gebhart/patrepeval huggingface dataset:
Biocatalytic synthesis of disaccharide high‐intensity sweeterner sucralose via a tetrachlororaffinose intermediate (1992)

A second high-yielding bioorganic synthesis of the highintensity sweetener sucralose (4,1',6'-trichloro-4,1',6'-trideoxygalactosucrose) is described. This procedure involves the chemical chlorination of raffinose to form a novel tetrachloroaffinose intermediate (6,4',1'',6''-tetrachloro-6,4',1'',6''-tetradeoxygalactoraffinose; TCR) followed by the enzymic hydrolysis of the alpha-1-6 glycosidic bond of TCR to give sucralose and 6-chlorogalactose. Commercial enzyme preparations and microorganisms were screened to select alpha-galactosidases which have high catalytic activity on this compound. The most active enzyme was produced by a strain of Mortierella vinacea and had a maximum rate of 118 mumol sucralose/g dry weight cells/h, which was approximately 5% of the activity toward raffinose, and a K(m) of 5.8 mM toward TCR. The enzyme could be used in the form of mycelial pellets in a continuous packed bed column reactor. The reaction was also studied in a water-immiscible hydrophilic organic solvent, such as methyl isobutyl ketone, to overcome the poor aqueous solubility of TCR and to increase volumetric productivity. Synthesis of raffinose was achieved from saturated aqueous solutions of galactose and sucrose using a selected alpha-galactosidase from Aspergillus niger. When raffinose is used as a starting material for sucralose synthesis, this route has fewer steps than either the preceeding method using glucose-6-acetate as an intermediate or the complete chemical synthesis from sucrose. The relative merits of the two bioorganic routes and the utility of such methods to synthesize new sugars are discussed.
Delineation of a Fundamental α-Ketoheterocycle Substituent Effect for Use in the Design of Enzyme Inhibitors (2006)

The synthesis and examination of a systematic series of 5-substituted 2-keto oxazoles as inhibitors of fatty acid amide hydrolase (FAAH) defined a fundamental substituent effect that led to the discovery of inhibitors with Ki's as low as 400 pM. The intrinsic basis of the relationship (-log Ki vs sigmap), which relates Ki with the Hammett sigmap constant of the substituent, the magnitude of the effect (rho = 3.01), and its predictive value (R2 = 0.91) suggest a widespread applicability in studies beyond FAAH.
Conjugation Chemistry and Bioapplications of Semiconductor Box Nanocrystals Prepared via Dendrimer Bridging (2003)

A new strategy, dendrimer bridging, is developed for simultaneous formation and functionalization of biocompatible and bioaccessible semiconductor box nanocrystalsa dendron box around each colloidal semiconductor nanocrystal. CdSe plain core or CdSe/CdS core/shell nanocrystals coated by a monolayer of organic dendron ligands (dendron nanocrystals) with hydroxyl groups as the terminal were chosen as the starting systems because of their potential biocompatibility and proven stability. A generation-two (G2) amine-terminated dendrimer was used as the cross-linking and functionalization reagent, which yielded much more stable cross-linked nanocrystals than the simple diamine or trisamine cross-linking reagents did. The chemical, thermal, and photochemical stability of the resulting amine-terminating box nanocrystals (amine box nanocrystals) formed by dendrimer bridging are comparable to that of the first generation box nanocrystals, achieved by ring-closing metathesis (RCM), that are not biocompatible and need to be further functionalized for bioapplications. As expected, the amine groups on the surface of the box nanocrystals provide versatile and reliable conjugation chemistry under mild conditions. Using one of the conjugation methods, biotin molecules were readily coupled onto the amine box nanocrystals. The biomedical applications of those superstable box nanocrystals were demonstrated by the quantitative and reproducible precipitation of the picomole amounts of avidin with the biotinylated box nanocrystals. Experimental results further revealed that the amine box nanocrystals and related derivatives are fully biocompatible to the tested system, have no detectable nonspecific binding, are extremely stable in the desired bioenvironment, and have no noticeable interference with the bioactivities. The exceptional thermal stability further warrants those biocompatible box nanocrystals to be employed in a large temperature range needed for certain applications, such as PCR.
Multiresolution signal representation for phase unwrapping and interferometric SAR processing (2002)

