were used to analyze the effect of tense and its interaction with the clusters, and to compare the clusters on the clinical and cognitive variables. Outcomes & results Cluster analyses revealed two main clusters, one with worse performances in the past and future than in the present (PWA_1 – 70% of the PWA), and the other with worse performances in the past and present than in the future (PWA_2 – 30%). The type and severity of aphasia, and cognitive test performance did not differ between the two clusters. On the other hand, the PWA_2 cluster had a longer time post-onset than the PWA_1 cluster. Conclusions Our results confirm the heterogeneity of verb inflection deficits in PWA. They suggest that most PWA would have difficulties with past and future tenses, questioning the presence of discourse linking in these two tenses. However, a minority of PWA, who are clinically and cognitively indistinguishable from the others, do not follow this pattern. Adopting the strategy of producing a morphologically simple tense in French – future – could explain the high performance in the future tense and the errors in substituting other tenses with the future in this subgroup. Finally, the clinical and research implications of this heterogeneity, in relation to therapies and the lack of consensus in the literature, are discussed.

Structural covariation between cerebellum and neocortex intrinsic structural covariation links cerebellum subregions to the cerebral cortex.

The human cerebellum is increasingly recognized to be involved in nonmotor and higher-order cognitive functions. Yet, its ties with the entire cerebral cortex have not been holistically studied in a whole brain exploration with a unified analytical framework. Here, we characterized dissociable cortical-cerebellar structural covariation patterns based on regional gray matter volume (GMV) across the brain in n = 38,527 UK Biobank participants. Our results invigorate previous observations in that important shares of cortical-cerebellar structural covariation are described as 1) a dissociation between the higher-level cognitive system and lower-level sensorimotor system and 2) an anticorrelation between the visual-attention system and advanced associative networks within the cerebellum. We also discovered a novel pattern of ipsilateral, rather than contralateral, cerebral-cerebellar associations. Furthermore, phenome-wide association assays revealed key phenotypes, including cognitive phenotypes, lifestyle, physical properties, and blood assays, associated with each decomposed covariation pattern, helping to understand their real-world implications. This systems neuroscience view paves the way for future studies to explore the implications of these structural covariations, potentially illuminating new pathways in our understanding of neurological and cognitive disorders.NEW & NOTEWORTHY Cerebellum's association with the entire cerebral cortex has not been holistically studied in a unified way. Here, we conjointly characterize the population-level cortical-cerebellar structural covariation patterns leveraging ∼40,000 UK Biobank participants whole brain structural scans and ∼1,000 phenotypes. We revitalize the previous hypothesis of an anticorrelation between the visual-attention system and advanced associative networks within the cerebellum. We also discovered a novel ipsilateral cerebral-cerebellar associations. Phenome-wide association (PheWAS) revealed real-world implications of the structural covariation patterns.

Characterization of a Monoclonal Antibody by Native and Denaturing Top-Down Mass Spectrometry.

Established in recent years as an important approach to unraveling the heterogeneity of intact monoclonal antibodies, native mass spectrometry has been rarely utilized for sequencing these complex biomolecules via tandem mass spectrometry. Typically, top-down mass spectrometry has been performed starting from highly charged precursor ions obtained via electrospray ionization under denaturing conditions (i.e., in the presence of organic solvents and acidic pH). Here we systematically benchmark four distinct ion dissociation methods─namely, higher-energy collisional dissociation, electron transfer dissociation, electron transfer dissociation/higher-energy collisional dissociation, and 213 nm ultraviolet photodissociation─in their capability to characterize a therapeutic monoclonal antibody, trastuzumab, starting from denatured and native-like precursor ions. Interestingly, native top-down mass spectrometry results in higher sequence coverage than the experiments carried out under denaturing conditions, with the exception of ultraviolet photodissociation. Globally, electron transfer dissociation followed by collision-based activation of product ions generates the largest number of backbone cleavages in disulfide protected regions, including the complementarity determining regions, regardless of electrospray ionization conditions. Overall, these findings suggest that native mass spectrometry can certainly be used for the gas-phase sequencing of whole monoclonal antibodies, although the dissociation of denatured precursor ions still returns a few backbone cleavages not identified in native experiments. Finally, a comparison of the fragmentation maps obtained under denaturing and native conditions strongly points toward disulfide bonds as the primary reason behind the largely overlapping dissociation patterns.

