Miracle-dz/UniFAR-FTUs huggingface dataset:
Memristive LIF Spiking Neuron Model and Its Application in Morse Code

The leaky integrate-and-fire (LIF) spiking model can successively mimic the firing patterns and information propagation of a biological neuron. It has been applied in neural networks, cognitive computing, and brain-inspired computing. Due to the resistance variability and the natural storage capacity of the memristor, the LIF spiking model with a memristor (MLIF) is presented in this article to simulate the function and working mode of neurons in biological systems. First, the comparison between the MLIF spiking model and the LIF spiking model is conducted. Second, it is experimentally shown that a single memristor could mimic the function of the integration and filtering of the dendrite and emulate the function of the integration and firing of the soma. Finally, the feasibility of the proposed MLIF spiking model is verified by the generation and recognition of Morse code. The experimental results indicate that the presented MLIF model efficiently performs good biological frequency adaptation, high firing frequency, and rich spiking patterns. A memristor can be used as the dendrite and the soma, and the MLIF spiking model can emulate the axon. The constructed single neuron can efficiently complete the generation and propagation of firing patterns.
Stimulation Parameters Used During Repetitive Transcranial Magnetic Stimulation for Motor Recovery and Corticospinal Excitability Modulation in SCI: A Scoping Review

There is a growing interest in non-invasive stimulation interventions as treatment strategies to improve functional outcomes and recovery after spinal cord injury (SCI). Repetitive transcranial magnetic stimulation (rTMS) is a neuromodulatory intervention which has the potential to reinforce the residual spinal and supraspinal pathways and induce plasticity. Recent reviews have highlighted the therapeutic potential and the beneficial effects of rTMS on motor function, spasticity, and corticospinal excitability modulation in SCI individuals. For this scoping review, we focus on the stimulation parameters used in 20 rTMS protocols. We extracted the rTMS parameters from 16 published rTMS studies involving SCI individuals and were able to infer preliminary associations between specific parameters and the effects observed. Future investigations will need to consider timing, intervention duration and dosage (in terms of number of sessions and number of pulses) that may depend on the stage, the level, and the severity of the injury. There is a need for more real vs. sham rTMS studies, reporting similar designs with sufficient information for replication, to achieve a significant level of evidence regarding the use of rTMS in SCI.
Carvacrol Arrests the Proliferation of Hypopharyngeal Carcinoma Cells by Suppressing Ornithine Decarboxylase and Hyaluronidase Activities

Carvacrol, a monoterpene known for its pharmacological activities, is present in the essential oil of Origanum majorana, Origanum vulgare, Thymus vulgaris, and Lippia graveolens. It is used in food as a flavoring and preservative agent in cosmetics and medicines because of its useful bioactivities in clinical practice. However, carvacrol was not much explored for its anticancer potential. Targeting enzymes involved in carcinogenesis, such as ornithine decarboxylase (ODC), cyclooxygenase-2 (COX-2), lipoxygenase-5 (LOX-5), and hyaluronidase (HYAL) by monoterpenes are amongst the efficient approaches for cancer prevention and treatment. In this study, the efficacy of carvacrol was investigated against deregulated cancer biomarkers/targets in organ-specific human cancer cell lines (FaDu, K562, and A549) utilizing in vitro, in silico, and in vivo approaches. The efficacy of carvacrol was evaluated on human cancer cell lines using neutral red uptake (NRU), sulpho rhodamine B (SRB), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays. The mechanistic study was carried out in cell-based test systems. Further, the potency of carvacrol was confirmed by the quantitative real-time PCR analysis and molecular docking studies. The in vivo anti-tumor potential of carvacrol was performed on mice S-180 model, and the toxicity examination was accomplished through in silico approach. Carvacrol significantly impeded the growth of FaDu, K562, and A549 cell lines with IC50 values ranging from 9.61 ± 0.05 to 81.32 ± 11.83 μM. Further, the efficacy of carvacrol was explored against different cancer targets in FaDu, K562, and A549 cell lines. Carvacrol inhibits the ODC, COX-2, LOX-5, and HYAL activities in FaDu cell line and ODC, COX-2, and HYAL activities in K562 cell line. The results were validated by expression analysis revealing the downregulation of the targeted gene with a significant change in the transcript level of ODC and HYAL in FaDu cell line with a fold change of 1.56 and 1.61, respectively. A non-significant effect of carvacrol was observed on the downstream signaling pathway of PI3K and HIF-1α/vascular endothelial growth factor (VEGF) in FaDu cells. The cell cycle, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and Annexin V-fluorescein isothiocyanate (FITC) experiments demonstrate that carvacrol induces apoptosis of FaDu cells. Further, the potency of carvacrol was also evaluated in vivo on mice S-180 tumor model, wherein it inhibits tumor growth (72%) at 75 mg/kg body weight (bw). ADMET studies predicted carvacrol as a safe molecule. Overall, carvacrol delayed the growth of FaDu, K562, and A549 cell lines by targeting enzymes involved in the carcinogenesis process. The existence of one hydroxyl group at the para position of carvacrol could be responsible for the anti-proliferative activity. Thus, carvacrol could be used as a pharmacophore to develop a safe and effective multi-targeted anti-cancer medicament.
Ralstonia solanacearum effector RipAF1 ADP-ribosylates host FBN1 to induce resistance against bacterial wilt

