gebhart/patrepeval huggingface dataset:
Enzymatic Synthesis of 3-Deoxy-<scp>d</scp>-<i>manno</i>-octulosonate 8-Phosphate, 3-Deoxy-<scp>d</scp>-<i>altro</i>-octulosonate 8-Phosphate, 3,5-Dideoxy-<scp>d</scp>-<i>gluco(manno)-</i>octulosonate 8-Phosphate by 3-Deoxy-<scp>d</scp>-<i>arabino</i>-heptulosonate 7-Phosphate Synthase (1998)

The phenylalanine-sensitive 3-deoxy-d-arabino-heptulosonate 7-phosphate (DAH 7-P) synthase (phe), a key enzyme involved in the biosynthesis of the aromatic amino acid phenylalanine, expressed by the Escherichia coli gene aroG, which catalyzes the condensation of d-erythrose 4-phosphate with phosphoenolpyruvate (PEP) to give DAH 7-P, was cloned into the expression vector pT7-7 for overexpression in E. coli. Purified enzyme from this expression system was used to demonstrate that DAH 7-P synthase (phe) also catalyses the aldol-type condensation of PEP with the 5-carbon analogues d-arabinose 5-phosphate, d-ribose 5-phosphate, and 2-deoxy-d-ribose 5-phosphate to yield 3-deoxy-d-manno-octulosonate 8-phosphate, 3-deoxy-d-altro-octulosonate 8-phosphate, and 3,5-dideoxy-d-gluco(manno)-octulosonate 8-phosphate, respectively, as determined by 1H NMR and other standard analytical methods. The kinetic parameters, Km and Vmax, for these reactions were determined. The 3- and 6-carbon phosphorylated monosaccharides, d,l-glyceraldehyde 3-phosphate and d-glucose 6-phosphate, as well as the nonphosphorylated 5-carbon analogues d-arabinose 5-phosphate, d-ribose 5-phosphate, and 2-deoxy-d-ribose 5-phosphate were not substrates.
A Cross-Species Study of PI3K Protein-Protein Interactions Reveals the Direct Interaction of P85 and SHP2 (2016)

Using a series of immunoprecipitation (IP)-tandem mass spectrometry (LC-MS/MS) experiments and reciprocal BLAST, we conducted a fly-human cross-species comparison of the phosphoinositide-3-kinase (PI3K) interactome in a drosophila S2R+ cell line and several NSCLC and human multiple myeloma cell lines to identify conserved interacting proteins to PI3K, a critical signaling regulator of the AKT pathway. Using H929 human cancer cells and drosophila S2R+ cells, our data revealed an unexpected direct binding of Corkscrew, the drosophila ortholog of the non-receptor protein tyrosine phosphatase type II (SHP2) to the Pi3k21B (p60) regulatory subunit of PI3K (p50/p85 human ortholog) but no association with Pi3k92e, the human ortholog of the p110 catalytic subunit. The p85-SHP2 association was validated in human cell lines, and formed a ternary regulatory complex with GRB2-associated-binding protein 2 (GAB2). Validation experiments with knockdown of GAB2 and Far-Western blots proved the direct interaction of SHP2 with p85, independent of adaptor proteins and transfected FLAG-p85 provided evidence that SHP2 binding on p85 occurred on the SH2 domains. A disruption of the SHP2-p85 complex took place after insulin/IGF1 stimulation or imatinib treatment, suggesting that the direct SHP2-p85 interaction was both independent of AKT activation and positively regulates the ERK signaling pathway.
Physiologically Based Pharmacokinetic Modelling to Predict Pharmacokinetics of Enavogliflozin, a Sodium-Dependent Glucose Transporter 2 Inhibitor, in Humans (2023)

Enavogliflozin is a sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor approved for clinical use in South Korea. As SGLT2 inhibitors are a treatment option for patients with diabetes, enavogliflozin is expected to be prescribed in various populations. Physiologically based pharmacokinetic (PBPK) modelling can rationally predict the concentration-time profiles under altered physiological conditions. In previous studies, one of the metabolites (M1) appeared to have a metabolic ratio between 0.20 and 0.25. In this study, PBPK models for enavogliflozin and M1 were developed using published clinical trial data. The PBPK model for enavogliflozin incorporated a non-linear urinary excretion in a mechanistically arranged kidney model and a non-linear formation of M1 in the liver. The PBPK model was evaluated, and the simulated pharmacokinetic characteristics were in a two-fold range from those of the observations. The pharmacokinetic parameters of enavogliflozin were predicted using the PBPK model under pathophysiological conditions. PBPK models for enavogliflozin and M1 were developed and validated, and they seemed useful for logical prediction.
Mechanics of Endothelial Cell Architecture and Vascular Permeability (2001)