Mass spectrometry-based structure-specific N-glycoproteomics and biomedical applications.

N-linked glycosylation is a common posttranslational modification of proteins that results in macroheterogeneity of the modification site. However, unlike simpler modifications, N-glycosylation introduces an additional layer of complexity with tens of thousands of possible structures arising from various dimensions, including different monosaccharide compositions, sequence structures, linking structures, isomerism, and three-dimensional conformations. This results in additional microheterogeneity of the modification site of N-glycosylation, i.e., the same N-glycosylation site can be modified with different glycans with a certain stoichiometric ratio. N-glycosylation regulates the structure and function of N-glycoproteins in a site- and structure-specific manner, and differential expression of N-glycosylation under disease conditions needs to be characterized through site- and structure-specific quantitative analysis. Numerous advanced methods ranging from sample preparation to mass spectrum analysis have been developed to distinguish N-glycan structures. Chemical derivatization of monosaccharides, online liquid chromatography separation and ion mobility spectrometry enable the physical differentiation of samples. Tandem mass spectrometry further analyzes the macro/microheterogeneity of intact N-glycopeptides through the analysis of fragment ions. Moreover, the development of search engines and AI-based software has enhanced our understanding of the dissociation patterns of intact N-glycopeptides and the clinical significance of differentially expressed intact N-glycopeptides. With the help of these modern methods, structure-specific N-glycoproteomics has become an important tool with extensive applications in the biomedical field.

Attention-Deficit/Hyperactivity Disorder Symptoms as a Function of Arousal and Executive Vigilance: Testing Halperin and Schulz’s Neurodevelopmental Model in a Sample of Community Adults

Halperin and Schulz’s neurodevelopmental model postulates that the onset of attention-deficit/hyperactivity disorder (ADHD) in childhood is due to subcortical alterations, whereas the disorder’s trajectory into adulthood depends on the development of executive functions. Based on a dimensional framework of ADHD, Coll-Martín et al. (2021) found support for the model in an adult community sample assessed on arousal and executive vigilance. The present study is a preregistered (https://osf.io/tkdq7) close replication of Coll-Martín et al. expressly aimed to test the two predictions of the model. A sample of college students (N = 292 valid; 49% women; 18–30 years, M = 21.7) from a Spanish university completed self-reports of ADHD symptoms in childhood (retrospectively) and adulthood and performed the online version of an attentional task (the ANTI-Vea). Our preregistered hypotheses achieved an acceptable statistical power for the effects of interest, even after accounting for random measurement error. Despite this, none of them replicated the findings of the original study: Only the unexpected negative correlation between executive vigilance and symptoms in childhood was significant, thereby not supporting the theoretical predictions. The lack of support for the dissociation pattern hypothesized by the neurodevelopmental model was robust to multiverse and exploratory analyses. At least in terms of vigilance, ADHD symptoms seem to share altered neurocognitive pathways across the lifespan, regardless of their time of onset. This challenges the notion of late-onset ADHD as a condition neuropsychologically distinct from child-onset ADHD. Future studies need to include complementary assessment methods and clinical groups.

Energy-Resolved In-Source Collison-Induced Dissociation for Isomer Discrimination.

