We propose InSituNet, a deep learning based surrogate model to support parameter space exploration for ensemble simulations that are visualized in situ. In situ visualization, generating ...visualizations at simulation time, is becoming prevalent in handling large-scale simulations because of the I/O and storage constraints. However, in situ visualization approaches limit the flexibility of post-hoc exploration because the raw simulation data are no longer available. Although multiple image-based approaches have been proposed to mitigate this limitation, those approaches lack the ability to explore the simulation parameters. Our approach allows flexible exploration of parameter space for large-scale ensemble simulations by taking advantage of the recent advances in deep learning. Specifically, we design InSituNet as a convolutional regression model to learn the mapping from the simulation and visualization parameters to the visualization results. With the trained model, users can generate new images for different simulation parameters under various visualization settings, which enables in-depth analysis of the underlying ensemble simulations. We demonstrate the effectiveness of InSituNet in combustion, cosmology, and ocean simulations through quantitative and qualitative evaluations.
Fungal marine microorganisms are a valuable source of bioactive natural products. Fungal secondary metabolites mainly comprise alkaloids, terpenoids, peptides, polyketides, steroids, and lactones. ...Proteins and peptides from marine fungi show minimal human toxicity and less adverse effects comparable to synthetic drugs. This review summarizes the chemistry and the biological activities of peptides that were isolated and structurally elucidated from marine fungi. Relevant fungal genera including
,
,
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, as well as
were extensively reviewed. About 131 peptides were reported from these 17 genera and their structures were unambiguously determined using 1D and 2D NMR (one and two dimensional nuclear magnetic resonance) techniques in addition to HRMS (high resolution mass spectrometry). Marfey and Mosher reactions were used to confirm the identity of these compounds. About 53% of the isolated peptides exhibited cytotoxic, antimicrobial, and antiviral activity, meanwhile, few of them showed antidiabetic, lipid lowering, and anti-inflammatory activity. However 47% of the isolated peptides showed no activity with respect to the examined biological activity and thus required further in depth biological assessment. In conclusion, when searching for bioactive natural products, it is worth exploring more peptides of fungal origin and assessing their biological activities.
Genus
represents a widely spread genus of fungi that is highly popular for possessing potent medicinal potential comprising mainly antimicrobial, cytotoxic and antioxidant properties. They are highly ...attributed to its richness by alkaloids, terpenes, steroids and polyketons. This review aimed to comprehensively explore the diverse alkaloids isolated and identified from different species of genus
that were found to be associated with different marine organisms regarding their chemistry and biology. Around 174 alkaloid metabolites were reported, 66 of which showed important biological activities with respect to the tested biological activities mainly comprising antiviral, antibacterial, antifungal, cytotoxic, antioxidant and antifouling activities. Besides, in silico studies on different microbial proteins comprising DNA-gyrase, topoisomerase IV, dihydrofolate reductase, transcriptional regulator TcaR (protein), and aminoglycoside nucleotidyl transferase were done for sixteen alkaloids that showed anti-infective potential for better mechanistic interpretation of their probable mode of action. The inhibitory potential of compounds vs. Angiotensin-Converting Enzyme 2 (ACE2) as an important therapeutic target combating COVID-19 infection and its complication was also examined using molecular docking. Fumigatoside E showed the best fitting within the active sites of all the examined proteins. Thus,
species isolated from marine organisms could afford bioactive entities combating infectious diseases.
For the last few years, the world has been going through a difficult time, and the reason behind this is severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), one of the significant members ...of the Coronaviridae family. The major research groups have shifted their focus towards finding a vaccine and drugs against SARS-CoV-2 to reduce the infection rate and save the life of human beings. Even the WHO has permitted using certain vaccines for an emergency attempt to cut the infection curve down. However, the virus has a great sense of mutation, and the vaccine’s effectiveness remains questionable. No natural medicine is available at the community level to cure the patients for now. In this study, we have screened the vast library of experimental drugs of Drug Bank with Schrodinger’s maestro by using three algorithms: high-throughput virtual screening (HTVS), standard precision, and extra precise docking followed by Molecular Mechanics/Generalized Born Surface Area (MMGBSA). We have identified 3-(7-diaminomethyl-naphthalen-2-YL)-propionic acid ethyl ester and Thymidine-5′-thiophosphate as potent inhibitors against the SARS-CoV-2, and both drugs performed impeccably and showed stability during the 100 ns molecular dynamics simulation. Both of the drugs are among the category of small molecules and have an acceptable range of ADME properties. They can be used after their validation in in-vitro and in-vivo conditions.
