gebhart/patrepeval huggingface dataset:
Engineering an Automaturing Transglutaminase with Enhanced Thermostability by Genetic Code Expansion with Two Codon Reassignments (2018)

In the present study, we simultaneously incorporated two types of synthetic components into microbial transglutaminase (MTG) from Streptoverticillium mobaraense to enhance the utility of this industrial enzyme. The first amino acid, 3-chloro-l-tyrosine, was incorporated into MTG in response to in-frame UAG codons to substitute for the 15 tyrosine residues separately. The two substitutions at positions 20 and 62 were found to each increase thermostability of the enzyme, while the seven substitutions at positions 24, 34, 75, 146, 171, 217, and 310 exhibited neutral effects. Then, these two stabilizing chlorinations were combined with one of the neutral ones, and the most stabilized variant was found to contain 3-chlorotyrosines at positions 20, 62, and 171, exhibiting a half-life 5.1-fold longer than that of the wild-type enzyme at 60 °C. Next, this MTG variant was further modified by incorporating the α-hydroxy acid analogue of N<sup>ε</sup>-allyloxycarbonyl-l-lysine (AlocKOH), specified by the AGG codon, at the end of the N-terminal inhibitory peptide. We used an Escherichia coli strain previously engineered to have a synthetic genetic code with two codon reassignments for synthesizing MTG variants containing both 3-chlorotyrosine and AlocKOH. The ester bond, thus incorporated into the main chain, efficiently self-cleaved under alkaline conditions (pH 11.0), achieving the autonomous maturation of the thermostabilized MTG. The results suggested that synthetic genetic codes with multiple codon reassignments would be useful for developing the novel designs of enzymes.
X-ray Photoelectron Spectroscopy Study of Sulfonated Polyethylene (1996)

Detailed X-ray photoelectron spectroscopy analysis of sulfonated high-density polyethylene (HDPE) prepared by using a gaseous mixture of SO3 + N2 was carried out. It was shown that the surface contains, apart from sulfonic acid groups, sulfate, keto, and polyene linkages. The evolution of the different surface groups depends upon the conditions of sulfonation.
Platinum porphyrin embedded in poly(1-trimethylsilyl-1-propyne) film as an optical sensor for trace analysis of oxygen (2000)

A highly gas permeable polymer, poly(1-trimethylsilyl-1-propyne) (poly(TMSP)), was applied as an optical oxygen sensing matrix using luminescence quenching of platinum octaethylporphyrin (PtOEP) by oxygen. PtOEP was homogeneously embedded in poly(TMSP) to give a mechanically tough film with a thickness of 10 μm. The luminescence intensity of PtOEP embedded in the poly(TMSP) film drastically decreased with an increase in oxygen concentration. The oxygen sensitivity of the film (I0/I100) was very high and estimated to be 225. The Stern–Volmer plot for the poly(TMSP) film-embedded PtOEP was obeyed at lower oxygen concentrations between 0 and 10% and the Stern–Volmer constant is estimated to be 5.7%−1. The limit of oxygen detection was less than 0.3%. The response times of PtOEP embedded in the poly(TMSP) film are 3.6 s on going from argon to oxygen and 73.2 s on going from oxygen to argon, respectively. These results indicate that PtOEP embedded in the poly(TMSP) film is a novel optical sensing material for trace analysis of oxygen.
The nonlinear field produced by 1-D and 2-D imaging arrays with plane and diverging wave modes for ultrafast imaging (2020)

Combining plane and diverging wave imaging (PWI/DWI) with tissue harmonic imaging (THI) may offer improvements in image quality in applications requiring very high frame rates (ultrafast). The beam shape and magnitude of the 2nd harmonic in tissue are important design considerations. We developed a numerical model based on the KZK equation and modeled three 1-D diagnostic arrays, L11-4v linear array, P4-2v phased array, and C5-2 convex array operating in PWI/DWI. Our numerical code predicts the nonlinear field of nonaxisymmetric sources and source configurations with elevation and no azimuthal foci (plane/diverging fields), which have not been modeled before. We showed that the second harmonic produced by ultrafast THI is 2-16 dB lower than that of focused beams for the imaging arrays considered when operated at the same maximum MI. This moderate difference of the second harmonic between PWI/DWI and focused ultrasound suggests that it is feasible to combine PWI/DWI and THI. We have also investigated harmonic generation produced by diagnostic 2-D arrays for 4-D THI. From our predictions for the second harmonic field we propose beamforming approaches for 4-D cardiac THI with focused ultrasound, PWI, and DWI that would result in frame rates of 10, 81, and 1275 Hz, respectively.
Structure−Activity Relationships in 1,4-Benzodioxan-Related Compounds. 7. Selectivity of 4-Phenylchroman Analogues for α1−Adrenoreceptor Subtypes (2002)