While mass spectrometry remains a gold-standard tool for analyte detection, characterization, and quantitation, isomer differentiation is often a challenge. Tandem mass spectrometry is a common approach to increase the selectivity of mass spectrometry and energy-resolved measurements can provide further improvements. However, not all mass spectrometers, especially those that are very compact and affordable, are amenable to such experiments. For instance, single-stage mass spectrometers with soft ionization provide no dissociation information and quadrupole ion trap instruments with resonant excitation do not necessarily provide as informative of energy-resolved curves, for instance when extensive sequential dissociation is responsible for much of the "fingerprint". In-source collision-induced dissociation (IS-CID) is one approach to overcoming these barriers to exploit the analytical selectivity of energy-resolved CID without the need for additional instrumentation; this approach could broaden the reach of these selectivity gains to additional user bases (e.g., educational settings, field portable devices). Here, we specifically investigate energy-resolved IS-CID with the goal of (1) comparing between energy-resolved appearance curves measured with true tandem mass spectrometry on a quadrupole time-of-flight instrument and those obtained using IS-CID, (2) evaluating the approach as a means of differentiating isomers/isobar sets, especially those with similar dissociation patterns, and (3) exploring additional analytical considerations relevant to method development and implementation. This proof-of-concept work establishes the analytical potential of this approach, opening doors for future method development for specific applications.

Comparative basolateral amygdala connectomics reveals dissociable single-neuron projection patterns to frontal cortex in macaques and mice

Basolateral amygdala (BLA) is a key hub for affect in the brain,1,2,3 and dysfunction within this area contributes to a host of psychiatric disorders.4,5 BLA is extensively and reciprocally interconnected with frontal cortex,6,7,8,9 and some aspects of its function are evolutionarily conserved across rodents, anthropoid primates, and humans.10 Neuron density in BLA is substantially lower in primates compared to murine rodents,11 and frontal cortex (FC) is dramatically expanded in primates, particularly the more anterior granular and dysgranular areas.12,13,14 Yet, how these anatomical differences influence the projection patterns of single BLA neurons to frontal cortex across rodents and primates is unknown. Using a barcoded connectomic approach, we assessed the single BLA neuron connections to frontal cortex in mice and macaques. We found that BLA neurons are more likely to project to multiple distinct parts of FC in mice than in macaques. Further, while single BLA neuron projections to nucleus accumbens were similarly organized in mice and macaques, BLA-FC connections differed substantially. Notably, BLA connections to subcallosal anterior cingulate cortex (scACC) in macaques were least likely to branch to other medial frontal cortex areas compared to perigenual ACC (pgACC). This pattern of connections was reversed in the mouse homologues of these areas, infralimbic and prelimbic cortex (IL and PL), mirroring functional differences between rodents and non-human primates. Taken together, these results indicate that BLA connections to FC are not linearly scaled from mice to macaques and instead the organization of single-neuron BLA connections is distinct between these species.

Investigating electron-induced dissociation dynamics in the organometallic precursor Fe(CO)5: a nonadiabatic molecular dynamics approach

This research employs excited states molecular dynamics simulations to explore the electron-induced dissociation behavior of Fe(CO)5 molecules, with the specific focus on electronic excitation. The study initiates with the detailed analysis of the molecule’s stable ground state structure. Subsequent simulations reveal distinctive dissociation patterns in various bonds, particularly noting the rapid dissociation of bonds between Fe and C1, Fe and C2, while those with Fe and C3 oscillate without complete dissociation. Emphasizing the influence of the transition from the highest occupied molecular orbital to the lowest unoccupied molecular orbital on reactivity, the investigation sheds light on the charge transfer phenomenon during dissociation through Bader analysis. Insights into transitions between excited and ground states are derived from the time evolution of the Kohn–Sham orbital. This study significantly contributes to understanding intricate dissociation mechanisms under electronic excitation, especially in molecules like Fe(CO)5 characterized by complex chemical bonds. Beyond theoretical exploration, the research holds practical significance for applications in nanomaterials, such as focused electron beam-induced deposition and the fabrication of nanoscale structures, enriching our comprehension of electronic-excitation-induced dissociation and advancing both theoretical understanding and practical applications in this field.

Financial and numerical abilities: patterns of dissociation in neurological and psychiatric diseases.