Ralstonia solanacearum (Rso) causes destructive bacterial wilt across a broad range of host plants by inducing jasmonic acid (JA) signaling while suppressing salicylic acid (SA) signaling pathways during disease development. In the present study, we show that Rso type III effector RipAF1 exerts a negative effect on bacterial virulence by subverting disease signaling in association with bacterial wilt. The ADP-ribosylation activity of RipAF1 was verified both in vivo and in vitro. Host fibrillin FBN1 was identified as a RipAF1-interacting protein that acted as a susceptible factor for bacterial wilt. In particular, RipAF1 directly ADP-ribosylates FBN1 at the E175/K207 residues, thus interfering with the mediation of disease signaling by FBN1. Together, these results suggest that RipAF1 exerts a role in defense induction by ADP-ribosylation of the susceptible factor FBN1 in the host plant.
Glucose Depletion Enhances the Stem Cell Phenotype and Gemcitabine Resistance of Cholangiocarcinoma Organoids through AKT Phosphorylation and Reactive Oxygen Species

Cancer cells are strongly dependent on the glycolytic pathway for generation of energy even under aerobic condition through a phenomenon known as the Warburg effect. Rapid proliferation of cancer cells is often accompanied by high glucose consumption and abnormal angiogenesis, which may lead to glucose depletion. In the present study, we investigated how cholangiocarcinoma cells adapt to glucose depletion using a 3D organoid culture system. We cultured organoids derived from cholangiocarcinoma under glucose-free condition and investigated cell proliferation, expression of stem cell markers and resistance to gemcitabine. Cholangiocarcinoma organoids cultured under glucose-free condition showed reduced proliferation but were able to survive. We also observed an increase in the expression of stem cell markers including LGR5 and enhancement of stem cell phenotypic characteristics such as resistance to gemcitabine through AKT phosphorylation and reactive oxygen species. These findings indicate that cholangiocarcinoma cells are able to adapt to glucose depletion through enhancement of their stem cell phenotype in response to changes in microenvironmental conditions.
Flagellar Motility During E. coli Biofilm Formation Provides a Competitive Disadvantage Which Recedes in the Presence of Co-Colonizers

In nature, bacteria form biofilms in very diverse environments, involving a range of specific properties and exhibiting competitive advantages for surface colonization. However, the underlying mechanisms are difficult to decipher. In particular, the contribution of cell flagellar motility to biofilm formation remains unclear. Here, we examined the ability of motile and nonmotile E. coli cells to form a biofilm in a well-controlled geometry, both in a simple situation involving a single-species biofilm and in the presence of co-colonizers. Using a millifluidic channel, we determined that motile cells have a clear disadvantage in forming a biofilm, exhibiting a long delay as compared to nonmotile cells. By monitoring biofilm development in real time, we observed that the decisive impact of flagellar motility on biofilm formation consists in the alteration of surface access time. Implementing a simple mathematical model to calculate surface access velocity for both motile (diffusion) and nonmotile (settling) cells, we discovered that the competitive advantage strongly depends on the geometry of the environment to be colonized. Interestingly, this advantage reverts for the smallest geometries, with a crossover at a height of 100 μm. We also report that the difference between and nonmotile cells in the ability to form a biofilm diminishes in the presence of cocolonizers, which could be due to motility inhibition through the consumption of key resources by the co-colonizers. We conclude that the impact of flagellar motility on surface colonization closely depends on the environment geometry and the population features, suggesting a unifying vision of the role of cell motility in surface colonization and biofilm formation.
Evolutionary Responses of a Reef-building Coral to Climate Change at the End of the Last Glacial Maximum

