Distinct States Research Articles

Capillary force-driven formation of native starch granule oleogels for 3D printing

3D printing has extremely high requirements for the design of food matrices with suitable rheological properties. Starch exhibits considerable potential as a material for 3D printing. However, there is limited research available on the direct fabrication of oleogels using starch granules as building blocks. In this study, we developed a simple approach to fabricate plant-based oleogels as edible 3D printable materials by exploiting capillary forces between starch granules. When a small amount of water (less than 5 wt%) was added to starch granules dispersed in an oil phase, a pendular bridging network was formed between the starch granules. The rheological properties of the starch-oil suspension were significantly changed, transitioning it from a fluid-like to a gel-like state. The rheological properties of the oleogel could be altered by varying the starch granule volume fraction, the amount of water added, the structure of starch granules, and the oil-water interfacial tension. Confocal laser microscopy imaging demonstrated that starch granule oleogels exhibit three distinct structural states: pendular state, pendular bridge network, and capillary aggregation. Furthermore, the presence of water was identified as a liquid bridge between starch granules. Additionally, starch granule oleogels exhibited excellent thermal stability and freeze-thaw stability. Overall, this approach enhances the feasibility of preparing starch oleogels and provides valuable insights for the personalized 3D printing of oleogels.

Elucidating dynamic conductive state changes in amorphous lithium lanthanum titanate for resistive switching devices

Exploration of novel resistive switching materials attracts attention to achieve neuromorphic computing that can surpass the limit of the current Von-Neumann computing for the time of Internet of Things (IoT). Battery materials priorly used to serve as an electrode or electrolyte have demonstrated metal-insulator transitions upon an electrical biasing due to resulting compositional change, which is desirable property for future resistive switching devices. For example, it has been suggested that solid-state electrolyte amorphous lithium lanthanum titanate (a-LLTO) changes in electronic conductivity depending on oxygen content. In this work, switching behavior of a-LLTO was investigated at both bulk- and nano-scale by employing a range of voltage sweep techniques, ultimately establishing a stable and optimal operating condition within the voltage window of − 3.5 V to 3.5 V. This voltage range effectively balances the desirable trait of a substantial resistance change by three orders of magnitude with the imperative avoidance of LLTO decomposition. Experiment and computation with different LLTO composition shows that LLTO has two distinct conductivity states due to Ti reduction. The distribution of these two states is discussed using simplified binary model, implying the conductive filament growth during low resistance state. Consequently, our study deepens understanding of LLTO electronic properties and encourages the interdisciplinary application of battery materials for resistive switching devices.

Development of an advanced ai-based model for human psychoemotional state analysis

The research focuses on developing a novel method for the automatic recognition of human psychoemotional states (PES) using deep learning technology. This method is centered on analyzing speech signals to classify distinct emotional states. The primary challenge addressed by this research is to accurately perform multiclass classification of seven human psychoemotional states, namely joy, fear, anger, sadness, disgust, surprise, and a neutral state. Traditional methods have struggled to accurately distinguish these complex emotional nuances in speech. The study successfully developed a model capable of extracting informative features from audio recordings, specifically mel spectrograms and mel-frequency cepstral coefficients. These features were then used to train two deep convolutional neural networks, resulting in a classifier model. The uniqueness of this research lies in its use of a dual-feature approach and the employment of deep convolutional neural networks for classification. This approach has demonstrated high accuracy in emotion recognition, with an accuracy rate of 0.93 in the validation subset. The high accuracy and effectiveness of the model can be attributed to the comprehensive and synergistic use of mel spectrograms and mel-frequency cepstral coefficients, which provide a more nuanced analysis of emotional expressions in speech. The method presented in this research has broad applicability in various domains, including enhancing human-machine interface interactions, implementation in the aviation industry, healthcare, marketing, and other fields where understanding human emotions through speech is crucial

Optimizing Treatment Strategy for Oligometastases/Oligo-Recurrence of Colorectal Cancer.