The present work investigates whether financial abilities can be associated with numerical abilities and with general cognitive abilities. We compared performance on numerical and financial tests, and on tests routinely used to measure general cognitive performance, in healthy controls and in a group of people with heterogeneous pathological conditions including mild cognitive impairment, amyotrophic lateral sclerosis, traumatic brain injury, and schizophrenia. Patients showed lower performances in both numerical and financial abilities compared to controls. Numerical and financial skills were positively correlated in both groups, but they correlated poorly with measures of general cognitive functioning. Crucially, only basic financial tasks -such as counting currencies- but not advanced ones -like financial judgments- were associated with numerical or general cognitive functioning in logistic regression analyses. Conversely, advanced financial abilities, but not basic ones, were associated with abstract reasoning. At a qualitative analysis, we found that deficits in numerical and financial abilities might double dissociate. Similarly, we observed double dissociations between difficulties in financial abilities and cognitive deficits. In conclusion, financial abilities may be independent of numerical skills, and financial deficits are not always related to the presence of cognitive difficulties. These findings are important for both clinical and legal practice.

Geomechanical responses of sand–clay interbedded gas hydrate-bearing deposits under depressurization-driven gas production at site UBGH2-6 in Ulleung Basin, offshore Korea

This study explores geomechanical responses of sand-clay interbedded hydrate reservoirs subjected to depressurization. A thermo-hydro-mechanically (T-H-M) coupled simulation code was created to simulate T-H-M interactions in layered hydrate reservoirs, utilizing an explicit two-way coupling scheme. The code was then used to model a hydrate reservoir analogous to a hydrate deposit system in Ulleung Basin, Offshore Korea (Site UBGH2-6). Hydrate reservoirs comprising thin and interbedded sand-clay layers exhibit unique geomechanical responses due to the localized gas hydrate dissociation along sand-clay layer interfaces. The localized dissociation pattern leads to accelerated sediment consolidations along the layer interfaces. The simulation results also reveal development of shear deformation along the sand-clay interfaces, which implies the layer interfaces may act as the main sources of sand productions and fines migration within a depressurized hydrate reservoir. Additional simulations are conducted to further investigate the effects of depressurization rate and formation wettability on gas productivity. Although faster depressurization speeds up initial gas production, ultimately, the production rate is governed by the final bottom hole pressure, regardless of the depressurization rate. Nonetheless, slower depressurization appears more favorable, given its capacity to mitigate initial geomechanical responses, such as reservoir compaction and sand production, thus preserving the long-term production potential of a hydrate reservoir. On the other hand, a cyclic depressurization scheme also proves to be able to mitigate the level of initial geomechanical responses, but only at the cost of reduced gas productivity. A comparative analysis with varying wettability indicates that water-wet reservoirs may be more favorable target for gas hydrate exploitation than gas-wet reservoirs. The presented results enhance understanding of complex hydrate reservoir dynamics and contribute to advancement of sustainable and efficient hydrate production techniques.

Investigation of the MDM2-binding potential of de novo designed peptides using enhanced sampling simulations

The tumor suppressor p53 plays a crucial role in cellular responses to various stresses, regulating key processes such as apoptosis, senescence, and DNA repair. Dysfunctional p53, prevalent in approximately 50 % of human cancers, contributes to tumor development and resistance to treatment. This study employed deep learning-based protein design and structure prediction methods to identify novel high-affinity peptide binders (Pep1 and Pep2) targeting MDM2, with the aim of disrupting its interaction with p53. Extensive all-atom molecular dynamics simulations highlighted the stability of the designed peptide in complex with the target, supported by several structural analyses, including RMSD, RMSF, Rg, SASA, PCA, and free energy landscapes. Using the steered molecular dynamics and umbrella sampling simulations, we elucidate the dissociation dynamics of p53, Pep1, and Pep2 from MDM2. Notable differences in interaction profiles were observed, emphasizing the distinct dissociation patterns of each peptide. In conclusion, the results of our umbrella sampling simulations suggest Pep1 as a higher-affinity MDM2 binder compared to p53 and Pep2, positioning it as a potential inhibitor of the MDM2-p53 interaction. Using state-of-the-art protein design tools and advanced MD simulations, this study provides a comprehensive framework for rational in silico design of peptide binders with therapeutic implications in disrupting MDM2-p53 interactions for anticancer interventions.

