Miracle-dz/UniFAR-FTUs huggingface dataset:
The Influence of Essential Oil Compounds on Antibacterial Activity of Mupirocin-Susceptible and Induced Low-Level Mupirocin-Resistant MRSA Strains

Because of the bacterial drug resistance development, it is reasonable to investigate chemical compounds capable of preventing the spread of resistance to mupirocin (MUP), commonly used in staphylococcal eradication. The objective of the study was to verify the influence of essential oil compounds (EOCs) on the antibacterial activity of MUP against mupirocin-susceptible (MupS) and induced low-level mupirocin-resistant (MupRL) methicillin-resistant Staphylococcus aureus (MRSA) strains. The following parameters were examined: MRSAMupS and MRSAMupRL susceptibility to EOCs (1,8-cineole, eugenol, carvacrol, linalool, (-)-menthone, linalyl acetate, and trans-anethole), the bacterial cell size distribution, and chemical composition by the use of Fourier Transform Infrared Spectroscopy (FTIR) and Raman spectroscopies. The MRSAMupS and MRSAMupRL strains were susceptible to all tested EOCs. 1,8-cineole and (-)-menthone showed synergistic activity against MRSAMupS in combination with mupirocin, whereas 1,8-cineole exhibited synergistic activity against MRSAMupRL as well. In-depth analysis showed that both MRSAMupS and MRSAMupRL displayed similar distributions of the bacterial cell size. The FTIR and Raman spectra of the MRSAMupS and MRSAMupRL strains showed differences in some regions. New bands in the MRSAMupRL Raman spectrum were observed. It was concluded that the use of 1,8-cineole in combination with mupirocin can increase the mupirocin activity against the MRSAMupS and MRSAMupRL strains.
Wavelength‐ and Tissue‐dependent Variations in the Mutagenicity of Cyclobutane Pyrimidine Dimers in Mouse Skin

The cyclobutane pyrimidine dimer (CPD) is a main mutagenic photolesion in DNA produced by UVR. We previously studied the wavelength‐dependent kinetics of mutation induction efficiency using monochromatic UVR sources and transgenic mice developed for mutation assay and established the action spectra of UVR mutagenicity in the mouse epidermis and dermis. Here, we further established the action spectra of CPD and pyrimidine(6‐4)pyrimidone photoproduct formation in the same tissues and in naked DNA using the same sources and mouse strain. Quantitative ELISA helped us estimate the photolesion formation efficiencies on a molecule‐per‐nucleotide basis. Using these action spectra, we confirmed that the UVR mutation mostly depends on CPD formation. Moreover, the mutagenicity of a CPD molecule (CPD mutagenicity) was found to vary by wavelength, peaking at approximately 313 nm in both the epidermis and dermis with similar wavelength‐dependent patterns. Thus, the CPD formation efficiency is a main determinant of UVR mutagenicity in mouse skin, whereas a wavelength‐dependent variation in the qualitative characteristics of CPD molecules also affects the mutagenic consequences of UVR insults. In addition, the CPD mutagenicity was always higher in the epidermis than in the dermis, suggesting different cellular responses to UVR between the two tissues irrespective of the wavelength.
Development of a vanillate biosensor for the vanillin biosynthesis pathway in E. coli

Genetically encoded small molecule sensors can facilitate metabolic engineering by enabling high-throughput detection of metabolite concentrations, directed evolution of host and pathway enzymes, and dynamic regulation. The engineered de novo vanillin biosynthesis pathway assembled in Escherichia coli is industrially relevant and ideal for biosensor deployment given that the pathway requires only three heterologous enzyme-catalyzed reactions, generates naturally occurring metabolites, and may benefit from dynamic regulation. However, pathway flux is stalled and diverted by the activity of the Homo sapiens catechol O-methyltransferase, which is intended to catalyze the conversion of protocatechuate to vanillate. To confront this challenge, we constructed and applied a vanillate sensor based on the Caulobacter crescentus VanR-VanO system. Using components from a previously characterized E. coli promoter library, we achieved greater than 14-fold dynamic range in our best rationally constructed sensor. We characterized sensor substrate specificity and found that this construct and an evolved variant are remarkably selective, exhibiting no detectable response to the regioisomer byproduct isovanillate. We then harnessed the evolved biosensor to conduct rapid bioprospecting of natural catechol O-methyltransferases. We identified eight that appear to have greater desired activity than the originally used variant, including three previously uncharacterized O-methyltransferases. Collectively, these efforts enrich our knowledge of how biosensing can aid metabolic engineering and constitute the foundation for future improvements in vanillin pathway productivity.
A Modular Spatial-Temporal Modeling Environment for GIS