WB4101 (1)-related compounds 5-10 were synthesized, and their biological profile at alpha(1)-adrenoreceptor (AR) subtypes and 5-HT(1A) serotoninergic receptors was assessed by binding assays in Chinese hamster ovary and HeLa cell membranes expressing the human cloned receptors. Moreover, their receptor selectivity was further determined in functional experiments in isolated rat prostate (alpha(1A)), vas deferens (alpha(1A)), aorta (alpha(1D)), and spleen (alpha(1B)). In functional assays, compound 5 was the most potent at alpha(1D)-ARs with a reversed selectivity profile (alpha(1D) > alpha(1A) > alpha(1B)) relative to both prototype 1 and phendioxan (2) (alpha(1A) > alpha(1D) > alpha(1B)), whereas compound 8, bearing a carbonyl moiety at position 1, was the most potent at alpha(1A)-ARs with a selectivity profile similar to that of prototypes. The least potent of the series was the trans isomer 6, suggesting that optimum alpha(1)-AR blocking activity in this series is associated with a cis relationship between the 2-side chain and the 4-phenyl ring rather than a trans relationship as previously observed for the 2-side chain and the 3-phenyl ring in 2 and related compounds. Binding affinity results were not in complete agreement with the selectivity profiles deriving from functional experiments. Although a firm explanation was not available, neutral and negative antagonism and receptor dimerization were considered as two possibilities to account for the difference between binding and functional affinities. Finally, compound 5 was selected for a modeling study in comparison with 1, mephendioxan (3), and open phendioxan (4) to achieve information on the physicochemical interactions that account for its high affinity toward alpha(1d/D)-ARs.
Composite photonic platform based on 2D semiconductor monolayers (2019)

We demonstrate phase modulation in the near IR by electrostatically doping 2D semiconductor monolayers integrated on SiN waveguides. We show a VπL of 1.4 Vcm and 0.8 Vcm for MoS2 and WS2, respectively.
Adipocyte-Derived Fibroblasts Promote Tumor Progression and Contribute to the Desmoplastic Reaction in Breast Cancer (2013)

Cancer-associated fibroblasts (CAF) comprise the majority of stromal cells in breast cancers, yet their precise origins and relative functional contributions to malignant progression remain uncertain. Local invasion leads to the proximity of cancer cells and adipocytes, which respond by phenotypical changes to generate fibroblast-like cells termed as adipocyte-derived fibroblasts (ADF) here. These cells exhibit enhanced secretion of fibronectin and collagen I, increased migratory/invasive abilities, and increased expression of the CAF marker FSP-1 but not α-SMA. Generation of the ADF phenotype depends on reactivation of the Wnt/β-catenin pathway in response to Wnt3a secreted by tumor cells. Tumor cells cocultivated with ADFs in two-dimensional or spheroid culture display increased invasive capabilities. In clinical specimens of breast cancer, we confirmed the presence of this new stromal subpopulation. By defining a new stromal cell population, our results offer new opportunities for stroma-targeted therapies in breast cancer.
Differentiation of human embryonic stem cells into Corticofugal projection neurons (2013)

Understanding how neuronal diversity is achieved within the cerebral cortex remains a major challenge in neuroscience. The surge of human embryonic stem cells (hESCs) as a novel model system provides a unique opportunity to study human corticogenesis in vitro and€ identify the mechanisms that promote neuronal differentiation to achieve neuronal diversity in the human brain. Here, we demonstrate the derivation of corticofugal neurons from a genetically engineered Fezf2-YFP hESC reporter line, and uncover two distinct Fezf2 subpopulations that are reminiscent of the 2 Fezf2-expressing neuronal subtypes in the developing mouse brain. Fezf2 is a transcription factor that is both necessary and sufficient for the specification of subcerebral projection neurons in mouse. Its role in human corticogenesis is still unknown. However, the high conservation of FEZF2 protein between mouse and human suggest that Fezf2 is a specific marker of human cerebral neurons as well. Two hypotheses drove our research: 1) Extrinsic factors that modulate in vivo developmental signaling pathways play a critical role in the differentiation of hESCs to a corticofugal fate in vitro; 2) Human embryonic stem cell-derived neurons can survive in vivo and extend axonal projections to specific targets in the rodent brain. Our research shows that hESCs-derived corticofugal neurons are an effective model system to investigate the molecular pathways that regulate human cortical differentiation, axon extension and survival, an endeavor that was until now proscribed due to the manipulation of human embryos.
Large Effective chi(2) Nonlinearity on a Si3N4-Chip (2017)

