gebhart/patrepeval huggingface dataset:
1,8‐Naphthyridine Derivatives: A Review of Multiple Biological Activities (2015)

The 1,8-naphthyridine group of compounds have gained special attention of researchers on account of their demonstrating a variety of interesting biological activities. A wide range of biological properties establishes them as potent scaffolds in therapeutic and medicinal research. The broad spectrum of activities primarily includes antimicrobial, antiviral, anticancer, anti-inflammatory, and analgesic activities. 1,8-Naphthyridine derivatives have also exhibited potential applications in neurological disorders such as Alzheimer's disease, multiple sclerosis, and depression. In addition, these synthetic derivatives have been found to possess activities such as anti-osteoporotic (α(v)β(3) antagonists), anti-allergic, antimalarial, gastric antisecretory, bronchodilator, anticonvulsant, anti-hypertensive, platelet aggregation inhibition, anti-oxidant, EGFR inhibition, protein kinase inhibition, ionotropic agent, β-3 antagonist, MDR modulator, adenosine receptor agonist, adrenoceptor antagonist, and pesticide activities. In spite of the widespread application of the 1,8-naphythyridine scaffolds, only a limited number of review articles are available till date. In this review, we attempt to compile and discuss the key data available in the literature for the multiple biological activities of 1,8-naphthyridine derivatives, in a chronological manner. This review compilation (with 199 references) may be helpful in understanding the diverse biological properties of 1,8-naphthyridines and provide insights into their mechanism of action. This may direct future research in the synthesis of new derivatives and exploring this scaffold for other possible biological activities.
Reversal of tau-dependent cognitive decay by blocking adenosine A1 receptors in mouse models of tauopathy (2022)

Abstract Background: Accumulation of tau is a characteristic hallmark of several neurodegenerative diseases and is associated with neuronal hypoactivity and presynaptic dysfunction. Oral administration of the adenosine A 1 receptor antagonist rolofylline (KW-3902) has been shown previously to reverse spatial memory deficits and to normalize the basic synaptic transmission in a mouse line expressing full-length proaggregant tau (Tau ΔK ). Methods: Using a combination of behavioral assays, imaging by PET with several PET-tracers, and analysis of brain tissue, we studied the curative reversal of tau pathology by blocking adenosine A1 receptors in transgenic mice expressing different types of tau and tau mutants. Results : We show by positron emission tomography using the tracer [ 18 F]CPFPX (a selective A1 receptor ligand) that intravenous injection of rolofylline effectively blocks A 1 receptors in the brain. Moreover, when administered to Tau ΔK mice, rolofylline can reverse tau pathology and synaptic decay. The beneficial effects are not restricted to the full-length Tau ΔK mouse line as they were also observed in a line with more aggressive tau pathology, expressing the amyloidogenic repeat domain of tau (TauRD ΔK ) with higher aggregation propensity. Both transgenic models develop a progressive tau pathology with missorting, phosphorylation, local accumulation of tau, loss of synapses and cognitive decline. TauRD ΔK causes pronounced neurofibrillary tangle assembly concomitant with neuronal death, whereas Tau ΔK accumulates only to tau pretangles without overt neuronal loss. A third model tested, the rTg4510 line has a high expression of mutant Tau P301L and hence a very aggressive phenotype starting at ~3 months of age. This line failed to reverse pathology upon rolofylline treatment, consistent with higher accumulation of tau-specific PET tracers and inflammation. Conclusions: Blocking adenosine A1 receptors by rolofylline can reverse pathology if the pathological potential of tau remains below a threshold value that depends on concentration and aggregation propensity. Thus, reversal is possible even in presence of potent pro-aggregant mutants near physiological tau levels but is overwhelmed by high levels of mutant tau, accompanied by intense neuroinflammation.
Synergistic antitumor effects of immunotherapy with recombinant interleukin-2 and recombinant tumor necrosis factor-alpha. (1988)

