Miracle-dz/UniFAR-FTUs huggingface dataset:
Estrogen regulates myogenic tone in hippocampal arterioles by enhanced basal release of nitric oxide and endothelial SKCa channel activity

Arteries and arterioles exhibit myogenic tone, a partially constricted state that allows further constriction or dilation in response to moment-to-moment fluctuations in blood pressure. The vascular endothelium that lines the internal surface of all blood vessels controls a wide variety of essential functions, including the contractility of the adjacent smooth muscle cells by providing a tonic vasodilatory influence. Studies conducted on large (pial) arteries on the surface of the brain have shown that estrogen lowers myogenic tone in female mice by enhancing nitric oxide (NO) release from the endothelium, however, whether this difference extends to the intracerebral microcirculation remains ambiguous. The existing incomplete picture of sex differences in cerebrovascular physiology combined with a deficiency in treatments that fully restore cognitive function after cerebrovascular accidents places heavy emphasis on the necessity to investigate myogenic tone regulation in the microcirculation from both male and female mice. We hypothesized that sex-linked hormone regulation of myogenic tone extends its influence on the microcirculation level, and sought to characterize it in isolated arterioles from the hippocampus, a major cognitive brain area. Using diameter measurements both in vivo (acute cranial window vascular diameter) and ex vivo (pressure myography experiments), we measured lower myogenic tone responses in hippocampal arterioles from female than male mice. By using a combined surgical and pharmacological approach, we found myogenic tone in ovariectomized (OVX) female mice matches that of males, as well as in endothelium-denuded arterioles. Interestingly, eNOS inhibition induced a larger constriction in female arterioles but only partially abolished the difference in tone. We identified that the remnant difference was mediated by a higher activity and expression of the small-conductance Ca2+-sensitive K+ (SK) channels. Collectively, these data indicate that eNOS and SK channels exert greater vasodilatory influence over myogenic tone in female mice at physiological pressures.
Attentional selection and communication through coherence: Scope and limitations

Synchronous neural oscillations are strongly associated with a variety of perceptual, cognitive, and behavioural processes. It has been proposed that the role of the synchronous oscillations in these processes is to facilitate information transmission between brain areas, the ‘communication through coherence,’ or CTC hypothesis.The details of how this mechanism would work, however, and its causal status, are still unclear. Here we investigate computationally a proposed mechanism for selective attention that directly implicates the CTC as causal. The mechanism involves alpha band (about 10 Hz) oscillations, originating in the pulvinar nucleus of the thalamus, being sent to communicating cortical areas, organizing gamma (about 40 Hz) oscillations there, and thus facilitating phase coherence and communication between them. This is proposed to happen contingent on control signals sent from higher-level cortical areas to the thalamic reticular nucleus, which controls the alpha oscillations sent to cortex by the pulvinar. We studied the scope of this mechanism in parameter space, and limitations implied by this scope, using a computational implementation of our conceptual model. Our results indicate that, although the CTC-based mechanism can account for some effects of top-down and bottom-up attentional selection, its limitations indicate that an alternative mechanism, in which oscillatory coherence is caused by communication between brain areas rather than being a causal factor for it, might operate in addition to, or even instead of, the CTC mechanism. Author summary The ability to select some stimulus or stimulus location from all of those available to our senses is critical to our ability to navigate our complex biological and social niche, and to organize appropriate actions to accomplish our goals, namely to survive and to reproduce. We study here a possible mechanism by which the brain could accomplish attentional selection. We show that the interaction between 10 Hz and 40 Hz neural oscillations can provide increases in coherence and information transmission between computationally modelled cortical areas. Our results support the idea that synchronization between oscillations facilitates communication between cortical areas. Limitations and sensitivities to the model, however, also point to the idea that the relation between coherence and communication could go in the opposite direction in some cases, particularly when attention is not involved.
The Role of Potassium and Calcium Currents in the Bistable Firing Transition