Development of an open source modeling environment for use with spatial-temporal data in a Geographic Information System (GIS) is presented. To date, legacy versions of MapWindow have lacked an integrated modeling environment suitable for linking together independent geospatial and temporal processes at a granular level. This new modeling environment allows users to easily create models which can take advantage of spatial and temporal data objects and analytical tools. The design approach focuses on an ITool interface that serves as an independent point for the run-time discovery of geoprocessing extensions. The user interface is automatically generated by the modeler when their tool is instantiated based on parameter characteristics on the ITool interface. The design is also versatile, allowing processes to also be run through a more traditional method of adding a reference and calling the processes as functions programatically.
Association of Blood Pressure During Thrombectomy for Acute Ischemic Stroke With Functional Outcome.

Background and Purpose- Optimal blood pressure (BP) targets during mechanical thrombectomy (MT) for acute ischemic stroke (AIS) are unknown, and randomized controlled trials addressing this issue are lacking. We aimed to perform a systematic review of studies evaluating the influence of periprocedural BP on functional outcome after MT. Methods- Studies assessing periprocedural BP effect on functional outcome published after January 1st, 2012 were included in the systematic review. The PRISMA checklist and flow diagram were followed for the design and reporting of this work. Results- Nine studies were included, for a total of 1037 patients. The heterogeneity in findings with respect to BP monitoring and studied parameters precluded a meta-analysis. Mean arterial pressure was the most frequently reported parameter to describe BP variability during MT, and systolic BP was the main parameter used to define periprocedural BP targets. Five studies suggested an association between 3 types of BP drops as predictors of poor functional outcome at 3 months: >40% drop in mean arterial pressure compared with baseline (odds ratio=2.8; [1.09-7.19]; P=0.032), lowest mean arterial pressure before recanalization (odds ratio=1.28; [1.01-1.62] per 10 mm Hg drop below 100 mm Hg; P=0.04), and MAP drops (odds ratio=4.38; [1.53-12.6] for drops >10%). Four studies did not show an association between BP during MT and functional outcome, including 3 studies with strict periprocedural systolic BP targets (within a 140-180 mm Hg). Conclusions- BP drops during MT may be associated with a worse functional outcome. When strict systolic BP targets are achieved, no association between BP and functional outcome was also noted. Both conclusions require further evaluation in randomized studies.
Volatile and phenolic compounds in freshwater diatom Nitzschia palea as a potential oxidative damage protective and anti-inflammatory source

Background: Nitzschia palea is a freshwater diatom species (Bacillariophyceae), is easy to cultivate, and is a primary producer of organic matters in aquatic environments. Materials and Methods: In this study, proximate composition in axenic culture of N. palea was determined, phenolic content and volatile compounds were determined for methanol and ethyl acetate extracts. Both the extracts were evaluated for eight different in vitro antioxidant and free radical scavenging activities. Macromolecular damage prevention properties were determined by electrophoretic methods, and antihemolytic activity was validated by lactate dehydrogenase assay, atomic force microscope, and scanning electron microscope image analysis. Results: Both the extracts showed antioxidant, macromolecular damage prevention, and antihemolytic properties. Among the two extracts, ethyl acetate extract showed high activity compared to methanol extract. Based on this result, ethyl acetate extract was evaluated for in vitro anti-inflammatory properties using RAW 264.7 cells. The extract showed IC50 value of 50.73 μg/mL and inhibition of inflammatory cytokines such as nitric oxide, tumor necrosis factor-alpha, and prostaglandin E2. The observed activity was correlated with identified important metabolites such as butyl isobutyl phthalate, pristane, and squalene of methanol extracts. Similar co-relation was observed for 7,9-di-tert-butyl-1-oxaspiro (4,5) deca-6,9-diene-2,8-dione, methyl palmitate, hentriacontane, and dibutyl phthalate were of ethyl acetate extract. Conclusion: The study concludes that N. palea has potentiality to isolate pharmacologically active metabolites using advanced chromatographic techniques, which can be useful in combating oxidative stress-related inflammatory diseases.
Nanomaterial‐Enabled Flexible and Stretchable Sensing Systems: Processing, Integration, and Applications