Phase unwrapping requires-implicitly or explicitly-phase gradient estimates for phase reconstruction. An asymptotically unbiased local frequency estimator based on multiresolution signal representation is presented. The proposed estimator is able to automatically trade-off resolution against estimation error. It is shown that interferometric SAR processing can be improved by employing a smoothed version of the unwrapped phase. Particularly, a novel method for slope-adaptive spectral shift filtering is introduced.
Novel Heterocyclic Trans Olefin Analogues of <i>N</i>-{4-[4-(2,3-Dichlorophenyl)piperazin-1-yl]butyl}arylcarboxamides as Selective Probes with High Affinity for the Dopamine D3 Receptor (2005)

Dopamine D3 receptor subtypes have been hypothesized to play a pivotal role in modulating the reinforcing and drug-seeking effects induced by cocaine. However, definitive pharmacological investigations have been hampered by the lack of highly D3 receptor selective compounds that can be used in vivo. To address this problem, the potent and D3-receptor-selective antagonist NGB 2904 (1, 9H-fluorene-2-carboxylic acid {4-[(2,3-dichlorophenyl)-piperazin-1-yl]-butyl}-amide, Ki (hD3) = 2.0 nM, Ki (hD2L) = 112 nM, D2/D3 selectivity ratio of 56) was chosen as a lead structure for chemical modification in an attempt to reduce its high lipophilicity (c log D = 6.94) while optimizing D3 receptor binding affinity and D2/D3 selectivity. A series of >30 novel analogues were synthesized, and their binding affinities were evaluated in competition binding assays in HEK 293 cells transfected with either D2(L), D3, or D4 human dopamine receptors using the high affinity, selective D2-like receptor antagonist (125)I-IABN. Structural diversity in the aryl amide end of the molecule was found to have a major influence on (sub)nanomolar D3 receptor affinity and D2/D3 selectivity, which was optimized using a more rigid trans-butenyl linker between the aryl amide and the piperazine. Several analogues demonstrated superior D3 receptor binding affinities and selectivities as compared to the parent ligand. Compound 29 (N-{4-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-trans-but-2-enyl}-4-pyridine-2-yl-benzamide) displayed the most promising pharmacological profile (Ki (hD3) = 0.7 nM, Ki (hD2L) = 93.3 nM, D2/D3 selectivity ratio of 133). In addition, this ligand inhibited quinpirole stimulation of mitogenesis at human dopamine D3 receptors transfected into Chinese hamster ovary (CHO) cells, with an EC50 value of 3.0 nM. Compound 29 was a nearly 5 times more potent antagonist at the D3 receptor than 1 (EC50 = 14.4 nM). Moreover, a decrease in c log D value of approximately 2 orders of magnitude was determined for this novel D3-receptor-preferring ligand, compared to 1. In summary, chemical modification of 1 has resulted in compounds with high affinity and selectivity for D3 receptors. The most promising candidate, compound 29, is currently being evaluated in animal models of cocaine abuse and will provide an important tool with which to elucidate the role of D3 receptors in drug reinforcement in vivo.
Phenotyping COPD exacerbations using imaging and blood-based biomarkers (2018)

Elevated CRP may indicate the presence of pneumonia, while elevated NT-proBNP may indicate cardiac dysfunction. These readily available blood-based biomarkers may provide more accurate phenotyping of AECOPD and enable the discovery of more precise therapies.
Synthesis and Biological Activity of Potent Heterocyclic Thiol‐Based Inhibitors of Endothelin‐Converting Enzyme‐1. (2003)

Abstract For Abstract see ChemInform Abstract in Full Text.
Graphitized silicon carbide microbeams: wafer-level, self-aligned graphene on silicon wafers (2014)