Coherent diffraction imaging methods enable imaging beyond lens-imposed resolution limits. In these methods, the object can be recovered by minimizing an error metric that quantifies the difference ...between diffraction patterns as observed, and those calculated from a present guess of the object. Efficient minimization methods require analytical calculation of the derivatives of the error metric, which is not always straightforward. This limits our ability to explore variations of basic imaging approaches. In this paper, we propose to substitute analytical derivative expressions with the automatic differentiation method, whereby we can achieve object reconstruction by specifying only the physics-based experimental forward model. We demonstrate the generality of the proposed method through straightforward object reconstruction for a variety of complex ptychographic experimental models.
Progeroid mouse models display phenotypes in multiple organ systems that suggest premature aging and resemble features of natural aging of both mice and humans. The prospect of a significant increase ...in the global elderly population within the next decades has led to the emergence of “geroscience,” which aims at elucidating the molecular mechanisms involved in aging. Progeroid mouse models are frequently used in geroscience as they provide insight into the molecular mechanisms that are involved in the highly complex process of natural aging. This review provides an overview of the most commonly reported nonneoplastic macroscopic and microscopic pathologic findings in progeroid mouse models (eg, osteoporosis, osteoarthritis, degenerative joint disease, intervertebral disc degeneration, kyphosis, sarcopenia, cutaneous atrophy, wound healing, hair loss, alopecia, lymphoid atrophy, cataract, corneal endothelial dystrophy, retinal degenerative diseases, and vascular remodeling). Furthermore, several shortcomings in pathologic analysis and descriptions of these models are discussed. Progeroid mouse models are valuable models for aging, but thorough knowledge of both the mouse strain background and the progeria-related phenotype is required to guide interpretation and translation of the pathology data.
Abstract The Late Cretaceous was a time of high eustatic sea level that enabled extensive epicontinental seaways and carbonate platforms across the Tethyan Realm, providing favorable habitats for ...oyster communities to flourish. This study focuses on the Campanian Tethyan oysters from the North Eastern Desert of Egypt regarding taxonomy, palaeoecology, and palaeobiogeography. Three oyster species, Nicaisolopha nicaisei (Coquand, 1862), Pycnodonte ( Phygraea ) vesicularis (Lamarck, 1806), and Ambigostrea bretoni (Thomas and Peron, 1891), were identified from the Campanian succession in two studied sections. The sampled specimens of the genus Nicaisolopha have undergone a systematic palaeontological revision. As a result, N. tissoti (Thomas and Peron, 1891) is considered herein a junior synonym of N. nicaisei (Coquand, 1862). Palaeobiogeographically, the likely primary migration pattern of the studied oysters suggests an east–west trend along the Southern Tethys margin. All identified oysters in this study exhibit a Tethyan affinity and are primarily abundant in two main provinces: the Southern Tethys and the Western Tethys. The macrofaunal contents are categorized into two fossil associations: the Nicaisolopha nicaisei association of the middle-late Campanian age and the Pycnodonte vesicularis association of the late Campanian age. These macrofaunal associations indicate a deepening trend during the middle-late Campanian age, suggesting a transition from shallow inner neritic to middle neritic environments. Additionally, it is observed that Pycnodonteinae tend to grow larger under eutrophic conditions, low-energy environments, and nutrient-rich waters with high carbonate contents.