Healthy brains display a wide range of firing patterns, from synchronized oscillations during slowwave sleep to desynchronized firing during movement. These physiological activities coexist with periods of pathological hyperactivity in the epileptic brain, where neurons can fire in synchronized bursts. Most cortical neurons are pyramidal regular spiking cells (RS) with frequency adaptation and do not exhibit bursts in current-clamp experiments (in vitro). In this work, we investigate the transition mechanism of spike-to-burst patterns due to slow potassium and calcium currents, considering a conductance-based model of a cortical RS cell. The joint influence of potassium and calcium ion channels on high synchronous patterns is investigated for different synaptic couplings (gsyn) and external current inputs (I). Our results suggest that slow potassium currents play an important role in the emergence of high-synchronous activities, as well as in the spike-to-burst firing pattern transitions. This transition is related to bistable dynamics of the neuronal network, where physiological asynchronous states coexist with pathological burst synchronization. The hysteresis curve of the coefficient of variation of the inter-spike interval demonstrates that a burst can be initiated by firing states with neuronal synchronization. Furthermore, we notice that high-threshold (IL) and low-threshold (IT) ion channels play a role in increasing and decreasing the parameter conditions (gsyn and I) in which bistable dynamics occur, respectively. For high values of IL conductance, a synchronous burst appears when neurons are weakly coupled and receive more external input. On the other hand, when the conductance IT increases, higher coupling and lower I are necessary to produce burst synchronization. In light of our results, we suggest that channel subtype-specific pharmacological interactions can be useful to induce transitions from pathological high bursting states to healthy states.
Hypoxia regulate developmental coronary angiogenesis potentially through VEGFR2- and SOX17-mediated signaling

Background Coronary vessels in embryonic mouse heart arises from multiple progenitor population including sinus venosus (SV), endocardium, and proepicardium. ELA/APJ signaling is shown to regulate coronary growth from SV pathway within the subepicardium, whereas VEGF-A/VEGF-R2 pathways is implicated to regulate coronary growth from endocardium pathway. Our previous study show hypoxia as a potential signaling cue to stimulate overall coronary growth and expansion within the myocardium. However, the role of hypoxia and its downstream signaling pathways in the regulation of coronary vessel development is not known. In this study, we investigated the role of hypoxia in coronary vessel development and have identified SOX17- and VEGF-R2-mediated signaling as a potential downstream pathway of hypoxia in the regulation of coronary vessel development. Results We show that hypoxia gain-of-function in the myocardium through upregulation of HIF-1α disrupts the normal pattern of coronary angiogenesis in developing mouse hearts and displays phenotype that is reminiscent of accelerated coronary growth. We show that VEGF-R2 expression is increased in coronary endothelial cells under hypoxia gain-of-function in vivo and in vitro. Furthermore, we show that SOX17 expression is upregulated in developing mouse heart under hypoxia gain-of-function conditions, whereas SOX17 expression is repressed under hypoxia loss-of-function conditions. Furthermore, our results show that SOX17 loss-of-function disrupts normal pattern of coronary growth. Conclusion Collectively, our data provide strong phenotypic evidence to show that hypoxia might regulate coronary growth in the developing mouse heart potentially through VEGF-R2- and SOX17-mediated downstream signaling pathways.
Identification of resistance mechanisms to small-molecule inhibition of TEAD-regulated transcription

The Hippo tumour suppressor pathway controls transcription by regulating nuclear abundance of YAP and TAZ, which activate transcription with the TEAD1-TEAD4 DNA-binding proteins. Recently, several small-molecule inhibitors of YAP and TEADs have been reported, with some now entering clinical trials for different cancers. Here, we investigated the cellular response to TEAD palmitoylation inhibitors, using a combination of genomic and genetic strategies. Genome-wide CRISPR/Cas9 screens identified genes that modulate the cellular response to TEAD inhibition, including members of the Hippo, MAPK and JAK-STAT signaling pathways. By exploring gene expression programs of mutant cells, we found that MAPK pathway hyperactivation confers resistance to TEAD inhibition by reinstating expression of a subset of YAP/TEAD target genes. Consistent with this, combined inhibition of TEAD and the MAPK protein MEK, synergistically blocked proliferation of several mesothelioma and lung cancer cell lines and more potently reduced the growth of patient-derived lung cancers in vivo. Collectively, we reveal mechanisms by which cells can overcome small-molecule inhibition of TEADs and potential strategies to enhance the anti-tumor activity of emerging Hippo pathway targeted therapies.
3D-Mol: A Novel Contrastive Learning Framework for Molecular Property Prediction with 3D Information