Currently proven methods that are used to obtain devices with high-quality graphene on silicon wafers involve the transfer of graphene flakes from a growth substrate, resulting in fundamental limitations for large-scale device fabrication. Moreover, the complex three-dimensional structures of interest for microelectromechanical and nanoelectromechanical systems are hardly compatible with such transfer processes. Here, we introduce a methodology for obtaining thousands of microbeams, made of graphitized silicon carbide on silicon, through a site-selective and wafer-scale approach. A Ni-Cu alloy catalyst mediates a self-aligned graphitization on prepatterned SiC microstructures at a temperature that is compatible with silicon technologies. The graphene nanocoating leads to a dramatically enhanced electrical conductivity, which elevates this approach to an ideal method for the replacement of conductive metal films in silicon carbide-based MEMS and NEMS devices.
A Macroporous Perovskite Manganite from Colloidal Templates with a Curie Temperaure of 320 K (2003)

A macroporous perovskite manganite, La0.7Ca0.3MnO3, exhibits a three-dimensionally ordered ferromagnetic network that is replicated from a colloidal polymer template. The spherical voids are interconnected via small channels.
Application of hydrophilic starch‐based coatings on polyethylene surfaces (2008)

Abstract Coatings were applied to polyethylene (PE) film surfaces by spraying formulations prepared from a jet cooked dispersion of waxy cornstarch, a water‐born epoxy resin, a wax emulsion, and a fluorinated surfactant. The air‐dried coatings were comprised of discontinuous areas of polymer that adhered tightly to the PE surface. Although the starch component separated rapidly from the coating when the film was placed in water at room temperature, heating the coated film for 24 h at 80°C increased the adhesion of starch and produced a surface coating that remained uniformly wet when the film was placed in water. Most of the starch, however, could be still be removed by gently rubbing the wet surface. If melamine‐formaldehyde resin was added to the formulation as a crosslinking agent for starch, and the coated film was then heated for 24 h at 80°C, most of the starch remained bonded to the wet coating, even after the surface was gently rubbed. Identification of successful spray application techniques and formulations will allow the development of commercial production methods for starch‐coated PE films and similar products. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Discovery of 4-[(2<i>S</i>)-2-{[4-(4-Chlorophenoxy)phenoxy]methyl}-1-pyrrolidinyl]butanoic Acid (DG-051) as a Novel Leukotriene A4 Hydrolase Inhibitor of Leukotriene B4 Biosynthesis (2009)

Both in-house human genetic and literature data have converged on the identification of leukotriene 4 hydrolase (LTA4H) as a key target for the treatment of cardiovascular disease. We combined fragment-based crystallography screening with an iterative medicinal chemistry effort to optimize inhibitors of LTA4H. Ligand efficiency was followed throughout our structure−activity studies. As applied within the context of LTA4H inhibitor design, the chemistry team was able to design a potent compound 20 (DG-051) (Kd = 26 nM) with high aqueous solubility (>30 mg/mL) and high oral bioavailability (>80% across species) that is currently undergoing clinical evaluation for the treatment of myocardial infarction and stroke. The structural biology−chemistry interaction described in this paper provides a sound alternative to conventional screening techniques. This is the first example of a gene-to-clinic paradigm enabled by a fragment-based drug discovery effort.
Power Generation From Concentrated Solar-Heated Air Using Buoyancy-Induced Vortices (2012)

