Miracle-dz/UniFAR-FTUs huggingface dataset:
Dual agonistic and antagonistic roles of ZC3H18 provide for co-activation of distinct nuclear RNA decay pathways

The RNA exosome is a versatile ribonuclease. In the nucleoplasm of mammalian cells, it is assisted by its adaptors the Nuclear EXosome Targeting (NEXT) complex and the PolyA eXosome Targeting (PAXT) connection. Via its association with the ARS2 and ZC3H18 proteins, NEXT/exosome is recruited to capped and short unadenylated transcripts. Conversely, PAXT/exosome was considered to target longer and adenylated substrates via their poly(A) tails. Here, mutational analysis of the core PAXT component ZFC3H1 uncovers a separate branch of the PAXT pathway, which targets short adenylated RNAs and relies on a direct ARS2-ZFC3H1 interaction. We further demonstrate that similar acidic-rich short linear motifs of ZFC3H1 and ZC3H18 compete for a common ARS2 epitope. Consequently, while promoting NEXT function, ZC3H18 antagonizes PAXT activity. We suggest that this unprecedented organization of RNA decay complexes provides co-activation of NEXT and PAXT at loci with abundant production of short exosome substrates.
A Generalized Approach To Darboux Transformations For Differential Equations

A GENERALIZED APPROACH TO DARBOUX TRANSFORMATIONS FOR DIFFERENTIAL EQUATIONS Mehmet Unlu, Ph.D. The University of Texas at Arlington, 2014 Supervising Professor: Tuncay Aktosun A Darboux transformation is a mathematical procedure to produce a solution to a differential equation when the solution to a related differential equation is known. The basic idea behind a Darboux transformation is to change the discrete spectrum of a linear differential operator in a controlled way without changing its continuous spectrum. For example, by using a Darboux transformation one can describe the change in a quantum mechanical system when some of its quantum levels are removed or some extra quantum levels are added. Darboux transformation formulas for various differential equations have been developed, but such formulas seem to be specific to those particular equations without much connection among them. In our method, we develop a generalized and unified approach for Darboux transformations that is applicable to a large class of differential equations. This approach uses the solution to a linear integral equation where the kernel and nonhomogeneous terms coincide. We apply our unified approach to some specific differential equations such as the Schrödinger equation and the Zakharov-Shabat system, and we relate our results to the existing results in the literature. We also apply our results to obtain exact iv solutions to various integrable nonlinear partial differential equations such as the Korteweg-de Vries equation and the nonlinear Schrödinger equation.
Torus knots obtained by twisting torus knots

A twisted torus knot is obtained from a torus knot by adding a number of full twists to some adjacent strands of the torus knot. In this paper, we show that if a twisted torus knot is a torus knot, then the number of added full twists is generically at most two in absolute value. We also show that this bound is the best possible by classifying twisted torus knots for which the upper bound is attained. 57N10
Is Sustainability Report Disclosure Implemented Properly? (A Case Study of Companies Listed in Sri-Kehati Index)

This study aims to identify sustainability reports conducted by companies listed in the Sri-Kehati index. This is a qualitative research and the GRI standards are a reference in disclosure. The result of the research shows that there is no guarantee that companies listed in the Sri-Kehati index will make a complete disclosure, especially compliance with GRI standards. Too many aspects or reporting standards should be implemented following global standards such as GRI. Based on SRDI calculation, shows that AKR Corporindo, Perusahaan Gas Negara (PGN), Bank BTN, Cikarang Listrindo, Indofood Sukses Makmur, and Semen Indonesia are classified as companies that make disclosures with the highest GRI index. Meanwhile, companies with low disclosures include Bumi Serpong Damai, Telkom, Jasa Marga, Sido Muncul, PP (Persero), Kalbe Farma, and Adi Sarana Armada.
ERP evidence for emotion-specific congruency effects between sentences and new words with disgust and sadness connotations

