Miracle-dz/UniFAR-FTUs huggingface dataset:
The Src Family Kinase Yes Triggers Hyperosmotic Activation of the Epidermal Growth Factor Receptor and CD95*

Hyperosmotic exposure of rat hepatocytes triggers epidermal growth factor receptor (EGFR) activation, which results in an activation of the CD95 system and sensitizes the cells toward apoptosis (Reinehr, R., Schliess, F., and Haüssinger, D. (2003) FASEB J. 17, 731–733). The mechanisms underlying the hyperosmotic EGFR activation were studied. Hyperosmotic exposure (405 mosm) resulted in a rapid activation of the Src kinase family members Yes, Fyn, and Lck. Hyperosmotic Yes, but not Fyn activation, was antioxidant-sensitive and was followed by a rapid Yes/EGFR association. PP-2 abolished the hyperosmotic activation of Fyn and Lck but not activation of Yes and EGFR and their association. However, these latter processes were prevented in the presence of SU6656. SU6656 and antioxidants, but not PP-2 and AG1478, also inhibited the hyperosmotic JNK activation. Cyclic AMP had no effect on hyperosmotic Yes and JNK activation but prevented EGFR/Yes association and EGFR activation in an H89-sensitive way. When the hyperosmolarity-induced Yes-EGFR protein complex started to disappear after 30 min, an association between EGFR and CD95 became apparent, which was followed by CD95 tyrosine phosphorylation and activation. SU6656 but not PP-2 also inhibited EGFR/CD95 association, CD95 tyrosine phosphorylation, CD95 membrane trafficking, and death-inducing signaling complex (DISC) formation. EGFR knockdown had no effect on hyperosmotic Yes activation but prevented CD95 tyrosine phosphorylation, membrane targeting, and DISC formation. Hyperosmotic EGFR and CD95 activation was also largely blunted following Yes knockdown. The data suggest that hyperosmotic signaling triggers an oxidative stress-dependent Yes activation, which is followed by JNK and EGFR activation and subsequent activation of the CD95 system. However, the functional relevance of hyperosmolarity-induced Fyn and Lck activation remains to be elucidated.
Regulation of leukocyte integrin function: Affinity vs. avidity

Leukocytes circulate freely in the bloodstream until receiving signals which activate adhesive mechanisms essential for immune responsiveness. Key mediators of these adhesion events are heterodimeric cell surface receptors called integrins. It is now apparent that several components may contribute to successful integrin‐mediated adhesion: alterations in individual receptors lead to enhanced affinity for ligand; integrin clustering causes an increase in avidity; by spreading, the adhering cell is less susceptible to shear force. Model systems have allowed us to examine the contribution of each of these factors in generating adhesion. In more physiologically relevant situations, it can now be questioned whether integrin‐mediated adhesion is regulated via alterations in receptor affinity or avidity, or whether both these mechanisms are involved. © 1996 Wiley‐Liss, Inc.
Discovering protocols and organizational structures in workflows

Workflow mining consists in analyzing the execution traces of a collaborative system in order to create a workflow. Most of the works in this area focus on the process discovery from log files, while very few of them address the organization aspect. On the other hand, the Agent technology, suitable for the design and development of cooperative systems, offers interaction languages and high-level protocols allowing the representation of fine-grained organizational structures (hierarchy, federation, coalition, market, among others). In this paper, we show how to enrich log files in order to integrate conversations among the actors of processes using a performative-based agent communication language (FIPA-ACL). This enrichment allows us to define algorithms to discover protocols and organizational structures. The organizational structures are represented by graphs where the nodes are the actors and the arcs relations among them (delegation, cooperation, information exchange, and so on). The interaction protocols (auction, contract net) are described by Petri nets. We provide some discovery algorithms as well as a brief description of a Java implementation coupled with a visualization tool called AGNA.
Overlearning Reveals Sensitive Attributes

"Overlearning" means that a model trained for a seemingly simple objective implicitly learns to recognize attributes and concepts that are (1) not part of the learning objective, and (2) sensitive from a privacy or bias perspective. For example, a binary gender classifier of facial images also learns to recognize races\textemdash even races that are not represented in the training data\textemdash and identities. We demonstrate overlearning in several vision and NLP models and analyze its harmful consequences. First, inference-time representations of an overlearned model reveal sensitive attributes of the input, breaking privacy protections such as model partitioning. Second, an overlearned model can be "re-purposed" for a different, privacy-violating task even in the absence of the original training data. We show that overlearning is intrinsic for some tasks and cannot be prevented by censoring unwanted attributes. Finally, we investigate where, when, and why overlearning happens during model training.
Neighborhood problems and health among older adults: received and donated social support and the sense of mastery as effect modifiers.