The antitumor activity of combination therapy with recombinant tumor necrosis-alpha (rhTNF-alpha) and recombinant interleukin-2 (rhIL-2) was assessed against established immunogenic (MCA-106) and nonimmunogenic (MCA-102) sarcomas at both s.c. and visceral (hepatic) sites. C57BL/6 (B6) mice were treated with a single i.v. dose of rhTNF-alpha (2, 4, 6, or 8 micrograms) followed by rhIL-2 (25,000 U) i.p. thrice daily for 5 consecutive days. Synergistic effects as measured by regression of tumor, prolongation of survival, and improved cure rates were found using the combination of rhTNF-alpha plus rhIL-2 compared to rhTNF-alpha alone or rhIL-2 alone in the treatment of the immunogenic sarcoma MCA-106. No significant antitumor effects were observed against the nonimmunogenic MCA-102 sarcoma. These findings were similar for both s.c. and large single hepatic tumor models. The effect of the timing of rhIL-2 injections in relation to rhTNF-alpha administration (concurrent, 2, 4, or 6 days post single rhTNF-alpha dose) was also evaluated. Substantial tumor regression and increased survival times were seen in mice with s.c. tumors when rhIL-2 therapy was delayed as much as 48 h after rhTNF-alpha administration. No antitumor response was noted with the combination compared to rhTNF-alpha alone when rhIL-2 was delayed for greater than 4 days. No increase in lethal toxicity during treatment course of the combination of rhTNF-alpha and rhIL-2 was noted at any schedule compared to single agent rhTNF-alpha therapy. A possible role of rhTNF-alpha in regulation of IL-2-dependent antitumor activity in vivo is discussed.
Yulink, predicted from evolutionary analysis, is involved in cardiac function (2021)

Overall, our data showed that Yulink is an evolutionarily conserved gene from zebrafish to human. Mechanistically Yulink regulated Serca2 expression in cardiomyocytes, presumably mediated through PPARγ nuclear entry. Deficiency of Yulink in mouse and human cardiomyocytes resulted in irregular Ca<sup>2+</sup> cycling, which may contribute to arrhythmogenesis.
In vitro antimicrobial potential of representative Mediterranean plant extracts against oral microorganisms (2016)

Bacteria, viruses, and fungi are capable of forming dynamic microbial networks, namely biofilms, on human substrata, causing numerous infectious diseases [1]. In the oral cavity, more than 700 microbial species have been recovered so far, resulting in the genesis of caries, gingivitis or periodontitis. Recent years have seen a focus in oral microbiology research on the elucidation and elimination of biofilm-related dental diseases [2,3]. The need to discover new efficient treatment strategies against oral microbial species has raised interest in novel therapeutic approaches. Especially the antimicrobial activity of natural products is highly acknowledged. The aim of the present study was to examine the antimicrobial potential of plant extracts of the Mediterranean against various microbial species. Representative genera of the Mediterranean were tested such as Cistus, Inula, Lavandula, Mentha, Origanum, Phlomis, Rosmarinus, Sideritis, Salvia, Satureja, Stachys and Thymus. Extracts were produced with accelerated solvent extraction and ultrasound assisted extraction using ethyl acetate and methanol/water 80:20, as the extraction solvents. Their profiles were generated using High Performance Thin Layer Chromatography revealing their high content in natural compounds. The extracts were screened against a panel of nine relevant pathogenic microorganisms, which constitute typical residents of the oral microflora, including one strain of Candida albicans. Additionally, Staphylococcus aureus and Escherichia coli, normally a part of skin and intestinal flora, served as reference bacterial strains. Two antimicrobial assays, the minimum inhibitory concentration (MIC) assay and the minimum bactericidal concentration (MBC) assay, were utilized. Extracts were less effective against C. albicans and exerted bactericidal effects at concentration range of 0.07 – 5.00 mg mL-1 on strict anaerobic bacteria and could therefore be considered as alternative natural anti-infectious agents.
The cationic polymerization of 2-vinylfuran on the surface of silica particles - an NMR spectroscopic study (1999)

The cationic polymerization of 2-vinylfuran initiated with triphenylmethyl chloride in conjunction with silica nanoparticles in suspension yields poly(2-vinylfuran)/silica hybrid particles and a soluble fraction of oligo(2-vinylfuran). 2-Vinylfuran cationically is polymerized via both the vinyl double bond and the 5-position of the furan ring. The formation of the resulting crosslinked poly(2-vinylfuran) network structure on the surface of the silica particles is examined by means of different kinds of NMR spectroscopy and an assignment of the signals is given.
MO401RENAL ANGINA INDEX IN ADULT CRITICAL CARE PATIENTS IN A POPULATION FROM BOGOTÁ – COLOMBIA (2021)