Introduction: The present study investigated how new words with acquired connotations of disgust and sadness, both negatively valenced but distinctive emotions, modulate the brain dynamics in the context of emotional sentences. Methods: Participants completed a learning session in which pseudowords were repeatedly paired with faces expressing disgust and sadness. An event-related potential (ERP) session followed the next day, in which participants received the learned pseudowords (herein, new words) combined with sentences and were asked to make emotional congruency judgment. Results: Sad new words elicited larger negative waveform than disgusting new words in the 146–228 ms time window, and emotionally congruent trials showed larger positive waveform than emotionally incongruent trials in the 304–462 ms time window. Moreover, the source localization in the latter suggested that congruent trials elicited larger current densities than incongruent trials in a number of emotion-related brain structures (e.g., the orbitofrontal cortex and cingulate gyrus) and language-related brain structures (e.g., the temporal lobe and the lingual gyrus). Discussion: These results suggested that faces are an effective source for the acquisition of words’ emotional connotations, and such acquired connotations can generate semantic and emotional congruency effects in sentential contexts.
Systemic Exophiala equina infection in an Eastern box turtle (Terrapene carolina carolina): a case report and literature review

Phaeohyphomycosis is an infection caused by melanized fungi. This disease has been reported in several animal species including invertebrates, cold-blooded vertebrates, mammals, and humans. Melanized fungi have similar phenotypical features and confirmation requires culture and molecular diagnostics. To exemplify this we present a case of a 333 g adult of unknown age, free-ranging, male Eastern box turtle (Terrapene carolina carolina) that was referred to the Turtle Rescue Team at North Carolina State University for evaluation of multilobulated masses occupying the entire left orbit and at the right forelimb on the plantarolateral aspect of the foot. A fine needle aspirate cytologic examination of the mass on the right forelimb revealed large numbers of inflammatory cells and fungal organisms. Histopathology of the skin biopsies from the right forefoot was consistent with phaeohyphomycosis. A course of antifungal medication was started (Fluconazole 21 mg/kg loading dose IV then 5 mg/kg PO SID q 30 days). Due to concern for the patient's quality of life and the lack of a curative treatment plan, humane euthanasia was elected. Gross and histological postmortem examination confirmed the presence of multiple coelomic masses similar in appearance to those observed in the left orbit and right forefoot indicating disseminated phaeohyphomycosis. A swab of the periocular mass was submitted for fungal culture and phenotypic identification. The isolate was later identified as Exophiala equina through a combination of phenotypic characterization and sequencing of the ITS region of the nuclear rDNA. Exophiala is a genus in the family Herpotrichiellaceae, order Chaetothyriales and is considered an opportunistic “black yeast” causing infection in aquatic invertebrates, fish, amphibians, reptiles, and mammals including humans. Exophiala equina is infrequently reported in animals, with only three cases in the literature including the herein report.
Chronic stress, neuroinflammation, and depression: an overview of pathophysiological mechanisms and emerging anti-inflammatories

In a subset of patients, chronic exposure to stress is an etiological risk factor for neuroinflammation and depression. Neuroinflammation affects up to 27% of patients with MDD and is associated with a more severe, chronic, and treatment-resistant trajectory. Inflammation is not unique to depression and has transdiagnostic effects suggesting a shared etiological risk factor underlying psychopathologies and metabolic disorders. Research supports an association but not necessarily a causation with depression. Putative mechanisms link chronic stress to dysregulation of the HPA axis and immune cell glucocorticoid resistance resulting in hyperactivation of the peripheral immune system. The chronic extracellular release of DAMPs and immune cell DAMP-PRR signaling creates a feed forward loop that accelerates peripheral and central inflammation. Higher plasma levels of inflammatory cytokines, most consistently interleukin IL-1β, IL-6, and TNF-α, are correlated with greater depressive symptomatology. Cytokines sensitize the HPA axis, disrupt the negative feedback loop, and further propagate inflammatory reactions. Peripheral inflammation exacerbates central inflammation (neuroinflammation) through several mechanisms including disruption of the blood–brain barrier, immune cellular trafficking, and activation of glial cells. Activated glial cells release cytokines, chemokines, and reactive oxygen and nitrogen species into the extra-synaptic space dysregulating neurotransmitter systems, imbalancing the excitatory to inhibitory ratio, and disrupting neural circuitry plasticity and adaptation. In particular, microglial activation and toxicity plays a central role in the pathophysiology of neuroinflammation. Magnetic resonance imaging (MRI) studies most consistently show reduced hippocampal volumes. Neural circuitry dysfunction such as hypoactivation between the ventral striatum and the ventromedial prefrontal cortex underlies the melancholic phenotype of depression. Chronic administration of monoamine-based antidepressants counters the inflammatory response, but with a delayed therapeutic onset. Therapeutics targeting cell mediated immunity, generalized and specific inflammatory signaling pathways, and nitro-oxidative stress have enormous potential to advance the treatment landscape. Future clinical trials will need to include immune system perturbations as biomarker outcome measures to facilitate novel antidepressant development. In this overview, we explore the inflammatory correlates of depression and elucidate pathomechanisms to facilitate the development of novel biomarkers and therapeutics.
An automated method to discover true events and classification of intracellular Ca2+ profiles for endothelium in situ injury assay