Blood vessel walls form a selective barrier to the transport of materials between blood and tissue, and the endothelium contributes significantly to this barrier function. The role of the endothelium is particularly important in thin-walled vessels, such as venules, because during tissue inflammation the endothelial junctions widen in localized areas and gaps form, thus compromising the barrier function. The mechanisms of endothelial gap formation are still under question. In this review we describe what is known about the structure of endothelial cell-cell junctions and how this structure can change during inflammation. We then consider two possible mechanisms by which endothelial gaps are formed: active endothelial cell contraction or breakdown of the junctional complex, followed by passive recoil. Using measured values of the mechanical properties of endothelial cells, and the forces to which they are subjected, we calculate that gap formation by breakdown of cellular adhesion, followed by passive recoil, is a feasible mechanism. Finally, since endothelial cell surfaces, including junctions, are coated with a glycocalyx, we consider the question of whether changes in the glycocalyx can markedly increase endothelial permeability. We conclude that gap formation can occur by active contraction or by breakdown of adhesion, depending on the inflammatory mediator, and that the responses of the glycocalyx may also play an important role in the regulation of microvascular permeability.
The Design and Evaluation of a Novel Submicron Amphotericin B Emulsion in Systemic Murine Cryptococcosis (2020)

A stable submicron amphotericin B (AmB) sterile emulsion was prepared using a combination of following three emulsifiers: phospholipids, poloxamer and sodium deoxycholate. The overall results indicate that in murine candidiasis, treatment with AmB submicron emulsion was more effective than Fungizone®, suggesting potential therapeutic application. The present data, using a murine cryptococcosis model, clearly suggest that the brain was more accessible to AmB from the micellar solution than from the emulsion. The difference in the observed survival data, as compared to the survival data of the mice treated with AmB emulsion, was also statistically significant. A control group of 10 infected mice treated with saline instead of AmB was included. The number of surviving animals in each group was recorded daily over a period of 45 days. Male albino BALB/c mice weighing 20 g each were injected through the tail vein with various doses of AmB either as Fungizone® or as various emulsion formulations at different concentrations.
Pparγ2 Is a Key Driver of Longevity in the Mouse (2009)

Aging involves a progressive physiological remodeling that is controlled by both genetic and environmental factors. Many of these factors impact also on white adipose tissue (WAT), which has been shown to be a determinant of lifespan. Interrogating a transcriptional network for predicted causal regulatory interactions in a collection of mouse WAT from F2 crosses with a seed set of 60 known longevity genes, we identified a novel transcriptional subnetwork of 742 genes which represent thus-far-unknown longevity genes. Within this subnetwork, one gene was Pparg (Nr1c3), an adipose-enriched nuclear receptor previously not associated with longevity. In silico, both the PPAR signaling pathway and the transcriptional signature of Ppargamma agonist rosiglitazone overlapped with the longevity subnetwork, while in vivo, lowered expression of Pparg reduced lifespan in both the lipodystrophic Pparg1/2-hypomorphic and the Pparg2-deficient mice. These results establish Ppargamma2 as one of the determinants of longevity and suggest that lifespan may be rather determined by a purposeful genetic program than a random process.
Classifying Grains Using Behaviour-Informed Machine Learning (2021)

Abstract Sorting granular materials such as ores, coffee beans, cereals, gravels and pills is essential forapplications in mineral processing, agriculture and waste recycling. Existing sorting methods are based on the detection of contrast in grain properties including size, colour, density and chemical composition. However, many grain properties cannot be directly detected in-situ, which significantly impairs sorting efficacy. We show here that a simple neural network can infer contrast in a wide range of grain properties by detecting patterns in their observable kinematics. These properties include grain size, density, stiffness, friction, dissipation and adhesion. This method of classification based on behaviour can significantly widen the range of granular materials that can be sorted. It can similarly be applied to enhance the sorting of other particulate materials including cells and droplets in microfluidic devices.
Molecular Recognition in the Selective Oxygenation of Saturated C-H Bonds by a Dimanganese Catalyst (2006)