Molecular property prediction offers an effective and efficient approach for early screening and optimization of drug candidates. Although deep learning based methods have made notable progress, most existing works still do not fully utilize 3D spatial information. This can lead to a single molecular representation representing multiple actual molecules. To address these issues, we propose a novel 3D structure-based molecular modeling method named 3D-Mol. In order to accurately represent complete spatial structure, we design a novel encoder to extract 3D features by deconstructing the molecules into three geometric graphs. In addition, we use 20M unlabeled data to pretrain our model by contrastive learning. We consider conformations with the same topological structure as positive pairs and the opposites as negative pairs, while the weight is determined by the dissimilarity between the conformations. We compare 3D-Mol with various state-of-the-art(SOTA) baselines on 7 benchmarks and demonstrate our outstanding performance in 5 benchmarks.
Profile Update: The Effects of Identity Disclosure on Network Connections and Language

Our social identities determine how we interact and engage with the world surrounding us. In online settings, individuals can make these identities explicit by including them in their public biography, possibly signaling a change to what is important to them and how they should be viewed. Here, we perform the first large-scale study on Twitter that examines behavioral changes following identity signal addition on Twitter profiles. Combining social networks with NLP and quasi-experimental analyses, we discover that after disclosing an identity on their profiles, users (1) generate more tweets containing language that aligns with their identity and (2) connect more to same-identity users. We also examine whether adding an identity signal increases the number of offensive replies and find that (3) the combined effect of disclosing identity via both tweets and profiles is associated with a reduced number of offensive replies from others.
GradTree: Learning Axis-Aligned Decision Trees with Gradient Descent

Decision Trees (DTs) are commonly used for many machine learning tasks due to their high degree of interpretability. However, learning a DT from data is a difficult optimization problem, as it is non-convex and non-differentiable. Therefore, common approaches learn DTs using a greedy growth algorithm that minimizes the impurity locally at each internal node. Unfortunately, this greedy procedure can lead to inaccurate trees. In this paper, we present a novel approach for learning hard, axis-aligned DTs with gradient descent. The proposed method uses backpropagation with a straight-through operator on a dense DT representation, to jointly optimize all tree parameters. Our approach outperforms existing methods on binary classification benchmarks and achieves competitive results for multi-class tasks. The implementation is available under: https://github.com/s-marton/GradTree
Hadamard integrator for time-dependent wave equations: Lagrangian formulation via ray tracing

We propose a novel Hadamard integrator for the self-adjoint time-dependent wave equation in an inhomogeneous medium. First, we create a new asymptotic series based on the Gelfand-Shilov function, dubbed Hadamard's ansatz, to approximate the Green's function of the time-dependent wave equation. Second, incorporating the leading term of Hadamard's ansatz into the Kirchhoff-Huygens representation, we develop an original Hadamard integrator for the Cauchy problem of the time-dependent wave equation and derive the corresponding Lagrangian formulation in geodesic polar coordinates. Third, to construct the Hadamard integrator in the Lagrangian formulation efficiently, we use a short-time ray tracing method to obtain wavefront locations accurately, and we further develop fast algorithms to compute Chebyshev-polynomial based low-rank representations of both wavefront locations and variants of Hadamard coefficients. Fourth, equipped with these low-rank representations, we apply the Hadamard integrator to efficiently solve time-dependent wave equations with highly oscillatory initial conditions, where the time step size is independent of the initial conditions. By judiciously choosing the medium-dependent time step, our new Hadamard integrator can propagate wave field beyond caustics implicitly and advance spatially overturning waves in time naturally. Moreover, since the integrator is independent of initial conditions, the Hadamard integrator can be applied to many different initial conditions once it is constructed. Both two-dimensional and three-dimensional numerical examples illustrate the accuracy and performance of the proposed method.
POSTOPERATIVE CORNEAL ASTIGMATISM FOLLOWING CATARACT PHACOEMULSIFICATION USING 3.2 MM CLEAR CORNEAL SUPERTEMPORAL INCISION: REPORT FROM A TERTIARY CARE HOSPITAL IN BIHAR