Climate change threatens the survival of coral reefs on a global scale, primarily through mass bleaching and mortality as a result of marine heatwaves. While these short-term effects are clear, predicting the fate of coral reefs over the coming century is a major challenge. One way to understand the longer-term effects of rapid climate change is to examine the response of coral populations to past climate shifts. Coastal and shallow-water marine ecosystems such as coral reefs have been reshaped many times by sea-level changes during the Pleistocene, yet, few studies have directly linked this with its consequences on population demographics, dispersal, and adaptation. Here we use powerful analytical techniques, afforded by haplotype phased whole-genomes, to establish such links for the reef-building coral, Acropora digitifera. We show that three genetically distinct populations are present in northwestern Australia, and that their rapid divergence since the last glacial maximum (LGM) can be explained by a combination of founder-effects and restricted gene flow. Signatures of selective sweeps, too strong to be explained by demographic history, are present in all three populations and overlap with genes that show different patterns of functional enrichment between inshore and offshore habitats. In contrast to rapid divergence in the host, we find that photosymbiont communities are largely undifferentiated between corals from all three locations, spanning almost 1000 km, indicating that selection on host genes and not acquisition of novel symbionts, has been the primary driver of adaptation for this species in northwestern Australia.
Novel Diels–Alder Type Adducts from Morus alba Root Bark Targeting Human Monoamine Oxidase and Dopaminergic Receptors for the Management of Neurodegenerative Diseases

In this study, we delineate the human monoamine oxidase (hMAO) inhibitory potential of natural Diels–Alder type adducts, mulberrofuran G (1), kuwanon G (2), and albanol B (3), from Morus alba root bark to characterize their role in Parkinson’s disease (PD) and depression, focusing on their ability to modulate dopaminergic receptors (D1R, D2LR, D3R, and D4R). In hMAO-A inhibition, 1–3 showed mild effects (50% inhibitory concentration (IC50): 54‒114 μM). However, 1 displayed moderate inhibition of the hMAO-B isozyme (IC50: 18.14 ± 1.06 μM) followed by mild inhibition by 2 (IC50: 57.71 ± 2.12 μM) and 3 (IC50: 90.59 ± 1.72 μM). Our kinetic study characterized the inhibition mode, and the in silico docking predicted that the moderate inhibitor 1 would have the lowest binding energy. Similarly, cell-based G protein-coupled receptors (GPCR) functional assays in vector-transfected cells expressing dopamine (DA) receptors characterized 1–3 as D1R/D2LR antagonists and D3R/D4R agonists. The half-maximum effective concentration (EC50) of 1–3 on DA D3R/D4R was 15.13/17.19, 20.18/21.05, and 12.63/‒ µM, respectively. Similarly, 1–3 inhibited 50% of the DA response on D1R/D2LR by 6.13/2.41, 16.48/31.22, and 7.16/18.42 µM, respectively. A computational study revealed low binding energy for the test ligands. Interactions with residues Asp110, Val111, Tyr365, and Phe345 at the D3R receptor and Asp115 and His414 at the D4R receptor explain the high agonist effect. Likewise, Asp187 at D1R and Asp114 at D2LR play a crucial role in the antagonist effects of the ligand binding. Our overall results depict 1–3 from M. alba root bark as good inhibitors of hMAO and potent modulators of DA function as D1R/D2LR antagonists and D3R/D4R agonists. These active constituents in M. alba deserve in-depth study for their potential to manage neurodegenerative disorders (NDs), particularly PD and psychosis.
Cryo-EM reveals an entangled kinetic trap in the folding pathway of a catalytic RNA