Although enzymes often incorporate molecular recognition elements to orient substrates selectively, such strategies are rarely achieved by synthetic catalysts. We combined molecular recognition through hydrogen bonding with C-H activation to obtain high-turnover catalytic regioselective functionalization of sp3 C-H bonds remote from the -COOH recognition group. The catalyst contains a Mn(mu-O)2Mn reactive center and a ligand based on Kemp's triacid that directs a -COOH group to anchor the carboxylic acid group of the substrate and thus modify the usual selectivity for oxidation. Control experiments supported the role of hydrogen bonding in orienting the substrate to achieve high selectivity.
Vertical nonpolar growth templates for light emitting diodes formed with GaN nanosheets (2012)

We demonstrate that nonpolar m-plane surfaces can be generated on uniform GaN nanosheet arrays grown vertically from the (0001)-GaN bulk material. InGaN/GaN multiple quantum wells (MQWs) grown on the facets of these nanosheets are demonstrated by cross-sectional transmission electron microscopy. Owing to the high aspect ratio of the GaN nanosheet structure, the MQWs predominantly grow on nonpolar GaN planes. The results suggest that GaN nanosheets provide a conduction path for device fabrication and also a growth template to reduce the piezoelectric field inside the active region of InGaN-based light emitting diodes.
Numerical Evaluation of the Long-Term Performance of KIGAM Geothermal Heat Pump System (2010)

Temperature change of the ground in the vicinity of borehole heat exchangers (BHEs) is important for the longterm operation of geothermal heat pump (GHP) systems. If there are differences between injected energy from heat pumps to BHEs in cooling season and rejected energy from heat pumps to BHEs in heating season and heat transfer is not sufficiently fast in the ground, temperature change of the ground affects on the performance of the GHP system. Vertical closed-loop GHP systems and monitoring systems were installed at the building of the Earthquake Research Center in Korea Institute of Geoscience and Mineral (KIGAM) in Daejeon, Korea. To evaluate the long-term performance of KIGAM GHP system where there are differences between injected energy from heat pumps to BHEs in cooling season and rejected energy from heat pumps to BHEs in heating season, numerical simulations are performed by using three-dimensional numerical model that can simulate temperature changes in the BHE with circulating fluid through the U-tubes as well as it computes groundwater flow and aquifer temperature changes. Temperature of the ground in the vicinity of BHEs is gradually increased during 25 years operation. The efficiency of the GHP system is decreased in the cooling season and increased in the heating season.
Laser ablation and contact formation for Cu-plated large area C-silicon industrial solar cells (2010)

In this work we demonstrate the successful implementation of laser ablation of SiN <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</sub> ARC to contact high ohmic emitters up to 120 Ω/sq with an advanced metallization on large area substrates. We propose Suns-Voc measurements as a fast and effective method to characterize the potential laser damage. We look at the laser ablation factors that can compromise the solar cell performance and we see how to limit the damage that can jeopardize the device performance. We define the laser ablation process window for emitters of different resistivity ranging from a typical 60 Ω/sq emitter to a emitter of 140 Ω/sq. A point-contact contacting scheme is proposed that leads to an improved V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">oc</sub> of the solar cell. Finally we present results of the electrical characterization of large area solar cells. Efficiencies up to 18.7% are obtained on large area, 160 μm thick CZ silicon substrates.
Evaluation of the Constituents of Vetiver Oil Against Anopheles minimus (Diptera: Culicidae), a Malaria Vector in Thailand (2017)