Abstract Background and Aims Clinical outcomes of Acute Kidney Injury (AKI) in ICU mainly depend on opportune preventive strategies. Thus, early identification of AKI is mandatory, and alternative diagnostic strategies become plausible: one of them, Renal Angina Index (RAI), described by Matsuura1, predicts the development of AKI KDIGO 2-3, at 7th day after admission to the intensive care unit according to a cut-off point &amp;gt;6 on a scale with a “creatinine score” (determined by the difference in serum creatinine between that at ICU admission and the first 24 hours in the ICU) and the impact of the patients medical history. 1Kidney Int Rep (2018) 3, 677-683. Our aim is to describe predictive capacity of the Renal Angina Index (RAI) in adult critical care patients in our population. Method We retrospectively selected from our Critical Care Nephrology database adult patients admitted in any of our hospital`s ICU between February to August 2020, excluding those at admission with diagnosis of AKI, serum creatinine &amp;gt; 2.5 mg/dl, or those receiving dialysis (acute or chronic) or kidney transplantation. We defined AKI according to KDIGO criteria. The RAI score was defined as the worst condition score multiplied by the creatinine score. The performance of the RAI score was assessed by Receiver Operating Characteristic (ROC) analysis power to detect a difference of 0.2 between the area under the curve (AUC), under the null hypothesis of AUC = 0.5 (no diagnostic accuracy). The optimal cut point was estimated with the Youden method. Results From 1204 new ICU patients, we included 372 patients (women 40.3%), with mean age 60.9 (18-98) (table 1). Main indication for ICU admission was medical conditions. Mean APACHE II was 22.9, hemodinamic support was required in 41,1% patients, mechanical ventilation in 58.6% patients and diabetes mellitus was present in 21.5% patients. AKI KDIGO 2-3 developed in 26.8% of patients. Mean creatinine at admission was statistically different in patients with AKI (CI 0.95 –0.51 - --0.15 mg/dl, p=0.0004). The requirement of hemodynamic (p = 0.003) and ventilatory support (p = 0.009), sepsis (p = 0.003), and COVID-19 (p = 0.03) were more frequent in patients who developed AKI. Renal replacement therapy was required in 39 (60%) of patients with severe AKI (incidence 10,5%). RAI cutt-off point determined by Youden method in the overall sample was 24, being significantly higher in patients who developed AKI (16.54 Vs 7.47, CI 0.95 –13.5--4.99, p &amp;lt;0.001). A cut-off point of 24 was required for the Best predictive capacity for severe AKI, with sensitivity, specificity, positive and negative likelihood ratio of 34%, 94%, 5.5 and 0.7 respectively. Conclusion In our population, RAI score requires a cutoff point much higher than that originally described to predict the development of severe AKI. Losing its discriminatory capacity.
Translocation of Single-Wall Carbon Nanotubes Through Solid-State Nanopores (2011)

We report the translocation of individual single-wall carbon nanotubes (SWNTs) through solid-state nanopores. Single-strand DNA oligomers are used to both disperse the SWNTs in aqueous solution and to provide them with a net charge, allowing them to be driven through the nanopores by an applied electric field. The resulting temporary interruptions in the measured nanopore conductance provide quantitative information on the diameter and length of the translocated nanotubes at a single-molecule level. Furthermore, we demonstrate that the technique can be utilized to monitor bundling of SWNT in solution by using complementary nucleotides to induce tube-tube agglomeration.
Metabolic Reconstruction and Modeling of Nitrogen Fixation in Rhizobium etli (2007)

Rhizobiaceas are bacteria that fix nitrogen during symbiosis with plants. This symbiotic relationship is crucial for the nitrogen cycle, and understanding symbiotic mechanisms is a scientific challenge with direct applications in agronomy and plant development. Rhizobium etli is a bacteria which provides legumes with ammonia (among other chemical compounds), thereby stimulating plant growth. A genome-scale approach, integrating the biochemical information available for R. etli, constitutes an important step toward understanding the symbiotic relationship and its possible improvement. In this work we present a genome-scale metabolic reconstruction (iOR363) for R. etli CFN42, which includes 387 metabolic and transport reactions across 26 metabolic pathways. This model was used to analyze the physiological capabilities of R. etli during stages of nitrogen fixation. To study the physiological capacities in silico, an objective function was formulated to simulate symbiotic nitrogen fixation. Flux balance analysis (FBA) was performed, and the predicted active metabolic pathways agreed qualitatively with experimental observations. In addition, predictions for the effects of gene deletions during nitrogen fixation in Rhizobia in silico also agreed with reported experimental data. Overall, we present some evidence supporting that FBA of the reconstructed metabolic network for R. etli provides results that are in agreement with physiological observations. Thus, as for other organisms, the reconstructed genome-scale metabolic network provides an important framework which allows us to compare model predictions with experimental measurements and eventually generate hypotheses on ways to improve nitrogen fixation.
Identification of Functionally Distinct Na-HCO3 Co-Transporters in Colon (2013)