OBJECTIVES This study examines the associations between perceived neighborhood problems and mental and physical health, exploring the extent to which received social support, donated social support, and the sense of mastery moderate those associations. METHODS In 2001-2002, face-to-face interviews were conducted with a sample of 1,167 adults over age 65 in several counties in Maryland and the District of Columbia. RESULTS For men, received support and perceived mastery buffer against the detrimental effects of neighborhood problems on anger. In contrast, donated support exacerbates the negative physical health effects of neighborhood problems. For women, donated support amplifies the effects of neighborhood problems on anger. However, with anger and depression, the buffering effects of received support become evident only after accounting for the interaction between neighborhood problems and donated support. DISCUSSION The findings have implications for the stress process model, the theoretical perspectives on different forms of social support, and the "buffering" and "cost of caring" predictions for women and men.
Greedy InfoMax for Biologically Plausible Self-Supervised Representation Learning

We propose a novel deep learning method for local self-supervised representation learning that does not require labels nor end-to-end backpropagation but exploits the natural order in data instead. Inspired by the observation that biological neural networks appear to learn without backpropagating a global error signal, we split a deep neural network into a stack of gradient-isolated modules. Each module is trained to maximize the mutual information between its consecutive outputs using the InfoNCE bound from Oord et al. [2018]. Despite this greedy training, we demonstrate that each module improves upon the output of its predecessor, and that the representations created by the top module yield highly competitive results on downstream classification tasks in the audio and visual domain. The proposal enables optimizing modules asynchronously, allowing large-scale distributed training of very deep neural networks on unlabelled datasets.
Glucose repression affects ion homeostasis in yeast through the regulation of the stress‐activated ENA1 gene

In this report we show that the ENA1/PMR2A gene is under glucose repression. The SNF1 protein kinase, acting independently from the HOG and calcineurin pathways, is essential to release ENA1 from glucose repression. The transcriptional repressor Ssn6p negatively regulates ENA1 expression and, like other glucose repressible genes, this repression is mediated in part by Mig1p. Deletion of a fragment from the ENA1 promoter that includes two Mig1p consensus binding sites gives a high level of expression in glucose without added salt. We suggest that regulation of ENA1 by the SNF1 pathway could be part of a general mechanism through which yeast cells respond to carbon source starvation by activating protective systems against different types of stress.
Integral p-adic étale cohomology of Drinfeld symmetric spaces

We compute the integral $p$-adic etale cohomology of Drinfeld symmetric spaces of any dimension. This refines the computation of the rational $p$-adic etale cohomology from Colmez-Dospinescu-Nizio{\l}. The main tools are: the computation of the integral de Rham cohomology from CDN and the integral $p$-adic comparison theorems of Bhatt-Morrow-Scholze and Cesnavicius-Koshikawa which replace the quasi-integral comparison theorem of Tsuji used in CDN.
On the identification of individual level pleiotropic, pure direct, and principal stratum direct effects without cross world assumptions

The analysis of natural direct and principal stratum direct effects has a controversial history in statistics and causal inference as these effects are commonly identified with either untestable cross world independence or graphical assumptions. This article demonstrates that the presence of individual level natural direct and principal stratum direct effects can be identified without cross world independence assumptions. We also define a new type of causal effect, called pleiotropy, that is of interest in genomics, and provide empirical conditions to detect such an effect as well. Our results are applicable for all types of distributions concerning the mediator and outcome.
Low Frequency Modes in Twisted Flatland : Ultra-soft Modes, Superlubricity to Strong Pinning