Colorectal cancer (CRC) is the third most common cancer, and nearly half of CRC patients experience metastases. Oligometastatic CRC represents a distinct clinical state characterized by limited metastatic involvement, demonstrating a less aggressive nature and potentially improved survival with multidisciplinary treatment. However, the varied clinical scenarios giving rise to oligometastases necessitate a precise definition, considering primary tumor status and oncological factors, to optimize treatment strategies. This review delineates the concepts of oligometastatic CRC, encompassing oligo-recurrence, where the primary tumor is under control, resulting in a more favorable prognosis. A comprehensive examination of multidisciplinary treatment with local treatments and systemic therapy is provided. The overarching objective in managing oligometastatic CRC is the complete eradication of metastases, offering prospects of a cure. Essential to this management approach are local treatments, with surgical resection serving as the standard of care. Percutaneous ablation and stereotactic body radiotherapy present less invasive alternatives for lesions unsuitable for surgery, demonstrating efficacy in select cases. Perioperative systemic therapy, aiming to control micrometastatic disease and enhance local treatment effectiveness, has shown improvements in progression-free survival through clinical trials. However, the extension of overall survival remains variable. The review emphasizes the need for further prospective trials to establish a cohesive definition and an optimized treatment strategy for oligometastatic CRC.

Distinct Molecular Processes Mediate Donor-derived Cell-free DNA Release From Kidney Transplants in Different Disease States.

Among all biopsies in the Trifecta-Kidney Study ( ClinicalTrials.gov NCT04239703), elevated plasma donor-derived cell-free DNA (dd-cfDNA) correlated most strongly with molecular antibody-mediated rejection (AMR) but was also elevated in other states: T cell-mediated rejection (TCMR), acute kidney injury (AKI), and some apparently normal biopsies. The present study aimed to define the molecular correlates of plasma dd-cfDNA within specific states. Dd-cfDNA was measured by the Prospera test. Molecular rejection and injury states were defined using the Molecular Microscope system. We studied the correlation between dd-cfDNA and the expression of genes, transcript sets, and classifier scores within specific disease states, and compared AMR, TCMR, and AKI to biopsies classified as normal and no injury (NRNI). In all 604 biopsies, dd-cfDNA was elevated in AMR, TCMR, and AKI. Within AMR biopsies, dd-cfDNA correlated with AMR activity and stage. Within AKI, the correlations reflected acute parenchymal injury, including cell cycling. Within biopsies classified as MMDx Normal and archetypal No injury (NRNI), dd-cfDNA still correlated significantly with rejection- and injury-related genes. TCMR activity (eg, the TCMR Prob classifier) correlated with dd-cfDNA, but within TCMR biopsies, top gene correlations were complex and not the top TCMR-selective genes. In kidney transplants, elevated plasma dd-cfDNA is associated with 3 distinct molecular states in the donor tissue: AMR, recent parenchymal injury (including cell cycling), and TCMR, potentially complicated by parenchymal disruption. Moreover, subtle rejection- and injury-related changes in the donor tissue can contribute to dd-cfDNA elevations in transplants considered to have no rejection or injury.

Basal forebrain cholinergic activity is necessary for upward firing rate homeostasis in the rodent visual cortex.

Bidirectional homeostatic plasticity allows neurons and circuits to maintain stable firing in the face of developmental or learning-induced perturbations. In the primary visual cortex (V1), upward firing rate homeostasis (FRH) only occurs during active wake (AW) and downward during sleep, but how this behavioral state-dependent gating is accomplished is unknown. Here, we focus on how AW enables upward FRH in V1 of juvenile Long Evans rats. A major difference between quiet wake (QW), when upward FRH is absent, and AW, when it is present, is increased cholinergic (ACh) tone, and the main cholinergic projections to V1 arise from the horizontal diagonal band of the basal forebrain (HDB ACh). We therefore chemogenetically inhibited HDB ACh neurons while inducing upward homeostatic compensation using direct activity-suppression in V1. We found that synaptic scaling up and intrinsic homeostatic plasticity, two important cellular mediators of upward FRH, were both impaired when HDB ACh neurons were inhibited. Most strikingly, HDB ACh inhibition flipped the sign of intrinsic plasticity so that it became anti-homeostatic, and this effect was phenocopied by knockdown of the M1 ACh receptor in V1, indicating that this modulation of intrinsic plasticity is the result of direct actions of ACh within V1. Finally, we found that upward FRH induced by visual deprivation was completely prevented by HDB ACh inhibition. Together, our results show that HDB ACh modulation is a key enabler of upward homeostatic plasticity and FRH, and more broadly suggest that neuromodulatory inputs can segregate upward and downward homeostatic plasticity into distinct behavioral states.