Thermally-stratified air layers overlying solar-heated ground are exploited for power generation by the deliberate formation of intense buoyancy-induced vertical columnar vortices, similar to naturally-occurring desert “dust devils.” In hot-climate regions, such buoyancy-driven columnar vortices occur spontaneously with core diameters of 1–50 m at the surface and heights up to one km, leading to flows with considerable angular and axial momentum. Unlike “dust devil” vortices, which are typically free to wander laterally and are therefore susceptible to crosswind, anchored columnar vortices are deliberately triggered and confined within a domain laterally bounded by an azimuthal array of stationary ground-mounted vertical vanes, and are sustained by continuous entrainment of heated air passing between these vanes. Hot air near the solar-heated ground plane sustains the anchored vortex, and electric power is generated by using the resulting rotational and vertical flow induced by an “anchored” vortex to drive a vertical-axis wind turbine coupled to an electric generator. This novel approach to the collection of solar energy provides a low-cost, scalable, and sustainable method for generation of electric power from vast amounts of solar-heated air in arid regions. Meter-scale laboratory experiments have demonstrated the nucleation and sustainment of strong, buoyancy-driven vortices above a thermally controlled ground plane. The present investigation focuses on fundamental mechanisms of columnar vortex formation, evolution, and dynamics using stereo particle image velocimetry (PIV), with particular emphasis on scaling and assessment of the available mechanical power. The strength and scaling of theses vortices can be significantly altered by adjustment of the vanes and the rate of sensible heat uptake by the air flow, related to the “buoyancy flux”. Recent outdoor tests of a meter-scale prototype coupled with a simple vertical-axis turbine placed on a surface directly heated by solar radiation, have demonstrated continuous rotation of the turbine with significant extraction of kinetic energy from the column vortex, in both the absence and presence of crosswind.
Cross-Lingual Discriminative Learning of Sequence Models with Posterior Regularization (2013)

We present a framework for cross-lingual transfer of sequence information from a resource-rich source language to a resourceimpoverished target language that incorporates soft constraints via posterior regularization.To this end, we use automatically word aligned bitext between the source and target language pair, and learn a discriminative conditional random field model on the target side.Our posterior regularization constraints are derived from simple intuitions about the task at hand and from cross-lingual alignment information.We show improvements over strong baselines for two tasks: part-of-speech tagging and namedentity segmentation.
Reciprocating constructed wetlands for treating industrial, municipal and agricultural wastewater (2001)

Scientists at the Tennessee Valley Authority (TVA), and in collaboration with the U.S. Environmental Protection Agency (EPA), are continuing to develop and refine an innovative wastewater treatment system referred to as reciprocating subsurface-flow constructed wetlands. Reciprocation relates to patented improvements in the design and operation of paired subsurface-flow constructed wetlands, such that contiguous cells are filled and drained on a frequent and recurrent basis. This operating technique turns the entire wetland system into a fixed-film biological reactor, in which it is possible to control redox potential in alternating aerobic and anaerobic zones. Reciprocating systems enable manipulation of wastewater treatment functions by controlling such parameters as hydraulic retention time, frequency of reciprocation, reciprocation cycle time, depth of reciprocation, and size and composition of substrate. These improved wetland technologies have been used for treating municipal/domestic wastewater, high strength animal wastewater, and mixed wastewater streams containing acids, recalcitrant compounds, solvents, antifreeze compounds, heavy metals, explosives, and fertilizer nutrients. Results from selected treatability studies and field demonstrations will be summarized with respect to conceptual design and treatment efficacy.
BrAD-seq: Breath Adapter Directional sequencing: a streamlined, ultra-simple and fast library preparation protocol for strand specific mRNA library construction (2015)

Next Generation Sequencing (NGS) is driving rapid advancement in biological understanding and RNA-sequencing (RNA-seq) has become an indispensable tool for biology and medicine. There is a growing need for access to these technologies although preparation of NGS libraries remains a bottleneck to wider adoption. Here we report a novel method for the production of strand specific RNA-seq libraries utilizing the terminal breathing of double-stranded cDNA to capture and incorporate a sequencing adapter. Breath Adapter Directional sequencing (BrAD-seq) reduces sample handling and requires far fewer enzymatic steps than most available methods to produce high quality strand-specific RNA-seq libraries. The method we present is optimized for 3-prime Digital Gene Expression (DGE) libraries and can easily extend to full transcript coverage shotgun (SHO) type strand-specific libraries and is modularized to accommodate a diversity of RNA and DNA input materials. BrAD-seq offers a highly streamlined and inexpensive option for RNA-seq libraries.
Acetylacetone-cleaving enzyme Dke1: a novel C-C-bond-cleaving enzyme from Acinetobacter johnsonii (2003)

