gebhart/patrepeval huggingface dataset:
The carboligation reaction of acetohydroxyacid synthase II: Steady-state intermediate distributions in wild type and mutants by NMR (2005)

The thiamin diphosphate (ThDP)-dependent enzyme acetohydroxyacid synthase (AHAS) catalyzes the first common step in branched-chain amino acid biosynthesis. By specific ligation of pyruvate with the alternative acceptor substrates 2-ketobutyrate and pyruvate, AHAS controls the flux through this branch point and determines the relative rates of synthesis of isoleucine, valine, and leucine, respectively. We used detailed NMR analysis to determine microscopic rate constants for elementary steps in the reactions of AHAS II and mutants altered at conserved residues Arg-276, Trp-464, and Met-250. In Arg276Lys, both the condensation of the enzyme-bound hydroxyethyl-ThDP carbanion/enamine (HEThDP) with the acceptor substrates and acetohydroxyacid release are slowed several orders of magnitude relative to the wild-type enzyme. We propose that the interaction of the guanidinium moiety of Arg-264 with the carboxylate of the acceptor ketoacid provides an optimal alignment of substrate and HEThDP orbitals in the reaction trajectory for acceptor ligation, whereas its interaction with the carboxylate of the covalent HEThDP-acceptor adduct plays a similar role in product release. Both Trp-464 and Met-250 affect the acceptor specificity. The high preference for ketobutyrate in the wild-type enzyme is lost in Trp464Leu as a consequence of similar forward rate constants of carboligation and product release for the alternative acceptors. In Met250Ala, the turnover rate is determined by the condensation of HEThDP with pyruvate and release of the acetolactate product, whereas the parallel steps with 2-ketobutyrate are considerably faster. We speculate that the specificity of carboligation and product liberation may be cumulative if the former is not completely committed.
Plap-1/Aspn lineage tracing and single-cell transcriptomics reveals cellular dynamics in the periodontal ligament (2022)

Summary Periodontal tissue supports teeth in the alveolar bone socket via fibrous attachment of the periodontal ligament (PDL). The PDL contains periodontal fibroblasts and stem/progenitor cells, collectively known as PDL cells (PDLCs), on top of osteoblasts and cementoblasts on the surface of alveolar bone and cementum, respectively. However, the characteristics and lineage hierarchy of each cell type remain poorly defined. This study identified periodontal ligament associated Protein-1 ( Plap-1 / Aspn ) as a PDL-specific extracellular matrix. We generated knock-in mice expressing CreER T2 and GFP specifically in Plap-1 -positive PDLCs. Genetic lineage tracing confirmed the long-standing hypothesis that PDLCs differentiated into osteoblasts and cementoblasts. A PDL single-cell atlas defined cementoblasts and osteoblasts as Plap-1 - Ibsp + Sparcl1 + and Plap-1 - Ibsp + Col11a2 + , respectively. Other populations such as Nes + mural cells, S100B + Schwann cells, and other non-stromal cells were also identified. RNA velocity analysis suggested that Plap-1 high Ly6a + cell population was the source of PDLCs. Lineage tracing of Plap-1 + PDLCs during the periodontal injury model showed periodontal tissue regeneration by PDLCs. Our study defines diverse cell populations in PDL and clarifies the role of PDLCs in periodontal tissue homeostasis and repair.
Figure S4 from TAS-114, a First-in-Class Dual dUTPase/DPD Inhibitor, Demonstrates Potential to Improve Therapeutic Efficacy of Fluoropyrimidine-Based Chemotherapy (2023)

&lt;p&gt;Expression levels of dUTPase in various tumor xenografts and antitumor efficacy of S-1 and TAS-114 combination in various xenograft models&lt;/p&gt;
GPAHRS – Navigation Enabler for More Autonomous Aircraft (2021)