Nanomaterial‐enabled flexible and stretchable electronics have seen tremendous progress in recent years, evolving from single sensors to integrated sensing systems. Compared with nanomaterial‐enabled sensors with a single function, integration of multiple sensors is conducive to comprehensive monitoring of personal health and environment, intelligent human–machine interfaces, and realistic imitation of human skin in robotics and prosthetics. Integration of sensors with other functional components promotes real‐world applications of the sensing systems. Here, an overview of the design and integration strategies and manufacturing techniques for such sensing systems is given. Then, representative nanomaterial‐enabled flexible and stretchable sensing systems are presented. Following that, representative applications in personal health, fitness tracking, electronic skins, artificial nervous systems, and human–machine interactions are provided. To conclude, perspectives on the challenges and opportunities in this burgeoning field are considered.
Cytotoxic action and proliferation in vitro and Analgesic Activity in vivo of Resin from Hymenaea stigonocarpa

Background: Hymenaea stigonocarpa Mart. (Fabaceae ) is one of the plant species commonly found in Brazilian cerrado. It is popularly known as jatobá-do-cerrado. Phytochemical studies of different parts of the plant demonstrated the presence of sesquiterpenes, diterpenes, and oligosaccharides. The species produces an opaque, translucent, pale yellow, or almost white resin rich in labdanóides compounds, widely used in folk medicine, but without proving its pharmacological actions. Objective: To analyze the H. stigonocarpa resin to confirm its pharmacological actions through specific tests for cicatrization, nociception, and cytotoxicity and to evaluate the chemical composition through the gas chromatography coupled to mass spectrometry (GC-MS). Materials and Methods: The cell proliferation/migration capacity was evaluated using the scratch assay method and the cell viability determined by the 3-[4,5-dimethylthiazol-2-yl]–tetrazolium 2,5-diphenyl-bromide cytotoxicity assay. In the pharmacological tests were performed Abdominal Contortions induced by acetic acid and Nociceptive Response evaluated by the Formalin Test. GC-MS was used to trace the profile of the bioactive compounds of the resin. Results: It was possible to verify the presence of terpene compounds with the labdanos skeleton. Structures that revealed important pharmacological actions regarding healing, evidenced by the scratch assay test and nociceptive activity demonstrated by the animal tests. No cytotoxic activity was detected at the dosages tested. Conclusion: The results obtained confirm the pharmacological action of the species and can be used to elaborate on new therapies, which will increase the therapeutic arsenal available to the population.
New immunodeficiency syndromes that help us understand the IFN-mediated antiviral immune response.

PURPOSE OF REVIEW Studying primary immunodeficiencies (PIDs) provides insights into human antiviral immunity in the natural infectious environment. This review describes new PIDs with genetic defects that impair innate antiviral responses. RECENT FINDINGS New genetic defects in the interferon (IFN) signaling pathway include IFNAR1 deficiency, which causes uncontrolled infections with measles-mumps-rubella or yellow fever vaccines, and possibly also cytomegalovirus (CMV); and IRF9 deficiency, which results in influenza virus susceptibility. Genetic defects in several pattern recognition receptors include MDA5 deficiency, which impairs viral RNA sensing and confers human rhinovirus susceptibility; RNA polymerase III haploinsufficiency, which impairs sensing of A:T-rich virus DNA and confers VZV susceptibility; and TLR3 deficiency, which causes HSV-1 encephalitis (HSE) or influenza virus pneumonitis. Defects in RNA metabolism, such as that caused by Debranching enzyme 1 deficiency, can cause virus meningoencephalitis. Finally, defects in host restriction factors for virus replication, such as in CIB1 deficiency, contribute to uncontrolled β-HPV infections. SUMMARY Several new PIDs highlight the role of type I/III IFN signaling pathway, virus sensors, and host virus restriction factors in human antiviral immunity.
A Bispecific Molecule Targeting CD40 and Tumor Antigen Mesothelin Enhances Tumor-Specific Immunity