Introduction: Endothelial cells (ECs), being located at the interface between flowing blood and vessel wall, maintain cardiovascular homeostasis by virtue of their ability to integrate chemical and physical cues through a spatio-temporally coordinated increase in their intracellular Ca2+ concentration ([Ca2+]i). Endothelial heterogeneity suggests the existence of spatially distributed functional clusters of ECs that display different patterns of intracellular Ca2+ response to extracellular inputs. Characterizing the overall Ca2+ activity of the endothelial monolayer in situ requires the meticulous analysis of hundreds of ECs. This complex analysis consists in detecting and quantifying the true Ca2+ events associated to extracellular stimulation and classifying their intracellular Ca2+ profiles (ICPs). The injury assay technique allows exploring the Ca2+-dependent molecular mechanisms involved in angiogenesis and endothelial regeneration. However, there are true Ca2+ events of nearly undetectable magnitude that are almost comparable with inherent instrumental noise. Moreover, undesirable artifacts added to the signal by mechanical injury stimulation complicate the analysis of intracellular Ca2+ activity. In general, the study of ICPs lacks uniform criteria and reliable approaches for assessing these highly heterogeneous spatial and temporal events. Methods: Herein, we present an approach to classify ICPs that consists in three stages: 1) identification of Ca2+ candidate events through thresholding of a feature termed left-prominence; 2) identification of non-true events, known as artifacts; and 3) ICP classification based upon event temporal location. Results: The performance assessment of true-events identification showed competitive sensitivity = [0.9995, 0.9831], specificity = [0.9946, 0.7818] and accuracy = [0.9978, 0.9579] improvements of 2x and 14x, respectively, compared with other methods. The ICP classifier enhanced by artifact detection showed 0.9252 average accuracy with the ground-truth sets provided for validation. Discussion: Results indicate that our approach ensures sturdiness to experimental protocol maneuvers, besides it is effective, simple, and configurable for different studies that use unidimensional time dependent signals as data. Furthermore, our approach would also be effective to analyze the ICPs generated by other cell types, other dyes, chemical stimulation or even signals recorded at higher frequency.
Chronic motor performance following different traumatic brain injury severity—A systematic review

