gebhart/patrepeval huggingface dataset:
Probing a protein–protein interaction by in vitro evolution (2006)

In this study, we used in vitro protein evolution with ribosome and phage display to optimize the affinity of a human IL-13-neutralizing antibody, a therapeutic candidate for the treatment of asthma, >150-fold to 81 pM by using affinity-driven stringency selections. Simultaneously, the antibody potency to inhibit IL-13-dependent proliferation in a cell-based functional assay increased 345-fold to an IC50 of 229 pM. The panoply of different optimized sequences resulting from complementarity-determining region-targeted mutagenesis and error-prone PCR using ribosome display was contrasted with that of complementarity-determining region-targeted mutagenesis alone using phage display. The data highlight the advantage of the ribosome-display approach in identifying beneficial mutations across the entire sequence space. A comparison of mutation hotspots from in vitro protein evolution to knockout mutations from alanine scanning demonstrated that in vitro evolution selects the most appropriate positions for improvements in potency without mutating any of the key residues within the functional paratope.
Online learning from click data for sponsored search (2008)

Sponsored search is one of the enabling technologies for today's Web search engines. It corresponds to matching and showing ads related to the user query on the search engine results page. Users are likely to click on topically related ads and the advertisers pay only when a user clicks on their ad. Hence, it is important to be able to predict if an ad is likely to be clicked, and maximize the number of clicks. We investigate the sponsored search problem from a machine learning perspective with respect to three main sub-problems: how to use click data for training and evaluation, which learning framework is more suitable for the task, and which features are useful for existing models. We perform a large scale evaluation based on data from a commercial Web search engine. Results show that it is possible to learn and evaluate directly and exclusively on click data encoding pairwise preferences following simple and conservative assumptions. We find that online multilayer perceptron learning, based on a small set of features representing content similarity of different kinds, significantly outperforms an information retrieval baseline and other learning models, providing a suitable framework for the sponsored search task.
Time slot assignment in SS/TDMA systems with intersatellite links (1987)

In this paper we study the time slot assignment problem in clusters of SS/TDMA satellite systems interconnected through intersatellite links. We show that the problem of finding an assignment which minimizes the total transmission time is NP-complete, i.e., computationally intractable, even for quite restricted intersatellite link patterns and simplified system models. Successively, we focus our attention on clusters of two satellites, proposing a branch-and-bound optimal algorithm and two fast heuristic algorithms. We investigate the performance of the proposed heuristic algorithms both by a theoretical worst case bound and by simulation trials showing that the produced solutions are close to the optimal on the average.
Structural Basis for Substrate Fatty Acyl Chain Specificity (2008)

Very-long-chain acyl-CoA dehydrogenase (VLCAD) is a member of the family of acyl-CoA dehydrogenases (ACADs). Unlike the other ACADs, which are soluble homotetramers, VLCAD is a homodimer associated with the mitochondrial membrane. VLCAD also possesses an additional 180 residues in the C terminus that are not present in the other ACADs. We have determined the crystal structure of VLCAD complexed with myristoyl-CoA, obtained by co-crystallization, to 1.91-A resolution. The overall fold of the N-terminal approximately 400 residues of VLCAD is similar to that of the soluble ACADs including medium-chain acyl-CoA dehydrogenase (MCAD). The novel C-terminal domain forms an alpha-helical bundle that is positioned perpendicular to the two N-terminal helical domains. The fatty acyl moiety of the bound substrate/product is deeply imbedded inside the protein; however, the adenosine pyrophosphate portion of the C14-CoA ligand is disordered because of partial hydrolysis of the thioester bond and high mobility of the CoA moiety. The location of Glu-422 with respect to the C2-C3 of the bound ligand and FAD confirms Glu-422 to be the catalytic base. In MCAD, Gln-95 and Glu-99 form the base of the substrate binding cavity. In VLCAD, these residues are glycines (Gly-175 and Gly-178), allowing the binding channel to extend for an additional 12A and permitting substrate acyl chain lengths as long as 24 carbons to bind. VLCAD deficiency is among the more common defects of mitochondrial beta-oxidation and, if left undiagnosed, can be fatal. This structure allows us to gain insight into how a variant VLCAD genotype results in a clinical phenotype.
Biocatalytic Cascade for the Synthesis of Enantiopure β‐Azidoalcohols and β‐Hydroxynitriles (2009)

Abstract A three‐step, two‐enzyme, one‐pot reaction sequence starting from prochiral α‐chloroketones leading to enantiopure β‐azidoalcohols and β‐hydroxynitriles is described. Asymmetric bioreduction of α‐chloroketones by hydrogen transfer catalysed by an alcohol dehydrogenase (ADH) established the stereogenic centre in the first step to furnish enantiopure chlorohydrin intermediates. Subsequent biocatalysed ring closure to the epoxide and nucleophilic ring opening with azide, N 3 – , or cyanide, CN – , both catalysed by a nonselective halohydrin dehalogenase (Hhe) proceeded with full retention of configuration to give enantiopure β‐azidoalcohols and β‐hydroxynitriles, respectively. Both enantiomers of various optically pure β‐azidoalcohols and β‐hydroxynitriles were synthesised. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2009)
Synthetic Organic Electrochemistry: An Enabling and Innately Sustainable Method (2016)

While preparative electrolysis of organic molecules has been an active area of research over the past century, modern synthetic chemists have generally been reluctant to adopt this technology. In fact, electrochemical methods possess many benefits over traditional reagent-based transformations, such as high functional group tolerance, mild conditions, and innate scalability and sustainability. In this Outlook we highlight illustrative examples of electrochemical reactions in the context of the synthesis of complex molecules, showcasing the intrinsic benefits of electrochemical reactions versus traditional reagent-based approaches. Our hope is that this field will soon see widespread adoption in the synthetic community.
Thin-Film Transistor Fabricated in Single-Crystalline Transparent Oxide Semiconductor (2003)