The toxicity of acetylacetone has been demonstrated in various studies. Little is known, however, about metabolic pathways for its detoxification or mineralization. Data presented here describe for the first time the microbial degradation of acetylacetone and the characterization of a novel enzyme that initiates the metabolic pathway. From an Acinetobacter johnsonii strain that grew with acetylacetone as the sole carbon source, an inducible acetylacetone-cleaving enzyme was purified to homogeneity. The corresponding gene, coding for a 153 amino acid sequence that does not show any significant relationship to other known protein sequences, was cloned and overexpressed in Escherichia coli and gave high yields of active enzyme. The enzyme cleaves acetylacetone to equimolar amounts of methylglyoxal and acetate, consuming one equivalent of molecular oxygen. No exogenous cofactor is required, but Fe(2+) is bound to the active protein and essential for its catalytic activity. The enzyme has a high affinity for acetylacetone with a K (m) of 9.1 microM and a k(cat) of 8.5 s(-1). A metabolic pathway for acetylacetone degradation and the putative relationship of this novel enzyme to previously described dioxygenases are discussed.
A nanoparticle-based microsensor for room temperature hydrogen detection (2006)

In this work, we report a novel micromachined hydrogen sensor operating at room temperature. The sensor has been successfully designed and fabricated, based on interdigitated conductometric microelectrodes integrating indium oxide (In/sub 2/O/sub 3/)-doped tin oxide (SnO/sub 2/) semiconductor nanocrystalline particles with platinum (Pt) nanoclusters. Very high H/sub 2/ sensitivity (110/spl times/10/sup 3/) with fast response and recovery has been observed for the presented sensor at room temperature and low hydrogen gas concentration. The nanomaterial/microdevice integration for a highly efficient sensor device with unprecedented functions has been explored and investigated systematically.
Supramolecular Complexes as Photoinitiated Electron Collectors: Applications in Solar Hydrogen Production (2010)

The urgent need for alternative fuel sources has stimulated research in solar hydrogen production. Photoinitiated electron collection is applicable in solar hydrogen production and uses light to collect reducing equivalents. Solar hydrogen production from water using mixed-metal supramolecular complexes through photoinitiated electron collection is summarized. Many successful systems couple multiple polyazine light absorber units that are electronically isolated to a single reactive metal. Upon optical excitation, these systems collect and deliver multiple electrons to substrates, such as water, producing hydrogen. The design considerations for a functioning system for light activated multi-electron reduction of water to produce hydrogen are described.
Simple, fast, and safe manual memory management (2017)

Safe programming languages are readily available, but many applications continue to be written in unsafe languages because of efficiency. As a consequence, many applications continue to have exploitable memory safety bugs. Since garbage collection is a major source of inefficiency in the implementation of safe languages, replacing it with safe manual memory management would be an important step towards solving this problem.
Covalent Immobilization of Peptides on Self-Assembled Monolayer Surfaces Using Soft-Landing of Mass-Selected Ions (2007)

Controlled immobilization of peptides onto N-hydroxysuccinimidyl ester functionalized self-assembled monolayer (SAM) surfaces using reactive landing of mass-selected ions has been demonstrated. Surface characterization using time-of-flight secondary ion mass spectrometry and grazing-incidence infrared reflection−absorption spectroscopy confirmed highly efficient covalent linkage through an amide bond formed between the SAM and the free amino group of the lysine side chain. Reactive landing opens a new way for controlled preparation of peptide arrays.
Complementary Cell-Free Translational Assay for Quantification of Amino Acids (2017)

In this study, we present a simple and economical method that enables rapid quantification of amino acids based on their polymerization into a signal-generating protein. This method harnesses amino acid-deficient cell-free protein synthesis systems that generate fluorescence signals in response to exogenous amino acids. When premixed with assay samples containing the amino acids in question, incubation of the cell-free synthesis reaction mixture rapidly resulted in the production of sfGFP, the fluorescence intensity of which was linearly proportional to the concentration of the amino acids. The assay method achieved a limit of detection as low as ∼100 nM and was successfully applied to the quantification of disease-related amino acids in biological samples. Compared with standard methods in current use that require chemical derivatization of amino acids and chromatographic equipment, the complementation assay method developed in this work enables the direct translation of amino acid titer into measurable biofluorescence intensity in a much shorter period, providing a more affordable and flexible option for the quantification of amino acids.