Introduction Traumatic brain injury (TBI) is now known to be a chronic disease, causing ongoing neurodegeneration and linked to increased risk of neurodegenerative motor diseases, such as Parkinson's disease and amyotrophic lateral sclerosis. While the presentation of motor deficits acutely following traumatic brain injury is well-documented, however, less is known about how these evolve in the long-term post-injury, or how the initial severity of injury affects these outcomes. The purpose of this review, therefore, was to examine objective assessment of chronic motor impairment across the spectrum of TBI in both preclinical and clinical models. Methods PubMed, Embase, Scopus, and PsycINFO databases were searched with a search strategy containing key search terms for TBI and motor function. Original research articles reporting chronic motor outcomes with a clearly defined TBI severity (mild, repeated mild, moderate, moderate–severe, and severe) in an adult population were included. Results A total of 97 studies met the inclusion criteria, incorporating 62 preclinical and 35 clinical studies. Motor domains examined included neuroscore, gait, fine-motor, balance, and locomotion for preclinical studies and neuroscore, fine-motor, posture, and gait for clinical studies. There was little consensus among the articles presented, with extensive differences both in assessment methodology of the tests and parameters reported. In general, an effect of severity was seen, with more severe injury leading to persistent motor deficits, although subtle fine motor deficits were also seen clinically following repeated injury. Only six clinical studies investigated motor outcomes beyond 10 years post-injury and two preclinical studies to 18–24 months post-injury, and, as such, the interaction between a previous TBI and aging on motor performance is yet to be comprehensively examined. Conclusion Further research is required to establish standardized motor assessment procedures to fully characterize chronic motor impairment across the spectrum of TBI with comprehensive outcomes and consistent protocols. Longitudinal studies investigating the same cohort over time are also a key for understanding the interaction between TBI and aging. This is particularly critical, given the risk of neurodegenerative motor disease development following TBI.
Innovative retargeted oncolytic herpesvirus against nectin4-positive cancers

Nectin4 is a recently discovered tumor associated antigen expressed in cancers that constitute relevant unmet clinical needs, including the undruggable triple negative breast cancer, pancreatic ductal carcinoma, bladder/urothelial cancer, cervical cancer, lung carcinoma and melanoma. So far, only one nectin4-specific drug—Enfortumab Vedotin—has been approved and the clinical trials that test novel therapeutics are only five. Here we engineered R-421, an innovative retargeted onco-immunotherapeutic herpesvirus highly specific for nectin4 and unable to infect through the natural herpes receptors, nectin1 or herpesvirus entry mediator. In vitro, R-421 infected and killed human nectin4-positive malignant cells and spared normal cells, e.g., human fibroblasts. Importantly from a safety viewpoint, R-421 failed to infect malignant cells that do not harbor nectin4 gene amplification/overexpression, whose expression level was moderate-to-low. In essence, there was a net threshold value below which cells were spared from infection, irrespective of whether they were malignant or normal; the only cells that R-421 targeted were the malignant overexpressing ones. In vivo, R-421 decreased or abolished the growth of murine tumors made transgenic for human nectin4 and conferred sensitivity to immune checkpoint inhibitors in combination therapies. Its efficacy was augmented by the cyclophosphamide immunomodulator and decreased by depletion of CD8-positive lymphocytes, arguing that it was in part T cell-mediated. R-421 elicited in-situ vaccination that protected from distant challenge tumors. This study provides proof-of-principle specificity and efficacy data justifying nectin4-retargeted onco-immunotherapeutic herpesvirus as an innovative approach against a number of difficult-to-drug clinical indications.
The mediating effect of somatic symptom disorder between psychological factors and quality of life among Chinese breast cancer patients

Objective We conducted this cross-sectional study to explore the mediating and predicting role of somatic symptom disorder (SSD) between psychological measures and quality of life (QOL) among Chinese breast cancer patients. Methods Breast cancer patients were recruited from three clinics in Beijing. Screening tools included the Patient Health Questionnaire-15 (PHQ-15), the Patient Health Questionnaire-9 (PHQ-9), the General Anxiety Disorder-7 scale (GAD-7), the Health Anxiety Scale (Whiteley Index-8, WI-8), the Somatic Symptom Disorder B-Criteria Scale (SSD-12), the Fear of Cancer Recurrence scale (FCR-4), the Brief Illness Perception Questionnaire (BIPQ-8), and the Functional Assessment of Cancer Therapy-Breast (FACT-B). Chi-square tests, nonparametric tests, mediating effect analysis, and linear regression analysis were used for the data analysis. Results Among the 264 participants, 25.0% were screened positive for SSD. The patients with screened positive SSD had a lower performance status, and a greater number of patients with screened positive SSD received traditional Chinese medicine (TCM) (p < 0.05). Strong mediating effects of SSD were found between psychological measures and QOL among patients with breast cancer after adjusting for sociodemographic variables as covariates (p < 0.001). The range of the percentage mediating effects was 25.67% (independent variable = PHQ-9) to 34.68% (independent variable = WI-8). Screened positive SSD predicted low QOL in physical (B = −0.476, p < 0.001), social (B = −0.163, p < 0.001), emotional (B = −0.304, p < 0.001), and functional (B = −0.283, p < 0.001) well-being, as well as substantial concerns caused by breast cancer (B = −0.354, p < 0.001). Conclusion Screened positive SSD had strong mediating effects between psychological factors and quality of life among breast cancer patients. Additionally, screened positive SSD was a significant predictor of lower QOL among breast cancer patients. Effective psychosocial interventions for improving QOL should consider the prevention and treatment of SSD or integrated SSD caring dimensions for breast cancer patients.
Hamiltonian and Action Principle formulations of plasma fluid models