More than just changeability: Specific factors are used to explain the changeability of personality traits.

Implicit theories and psychological essentialism are valuable frameworks used to model how changeable many traits are perceived to be. These frameworks, however, characterise changeability as a broad and generalised construct and do not fully capture the nuance and specificity involved in personality changeability. We therefore sought to deconstruct implicit theories about changeability into underlying more specific aspects of changeability. We measured how changeable people theorise personality traits to be according to three underlying specific factors: volitional control, context and age. We investigated how specific implicit theories about changeability vary across different personality traits. We show that two personality traits (agreeableness and conscientiousness) are linked to dissociable patterns of specific factors used to explain how changeable they are. These findings yield new insight into the way people explain why personality traits are changeable and demonstrate that different types of reasons are used to explain the changeability of agreeableness and conscientiousness.

Abstract 2115: Assessing BCL2 protein complex level in peripheral blood mononuclear cells as a surrogate pharmacodynamic biomarker of BCL2 inhibitors in hematological cancers

Abstract In the last decade, cancer therapeutics have adhered to the practice of administering drugs at the maximum tolerated dose (MTD) selected from limited patient cohorts. The emergence of targeted therapies has disrupted this dose selection paradigm, as optimal efficacy may be achievable at lower dose than MTD. Recently, a regulatory agency initiated "OPTIMUS" to redefine the dose selection process, recommending quantitative assessments of drug efficacy in relation to the target protein throughout development and clinical trials. ABT-199 is a protein interaction inhibitor that specifically disrupts the interaction of BCL2 protein. Consequently, the assessment of changes in the level of BCL2 protein complex is necessary to evaluate the ABT-199 efficacy for optimal dose selection. In this study, we adapted the Single-molecule Protein Interaction Detection platform for evaluating pharmacodynamics of BCL2 inhibitors in clinical samples. We assessed the dissociation of two BCL2-related biomarkers, BCL2-BAX and BCL2-BIM, from a model system under various ABT-199 doses. Following one hour treatment with 300 nM of ABT-199, the BCL2-BAX complex dissociated almost by 40%, while 80% of the BCL2-BIM complex remained. The reduction of the BCL2-BIM complex was not changed when extending the treatment for 3 hours, indicating that the BCL2-BAX complex may serve as a more sensitive biomarker for assessing the target engagement of ABT-199. To determine the assay sensitivity, we evaluated the ABT-199 response across different cell numbers and found that 100,000 cells are sufficient for performing the BCL2-BAX assay. Subsequently, we validated the utility of our method in assessing clinical samples, specifically BMMCs and PBMCs. We collected 4 PBMCs and the corresponding BMMCs from hematological cancer patients and treated them with various doses of ABT-199 ex vivo. With 100,000 BMMCs and 1,000,000 PBMCs, we can generate dose-response curves for the BCL2-BAX complex at doses of ABT-199 ranging from 1 to 1,000 nM. To explore the feasibility of employing the BCL2-BAX complex in PBMCs as a surrogate biomarker for assessing ABT-199 engagement with BCL2 in BMMCs, we compared the averaged dose-response curves from 4 PBMCs with that of BMMCs. Remarkably, the two curves showed a coherent dissociation trend, indicating that the biochemical effect of ABT-199 on the BCL2-BAX complex may be conserved across different sample types. Collectively, we have developed a target engagement assay for BCL2 inhibitors by measuring the BCL2-BAX complex. Notably, we observed a consistent dissociation pattern of the BCL2-BAX complex by ABT-199 treatment in both PBMCs and BMMCs. This molecular information offers an alternative way to assess the pharmacodynamics of BCL2 inhibitors, particularly in the case where collecting a series of BMMCs with sufficient amounts may not be feasible. Citation Format: Hongwon Lee, Byungsan Choi, Saem Hong, Yunseo Lee, Tae-Young Yoon, Janghee Woo. Assessing BCL2 protein complex level in peripheral blood mononuclear cells as a surrogate pharmacodynamic biomarker of BCL2 inhibitors in hematological cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2115.