This project has received funding from the Clean Sky 2 Joint Undertaking (JU) under grant agreement No 945583. The JU receives support from the European Union’s Horizon 2020 research and innovation programme and the Clean Sky 2 JU members other than the Union. The results, opinions, conclusions, etc. presented in this work are those of the author(s) only and do not necessarily represent the position of the JU; the JU is not responsible for any use made of the information contained herein. Prototype of the new Honeywell GPS-aided MEMS based navigation system (GPAHRS) has been validated through a large flight-test campaign performed under the Clean Sky 2 Large Passenger Aircraft (LPA) Platform 3 project. The campaign itself (more than 200 flight hours in total) was focused on the business jets (Dassault Falcon 900EX), commercial jets (Airbus A330), and regional aircrafts and various flight test scenarios. This paper provides an overview of the GPAHRS system itself, its integration within the Flight Test Bed (FTB) equipment, and most importantly, performance (in terms of accuracy and integrity) validation of results obtained during the campaign.
Nanofiller induced electroactive phase formation in solution derived poly(vinylidene fluoride) polymer composites (2015)

Electroactive self-standing flexible composite poly(vinylidene fluoride) ( PVDF) films were prepared by simple solution casting method. In this study we investigated the effect of two different nanofillers, namely GNPs and ZnO NRs and the use of five different hexahydrate salts (HS) on the nucleation of the electroactive phase in the solution derived PVDF films. FT-IR analysis revealed that both HS dissolution and nanofillers dispersion in the PVDF matrix induced the electroactive phase formation without any electrical poling ascribed to their strong surface interaction with the polymeric chains. Moreover, we observed that the electroactive phase is still present when HS dissolution is combined with nanofiller dispersion, thus opening the route to the possibility of tailoring the operating frequency of the resulting electroactive material. This versatile electroactive phase induction by the nanofillers is a prominent way for production of large-area flexible piezoelectric films.
Power system small signal stability region with time delay (2006)

DOI: 10.1049/cp:20062023 ISBN: 0 86341 246 7 Location: Hong Kong, China Conference date: 30 Oct.-2 Nov. 2006 Format: PDF (5 pages)
Evidence for a gem-Diol Reaction Intermediate in Bacterial C−C Hydrolase Enzymes BphD and MhpC from 13C NMR Spectroscopy (2006)

C-C hydrolase enzymes MhpC and BphD catalyze the hydrolytic C-C cleavage of meta-ring fission intermediates on the Escherichia coli phenylpropionic acid and Burkholderia xenovorans LB400 biphenyl degradation pathways and are both members of the alpha/beta-hydrolase family containing a Ser-His-Asp catalytic triad. The catalytic mechanism of this family of enzymes is thought to proceed via a gem-diol reaction intermediate, which has not been observed directly. Site-directed single mutants of BphD in which catalytic residues His-265 and Ser-112 were replaced with Ala were found to possess 10(4)-fold reduced k(cat) values, and in each case, the C-C cleavage step was shown by pre-steady-state kinetic analysis to be rate-limiting. The processing of a 6-(13)C-labeled aryl-containing substrate by these H265A or S112A mutant BphD enzymes was monitored directly by (13)C NMR spectroscopy. A new line-broadened signal was observed at 128 ppm for each enzyme, corresponding to the proposed gem-diol reaction intermediate, over a time scale of 1-24 h. A similar signal was observed upon incubation of the (13)C-labeled substrate with an H114A MhpC mutant, which is able to accept the 6-phenyl-containing substrate, on a shorter time scale. The direct observation of a gem-diol intermediate provides further evidence that supports a general base mechanism for this family of enzymes.
Temperature-Dependent Hydrogen Electrochemistry on Platinum Low-Index Single-Crystal Surfaces in Acid Solutions (1997)

The hydrogen evolution (HER) and the hydrogen oxidation reaction (HOR) were studied on platinum single crystals in a sulfuric acid solution over the temperature range 274−333 K. We found, for the first time, that at a fixed temperature (274 K) the exchange current densities (io) increase in the order (111) ≪ (100) < (110), with the io on the (110) surface being 3 times that on the (111) surface. We also found that each crystal face has an unique, temperature-dependent Tafel slope for the HOR, and that the activation energies for the HER and the HOR decrease in the sequence > > , the same sequence as the order of activity. These differences in activation energy with crystal face are attributed to structure-sensitive heats of adsorption of the active intermediate, Had, whose physical state is unclear. We analyzed the kinetic data with a model for the coupling of this unknown state, Had, with the well-known adsorbed state of hydrogen, Hupd, whose adsorption energy is strongly structure-sensitive. We concluded that on Pt(110), the reaction follows the Tafel−Volmer mechanism with the Tafel (recombination) step rate determining. On Pt(100), the reaction follows the Heyrovsky−Volmer sequence, with the Heyrovsky (ion−atom) reaction step being the rate-determining step. The reaction mechanism on Pt(111) could not, however, be resolved by analyzing the kinetic parameters. The relatively low activity and high activation energy for the (111) surface is attributed to strong repulsive interaction between Had adatoms on this surface.
Low-contrast visual acuity versus low-luminance visual acuity in choroideremia (2020)