The development of resistance by mosquitoes to current synthetic compounds has resulted in reduced effectiveness of prevention and control methods worldwide. An alternative nonchemical based control tools are needed to be evaluated particularly plant-derived essential oils. Several components of vetiver oil have been documented as insect repellents. However, detailed knowledge of those components action against insect remains unknown. In this study, behavioral response of Anopheles minimus to four constituents of vetiver oil (valencene, terpinen-4-ol, isolongifolene, vetiverol) was evaluated by using the high-throughput screening assay system. Vetiverol and isolongifolene exhibited strong contact irritancy action at 1.0% (80.2% escaping) and 5.0% (81.7% escaping) concentration, respectively, while moderate action was found in both valencene and terpinen-4-ol at 5.0% (57.6% escaping). Only at 1.0% (0.7 spatial activity index [SAI]) and 5.0% (1.0 SAI) of valencene and 0.5% (0.7 SAI) of isolongifolene showed spatial repellency activity. High mortality (58.9-98.2%) was recorded in all concentration of vetiverol and isolongifolene. Meanwhile, valencene exhibited high mortality only at 5.0%, terpinen-4-ol showed very low toxic action (0-4.3%) in all concentration. These proved that valencene in vetiver oil is the promising constituent that can be developed as an alternative mosquito control mean in efforts to prevent disease transmission.
The development of oral vaccines against parasitic diseases utilizing live attenuated<i>Salmonella</i> (1995)

Genetically defined, live attenuated Salmonella vaccines are proving useful both as oral vaccines against salmonellosis and for the development of multivalent vaccines based on the expression of heterologous antigens in such strains. Several candidate attenuated S. typhi strains are at present being evaluated as new single dose oral typhoid vaccines in human volunteers. The emergence of such a vaccine will facilitate the development of multivalent vaccines for humans. Many antigens from different infectious organisms have been expressed in attenuated Salmonella. A focus of this work has been on developing vaccines against parasitic diseases. This review will summarize the efforts that have been made in this area.
Data from Characterization of a Naturally Occurring Breast Cancer Subset Enriched in Epithelial-to-Mesenchymal Transition and Stem Cell Characteristics (2023)

&lt;div&gt;Abstract&lt;p&gt;Metaplastic breast cancers (MBC) are aggressive, chemoresistant tumors characterized by lineage plasticity. To advance understanding of their pathogenesis and relatedness to other breast cancer subtypes, 28 MBCs were compared with common breast cancers using comparative genomic hybridization, transcriptional profiling, and reverse-phase protein arrays and by sequencing for common breast cancer mutations. MBCs showed unique DNA copy number aberrations compared with common breast cancers. &lt;i&gt;PIK3CA&lt;/i&gt; mutations were detected in 9 of 19 MBCs (47.4%) versus 80 of 232 hormone receptor–positive cancers (34.5%; &lt;i&gt;P&lt;/i&gt; = 0.32), 17 of 75 &lt;i&gt;HER-2&lt;/i&gt;–positive samples (22.7%; &lt;i&gt;P&lt;/i&gt; = 0.04), 20 of 240 basal-like cancers (8.3%; &lt;i&gt;P&lt;/i&gt; &lt; 0.0001), and 0 of 14 claudin-low tumors (&lt;i&gt;P&lt;/i&gt; = 0.004). Of 7 phosphatidylinositol 3-kinase/AKT pathway phosphorylation sites, 6 were more highly phosphorylated in MBCs than in other breast tumor subtypes. The majority of MBCs displayed mRNA profiles different from those of the most common, including basal-like cancers. By transcriptional profiling, MBCs and the recently identified claudin-low breast cancer subset constitute related receptor-negative subgroups characterized by low expression of GATA3-regulated genes and of genes responsible for cell-cell adhesion with enrichment for markers linked to stem cell function and epithelial-to-mesenchymal transition (EMT). In contrast to other breast cancers, claudin-low tumors and most MBCs showed a significant similarity to a “tumorigenic” signature defined using CD44&lt;sup&gt;+&lt;/sup&gt;/CD24&lt;sup&gt;−&lt;/sup&gt; breast tumor–initiating stem cell–like cells. MBCs and claudin-low tumors are thus enriched in EMT and stem cell–like features, and may arise from an earlier, more chemoresistant breast epithelial precursor than basal-like or luminal cancers. &lt;i&gt;PIK3CA&lt;/i&gt; mutations, EMT, and stem cell-like characteristics likely contribute to the poor outcomes of MBC and suggest novel therapeutic targets. [Cancer Res 2009;69(10):4116–24]&lt;/p&gt;&lt;/div&gt;
Dynamic decay of a single vortex into vortex-antivortex pairs (2014)