Can the neural representation of physical pain predict empathy for pain in others?

The question of whether physical pain and vicarious pain have some shared neural substrates is unresolved. Recent research has argued that physical and vicarious pain are represented by dissociable multivariate brain patterns by creating biomarkers for physical pain (Neurologic Pain Signature, NPS) and vicarious pain (Vicarious Pain Signature, VPS), respectively. In the current research, the NPS and two versions of the VPS were applied to three fMRI datasets (one new, two published) relating to vicarious pain which focused on between-subject differences in vicarious pain (Datasets 1 and 3) and within-subject manipulations of perspective taking (Dataset 2). Results show that (i) NPS can distinguish brain responses to images of pain vs no-pain and to a greater extent in vicarious pain responders who report experiencing pain when observing pain and (ii) neither version of the VPS mapped on to individual differences in vicarious pain and the two versions differed in their success in predicting vicarious pain overall. This study suggests that the NPS (created to detect physical pain) is, under some circumstances, sensitive to vicarious pain and there is significant variability in VPS measures (created to detect vicarious pain) to act as generalizable biomarkers of vicarious pain.

Survey of the multi-stage mass spectrometry of common ionic liquid cations and some polyfluorinated ions

Ionic liquids are useful for many applications and the structural diversity as a class is ever increasing. Knowledge of gas-phase dissociation pathways can inform analytical method development for the characterization of novel syntheses, degradation products, or environmental contaminants, and can inform our knowledge of the fate of ionic liquid species in the gas phase (e.g., after ejection by electrospray spacecraft thrusters). In this work, the N-heterocyclic (NHC) ions:1-butyl-1-methylpiperidinium (BMPi), 1-methyl-1-propylpiperidinium (MPPi), 1-butyl-1-methylpyrrolidinium (BMPyr), 1-ethyl-1-methylpyrrolidinium (EMPyr), 1-butylpyridinium (BPy), and 1-Butyl-1-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl) imidazolium (BFIm) were studied. An additional fluorinated anion, nonafluorobutanesulfonate (NFBS), was also studied. Collision-induced dissociation mass spectrometry (CID-MS), as MS2 and MS3 using an ion trap mass spectrometer and energy-resolved breakdown curves using a quadrupole time-of-flight mass spectrometer, were used to determine dissociation patterns. Assignment of proposed dissociation pathways were made based on the experimental results and complementary computational chemistry. It was observed that for aromatic NHCs, cleavage at the C–N bond was preferred, to generate alkene-based neutral losses. Non-aromatic NHCs typically generated both alkane- and alkene-based neutral losses. Breakdown curves, supported by theoretical thermodynamic calculations, suggest that the loss of the alkane is the favorable dissociation pathway. Additionally, some ring-opening and ring contraction reactions via C–C bond cleavage were observed in non-aromatic species, whereas the intact aromatic NHC is typically a stable terminal ion. The polyfluorinated imidazolium fragmented via the breaking of C–N, C–C, and C–F bonds. The fluorinated anion, NFBS, fragmented by C–C and C–S bond cleavage to generate fluoroalkene, sulfur dioxide, and sulfur trioxide neutral losses. Beyond these broad stroke findings, the dissociation pathways of the seven ionic liquid ions were mapped using evidence from MS3, breakdown curves, and computational chemistry together assigning product ions as either arising from competitive or sequential pathways and proposing tentative structures. Some of the ionic liquid ions showed class-based product ions which will be useful in analytical development for their characterization. Finally, these results were contextualized within previous literature reports on other ionic liquid species.