Functional RNAs fold through complex pathways that can contain misfolded “kinetic traps. ” A complete model of RNA folding requires understanding the formation of such misfolded states, but they are difficult to characterize due to their transient and potentially conformationally dynamic nature. We used cryo-electron microscopy (cryo-EM) to visualize a long-lived misfolded state in the folding pathway of the Tetrahymena thermophila group I intron, a paradigmatic RNA structure-function model system. The structure revealed how this state forms native-like secondary structure and tertiary contacts but contains two incorrectly crossed strands, consistent with a previous model. This incorrect topology mispositions a critical catalytic domain and cannot be resolved locally, as extensive refolding is required. This work provides a structural framework for interpreting decades of biochemical and functional studies and demonstrates the power of cryo-EM for the exploration of RNA folding pathways.
Overactivation of a sleep-active neuron decouples survival from the need to sleep

Sleep is a state of behavioral quiescence that is closely associated with survival. Sleep- 12 active neurons promote sleep and survival. It is not known, however, whether sleep-active 13 neurons need to cause sleep to promote survival. Here, we tested how depolarization of the 14 sleep-active RIS neuron in Caenorhabditis elegans controls sleep and survival during 15 larval starvation. Survival always increased with raised RIS depolarization. RIS 16 depolarization promoted sleep over a long range. Unexpectedly, however, high levels of 17 RIS depolarization caused a nearly complete loss of sleep. Similarly, overexpression of 18 sleep-inducing FLP-11 neuropeptides in RIS inhibited sleep, indicating that overactive 19 transmission from RIS inhibits sleep. Despite the loss of sleep, survival was normal 20 following FLP-11 overexpression. Thus, RIS overactivation abolishes sleep yet supports 21 survival. These results indicate that regulation of sleep and survival are separable functions 22 of a sleep-active neuron that are normally coupled but can be uncoupled by sleep-neuron 23 over activation.
High-level motor planning allows flexible walking at different gait patterns in a neuromechanical model

Humans are able to adopt almost any desired gait pattern on the fly when walking. We postulate that this flexibility in humans is partially due to the ability to control the whole body during walking as a volitional, goal-directed movement that can be planned and changed, rather than having to rely on habitual, reflexive control that is adapted over long time-scales. Here we present a neuromechanical model that accounts for this flexibility by combining movement goals and motor plans on a kinematic task level with low-level spinal feedback loops. We show that the model is able to walk at a wide range of different gait patterns by choosing a small number of high-level control parameters representing a movement goal. A larger number of parameters governing the low-level reflex loops in the spinal cord, on the other hand, remains fixed. We also show that the model is able to generalize the learned behavior by re-combining the high-level control parameters and walk with gait patterns it had not encountered before. Furthermore, the model can transition between different gaits without loss of balance by switching to a new set of control parameters in real time.
The purified recombinant FAT domain of the Focal Adhesion Kinase does not bind directly to recombinant Talin or MBD2 in vitro

Controlled localization and activation of the focal adhesion kinase (FAK) functionally links adhesion, migration and survival of the cell. The C-terminal focal adhesion targeting (FAT) domain of FAK is an important regulator of the localization, activation and molecular associations of FAK. Here, we aimed to investigate the structural basis for how FAK FAT binds to Talin and MBD2, which were previously reported to be cytoplasmic and nuclear ligands, respectively. Using several biophysical methods with purified recombinantly expressed protein constructs, we failed to observe measurable interactions between FAT and either the Talin FERM domain or MBD2. We conclude that the association of FAT with these proteins requires additional factors or post-translational modifications not present in bacterially produced purified proteins.
Impact of temperature and time on DNA-free Cas9-ribonucleoprotein mediated gene editing in wheat protoplasts and immature embryos