vii Chapter 1. The need for Hamiltonian and Lagrangian methods 1 1.1 A brief historical overview . 1 1.2 The motivation . 4 1.3 Summary of the thesis . 7 Chapter 2. Hamiltonian and Action Principles: The basics 11 2.1 Hamilton’s Principle of Least Action . 11 2.2 The Lagrangian and Eulerian viewpoints of fluids and magnetofluids . 12 2.2.1 The Lagrangian variable q(a, t) and its properties . 13 2.2.2 Attributes, observables, and the Lagrange to Euler map 15 2.2.3 A note on Lie-dragged dynamical equations . 21 2.3 A general procedure for building an action principle for continuum models . 23 2.4 Ideal MHD: the Newcomb action . 25 2.5 Ideal MHD: Reduction to noncanonical Hamiltonian dynamics 27 2.5. 1 Noncanonical Hamiltonian formulation of ideal MHD . 28 2.6 Noncanonical Hamiltonian dynamics . 33 Chapter 3. A two-dimensional MHD model with gyroviscosity 39 3.1 Finite Larmor Radius effects: A discussion . 39 3.2 Building an action principle for the 2D gyroviscous fluid model 41 3.2.1 The observables of the 2D gyroviscous model . 42 3.2.2 Constructing the gyroviscous action . 45 3.2.3 The Eulerian equations and the gyromap . 49
Zonation of the active methane-cycling community in deep subsurface sediments of the Peru trench

The production and anaerobic oxidation of methane (AOM) by microorganisms is widespread in organic-rich deep subseafloor sediments. Yet, the organisms that carry out these processes remain largely unknown. Here we identify members of the methane-cycling microbial community in deep subsurface, hydrate-containing sediments of the Peru Trench by targeting functional genes of the alpha subunit of methyl coenzyme M reductase (mcrA). The mcrA profile reveals a distinct community zonation that partially matches the zonation of methane oxidizing and –producing activity inferred from sulfate and methane concentrations and carbon-isotopic compositions of methane and dissolved inorganic carbon (DIC). McrA appears absent from sulfate-rich sediments that are devoid of methane, but mcrA sequences belonging to putatively methane-oxidizing ANME-1a-b occur from the zone of methane oxidation to several meters into the methanogenesis zone. A sister group of ANME-1a-b, referred to as ANME-1d, and members of putatively aceticlastic Methanothrix (formerly Methanosaeta) occur throughout the remaining methanogenesis zone. Analyses of 16S rRNA and mcrA-mRNA indicate that the methane-cycling community is alive throughout (rRNA to 230 mbsf) and active in at least parts of the sediment column (mRNA at 44 mbsf). Carbon-isotopic depletions of methane relative to DIC (−80 to −86‰) suggest mostly methane production by CO2 reduction and thus seem at odds with the widespread detection of ANME-1 and Methanothrix. We explain this apparent contradiction based on recent insights into the metabolisms of both ANME-1 and Methanothricaceae, which indicate the potential for methanogenetic growth by CO2 reduction in both groups.