Repertoire of dynamical states in dissimilarly coupled Van der Pol oscillators

We have considered dissimilarly coupled Van der Pol oscillators with an offset parameter which determines the degree of heterogeneity of the dissimilar coupling strength. Increasing degree of heterogeneity for decreasing values of the offset parameter results in a rich repertoire of bifurcation transitions and dynamical states including epochs of period doubling bifurcation. Two distinct multi-stable states are also observed along with several symmetry breaking dynamical states. We have deduced analytical stability conditions for Hopf and pitch-fork bifurcations through a linear stability analysis of symmetry preserving states, namely, trivial steady state and oscillation death state. The analytical conditions are found to match exactly with the simulation results in the two-parameter phase diagram. In addition to torus bifurcation, crisis and crisis induced intermittency routes to chaos are also observed for an appropriate heterogeneity of the dissimilar coupling strength. The period doubling bifurcation is characterized using the largest Lyapunov exponents of the dissimilarly coupled Van der Pol oscillators.

Cavity‐Assisted Atomic External Momenta State Teleportation

AbstractThe quantized momentum eigenstates of neutral atoms offer high resistance to decoherence and thus suggests a viable alternative for quantum informatics tasks including teleportation. In this work, a scheme is suggested to teleport an unknown superposition of two distinct external momentum states of a neutral atom onto the similar momentum states of a distant atom at the receiving end through the off‐resonant atomic Bragg diffraction (ABD). In order to teleport this unknown state from the sender, that is, Alice, to the receiver, that is, Bob, a pre‐existing entangled link formed through a high‐Q cavity at Alice's end and momentum states of a neutral atom at the Bob's end are utilized. Further, while citing the realistic experimental parameters, it is demonstrated that the proposal can easily be implemented experimentally under the prevailing cavity‐QED atom‐field research scenario. The proposal is also generalized to cover the teleportation of the multipartite entangled momenta states and the case of multipartite GHZ entangled states is elucidated in details. However, the procedure is generic and can be extended to cover the teleportation schematics for any arbitrary atomic momenta states.

Zonation Method for Efficient Training of Collaborative Multi-Agent Reinforcement Learning in Double Snake Game

This paper proposes a zonation method for training the two reinforcement learning agents. We demonstrate the method's effectiveness in the double snake game. The game consists of two snakes operating in a fully cooperative setting to maximize the score. The problem in this game can be related to real-world problems, namely, coordination in autonomous driving cars and the operation of collaborative mobile robots in warehouse applications. Here, we use a deep Q-network algorithm to train the two agents to play the double snake game collaboratively through a decentralized approach, where distinct state and reward functions are assigned to each agent. To improve training efficiency, we utilize the snake sensory data of the surrounding objects as the input state to reduce the neural network complexity. The obtained result show that the proposed approaches can be used to train collaborative multi-agent efficiently, especially in the limited computing resources and training time environment

LATE-LIFE PLASMA PROTEINS ASSOCIATE WITH PREVALENT AND INCIDENT FRAILTY: A PROTEOMIC ANALYSIS

Abstract Proteomic approaches have unique advantages in the identification of biological pathways that influence physical frailty, a multifactorial geriatric syndrome predictive of adverse health outcomes in older adults. To date, few proteomic studies included prefrailty as a separate state or follow the participants for incident frailty. We evaluated 4955 plasma proteins (log 2-transformed and standardized) measured using SomaScan in the Atherosclerosis Risk in Community (ARIC) study. We used multinomial logistic regression models for the cross-sectional associations of the proteins with prefrailty and frailty as two distinct states (N=3838), and logistic regression models for the longitudinal associations with incident frailty over the 6-year follow-up (N=1708). After adjusting for demographics, health indicators, and comorbidities, 136 and 186 proteins were cross-sectionally associated with prefrailty and frailty, respectively, after Bonferroni correction (p< 1.01x10-5); 24 and 84 of which were replicated in the Cardiovascular Health Study (CHS) using the same models (FDR p< 0.05). Notably, higher odds of prefrailty and frailty were observed with higher concentrations of growth differentiation factor 15 (GDF15; OR[discovery]=1.50 and 2.17, respectively), transgelin (TAGLN; OR[discovery]=1.43 and 2.43, respectively), and insulin-like growth factor-binding protein 2 (IGFBP2; OR[discovery]=1.43 and 2.08, respectively), and lower concentration of growth hormone receptor (GHR, OR[discovery]=0.70 and 0.47, respectively). Longitudinally, triggering receptor expressed on myeloid cells 1 (TREM1) predicted incident frailty (OR[discovery]=1.64). Pathway and upstream regulator analyses revealed that mechanisms related to lipid metabolism, axonal guidance, inflammation and cell senescence became dysregulated in the prefrail stage and persisted into frail stage, offering new insights into frailty etiology and targets for early intervention.