Pain suffering and the self. An active allostatic inference explanation.

Distributed processing that gives rise to pain experience is anchored by a multidimensional self-model. I show how the phenomenon of pain asymbolia and other atypical pain-related conditions (Insensitivity to Pain, Chronic Pain, 'Social' Pain, Insensitivity to Pain, Chronic Pain, 'Social' Pain, empathy for pain and suffering) can be explained by this idea. It also explains the patterns of association and dissociation among neural correlates without importing strong modular assumptions. It treats pain processing as a species of allostatic active inference in which the mind co-ordinates its processing resources to optimize basic bodily functioning at different time scales. The self is inferred to be source and target of regulation in this process. The self-modelling account reconciles conflicting deaffectualization and depersonalization accounts of pain asymbolia by showing how depersonalization and pain asymbolia arise at different levels of hierarchical self modelling.

Three-dimensional pore-scale study of methane hydrate dissociation mechanisms based on micro-CT images

&lt;p&gt;Methane hydrate is a promising source of alternative energy. An in-depth understanding of the hydrate dissociation mechanism is crucial for the efficient extraction. In the present work, a comprehensive set of pore-scale numerical studies of hydrate dissociation mechanisms is presented. Pore-scale lattice Boltzmann (LB) models are proposed to simulate the multiphysics process during methane hydrate dissociation. The numerical simulations employ the actual hydrate sediment pore structure obtained by the micro-CT imaging. Experimental results of xenon hydrate dissociation are compared with the numerical simulations, indicating that the observed hydrate pore habits evolution is accurately captured by the proposed LB models. Furthermore, simulations of methane hydrate dissociation under different sediment water saturations, fluid flow rates and thermal conditions are conducted. Heat and mass transfer limitations both have significant effects on the methane hydrate dissociation rate. The bubble movement can further influence the dissociation process. Dissociation patterns can be divided into three categories, uniform, non-uniform and wormholing. The fluid flow impacts hydrate dissociation rates differently in three-dimensional real structures compared to two-dimensional idealized ones, influenced by variations in hydrate pore habits and flow properties. Finally, upscaling investigations are conducted to provide the permeability and kinetic models for the representative elementary volume (REV)-scale production forecast. Due to the difference in the hydrate pore habits and dissociation mechanisms, the three-dimensional upscaling results contrast with prior findings from two-dimensional studies. The present work provides a paradigm for pore-scale numerical simulation studies on the hydrate dissociation, which can offer theoretical guidance on efficient hydrate extraction.&lt;/p&gt;

Ultrafast fragmentation of highly-excited doubly-ionized deoxyribose: role of the liquid water environment.

Ab initio molecular dynamics simulations are used to investigate the fragmentation dynamics following the double ionization of 2-deoxy-D-ribose (DR), a major component in the DNA chain. Different ionization scenarios are considered to provide a complete picture. First focusing on isolated DR2+, fragmentation patterns are determined for the ground electronic state, adding randomly distributed excitation energy to the nuclei. These patterns differ for the two isomers studied. To compare thermal and electronic excitation effects, Ehrenfest dynamics are also performed, allowing to remove the two electrons from selected molecular orbitals. Two intermediate-energy orbitals, localized on the carbon chain, were selected. The dissociation pattern corresponds to the most frequent pattern obtained when adding thermal excitation. On the contrary, targeting the four deepest orbitals, localized on the oxygen atoms, leads to selective ultrafast C-O and/or O-H bond dissociation. To probe the role of environment, a system consisting of a DR molecule embedded in liquid water is then studied. The two electrons are removed from either the DR or the water molecules directly linked to the sugar through hydrogen bonds. Although the dynamics onset is similar to that of isolated DR when removing the same deep orbitals localized on the sugar oxygen atoms, the subsequent fragmentation patterns differ. Sugar damage also occurs following the Coulomb explosion of neighboring H2O2+ molecules due to interaction with the emitted O or H atoms.