The low-luminance visual acuity test may be a useful additional clinical trial outcome measure for early-to-moderate disease, when high-contrast visual acuity is preserved.
Fast Anomaly Detection for Large Data Centers (2010)

Recent spates of cyber attacks towards cloud computing services running in large data centers have made it imperative to develop effective techniques to detect anomalous behaviors in the "clouds". In this paper, we propose to use the distributions of IP address octets and centroid based measures to characterize the inherent IP structure in high-volume data center traffic, and subsequently design a simple yet effective algorithm to detect abnormal traffic patterns caused by network attacks such as worms, virus, and denial of service attacks. We evaluate the effectiveness and efficiency of this algorithm with synthetic traffic that combines real data center traffic collected from a large Internet content provider with worm traces and denial of service attacks. The experiment results show that our algorithm consistently diagnoses the abnormal traffic from normal ones, and does so in a short time with a low false alarm rate. We believe that the proposed approach could be potentially deployed in real-time data center environments to enhance the security and high availability of cloud computing.
Different Pathways of Postreceptor Desensitization following Chronic Insulin Treatment and in Cells Overexpressing Constitutively Active Insulin Receptors (1996)

We have reported previously that substitution of the transmembrane domain of the insulin receptor with that of the erbB-2 oncogene (IRerbV-->E) results in constitutive activation of the insulin receptor kinase. Compared to NIH3T3 cells overexpressing wild-type insulin receptors (IRwt), cells overexpressing IRerbV-->E displayed a decrease in IRS-1 protein content by 55%, but basal tyrosine phosphorylation of IRS-1 was increased. This resulted in an increased association of IRS-1 with the p85 subunit of phosphatidylinositol 3-kinase, increased phosphatidylinositol 3-kinase activity in anti-IRS-1 immunoprecipitates, constitutive activation of p70 S6 protein kinase, and an increased association of Grb2 with Shc in the absence of ligand. However, Grb2 association with IRS-1 could not be detected in the basal or insulin-stimulated states, and mitogen-activated protein kinase (MAPK) activity could not be stimulated by insulin, epidermal growth factor, or platelet-derived growth factor. In contrast to IRerbV-->E, the insulin receptor content and its tyrosine phosphorylation were significantly decreased in IRwt cells chronically stimulated (>24 h) with insulin. With decreased IRS-1 content, tyrosine phosphorylation of IRS-1 was decreased by over 75%, leading to decreased IRS-1-associated PI 3-kinase and Grb2. In addition, Grb2 association with Shc and activation of MAPK and the p70 S6 kinase were insensitive to insulin stimulation. By contrast, association of Grb2 with Shc and activation of MAPK, but not the p70 S6 kinase, could be stimulated by epidermal growth factor or platelet-derived growth factor. These data suggest that there are multiple levels of postreceptor desensitization to insulin action. These are used somewhat differently in these two different models, probably due in part to the difference in receptor down-regulation.
Relation entre dilution de l'azote et cinétique de croissance chez les graminées (1986)

La relation entre la production de biomasse et la teneur en azote de la plante en phase végétative est étudiée chez des individus isolés de Dactylis glomerata L. cultivés en milieu hydroponique et dans des conditions d'environnement contrôlées.Les différents traitements expérimentaux incluant l'effet de la concentration en nitrate, de l'éclairement et de la température, confirment la généralité du processus de dilution de l'azote dans la plante au cours de la croissance.Ce processus est analysé sur la base d'un modèle de croissance à deux composantes.La variation de la composition chimique de la plante est décrite en termes de variation du rapport de ces composantes.Dans cette approche, la teneur en azote de la plante varie linéairement avec la vitesse de croissance relative, en accord avec nos observations expérimentales.Nous montrons que cette relation permet de rendre compte de la variation de la teneur en azote au cours de la croissance, mesurée dans le cas de cultures de différentes graminées en milieu naturel.
Imperfect DNA lesion repair in the semiconservative quasispecies model: Derivation of the Hamming class equations and solution of the single-fitness peak landscape (2004)