Dissecting clinical and biological heterogeneity in clinical states of bipolar disorder: a 10-year retrospective study from China.

To dissect clinical and biological heterogeneity in clinical states of bipolar disorder (BD), and investigate if neuropsychological symptomatology, comorbidity, vital signs, and blood laboratory indicators are predictors of distinct BD states. A retrospective BD cohort was established with data extracted from a Chinese hospital's electronic medical records (EMR) between 2009 and 2018. Subjects were inpatients with a main discharge diagnosis of BD and were assessed for clinical state at hospitalization. We categorized all subjects into manic state, depressive state, and mixed state. Four machine learning classifiers were utilized to classify the subjects. A Shapley additive explanations (SHAP) algorithm was applied to the classifiers to aid in quantifying and visualizing the contributions of each feature that drive patient-specific classifications. A sample of 3,085 records was included (38.54% as manic, 56.69% as depressive, and 4.77% as mixed state). Mixed state showed more severe suicidal ideation and psychomotor abnormalities, while depressive state showed more common anxiety, sleep, and somatic-related symptoms and more comorbid conditions. Higher levels of body temperature, pulse, and systolic and diastolic blood pressures were present during manic episodes. Xgboost achieved the best AUC of 88.54% in manic/depressive states classification; Logistic regression and Random forest achieved the best AUCs of 75.5 and 75% in manic/mixed states and depressive/mixed states classifications, respectively. Myocardial enzymes and the non-enzymatic antioxidant uric acid and bilirubin contributed significantly to distinguish BD clinical states. The observed novel biological associations with BD clinical states confirm that biological heterogeneity contributes to clinical heterogeneity of BD.

Signaling network analysis reveals fostamatinib as a potential drug to control platelet hyperactivation during SARS-CoV-2 infection.

Pro-thrombotic events are one of the prevalent causes of intensive care unit (ICU) admissions among COVID-19 patients, although the signaling events in the stimulated platelets are still unclear. We conducted a comparative analysis of platelet transcriptome data from healthy donors, ICU, and non-ICU COVID-19 patients to elucidate these mechanisms. To surpass previous analyses, we constructed models of involved networks and control cascades by integrating a global human signaling network with transcriptome data. We investigated the control of platelet hyperactivation and the specific proteins involved. Our study revealed that control of the platelet network in ICU patients is significantly higher than in non-ICU patients. Non-ICU patients require control over fewer proteins for managing platelet hyperactivity compared to ICU patients. Identification of indispensable proteins highlighted key subnetworks, that are targetable for system control in COVID-19-related platelet hyperactivity. We scrutinized FDA-approved drugs targeting indispensable proteins and identified fostamatinib as a potent candidate for preventing thrombosis in COVID-19 patients. Our findings shed light on how SARS-CoV-2 efficiently affects host platelets by targeting indispensable and critical proteins involved in the control of platelet activity. We evaluated several drugs for specific control of platelet hyperactivity in ICU patients suffering from platelet hyperactivation. The focus of our approach is repurposing existing drugs for optimal control over the signaling network responsible for platelet hyperactivity in COVID-19 patients. Our study offers specific pharmacological recommendations, with drug prioritization tailored to the distinct network states observed in each patient condition. Interactive networks and detailed results can be accessed at https://fostamatinib.bioinfo-wuerz.eu/.