A bispecific molecule with conditional activity was engineered to target both an immune activator and a tumor-specific surface antigen. The strategy shows potential to enhance tumor-specific immune activation and reduce systemic toxicity. Agonistic CD40 monoclonal antibodies (mAb) have demonstrated some clinical activity, but with dose-limiting toxicity. To reduce systemic toxicity, we developed a bispecific molecule that was maximally active in the presence of a tumor antigen and had limited activity in the absence of the tumor antigen. LB-1 is a bispecific molecule containing single-chain Fv domains targeting mouse CD40 and the tumor antigen mesothelin. LB-1 exhibited enhanced activity upon binding to cell-surface mesothelin but was less potent in the absence of mesothelin binding. In a mouse model implanted with syngeneic 4T1 tumors expressing cell-surface mesothelin, LB-1 demonstrated comparable antitumor activity as an agonistic CD40 mAb but did not cause elevation of serum cytokines and liver enzymes, as was observed in anti-CD40–treated mice. The results from our study of LB-1 were used to develop a human cross-reactive bispecific molecule (ABBV-428) that targeted human CD40 and mesothelin. ABBV-428 demonstrated enhanced activation of antigen-presenting cells and T cells upon binding to cell-surface mesothelin, and inhibition of cultured or implanted PC3 tumor cell growth after immune activation. Although expression of cell-surface mesothelin is necessary, the bispecific molecules induced immune-mediated antitumor activity against both mesothelin+ and mesothelin− tumor cells. ABBV-428 represents a class of bispecific molecules with conditional activity dependent on the binding of a tumor-specific antigen, and such activity could potentially maximize antitumor potency while limiting systemic toxicity in clinical studies.
Tungsten-Doped L10-PtCo Ultrasmall Nanoparticles as High-Performance Fuel Cell Cathode.

The commercialization of proton exchange membrane fuel cells (PEMFCs) relies on highly active and stable electrocatalysts for oxygen reduction reaction (ORR) in acid media. The most successful catalysts for this reaction are nanostructured Pt-alloy with a Pt-skin. Here, we report the synthesis of ultrasmall and ordered L1 0 -PtCo nanoparticle ORR catalysts further doped with a few percent of transition metals (i.e., W, Ga, and Zn). Compared to commercial Pt/C catalyst, the L1 0 -W-PtCo/C catalyst shows significant improvement in both initial activity and high-temperature stability. Importantly, the L1 0 -W-PtCo/C catalyst achieves high activity and stability in the PEMFC after 50k voltage cycles at 80 °C, superior to the DOE 2020 targets. Extended X-ray absorption fine structure analysis and density functional theory calculations reveal that W doping not only stabilizes the ordered intermetallic structure, but also tunes the Pt-Pt distances in such a way to optimize the binding energy between Pt and O intermediates on the surface. This work demonstrates a new strategy of stabilizing the intermetallic nanoparticles with transition metal doping to improve the performance of electrocatalysts.
Coexistence of colon adenocarcinoma, diffuse large B-cell lymphoma, and myelodysplastic syndrome