Na-HCO3 cotransport (NBC) regulates intracellular pH (pHi) and HCO3 secretion in rat colon. NBC has been characterized as a 5,5'-diisothiocyanato-2-2'-stilbene (DIDS)-sensitive transporter in several tissues, while the colonic NBC is sensitive to both amiloride and DIDS. In addition, the colonic NBC has been identified as critical for pHi regulation as it is activated by intravesicular acid pH. Molecular studies have identified several characteristically distinct NBC isoforms [i.e. electrogenic (NBCe) and electroneutral (NBCn)] that exhibit tissue specific expression. This study was initiated to establish the molecular identity and specific function of NBC isoforms in rat colon. Northern blot and reverse transcriptase PCR (RT-PCR) analyses revealed that electrogenic NBCe1B or NBCe1C (NBCe1B/C) isoform is predominantly expressed in proximal colon, while electroneutral NBCn1C or NBCn1D (NBCn1C/D) is expressed in both proximal and distal colon. Functional analyses revealed that amiloride-insensitive, electrogenic, pH gradient-dependent NBC activity is present only in basolateral membranes of proximal colon. In contrast, amiloride-sensitive, electroneutral, [H(+)]-dependent NBC activity is present in both proximal and distal colon. Both electrogenic and electroneutral NBC activities are saturable processes with an apparent Km for Na of 7.3 and 4.3 mM, respectively; and are DIDS-sensitive with apparent Ki of 8.9 and 263.8 µM, respectively. In addition to Na-H exchanger isoform-1 (NHE1), pHi acidification is regulated by a HCO3-dependent mechanism that is HOE694-insensitive in colonic crypt glands. We conclude from these data that electroneutral, amiloride-sensitive NBC is encoded by NBCn1C/D and is present in both proximal and distal colon, while NBCe1B/C encodes electrogenic, amiloride-insensitive Na-HCO3 cotransport in proximal colon. We also conclude that NBCn1C/D regulates HCO3-dependent HOE694-insensitive Na-HCO3 cotransport and plays a critical role in pHi regulation in colonic epithelial cells.
ChemInform Abstract: ISOXAZOLE 4. MITT. DARST. VON ISOXAZOLEN UEBER INTERMEDIAERE ISOXAZOLINE (1971)

Abstract Die Nitriloxide (I) reagieren mit den Olefinen (II) bzw. (V) durch 1,3‐dipolare Cycloaddition über die Isoxazoline (III) bzw. (VI) zu den Isoxazolen (IV) (65‐95% Ausbeute) bzw. (VII) (60‐86%).
Characterization of a Novel Two-Component Regulatory System, HptRS, the Regulator for the Hexose Phosphate Transport System in Staphylococcus aureus (2015)

Hexose phosphate is an important carbon source within the cytoplasm of host cells. Bacterial pathogens that invade, survive, and multiply within various host epithelial cells exploit hexose phosphates from the host cytoplasm through the hexose phosphate transport (HPT) system to gain energy and synthesize cellular components. In Escherichia coli, the HPT system consists of a two-component regulatory system (UhpAB) and a phosphate sensor protein (UhpC) that tightly regulate expression of a hexose phosphate transporter (UhpT). Although growing evidence suggests that Staphylococcus aureus also can invade, survive, and multiply within various host epithelial cells, the genetic elements involved in the HPT system in S. aureus have not been characterized yet. In this study, we identified and characterized the HPT system in S. aureus that includes the hptRS (a novel two-component regulatory system), the hptA (a putative phosphate sensor), and the uhpT (a hexose phosphate transporter) genes. The hptA, hptRS, and uhpT markerless deletion mutants were generated by an allelic replacement method using a modified pMAD-CM-GFPuv vector system. We demonstrated that both hptA and hptRS are required to positively regulate transcription of uhpT in response to extracellular phosphates, such as glycerol-3-phosphate (G3P), glucose-6-phosphate (G6P), and fosfomycin. Mutational studies revealed that disruption of the hptA, hptRS, or uhpT gene impaired the growth of bacteria when the available carbon source was limited to G6P, impaired survival/multiplication within various types of host cells, and increased resistance to fosfomycin. The results of this study suggest that the HPT system plays an important role in adaptation of S. aureus within the host cells and could be an important target for developing novel antistaphylococcal therapies.
Automated Modular Fixture Planning: Accuracy, Clamping, and Accessibility Analysis (1997)