Using coherent photon conversion (CPC) we generate large effective Ï(2) nonlinearities in a Ï(3)-nonlinear Si3N4 microring-resonator and measure an effective second harmonic generation efficiency of 77%/mW.
Electronic load interface for improving PV dual‐converter system operational margin (2013)

An electronic load interface (ELI) for improving the operational margin of a photovoltaic (PV) dual‐converter system under dynamic conditions is presented. The ELI – based on a modified buck–boost converter – interfaces the output of the converters and the load system. It improves the operational margin of the PV dual‐converter system by extending the conditions under which the dual‐converter system operates at the maximum power point. The ELI is activated as and when needed, so as minimise system losses. By employing the ELI, utilisation and efficiency of a PV dual‐converter system increases. In general, the concept of the ELI can be applied to multi‐converter PV systems – such as multi‐converter inverters, and multi‐converter DC–DC converter systems – for performance and efficiency improvement.
Mannitol‐Guided delivery of ciprofloxacin in artificial cystic fibrosis mucus model (2010)

Abstract Abnormal airway mucus presents a significant challenge for inhalational drug delivery. Recognizing the thick and tenacious airway mucus seen in the cystic fibrosis (CF) patients as a critical barrier to effective drug delivery, both into the mucus layer itself as well as across that layer to the underlying airway epithelium, we hypothesize that mannitol or NaCl can form inhalable drug carriers, improve drug penetration into the mucus, and ultimately enhance the drug's therapeutic effect. The objective of this study is to test whether mannitol and NaCl particles, as inhalable drug carriers, improve drug delivery into and enhance a drug's activity within a mucus‐like material. Microparticles containing Ciprofloxacin (Cipro), an active ingredient, and either mannitol or NaCl were produced by spray‐drying. Cipro encapsulated in mannitol particles (Cipro–mannitol) was significantly more effective at killing Pseudomonas aeruginosa ( P. aeruginosa ) grown in artificial mucus (AM) than Cipro encapsulated in either NaCl particles (Cipro–NaCl) or in hydrophobic particles consisting of dipalmitoylphosphatidylcholine (DPPC), albumin, and lactose (Cipro–DAL). The relatively high antibacterial effectiveness of Cipro–mannitol was not due to the effect of mannitol on bacteria or on Cipro. Rather, the unique performance of the mannitol‐based particles in AM is attributable to its ability to increase local water content in the AM and enhance drug penetration into it. Mannitol is a promising excipient for inhalable microparticles that facilitate the drug delivery into the CF mucus. Biotechnol. Bioeng. 2011; 108:1441–1449. © 2010 Wiley Periodicals, Inc.
In vitro antiviral activity of the anti-HCV drugs daclatasvir and sofosbuvir against SARS-CoV-2, the aetiological agent of COVID-19 (2021)

Daclatasvir, alone or in combination with sofosbuvir, at higher doses than used against HCV, may be further fostered as an anti-COVID-19 therapy.
A 380-gene meta-signature of active tuberculosis compared with healthy controls (2016)

Mycobacterium tuberculosis is estimated to have infected one third of the world's population and continues to be a significant cause of mortality and morbidity [1]. There is a need for new and improved diagnostics or treatment-monitoring tools and blood-based mRNA diagnostics are a potential solution [2]. Gene expression microarray analysis of human blood has been widely used to profile the host transcriptional response in active tuberculosis (TB) to identify potential biomarkers and better understand the host immune response [2]. So far, there has been a relative lack of concordance in the actual genes being identified from the published studies [2, 3], although there has been agreement in some of the pathways identified. Interferon (IFN) signalling has been identified as a dominant signature in many of the individual studies [2, 4]; however, when significant gene lists were combined from eight publicly available TB datasets, TREM1 (triggering receptor expressed on myeloid cells 1) signalling became the most significant pathway [5]. Modular and meta-profiling identify a common transcriptional response of patients with TB versus healthy controls <http://ow.ly/YvEP7>
ChemInform Abstract: Chemical Control of Stem Cell Fate and Developmental Potential (2011)

Abstract Review: 396 refs.
Generation of heralded entangled photon combs at telecom wavelength with rubidium Rydberg atom cavity QED (2020)