We study the effects of twisting on low frequency shear (SM) and layer breathing (LBM) modes in bilayer $\mathrm{MoS_{2}}$ using fully atomistic classical simulations. We show that these low frequency modes are extremely sensitive to twist and can be used to infer the twist angle. We find unique optical "ultra-soft" SMs (frequency $< 1\ \mathrm{cm^{-1}}$) for any non-zero twist, corresponding to an \textit{effective} translation of the moir{e} superlattice by relative displacement of the constituent layers in a non-trivial way. Additionally, for small twists ($\theta \lesssim 3\degree ,\ \gtrsim 57\degree$) new high-frequency SMs appear identical to those in stable bilayer $\mathrm{MoS_{2}}$ ($\theta = 0\degree/60\degree$) due to the overwhelming growth of stable stacking regions in relaxed twisted structures. Our study reveals the possibility of an intriguing, $\theta$ dependent superlubric to pinning behavior and of the existence of ultra-soft modes in \textit{all} two-dimensional (2D) materials, which can be used to controllably tune physical properties.
Management of diabetic dyslipidemia: An update

Diabetic dyslipidemia is a cluster of lipoprotein abnormalities characterized by increased triglyceride level, decreased high-density lipoprotein-cholesterol levels and increase in small dense low-density lipoprotein (LDL) particles. It is extremely common in type 2 diabetes (T2DM) affecting around 70 % of patients. Diabetic is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD) which is the most common cause of death in the United States and LDL-cholesterol is the number 1 predictor of ASCVD events in T2DM. The purpose of this review is to discuss the pathophysiology and treatment of diabetic dyslipidemia. In this review, we have discussed both non-pharmacological and pharmacological treatment modalities including major treatment trials which have impacted the cardiovascular outcomes in patients with diabetes. Statin therapy is the mainstay of treatment to reduce ASCVD by decreasing LDL-C by 30%-49% or at least 50% depending on risk level. Attractive adjunctive therapies include Ezetimibe which is more cost effective and PCSK9 inhibitors which display potent LDL-cholesterol lowering and ASCVD event reduction. For severe hypertriglyceridemia, to avert the risk of pancreatitis, both fish oil and fenofibrate in concert with diet is the best strategy.
Myokine/Adipokine Response to “Aerobic” Exercise: Is It Just a Matter of Exercise Load?

Purpose Exercise health benefits are partly mediated by exertional changes in several myokines/adipokines. This study aimed to compare the acute response of some of these biomarkers to aerobic exercise performed at the intensity corresponding to the maximum fat oxidation rate (FATmax) or the “anaerobic” threshold (AT). Methods Following a cross-over, counterbalanced design, 14 healthy untrained men (23 ± 1 years) performed a 45-min exercise bout at their FATmax or AT intensity (been previously determined through incremental exercise tests). The concentration of interleukin (IL)-15, follistatin, myostatin, fibroblast-growth factor (FGF)-21, irisin, resistin, and omentin was measured at baseline and 0, 1, 3, 24, 48, and 72 h post-exercise. Results AT exercise was performed at a higher intensity (85 ± 8 vs. 52 ± 14% of maximal oxygen uptake [VO2 max], p < 0.001) and induced a higher energy expenditure (p < 0.001) than FATmax, whereas a greater fat oxidation was observed in the latter (p < 0.001). A higher peak response of FGF-21 (+90%, p < 0.01) and follistatin (+49%, p < 0.05) was found after AT-exercise, as well as a trend toward a higher peak level of omentin (+13%, p = 0.071) and a greater decrease in resistin (−16%, p = 0.073). Conclusion Increasing exercise load (from FATmax to AT) results in a higher response of FGF-21, follistatin and omentin to aerobic exercise, with the subsequent potential cardiometabolic benefits. No effects were, however, observed on the remainder of biomarkers. Future research should address if manipulating other exercise variables (e.g., type, frequency) can promote a higher myokine/adipokine response.
Antiepileptic Effects of a Novel Non-invasive Neuromodulation Treatment in a Subject With Early-Onset Epileptic Encephalopathy: Case Report With 20 Sessions of HD-tDCS Intervention