Background: Cataract poses both a significant socioeconomic burden and a public health concern as it is the leading cause of blindness worldwide and a major cause of visual disability throughout the African continent. The current treatment for cataract is surgery and while phacoemulsification remains the more advanced and technically superior method of cataract surgery, manual small incision cataract surgery (MSICS) is the most popular surgical management option for cataracts in developing countries. Materials and Methods: A retrospective study was performed under the Department of Ophthalmology of Darbhanga Medical College and Hospital, Darbhanga, Bihar. The study was conducted on 162 eyes of 148 patients who were operated upon for cataract with intraocular lens implantation in the year May 2022 to April 2023. The follow up period was 6 months. The study was approved by the Institutional ethics Committee. Informed consent was obtained from each patient before enrollment. The patients underwent cataract surgery by phacoemulsification through 3.2 mm superotemporal clear corneal incision (approx. 0.5mm central to the limbus). They were divided into two groups depending upon, “With the Rule” (Group A) or “Against the Rule” (Group B). Result: Group A comprised of 68 eyes with mean astigmatism before surgery was 0.79 D and median astigmatism was 0.76 while group B had 94 eyes with a mean and median astigmatism of 0.81 D and 0.78 D, respectively. The mean and median increase in astigmatism post operatively in the two groups was calculated. Conclusion: Superotemporal, 3.2 mm clear corneal incision is quite stable and does not significantly increase post operative astigmatism when followed up over a long (several months to years) period of time. This size and site of the incision have also proved to be superior to smaller or larger and superior or sclera incisions respectively.
SACRO: Semi-Automated Checking Of Research Outputs

Output checking can require significant resources, acting as a barrier to scaling up the research use of confidential data. We report on a project, SACRO, that is developing a general-purpose, semi-automatic output checking systems that works across the range of restricted research environments. SACRO is designed to • Automate checking of most common statistics, using best-practice principles-based modelling.
A Visualization System for Hexahedral Mesh Quality Study

In this paper, we introduce a new 3D hex mesh visual analysis system that emphasizes poor-quality areas with an aggregated glyph, highlights overlapping elements, and provides detailed boundary error inspection in three forms. By supporting multi-level analysis through multiple views, our system effectively evaluates various mesh models and compares the performance of mesh generation and optimization algorithms for hexahedral meshes.
Effects of Sedentary Lifestyle and Physical Activity in Gaming Disorder

: We are exposed to Nonylphenol which is an endocrine disrupting chemical used in the plastic industry, in our daily life without realizing it. The aim of this study was to evaluate the effect of Nonylphenol (NP) on heart tissue and the protectiveness of melatonin treatment on the heart damage with histopathological and immunohistological parameters. Twenty-one female rats were randomly divided into three groups: Control, NP, and Melatonin+NP. Heart tissues were removed two weeks later in all groups. Histopathological evaluation was performed with Hematoxylin&Eosin staining. IL-1β, IL-6, and Caspase-3 expression in heart tissues were detected immunohistochemically. Melatonin had a protective effect on heart tissue against NP-induced histopathological changes such as necrosis, hemorrhage, and inflammation. According to our results, the immunoreactivity intensity of inflammation markers such as IL-1β and IL-6 was significantly lower in the Melatonin+NP group than in the NP group. Finally, we investigated the pro-apoptotic marker caspase-3 immunoreactivity, which may explain the apoptotic effects of NP on the heart. According to our findings, melatonin significantly reduced the caspase-3 expression induced by NP. Our results showed that pretreatment with melatonin is beneficial to protect from NP-induced heart damage. These findings reinforce the protective effects of melatonin on heart tissue and more clinical studies are needed.
Collective Action: Experimental Evidence