STATE VARIATION IN CANNABIS REGULATIONS CONCERNING OLDER AMERICANS

Abstract As of 2022, 21 states have fully legalized cannabis, 23 legalize for medical use only, and 6 states prohibit cannabis use entirely. While previous research has associated discrete aspects of state cannabis regulation with individual outcomes, little is known about the administrative rules most relevant to older persons. We previously have observed how the progressive approach to legalization across the United States, which includes flexible regulation on legal access, medical program eligibility and qualifying conditions, potency limits, care giver autonomy and others has corresponded with increased accessibility and use of cannabis among Americans over 65 years old. In this study, we source data on seven distinct state regulations pertaining to older persons and measured each on a scale reflecting permissiveness relevant to access and use. We used individual item measures to construct aggregated scores of state policies and charted changes within and among these seven state policies from 2016 to 2022. This research advances scientific understanding by capturing finite distinctions among state regulatory approaches most likely to impact older persons and offering reliable time-varying measures to be included in multi-level model formulations.

Transient dynamics mask the resilience of coral reefs

Coral reefs are model systems for studies of ecological resilience, with communities generally exhibiting multiple stable states and more resilient regions trending towards a single, coral-dominated, regime. We expand the theory of ecological resilience beyond the concepts of distinct stable states to integrate emerging ideas from transient dynamics as long-term intermediate states with no pronounced trend towards equilibria. We show that low coral abundance, together with stochastic larval supply and disturbance, can trap otherwise resilient reefs in a persistent intermediate state whose long-term outcome is difficult to predict. Common metrics, such as the ecosystem slowing down before crossing tipping points and using historical coral cover trends, may become unreliable predictors of future behaviour. Helping reefs out of transient states requires agile management that allows for short-term, targeted interventions after which natural ecological feedbacks can take over.

On the numerical structure of local and nationwide government spending multipliers: what can we learn from the Greek crisis?

ABSTRACT It has been recognised that the fiscal multiplier is a function of structural features of the economy and policy reaction parameters. Moreover, the debate on the magnitude of the multiplier along the business cycle has also been the subject of disputed debates. On these grounds, we look at the Greek case by calibrating a NUTS-2 interregional general equilibrium model using data for distinct states of the Greek economy during the development of the recent crisis. Whether this matters for local and nationwide multipliers depends on qualitative differences in the numerical structure of the model. As governments have to decide how to conduct fiscal policy, our results on the Greek case provide insights to policymakers on the reach of their actions in a spatially integrated system.

Overview of Gene Expression Dynamics during Human Oogenesis/Folliculogenesis.

The oocyte transcriptome follows a tightly controlled dynamic that leads the oocyte to grow and mature. This succession of distinct transcriptional states determines embryonic development prior to embryonic genome activation. However, these oocyte maternal mRNA regulatory events have yet to be decoded in humans. We reanalyzed human single-oocyte RNA-seq datasets previously published in the literature to decrypt the transcriptomic reshuffles ensuring that the oocyte is fully competent. We applied trajectory analysis (pseudotime) and a meta-analysis and uncovered the fundamental transcriptomic requirements of the oocyte at any moment of oogenesis until reaching the metaphase II stage (MII). We identified a bunch of genes showing significant variation in expression from primordial-to-antral follicle oocyte development and characterized their temporal regulation and their biological relevance. We also revealed the selective regulation of specific transcripts during the germinal vesicle-to-MII transition. Transcripts associated with energy production and mitochondrial functions were extensively downregulated, while those associated with cytoplasmic translation, histone modification, meiotic processes, and RNA processes were conserved. From the genes identified in this study, some appeared as sensitive to environmental factors such as maternal age, polycystic ovary syndrome, cryoconservation, and in vitro maturation. In the future, the atlas of transcriptomic changes described in this study will enable more precise identification of the transcripts responsible for follicular growth and oocyte maturation failures.

Controllable multi-polarization laser beam generation and manipulation in a cylindrical cavity

The manipulation of spatial and polarization attributes in vector laser beams can be intricately controlled through a variety of methodologies including spatial light modulators, q-plates, optical cavities, and mode-selective coupling. Among these techniques, optical cavities exhibit notable merits as they enable the targeted amplification of desired polarization elements with significant efficiency and stability. This research article introduces a direct methodology to generate multiple polarized laser beams, leveraging a cylindrical laser cavity housing a birefringent c-cut Nd:YVO4 gain crystal. This technique facilitates the creation of Hermite-Gaussian modes exhibiting distinct polarization states. By exploiting specific geometrical arrangements involving optical Z-mode and W-mode, the degenerate laser cavity facilitates the concurrent production of numerous distinguishable elliptically and linearly polarized beams, obviating the necessity for supplementary optical components. Notably, this approach provides advanced control over the polarization of resulting beams through precise adjustments of pumping offset and cavity length. The polarization states are subjected to quantitative scrutiny through phase retardation analysis. This investigation introduces an innovative avenue for the generation of coherent multi-beams, thereby propelling progress across a wide spectrum of scientific and technological domains.