The current clinical investigation examined high-definition transcranial direct current stimulation (HD-tDCS) as a focal, non-invasive, anti-epileptic treatment in a child with early-onset epileptic encephalopathy. We investigated the clinical impact of repetitive (20 daily sessions) cathode-centered 4 × 1 HD-tDCS (1 mA, 20 min, 4 mm ring radius) over the dominant seizure-generating cortical zone in a 40-month-old child suffering from a severe neonatal epileptic syndrome known as Ohtahara syndrome (OS). Seizures and epileptiform activity were monitored and quantified using video-EEG over multiple days of baseline, intervention, and post-intervention periods. Primary outcome measures were changes in seizure frequency and duration on the last day of intervention versus the last baseline day, preceding the intervention. In particular, we examined changes in tonic spasms, tonic-myoclonic seizures (TM-S), and myoclonic seizures from baseline to post-intervention. A trend in TM-S frequency was observed indicating a reduction of 73% in TM-S frequency, which was non-significant [t(4) = 2.05, p = 0.1], and denoted a clinically significant change. Myoclonic seizure (M-S) frequency was significantly reduced [t(4) = 3.83, p = 0.019] by 68.42%, compared to baseline, and indicated a significant clinical change as well. A 73% decrease in interictal epileptic discharges (IEDs) frequency was also observed immediately after the intervention period, compared to IED frequency at 3 days prior to intervention. Post-intervention seizure-related peak delta desynchronization was reduced by 57%. Our findings represent a case-specific significant clinical response, reduction in IED, and change in seizure-related delta activity following the application of HD-tDCS. The clinical outcomes, as noted in the current study, encourage the further investigation of this focal, non-invasive neuromodulation procedure in other severe electroclinical syndromes (e.g., West syndrome) and in larger pediatric populations diagnosed with early-onset epileptic encephalopathy. Clinical Trial Registration: www.ClinicalTrials. gov, identifier NCT02960347, protocol ID: Meiron 2013-4.
Exploring the Onset of a Male-Biased Interpretation of Masculine Generics Among French Speaking Kindergarten Children

In French, and other gender marked languages, there are two ways to interpret a grammatical masculine form when used to refer to social roles or occupations [e.g., les magiciens (the magiciansmasculine)]. It can refer to a group composed of only men (specific use of the masculine form), or one composed of both women and men (generic use). Studies of adults revealed that the rule that masculine forms can be interpreted as inclusive of either gender is not readily applied. To gain a better understanding of the processes shaping this phenomenon, we present a follow-up study (N = 52) to Lévy et al. (2016) to explore how French-speaking kindergarten children (3–5 years of age) resolve the semantic ambiguity of the grammatical masculine form when presented with role or occupation nouns. In a paradigm where participants’ gazes were monitored, children were presented with pictures of a pair of two boys and a pair of one girl and one boy and were prompted to Look at the [role nounmasculinepluralform]. First, the results suggest a stereotype effect in that children more strongly directed their gaze toward the boy-boy picture for stereotypical male role nouns, but toward the girl-boy picture for stereotypical female role nouns. Second, in the non-stereotypical/neutral condition we did not find an indication of any own-sex preference (as in Lévy et al., 2016), but of an influence of the role nouns’ grammatical gender, in that children more strongly directed their gaze toward boy-boy pictures than toward girl-boy pictures. We suggest that a specific interpretation of masculine forms might already start to emerge between 3 and 5 years of age, while gender stereotypes are still activated.
The Influence of Anxiety on the Recognition of Facial Emotion Depends on the Emotion Category and Race of the Target Faces

The recognition of emotional facial expressions is critical for our social interactions. While some prior studies have shown that a high anxiety level is associated with more sensitive recognition of emotion, there are also reports supporting that anxiety did not affect or reduce the sensitivity to the recognition of facial emotions. To reconcile these results, here we investigated whether the effect of individual anxiety on the recognition of facial emotions is dependent on the emotion category and the race of the target faces. We found that, first, there was a significant positive correlation between the individual anxiety level and the recognition sensitivity for angry faces but not for sad or happy faces. Second, while the correlation was significant for both low- and high-intensity angry faces during the recognition of the observer's own-race faces, there was significant correlation only for low-intensity angry faces during the recognition of other-race faces. Collectively, our results suggest that the influence of anxiety on the recognition of facial emotions is flexible depending on the characteristics of the target face stimuli including emotion category and race.
Exploring perceptions of meaningfulness in visual representations of bivariate relationships