We conducted a laboratory experiment to test the comparative statics predictions of a new approach to collective action games based on the method of stability sets. We find robust support for the main theoretical predictions. As we increase the payoff of a successful collective action (accruing to all players and only to those who contribute), the share of cooperators increases. The experiment also points to new avenues for refining the theory. We find that, as the payoff of a successful collective action increases, subjects tend to upgrade their prior beliefs as to the expected share of cooperators. Although this does not have a qualitative effect on comparative static predictions, using the reported distribution of beliefs rather than an ad hoc uniform distribution reduces the gap between theoretical predictions and observed outcomes. This finding also allows us to decompose the mechanism that leads to more cooperation into a “belief effect” and a “range of cooperation effect”.
Chapter 32 Mind the Traps! Design Guidelines for Rigorous BCI Experiments.

Authors: * C. Jeunet (Inria, France / EPFL, Switzerland, camille.jeunet@inria.fr) S. Debener (University of Oldenburg, Germany, stefan.debener@uni-oldenburg.de) F. Lotte (Inria, France, fabien.lotte@inria.fr) J. Mattout (Inserm, France, jeremie.mattout@inserm.fr) R. Scherer (Graz University of Technology, Austria, reinhold.scherer@tugraz.at) C. Zich (University of Oldenburg, Germany / University of Oxford, UK, catharina.zich@unioldenburg.de)
Edinburgh Research Explorer Functional Analysis of RNA Structures Present at the 3 ' Extremity of the Murine Norovirus Genome: the Variable Polypyrimidine Tract Plays a Role in Viral Virulence (vol 84, pg 2859, 2010)

Interactions of host cell factors with RNA sequences and structures in the genomes of positive-strand RNA viruses play various roles in the life cycles of these viruses. Our understanding of the functional RNA elements present in norovirus genomes to date has been limited largely to in vitro analysis. However, we recently used reverse genetics to identify evolutionarily conserved RNA structures and sequences required for norovirus replication. We have now undertaken a more detailed analysis of RNA structures present at the 3 (cid:1) extremity of the murine norovirus (MNV) genome. Biochemical data indicate the presence of three stable stem-loops, including two in the untranslated region, and a single-stranded polypyrimidine tract [p(Y)] of variable length between MNV isolates, within the terminal stem-loop structure. The well-characterized host cell pyrimidine binding proteins PTB and PCBP bound the 3 (cid:1) -untranslated region via an interaction with this variable sequence. Viruses lacking the p(Y) tract were viable both in cell culture and upon mouse infection, demon- strating that this interaction was not essential for virus replication. However, competition analysis with wild-type MNV in cell culture indicated that the loss of the p(Y) tract was associated with a ﬁtness cost. Furthermore, a p(Y)-deleted mutant showed a reduction in virulence in the STAT1 (cid:1) / (cid:1) mouse model, highlighting the role of RNA structures in norovirus pathogenesis. This work highlights how, like with other positive-strand RNA viruses, RNA structures present at the termini of the norovirus genome play important roles in virus replication and virulence. Virulence studies. Sex-matched STAT1 (cid:2) (Taconic) were inoculated by oral gavage with 1,000 TCID 50 of either wild-type (v) or SL3 GNRA (v) virus (group size, 8 and 8 females per virus). Mock inoculations for the negative control group were performed using an uninfected lysate from 264.7 cells in an identical manner to that for the virus stocks (group size, were for the onset of piloerection, anorexia, and characterized