This paper develops a Hamming class formalism for the semiconservative quasispecies equations with imperfect lesion repair, first presented and analytically solved in Y. Brumer and E.I. Shakhnovich (q-bio.GN/0403018, 2004). Starting from the quasispecies dynamics over the space of genomes, we derive an equivalent dynamics over the space of ordered sequence pairs. From this set of equations, we are able to derive the infinite sequence length form of the dynamics for a class of fitness landscapes defined by a master genome. We use these equations to solve for a generalized single-fitness-peak landscape, where the master genome can sustain a maximum number of lesions and remain viable. We determine the mean equilibrium fitness and error threshold for this class of landscapes, and show that when lesion repair is imperfect, semiconservative replication displays characteristics from both conservative replication and semiconservative replication with perfect lesion repair. The work presented here provides a formulation of the model which greatly facilitates the analysis of a relatively broad class of fitness landscapes, and thus serves as a convenient springboard into biological applications of imperfect lesion repair.
PMCE: efficient inference of expressive models of cancer evolution with high prognostic power (2022)

Motivation: Driver (epi)genomic alterations underlie the positive selection of cancer subpopulations, which promotes drug resistance and relapse. Even though substantial heterogeneity is witnessed in most cancer types, mutation accumulation patterns can be regularly found and can be exploited to reconstruct predictive models of cancer evolution. Yet, available methods can not infer logical formulas connecting events to represent alternative evolutionary routes or convergent evolution. Results: We introduce PMCE, an expressive framework that leverages mutational profiles from cross-sectional sequencing data to infer probabilistic graphical models of cancer evolution including arbitrary logical formulas, and which outperforms the state-of-the-art in terms of accuracy and robustness to noise, on simulations. The application of PMCE to 7866 samples from the TCGA database allows us to identify a highly significant correlation between the predicted evolutionary paths and the overall survival in 7 tumor types, proving that our approach can effectively stratify cancer patients in reliable risk groups. Availability and implementation: PMCE is freely available at https://github.com/BIMIB-DISCo/PMCE, in addition to the code to replicate all the analyses presented in the manuscript.
Transforming Growth Factor-β1 Inhibits Cytokine-mediated Induction of Human Metalloelastase in Macrophages (2000)

Matrix metalloproteinases (MMP) have been identified in vulnerable areas of atherosclerotic plaques and may contribute to plaque instability through extracellular matrix degradation. Human metalloelastase (MMP-12) is a macrophage-specific MMP with broad substrate specificity and is capable of degrading proteins found in the extracellular matrix of atheromas. Despite its potential importance, little is known about the regulation of MMP-12 expression in the context of atherosclerosis. In this study, we report that in human peripheral blood-derived macrophages, MMP-12 mRNA was markedly up-regulated by several pro-atherosclerotic cytokines and growth factors including interleukin-1beta, tumor necrosis factor-alpha, macrophage colony-stimulating factor, vascular endothelial growth factor, and platelet-derived growth factor-BB. In contrast, the pleiotropic anti-inflammatory growth factor transforming growth factor-beta1 (TGF-beta1) inhibited cytokine-mediated induction of MMP-12 mRNA, protein, and enzymatic activity. Analyses of MMP-12 promoter through transient transfections and electrophoretic mobility shift assays indicated that both its induction by cytokines and its inhibition by TGF-beta1 depended on signaling through an AP-1 site at -81 base pairs. Moreover, the inhibitory effect of TGF-beta1 on MMP-12 was dependent on Smad3. Taken together, MMP-12 is induced by several factors implicated in atherosclerosis. The inhibition of MMP-12 expression by TGF-beta1 suggests that TGF-beta1, acting via Smad3, may promote plaque stability.
Identifying the Active Oxygen Species in SnO2 Based Gas Sensing Materials: An Operando IR Spectrsocopy Study (2015)

This work demonstrates that it is possible to follow the surface chemistry of oxygen on SnO2 based gas sensing materials using operando diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). The inherent difficulties, due to the intrinsic properties of the studied oxide and the limitations of the method, were overcome by comparing the results obtained for two different materials and by use of isotopically labeled gases together with the simultaneous measurement of the sensor signals. In spite of the differences in the surface composition and reactivity between the different materials, the experimental results show that the reactive oxygen species are similar in nature and the gas recognition takes place by the interplay of surface reduction and (re)oxidation.
Figure S1 from Bladder Cancer Outcome and Subtype Classification by Gene Expression (2023)