We proposed a protocol to generate entangled photon-comb pairs using rubidium Rydberg atoms inside an optical cavity. Rydberg blockade isolates a single excitation and the heralding enables non-destructive detection of the presence of photon-pairs.
Photoelectrochemical reduction of meta-halonitrobenzenes and related species (1995)

Dual photo- and electro-chemical activation of m-chloronitrobenzene and m-bromonitrobenzene in acetonitrile solution leads to halide loss through a photo-ECE mechanism. This proceeds via absorption of visible light by the radical anions [X-C6H4NO2]˙–, which is followed by fragmentation forming the C6H4NO2 aryl radical. The latter reacts with the solvent system forming nitrobenzene which is further reduced at the electrode with the generation of [C6H5NO2]˙–. Reduction of m-iodonitrobenzene leads to iodide loss without the need for irradiation. However, this process is accelerated by visible light. In contrast the dual activation of p-cyanonitrobenzene, p-dinitrobenzene, phenyl 4-nitrophenyl sulfone, methyl 4-nitrophenyl sulfone, phenyl 4-nitrophenyl sulfoxide or methyl 4-nitrophenyl sulfoxide failed to induce the leaving of any substituent suggesting that the process may be selective to halo-compounds.
Functional characterization of the Xcs and Xps type II secretion systems from the plant pathogenic bacterium Xanthomonas campestris pv vesicatoria (2010)

*Type II secretion (T2S) systems of many plant-pathogenic bacteria often secrete cell wall-degrading enzymes into the plant apoplast. *Here, we show that the Xps-T2S system from the plant pathogen Xanthomonas campestris pv vesicatoria (Xcv) promotes disease and contributes to the translocation of effector proteins that are delivered into the plant cell by the type III secretion (T3S) system. *The Xcs-T2S system instead lacks an obvious virulence function. However, individual xcs genes can partially complement mutants in homologous xps genes, indicating that they encode functional components of T2S systems. Enzyme activity assays showed that the Xps system contributes to secretion of proteases and xylanases. We identified the virulence-associated xylanase XynC as a substrate of the Xps system. However, homologs of known T2S substrates from other Xanthomonas spp. are not secreted by the T2S systems from Xcv. Thus, T2S systems from Xanthomonas spp. appear to differ significantly in their substrate specificities. *Transcript analyses revealed that expression of xps genes in Xcv is activated by HrpG and HrpX, key regulators of the T3S system. By contrast, expression of xynC and extracellular protease and xylanase activities are repressed by HrpG and HrpX, suggesting that components and substrates of the Xps system are differentially regulated.
High‐pressure rheology and viscoelastic scaling predictions of polymer melts containing liquid and supercritical carbon dioxide (2001)

Abstract High‐pressure rheological behavior of polymer melts containing dissolved carbon dioxide (CO 2 ) at concentrations up to 6 wt % were investigated using a high‐pressure extrusion slit die rheometer. In particular, the steady shear viscosity of poly(methyl methacrylate), polypropylene, low‐density polyethylene, and poly(vinylidene fluoride) with dissolved CO 2 were measured for shear rates ranging from 1 to 500 s −1 and under pressure conditions up to 30 MPa. The viscosity of all samples revealed a reduction in the presence of CO 2 with its extent dependent on CO 2 concentration, pressure, and the polymer used. Two types of viscoelastic scaling models were developed to predict the effects of both CO 2 concentration and pressure on the viscosity of the polymer melts. The first approach utilized a set of equations analogous to the Williams–Landel–Ferry equation for melts between the glass‐transition temperature ( T g ) and T g + 100 °C, whereas the second approach used equations of the Arrhenius form for melts more than 100 °C above T g . The combination of these traditional viscoelastic scaling models with predictions for T g depression by a diluent (Chow model) were used to estimate the observed effects of dissolved CO 2 on polymer melt rheology. In this approach, the only parameters involved are physical properties of the pure polymer melt that are either available in the existing literature or can be measured under atmospheric conditions in the absence of CO 2 . The ability of the proposed scaling models to accurately predict the viscosity of polymer melts with dissolved high‐pressure CO 2 were examined for each of the polymer systems. © 2001 John Wiley &amp; Sons, Inc. J Polym Sci Part B: Polym Phys 39: 3055–3066, 2001
Supplementary Table 2 from Discovery and Characterization of Novel Mutant FLT3 Kinase Inhibitors (2023)

Supplementary Table 2 from Discovery and Characterization of Novel Mutant FLT3 Kinase Inhibitors
Compound FC-10696 Inhibits Egress of Marburg Virus (2021)