Multifaceted SOX2-chromatin interaction underpins pluripotency progression in early embryos.

Pioneer transcription factors (TFs), such as OCT4 and SOX2, play crucial roles in pluripotency regulation. However, the master TF-governed pluripotency regulatory circuitry was largely inferred from cultured cells. In this work, we investigated SOX2 binding from embryonic day 3.5 (E3.5) to E7.5 in the mouse. In E3.5 inner cell mass (ICM), SOX2 regulates the ICM-trophectoderm program but is dispensable for opening global enhancers. Instead, SOX2 occupies preaccessible enhancers in part opened by early-stage expressing TFs TFAP2C and NR5A2. SOX2 then widely redistributes when cells adopt naive and formative pluripotency by opening enhancers or poising them for rapid future activation. Hence, multifaceted pioneer TF-enhancer interaction underpins pluripotency progression in embryos, including a distinctive state in E3.5 ICM that bridges totipotency and pluripotency.

Distinct states of nucleolar stress induced by anticancer drugs

Ribosome biogenesis is a vital and highly energy-consuming cellular function occurring primarily in the nucleolus. Cancer cells have an elevated demand for ribosomes to sustain continuous proliferation. This study evaluated the impact of existing anticancer drugs on the nucleolus by screening a library of anticancer compounds for drugs that induce nucleolar stress. For a readout, a novel parameter termed ‘nucleolar normality score’ was developed that measures the ratio of the fibrillar center and granular component proteins in the nucleolus and nucleoplasm. Multiple classes of drugs were found to induce nucleolar stress, including DNA intercalators, inhibitors of mTOR/PI3K, heat shock proteins, proteasome, and cyclin-dependent kinases (CDKs). Each class of drugs induced morphologically and molecularly distinct states of nucleolar stress accompanied by changes in nucleolar biophysical properties. In-depth characterization focused on the nucleolar stress induced by inhibition of transcriptional CDKs, particularly CDK9, the main CDK that regulates RNA Pol II. Multiple CDK substrates were identified in the nucleolus, including RNA Pol I– recruiting protein Treacle, which was phosphorylated by CDK9 in vitro. These results revealed a concerted regulation of RNA Pol I and Pol II by transcriptional CDKs. Our findings exposed many classes of chemotherapy compounds that are capable of inducing nucleolar stress, and we recommend considering this in anticancer drug development.

Distinct states of nucleolar stress induced by anticancer drugs

Ribosome biogenesis is a vital and highly energy-consuming cellular function occurring primarily in the nucleolus. Cancer cells have an elevated demand for ribosomes to sustain continuous proliferation. This study evaluated the impact of existing anticancer drugs on the nucleolus by screening a library of anticancer compounds for drugs that induce nucleolar stress. For a readout, a novel parameter termed ‘nucleolar normality score’ was developed that measures the ratio of the fibrillar center and granular component proteins in the nucleolus and nucleoplasm. Multiple classes of drugs were found to induce nucleolar stress, including DNA intercalators, inhibitors of mTOR/PI3K, heat shock proteins, proteasome, and cyclin-dependent kinases (CDKs). Each class of drugs induced morphologically and molecularly distinct states of nucleolar stress accompanied by changes in nucleolar biophysical properties. In-depth characterization focused on the nucleolar stress induced by inhibition of transcriptional CDKs, particularly CDK9, the main CDK that regulates RNA Pol II. Multiple CDK substrates were identified in the nucleolus, including RNA Pol I– recruiting protein Treacle, which was phosphorylated by CDK9 in vitro. These results revealed a concerted regulation of RNA Pol I and Pol II by transcriptional CDKs. Our findings exposed many classes of chemotherapy compounds that are capable of inducing nucleolar stress, and we recommend considering this in anticancer drug development.