Recent advances in phase-retrieval-based x-ray imaging methods have demonstrated the ability to reconstruct 3D distortion vector fields within a nanocrystal by using coherent diffraction information ...from multiple crystal Bragg reflections. However, these works do not provide a solution to the challenges encountered in imaging lattice distortions in crystals with significant defect content that result in phase wrapping. Moreover, these methods only apply to isolated crystals smaller than the x-ray illumination, and therefore cannot be used for imaging of distortions in extended crystals. We introduce multi-peak Bragg ptychography which addresses both challenges via an optimization framework that combines stochastic gradient descent and phase unwrapping methods for robust image reconstruction of lattice distortions and defects in extended crystals. Our work uses modern automatic differentiation toolsets so that the method is easy to extend to other settings and easy to implement in high-performance computers. This work is particularly timely given the broad interest in using the increased coherent flux in fourth-generation synchrotrons for innovative material research.
Purpose
The aim of this study was to review the effect of selective laser melting (SLM) procedure on the properties of dental structures made of Co‐Cr alloys and to evaluate its quality and compare ...it to those produced by conventional casting and milling fabrication techniques.
Materials and Methods
A computerized database search using PubMed and Scopus was conducted for peer‐reviewed scientific research studies regarding the use of SLM in Co‐Cr dental alloys with no restrictions for publication years. The search engines provided hundreds of results, and only 48 scientific research papers, case studies, or literature reviews were considered relevant for this review.
Results
The innovative manufacturing concept of SLM offers many advantages compared with casting and milling fabrication techniques. SLM provides different microstructure from casting and milling with minimal internal porosity and internal fitting, marginal adaptation, and comparable bond strength to porcelain. Mechanical and electrochemical properties of SLM structures are enhanced compared to cast, while clinical longevity of single‐metal ceramic crowns is comparable to Au‐Pt dental alloy.
Conclusion
The SLM technique provides dental prosthetic restorations more quickly and less expensively without compromising their quality compared with restorations prepared by casting and milling techniques. Clinical significance: The current SLM devices provide metallic restorations made of Co‐Cr alloys for removable and fixed partial dentures without compromising the alloy or restoration properties at a fraction of the time and cost, showing great potential to replace the aforementioned fabrication techniques in the long term; however, further clinical studies are essential to increase the acceptance of this technology by the worldwide dental community.
Purpose Expanding indications for robot-assisted partial nephrectomy raise major oncologic concerns for positive surgical margins. Previous reports showed no correlation between positive surgical ...margins and oncologic outcomes. We report a multi-institutional experience with the oncologic outcomes of positive surgical margins on robot-assisted partial nephrectomy. Materials and Methods Pathological and clinical followup data were reviewed from an institutional review board approved, prospectively maintained joint database from 5 institutions. Tumors with malignant pathology were isolated and statistically analyzed for demographics and oncologic followup. The log rank test was used to compare recurrence-free and metastasis-free survival between patients with positive and negative surgical margins. The proportional hazards method was used to assess the influence of multiple factors, including positive surgical margins, on recurrence and metastasis. Results A total of 943 robot-assisted partial nephrectomies for malignant tumors were successfully completed. Of the patients 21 (2.2%) had positive surgical margins on final pathological assessment, resulting in 2 groups, including the 21 with positive surgical margins and 922 with negative surgical margins. Positive surgical margin cases had higher recurrence and metastasis rates (p <0.001). As projected by the Kaplan-Meier method in the population as a whole at followup out to 63.6 months, 5-year recurrence-free and metastasis-free survival was 94.8% and 97.5%, respectively. There was a statistically significant difference in recurrence-free and metastasis-free survival between patients with positive and negative surgical margins (log rank test <0.001), which favored negative surgical margins. Positive surgical margins showed an 18.4-fold higher HR for recurrence when adjusted for multiple tumors, tumor size, tumor growth pattern and pathological stage. Conclusions Positive surgical margins on final pathological evaluation increase the HR of recurrence and metastasis. In addition to pathological and molecular tumor characteristics, this should be considered to plan appropriate management.
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