Abstract Rationale: Cases of coexistence of 2 cancers, such as colorectal cancer and diffuse large B-cell lymphoma (DLBCL), colorectal cancer and myelodysplastic syndrome (MDS), and DLBCL with MDS, have been reported, whereas the coexistence of 3 different cancers in a patient is extremely rare. Here we report a case of co-occurrence of colon adenocarcinoma, DLBCL, and MDS in a 78-year-old Chinese man. Patient concerns: He presented to our hospital with palpable lumps in the abdomen without any of the following symptoms including abdominal pain, fever, contact pain, tenesmus, changes in bowel habits and shape, nausea, and vomiting. Diagnoses: The patient was first diagnosed with sigmoid colon adenocarcinoma and DLBCL in the right ascending colon using enhanced computed tomography, colonoscopy, and immunohistochemistry. After resection of the sigmoid adenocarcinoma and DLBCL, MDS was diagnosed according to the results of routine blood tests, bone marrow aspiration smear, and flow cytometry. Interventions: Overall, the patient was treated with surgical resection of the sigmoid adenocarcinoma and DLBCL of the colon, combined with 4 cycles of chemotherapies targeting MDS. Outcomes: Blood test results and follow-up indicated that the treatment regimen showed promising outcomes. Lessons: In conclusion, a case of synchronous existence of colon cancer, DLBCL, and MDS is reported, which suggests that careful attention should be paid clinically to checking the state of bone marrow for elderly cancer patients. Efforts are also needed to establish an effective system for distinguishing the origin of multi-existent cancers and to develop effective therapeutic regimens for multi-existent cancers with fewer side effects.
Cyber-Physical Engineering of Distributed Automation Systems in Energy Domain

The main focus of this thesis is in the domain of Energy Systems, specifically in the engineering of modern Smart Grid (SG) automation systems. The SG has been categorized as a Cyber-Physical System (CPS), a complex system which exhibits tight integration between the cyber and the physical processes and their interactions in a networked environment. The complexity and the computation of the automation system are expected to increase with the promise of a ”smart” electric grid which is capable of self-healing, self-reconfiguration and become more resilient against cyber-attacks. These automation software systems require control strategies which are distributed in execution and require very tight integrations and interactions between various modular software and hardware components. As the automation system becomes more software intensive, we hypothesize that existing design practices of developing the substation automation software system would struggle to cope with the distributed design challenges of the Smart Grid and they could be substantially enhanced by the application of model-driven design, distributed software architectures and semantic models. Model-driven engineering (MDE) is a software design paradigm that leverages the use of abstraction models at different stages of the design process for engineering complex software systems. MDE is widely used in the software engineering domain and it has proven to be effective when designing and maintaining large-scale software applications. One of the core tenants of MDE is model transformation and it is considered the heart and soul of MDE. The standard modelling language that is used for MDE in software engineering is the Unified Modelling Language (UML), which is a visual language with a wide array of tool support. Despite its popularity in the software domain, UML models still have its limitations. In particular, the lack of uniformed semantics between its 13 different visual diagrams and the lack of formal notations. In this thesis, we propose the Cyber-Physical Engineering (CPE) framework, an MDE framework which combines semantic models and MDE based automatic model transformation in order to autogenerate both the automation control system and the simulation plant model from the physical and functional specifications of CPS systems. All the scientific papers included in this thesis contributes towards the proposed Cyber-Physical Engineering methodology which includes MDE using semantic models, formal modelling of functional requirements and co-simulation testing of CPS systems. The contribution of the thesis is fivefold. Firstly, the thesis proposes the CPE framework, which is based on the use of semantic web modelling language where logical reasoning can be applied to the models. The modelling language that is used is the Web Ontology Language (OWL), which is a declarative language with a strong formal foun-
Tumor microenvironment and immunology of ovarian cancer: 12th Biennial Rivkin Center Ovarian Cancer Research Symposium

The 12th Biennial Ovarian Cancer Research Symposium organized by the Rivkin Center for Ovarian Cancer and the American Association for Cancer Research held on September 13–15, 2018 covered cutting edge and relevant research topics in ovarian cancer biology and therapy. Sessions included detection and prevention, genomics and molecular mechanisms, tumor microenvironment and immunology, novel therapeutics, and an education session. In this article we provide an overview of the key findings presented in the tumor microenvironment and immunology session.