Researchers often need to consider the practical significance of a relationship. For example, interpreting the magnitude of an effect size or establishing bounds in equivalence testing requires knowledge of the meaningfulness of a relationship. However, there has been little research exploring the degree of relationship among variables (e.g., correlation, mean difference) necessary for an association to be interpreted as meaningful or practically significant. In this study, we presented statistically trained and untrained participants with a collection of figures that displayed varying degrees of mean difference between groups or correlations among variables and participants indicated whether or not each relationship was meaningful. The results suggest that statistically trained and untrained participants differ in their qualification of a meaningful relationship, and that there is significant variability in how large a relationship must be before it is labeled meaningful. The results also shed some light on what degree of relationship is considered meaningful by individuals in a context-free setting.
Oxidative Stress and the Pathogenesis of Cholestasis

Cholestasis is a reduction in bile flow that occurs from a variety of causes in humans. This produces hepatocellular injury and fibrosis. Considering that there are limited therapies for this disease, there has been interest in understanding the mechanism by which cholestasis produces injury. Studies have demonstrated that oxidative stress occurs in livers of humans with cholestasis. In vitro studies have demonstrated that bile acids kill hepatocytes by a mechanism that depends upon reactive oxygen species (ROS). Further studies, however, have demonstrated that this mechanism is of limited importance in vivo. Cholestasis also initiates an inflammatory response resulting in accumulation of neutrophils in the liver. Inhibition of neutrophil function reduces oxidative stress and liver injury suggesting that neutrophils are an important source of damaging ROS in vivo. Furthermore, inhibition of ROS during cholestasis reduces fibrosis. Collectively, these studies suggest that ROS are important for pathologic changes that occur during cholestasis.
Systems Chemical Genetics-Based Drug Discovery: Prioritizing Agents Targeting Multiple/Reliable Disease-Associated Genes as Drug Candidates

Genetic disease genes are considered a promising source of drug targets. Most diseases are caused by more than one pathogenic factor; thus, it is reasonable to consider that chemical agents targeting multiple disease genes are more likely to have desired activities. This is supported by a comprehensive analysis on the relationships between agent activity/druggability and target genetic characteristics. The therapeutic potential of agents increases steadily with increasing number of targeted disease genes, and can be further enhanced by strengthened genetic links between targets and diseases. By using the multi-label classification models for genetics-based drug activity prediction, we provide universal tools for prioritizing drug candidates. All of the documented data and the machine-learning prediction service are available at SCG-Drug (http://zhanglab.hzau.edu.cn/scgdrug).
1-Aminocyclopropane-1-Carboxylic Acid Oxidase (ACO): The Enzyme That Makes the Plant Hormone Ethylene

The volatile plant hormone ethylene regulates many plant developmental processes and stress responses. It is therefore crucial that plants can precisely control their ethylene production levels in space and time. The ethylene biosynthesis pathway consists of two dedicated steps. In a first reaction, S-adenosyl-L-methionine (SAM) is converted into 1-aminocyclopropane-1-carboxylic acid (ACC) by ACC-synthase (ACS). In a second reaction, ACC is converted into ethylene by ACC-oxidase (ACO). Initially, it was postulated that ACS is the rate-limiting enzyme of this pathway, directing many studies to unravel the regulation of ACS protein activity, and stability. However, an increasing amount of evidence has been gathered over the years, which shows that ACO is the rate-limiting step in ethylene production during certain dedicated processes. This implies that also the ACO protein family is subjected to a stringent regulation. In this review, we give an overview about the state-of-the-art regarding ACO evolution, functionality and regulation, with an emphasis on the transcriptional, post-transcriptional, and post-translational control. We also highlight the importance of ACO being a prime target for genetic engineering and precision breeding, in order to control plant ethylene production levels.