Abstract Automated fixture design has become a research focus in process planning and CAD/CAM integration. An automated fixture configuration design system has been developed where when fixturing surfaces and points are specified, modular fixture components can be automatically selected and placed into position with satisfying assemble conditions. A geometric analysis has been conducted to determine the fixturing surfaces and points which provide feasible geometric constraints and assembly relationships with modular fixtures. This paper presents analyses on fixturing accuracy, clamp planning, fixturing accessibility, and clamping stability. When a fixture planning is determined, the analysis results can be applied to verify the performance of the fixture design.
Culture‐enriched community profiling improves resolution of the vertebrate gut microbiota (2021)

Abstract Vertebrates harbour gut microbial communities containing hundreds of bacterial species, most of which have never been cultivated or isolated in the laboratory. The lack of cultured representatives from vertebrate gut microbiotas limits the description and experimental interrogation of these communities. Here, we show that representatives from &gt;50% of the bacterial genera detected by culture‐independent sequencing in the gut microbiotas of fence lizards, house mice, chimpanzees, and humans were recovered in mixed cultures from frozen faecal samples plated on a panel of nine media under a single growth condition. In addition, culturing captured &gt;100 rare bacterial genera overlooked by culture‐independent sequencing, more than doubling the total number of bacterial sequence variants detected. Our approach recovered representatives from 23 previously uncultured candidate bacterial genera, 12 of which were not detected by culture‐independent sequencing. Results identified strategies for both indiscriminate and selective culturing of the gut microbiota that were reproducible across vertebrate species. Isolation followed by whole‐genome sequencing of 161 bacterial colonies from wild chimpanzees enabled the discovery of candidate novel species closely related to the opportunistic pathogens of humans Clostridium difficile and Hungatella hathewayi . This study establishes culturing methods that improve inventories and facilitate isolation of gut microbiota constituents from a wide diversity of vertebrate species.
Measurement of high-Q microcavity resonance in a GaAs/Al/sub x/O/sub y/ photonic bandgap air-bridge microcavity near λ=1550 nm (2003)

Summary form only given. Periodically spaced holes in a high dielectric contrast waveguide system lead to the formation of a one-dimensional photonic bandgap (PBG). A change in the spacing between the two center holes places a defect state in the photonic bandgap and creates an optical resonance. The modal volume of the resonance in such a structure is of the the order (/spl lambda//2n), where n is the refractive index of the material. Such devices have previously been studied in the Si/SiO/sub 2/ material system. This work presents observations of photonic resonances in GaAs/Al/sub x/O/sub y/ PBG microcavities. The III-V compound semiconductor system offers the possibilities of active as well as electro-optically controlled devices. These results are for air bridge microcavities, where the oxide material under the PBG crystal has been etched away, suspending the cavity in air to provide a greater index contrast and higher confinement.
Microstructural model for prediction of stress-strain curves of amorphous and semicrystalline elastomers (1997)

A fundamental microstructural model was developed to calculate the stress–strain curves of rubbery amorphous polymers and of semicrystalline polymers with a rubbery amorphous phase by numerical simulations. The rubbery amorphous phase was treated by using a version of the theory of rubber elasticity with finite extensibility. Physical entanglements and chemical crosslinks were both allowed. Slippage was implemented by a Monte Carlo algorithm controlled by kinetic parameters such as the activation energy and activation volume for slippage. The crystalline phase was treated in a very idealized manner, including a crude representation of tie chains but not taking the internal structure of the crystallites into account. A two-dimensional embodiment of the model was implemented into software. For amorphous polymers, while lacking truly quantitative accuracy, the model showed sufficiently good agreement with the experimental trends to be used as a qualitative or semiquantitative predictive tool, and it is currently being used in this manner. The more complex semicrystalline version was less accurate and will need to be improved in future work. Most of the limitations of the semicrystalline version could be ascribed unambiguously to specific simplifications made in the software implementation to reduce the amount of computer time required for the calculations. © 1997 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 35: 2715–2739, 1997