&lt;p&gt;Kaplan-Meier survival curves&lt;/p&gt;
Patch Clamp Studies on V-type ATPase of Vacuolar Membrane of Haploid Saccharomyces cerevisiae (1999)

A method for obtaining giant protoplasts of Escherichia coli (the spheroplast incubation (SI) method: Kuroda et al. (Kuroda, T., Okuda, N., Saitoh, N., Hiyama, T., Terasaki, Y., Anazawa, H., Hirata, A., Mogi, T., Kusaka, I., Tsuchiya, T., and Yabe, I. (1998) J. Biol. Chem. 273, 16897-16904) was adapted to haploid cells of Saccharomyces cerevisiae. The yeast cell grew to become as large as 20 micrometer in diameter and to contain an oversized vacuole inside. A patch clamp technique in the whole cell/vacuole recording mode was applied for the vacuole isolated by osmotic shock. At zero membrane potential, ATP induced a strong current (as high as 100 pA; specific activity, 0.1 pA/micrometer(2)) toward the inside of the vacuole. Bafilomycin A(1,) a specific inhibitor of the V-type ATPase, strongly inhibited the activity (K(i) = 10 nM). Complete inhibition at higher concentrations indicated that any other ATP-driven transport systems were not expressed under the present incubation conditions. This current was not observed in the vacuoles prepared from a mutant that disrupted a catalytic subunit of the V-type ATPase (RH105(Deltavma1::TRP)). The K(m) value for the ATP dose response of the current was 159 microM and the H(+)/ATP ratio estimated from the reversible potential of the V-I curve was 3.5 +/- 0.3. These values agreed well with those previously estimated by measuring the V-type ATPase activity biochemically. This method can potentially be applied to any type of ion channel, ion pump, and ion transporter in S. cerevisiae, and can also be used to investigate gene functions in various organisms by using yeast cells as hosts for homologous and heterogeneous expression systems.
Selection of Lineage Guiding Metabolites in Stem Cell Cultures (2015)

This study reports the use of self assembled peptide (F2S) hydrogels and cellular metabolomics to identify a number of innate molecules that are integral to the metabolic processes which drive cellular differentiation. Current methods for achieving this wholly depend on the use of chemical induction media which generally comprise synthetic molecules or attempting to match the physical environment to that of targeted tissue types. By culturing pericytes on F2S hydrogels with varied mechanical qualities, these cells were induced to undergo neuronal (2 kPa), chondrogenic (15 kPa) and osteogenic (40kPa) differentiation. Because the system relies solely on mechanical tuning of a uniform substrate, alterations in cell behaviour by way of total metabolism could be used to mine for selective compounds of interest by way of patterned depletion. When the selected metabolites (ceramide, lysophosphatidic acid and cholesterol sulphate respectively) were reintroduced into stem cells cultures, they were observed as having the ability to direct differentiation in their own right and with similar efficacy to routinely used induction media. Interestingly, it was also observed that these metabolites, when introduced in vitro, have distinct effects on stem cell behaviour dependent on whether the cells are amenable to them. That is, metabolic functions are innately coupled to the pericytes physical and morphological states. This approach shows that simple metabolites provide an alternative means to direct stem cell differentiation and that materials can be used to identify them simply and quickly which has clear implications for stem cell drug discovery.
A New Lithium Cathode LiCoMnO[sub 4]: Toward Practical 5 V Lithium Batteries (1999)

Lithium batteries can operate over by the incorporation of a potentially large family of new lithium cathode materials based on spinel‐structure oxides in the system , one of which, , exhibits a discharge capacity of at a long plateau centered on in a cell, , propylene carbonate/, and therefore has superior energy density to , the favored cathode in next‐generation lithium batteries. ©1998 The Electrochemical Society
ChemInform Abstract: Alkylation of Guanine. Part 2. The Synthesis of Acyclic Guanosine Analogs via the Precursor 7‐Methyl‐10‐oxo‐9,10‐dihydropyrimido[1,2‐a]purine. (1986)

Abstract Alkylation of the title compound (III) with (IV) gives the isomers (Wand (VI); the product ratio (but not the yields) remains unaffected if K 2 CO 3 is replaced by other bases.