Marburg virus (MARV) VP40 protein (mVP40) directs egress and spread of MARV, in part, by recruiting specific host WW domain-containing proteins via its conserved PPxY late (L) domain motif to facilitate efficient virus-cell separation. We reported previously that small-molecule compounds targeting the viral PPxY/host WW domain interaction inhibited VP40-mediated egress and spread. Here, we report on the antiviral potency of novel compound FC-10696, which emerged from extensive structure-activity relationship (SAR) of a previously described series of PPxY inhibitors. We show that FC-10696 inhibits egress of mVP40 virus-like particles (VLPs) and egress of authentic MARV from HeLa cells and primary human macrophages. Moreover, FC-10696 treated-mice displayed delayed onset of weight loss and clinical signs and significantly lower viral loads compared to controls, with 14% of animals surviving 21 days following a lethal MARV challenge. Thus, FC-10696 represents a first-in-class, host-oriented inhibitor effectively targeting late stages of the MARV life cycle.
Transformation‐Toughened Ceramic Multilayers with Compositional Gradients (1998)

The processing and the thermomechanical characteristics of zirconia‐toughened alumina (ZTA) ceramic multilayers, with through‐thickness gradients in the concentrations of the tetragonal and monoclinic zirconia phases, are studied both theoretically and experimentally. Analytical solutions for the evolution of thermal strains, internal stresses, and the overall curvature changes in response to various temperatures were derived using known plate theory formulations. Compositionally graded multilayer stacks and complex shapes of ZTA ceramics were fabricated by three‐dimensional printing (3DP). The relative fractions of the tetragonal to monoclinic ZrO 2 phases were varied in a prescribed fashion. Phase transformation of ZrO 2 in ZTA during cooling from the sintering temperature was controlled by doping different amounts of Y 2 O 3 through the thickness of the ZTA multilayer plate. The local content of monoclinic ZrO 2 through the thickness was characterized by X‐ray diffraction analysis. The microstructure, some basic mechanical properties, and thermal expansion behavior of the 3DP ZTA system were also characterized. Thermally induced curvature of the ZTA multilayer plate was measured, and the experimental results were compared with the predictions based on the analytical solutions. Symmetric ZTA multilayers with surface compression were also prepared by 3DP and tested for flexural strength. Results showed a significant increase in strength from the monolithic specimens to the compositionally controlled ones. Results from the compression tests of notched ZTA blocks demonstrated the role of m ‐ZTA shield zones in enhancing the load‐bearing characteristics. This study also demonstrated the possibility that commonly available computational tools can be used to design and construct complex shapes with compositional variation to enhance and control mechanical properties.
PI3K Pathway Effectors pAKT and FOXO1 as Novel Markers of Endometrioid Intraepithelial Neoplasia (2018)

The diagnosis of endometrioid intraepithelial neoplasia (EIN) is challenging owing to limited sampling, hormonal status, and other confounding histologic variables. Markers such as PTEN or PAX2 can delineate EIN in some cases, but are not wholly reliable. Clearly, new markers of EIN are needed. We explored several potential markers of EIN based rationally on molecular pathways most frequently misregulated in endometrial cancer: the 3-phosphoinositide kinase (PI3K)/AKT, β-catenin, and mismatch repair pathways. We studied PTEN, PAX2, β-catenin, and MLH1, in conjunction with 2 new markers-FOXO1 and phosphorylated AKT (pAKT)-not previously investigated in EIN. Benign (n=14) and EIN (n=35) endometria were analyzed by immunohistochemistry. Staining patterns were interpreted, tabulated, and scored by "clonal distinctiveness" in neoplastic lesions; that is, pattern alterations relative to normal glands. In normal endometria, FOXO1 was cytoplasmic in proliferative phase, but nuclear in secretory phase, showing that PI3K/FOXO1 participates in endometrial cycling and that FOXO1 is a readout of PI3K status. pAKT expression was low across normal endometria. FOXO1 or pAKT expression was altered in the majority of EINs (27/35, 77%), with FOXO1 and pAKT being co-altered only in some (20/35, 57%). β-catenin or MLH1 also exhibited clonal distinctiveness in EINs, showing that these are also useful markers in some cases. This is the first study to demonstrate the potential of pAKT and FOXO1 as biomarkers in the histopathologic evaluation of EIN. However, variability in expression poses challenges in interpretation.
Low Loss Steerable Reflectarray Antenna for Space Application (2002)

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