The advancement of precision engineering for crop trait improvement is important in the face of rapid population growth, climate change, and disease. To this end, targeted double-stranded break technology using RNA-guided Cas9 has been adopted widely for genome editing in plants. Agrobacterium or particle bombardment-based delivery of plasmids encoding Cas9 and guide RNA (gRNA) is common, but requires optimization of expression and often results in random integration of plasmid DNA into the plant genome. Recent advances have described gene editing by the delivery of Cas9 and gRNA as pre-assembled ribonucleoproteins (RNPs) into various plant tissues, but with moderate efficiency in resulting regenerated plants. In this report we describe significant improvements to Cas9-RNP mediated gene editing in wheat. We demonstrate that Cas9-RNP assays in protoplasts are a fast and effective tool for rational selection of optimal gRNAs for gene editing in regenerable immature embryos (IEs), and that high temperature treatment enhances gene editing rates in both tissue types. We also show that Cas9-mediated editing persists for at least 14 days in gold particle bombarded wheat IEs. The regenerated edited wheat plants in this work are recovered at high rates in the absence of exogenous DNA and selection. With this method, we produce knockouts of a set of three homoeologous genes and two pathogenic effector susceptibility genes that result in insensitivity to corresponding necrotrophic effectors produced by Parastagonospora nodorum. The establishment of highly efficient, DNA-free gene editing technology holds promise for accelerated trait diversity production in an expansive array of crops.
Algorithmic Classification of Layouts of BPMN Diagrams

Previous research is concerned with diﬀerences in BPMN diagram layout, e.g., with regards to understandability. However, lay-outs have neither been formally described nor their classiﬁcation been automated. We aim at formalizing BPMN layouts and automating diagram layout classiﬁcation for BPMN diagrams: We calculate sequence ﬂow directions and encode them. By using regular expressions, these are clustered to diagram layouts. This results in a set of formally described BPMN layouts and a corresponding algorithm which we implemented in a tool. The results are very similar to previous work of manual layout classiﬁcation on the GitHub process set. Researchers can use our deﬁnition when conducting BPMN diagram analysis and industry experts can use our tool for validating models against their layout guidelines.
RFID network optimization based on multi-species coevolution

In real applications of large-scale network of RFID,management of RFID networks such as network optimal distribution,collision reduction and reading rate improvement is important for RFID service quality decision.Mathematical optimization models for RFID network planning and readers anti-collision were set up. Based on mutualism of species,a novel optimization algorithm—the Symbiotic Multi-species optimization(SMSO) was developed.The simulation results show the high efficiency of SMSO in solving RFID network planning and anti-collision problems,and its considerable potential in optimizing capacity,convergence rate and premature convergence overcomming.
The LQG/LTR Design Procedure for Nonlinear Robot Manipulators

In this thesis, the multivariable robust control of nonlinear manipulator systems is based on the compute torque method and the LQG/LTR design procedure was proposed. This controller is able to handle the system that have modeling errors and external disturbances while it keeps the close-loop system robustness and satisfied the prescribed performance. In this research, the computed toque method is applied to design the proposed control law to form the main control structure by using the benefit of its feedback linearization strategy. The error dynamics of the plant is then formulated to the standard H2/H∞ control problem, which is easy to be applied by the LQG/LTR design procedure to find the optimal control gain and observer gains in the process of matching the target loop. With regard to the non-can- celing nonlinear terms, the closed-loop system is formulated to the Lu're-type problem form with sector-bounded uncer- tainties, which is then analyzed by the Multivariable Circle Criterion to discuss the stability and robustness. To verify the feasibility of proposed controller, one example with various external disturbances and parameter uncertainties is made and its computer simulation result shows the efficiency and feasibility of the proposed design methodology.
18 F-Fluciclovine – Avid Axillary Lymph Nodes After COVID-19 Vaccination on PET/CT for Suspected Recurrence of Prostate Cancer

Abnormally increased 18 F-FDG avidity of axillary lymph nodes has become a frequent diagnostic dilemma on PET/CT in the current climate of global vaccinations directed against severe acute respi-ratory syndrome coronavirus 2. This avidity is due to the in ﬂ ammatory response evoked by vaccines and the nonspeci ﬁ c nature of 18 F-FDG uptake, which is increased in both malignant and in ﬂ ammatory processes. Similarly, 18 F- ﬂ uciclovine, an amino acid analog indicated for the assessment of biochemical recurrence of prostate cancer, may also demonstrate nonspeci ﬁ c in ﬂ ammatory uptake. We report a case of 18 F- ﬂ uciclovine PET/CT obtained for concern about prostate cancer. In this case, iso-lated avid lymph nodes were seen in the left axilla. A screen-ing questionnaire revealed that the patient had recently received the second dose of the P ﬁ zer-BioNTech coronavirus disease 2019 vaccine in his left shoulder, and hence, the uptake was determined to be reactive.