A variety of metastable states, including vortices, antivortices, and their combinations, is typical for magnetically soft, thin films and patterned structures. The physics of individual spin vortices in patterned structures has been rather extensively explored. In contrast, there are few studies of the vortex–antivortex–vortex (v-av-v) system, in part because the configuration is rather challenging to obtain experimentally. We demonstrate herein how a recently proposed resonant-spin-ordering technique can be used to induce the dynamic decay of a single vortex into v-av states in elongated elements. The approach is based on first driving the system from the linear regime of constant vortex gyrations to the non-linear regime of vortex-core reversals at a fixed excitation frequency, and then subsequently reducing the excitation field back to the linear regime. This procedure stabilizes the system into a v-av-v state that is completely decoupled from the initialization excitation frequency. The newly acquired state is stable in remanence. The dynamic response of this system is expected to demonstrate a number of collective modes, depending on the combination of the vortex core polarities, and/or the excitation field direction, and, hence, is of interest for future studies.
Evaluation of fatigue damage in steels using Preisach model analysis of magnetic hysteresis measurements (2001)

The Preisach model analysis of magnetic hysteresis measurements has been applied to evaluate the microstructural changes in steels subjected to cyclic loading. Families of hysteresis loops were measured to obtain the Preisach-like functions. Barkhausen effect signals were also measured. The Preisach representation was found to be more sensitive to the increase in the number of stress cycles during the stable fatigue stage than the traditional hysteresis loop properties and Barkhausen effect signals.
High Resolution Characterization of Myosin IIC Protein Tailpiece and Its Effect on Filament Assembly (2013)

The motor protein nonmuscle myosin II (NMII) must undergo dynamic oligomerization into filaments to perform its cellular functions. A small nonhelical region at the tail of the long coiled-coil region (tailpiece) is a common feature of all dynamically assembling myosin II proteins. This tailpiece is a key regulatory domain affecting NMII filament assembly properties and is subject to phosphorylation in vivo. We previously demonstrated that the positively charged region of the tailpiece binds to assembly-incompetent NMII-C fragments, inducing filament assembly. In the current study, we investigated the molecular mechanisms by which the tailpiece regulates NMII-C self-assembly. Using alanine scan, we found that specific positive and aromatic residues within the positively charged region of the tailpiece are important for inducing NMII-C filament assembly and for filament elongation. Combining peptide arrays with deletion studies allowed us to identify the tailpiece binding sites in the coiled-coil rod. Elucidation of the mechanism by which the tailpiece induces filament assembly permitted us further investigation into the role of tailpiece phosphorylation. Sedimentation and CD spectroscopy identified that phosphorylation of Thr(1957) or Thr(1960) inhibited the ability of the tailpiece to bind the coiled-coil rod and to induce NMII-C filament formation. This study provides molecular insight into the role of specific residues within the NMII-C tailpiece that are responsible for shifting the oligomeric equilibrium of NMII-C toward filament assembly and determining its morphology.
Low-temperature superplasticity in a nanocomposite iron alloy derived from a metallic glass (2003)

The focus of this research was to use the solid state glass devitrification transformation to develop nanocomposite microstructures in iron-based materials. Mechanical deformation studies on the nanocomposite structures at room temperature revealed that although they exhibited high yield strength (975–1200 MPa), they were brittle and exhibited no tensile elongation. A specialized two-step annealing process was employed which involved first holding for extended times below the crystallization onset temperature to devitrify extremely fine matrix grains followed by heating to temperatures above the crystallization onset temperature for short times. Using this approach, nanocomposite microstructures could be formed consisting of α-Fe, Fe23C6 and Fe3B type triplex matrix phases of the order of 75 nm in size which were stabilized by dispersions of 2–10 nm α-Fe precipitates along the grain boundaries and embedded in the Fe23C6 type phase. At 750 °C and a strain rate of 10−3 s−1 this stabilized nanoscale microstructure was found to exhibit superplasticity with an ultimate tensile strength of 1800 MPa and a tensile elongation of 230%. Subsequent testing using 'jump tests' revealed that the strain rate sensitivity factor was equal to 0.51, which, consistent with the microstructural observations, revealed that the main mechanism for elevated temperature deformation was grain boundary sliding/rotational processes.