We report the fabrication of transparent field-effect transistors using a single-crystalline thin-film transparent oxide semiconductor, InGaO3(ZnO)5, as an electron channel and amorphous hafnium oxide as a gate insulator. The device exhibits an on-to-off current ratio of approximately 106 and a field-effect mobility of approximately 80 square centimeters per volt per second at room temperature, with operation insensitive to visible light irradiation. The result provides a step toward the realization of transparent electronics for next-generation optoelectronics.
Development of artificial articular cartilage (2000)

Attempts have been made to develop an artificial articular cartilage on the basis of a new viewpoint of joint biomechanics in which the lubrication and load-bearing mechanisms of natural and artificial joints are compared. Polyvinyl alcohol hydrogel (PVA-H), 'a rubber-like gel', was investigated as an artificial articular cartilage and the mechanical properties of this gel were improved through a new synthetic process. In this article the biocompatibility and various mechanical properties of the new improved PVA-H is reported from the perspective of its usefulness as an artificial articular cartilage. As regards lubrication, the changes in thickness and fluid pressure of the gap formed between a glass plate and the specimen under loading were measured and it was found that PVA-H had a thicker fluid film under higher pressures than polyethylene (PE) did. The momentary stress transmitted through the specimen revealed that PVA-H had a lower peak stress and a longer duration of sustained stress than PE, suggesting a better damping effect. The wear factor of PVA-H was approximately five times that of PE. Histological studies of the articular cartilage and synovial membranes around PVA-H implanted for 8-52 weeks showed neither inflammation nor degenerative changes. The artificial articular cartilage made from PVA-H could be attached to the underlying bone using a composite osteochondral device made from titanium fibre mesh. In the second phase of this work, the damage to the tibial articular surface after replacement of the femoral surface in dogs was studied. Pairs of implants made of alumina, titanium or PVA-H on titanium fibre mesh were inserted into the femoral condyles. The two hard materials caused marked pathological changes in the articular cartilage and menisci, but the hydrogel composite replacement caused minimal damage. The composite osteochondral device became rapidly attached to host bone by ingrowth into the supporting mesh. The clinical implications of the possible use of this material in articular resurfacing and joint replacement are discussed.
Beneficial effects of peroxynitrite decomposition catalyst in a rat model of splanchnic artery occlusion and reperfusion (2000)

The aim of the present study was to investigate the protective effect of the peroxynitrite decomposition catalyst 5,10,15, 20-tetrakis(2,4,6-trimethyl-3,5-disulfonatophenyl)-porphyrinato iron (III) (FeTMPS) in a model of splanchnic artery occlusion shock (SAO). SAO shock was induced in rats by clamping both the superior mesenteric artery and the celiac trunk for 45 min, followed by release of the clamp (reperfusion). At 60 min after reperfusion, animals were killed for histological examination and biochemical studies. There was a marked increase in the oxidation of dihydrorhodamine 123 to rhodamine (a marker of peroxynitrite-induced oxidative processes) in the plasma of the SAO-shocked rats after reperfusion, but not during ischemia alone. Immunohistochemical examination demonstrated a marked increase in the immunoreactivity to nitrotyrosine, an index of nitrogen species such as peroxynitrite, in the necrotic ileum in shocked rats. SAO-shocked rats developed a significant increase of tissue myeloperoxidase and malonaldehyde activity, and marked histological injury to the distal ileum. SAO shock was also associated with a significant mortality (0% survival at 2 h after reperfusion). Reperfused ileum tissue sections from SAO-shocked rats showed positive staining for P-selectin localized mainly in the vascular endothelial cells. Ileum tissue sections obtained from SAO-shocked rats and stained with antibody to ICAM-1 showed a diffuse staining. Administration of FeTMPS significantly reduced ischemia/reperfusion injury in the bowel, and reduced lipid and the production of peroxynitrite during reperfusion. Treatment with PN catalyst also markedly reduced the intensity and degree of P-selectin and ICAM-1 staining in tissue sections from SAO-shocked rats and improved survival. Our results clearly demonstrate that peroxynitrite decomposition catalysts exert a protective effect in SAO and that this effect may be due to inhibition of the expression of adhesion molecules and the tissue damage associated with peroxynitrite-related pathways.
Text mining for biology - the way forward: opinions from leading scientists (2008)

This article collects opinions from leading scientists about how text mining can provide better access to the biological literature, how the scientific community can help with this process, what the next steps are, and what role future BioCreative evaluations can play. The responses identify several broad themes, including the possibility of fusing literature and biological databases through text mining; the need for user interfaces tailored to different classes of users and supporting community-based annotation; the importance of scaling text mining technology and inserting it into larger workflows; and suggestions for additional challenge evaluations, new applications, and additional resources needed to make progress.
Aerosol-assisted synthesis of monodisperse single-crystalline α-cristobalite nanospheres (2011)

Monodisperse single-crystalline α-cristobalite nanospheres have been synthesized by hydrocarbon-pyrolysis-induced carbon deposition on amorphous silica aerosol nanoparticles, devitrification of the coated silica at high temperature, and subsequent carbon removal by oxidation. The nanosphere size can be well controlled by tuning the size of the colloidal silica precursor. Uniform, high-purity nanocrystalline α-cristobalite is important for catalysis, nanocomposites, advanced polishing, and understanding silica nanotoxicology.
Matrix Metalloproteinase-3 Causes Dopaminergic Neuronal Death through Nox1-Regenerated Oxidative Stress (2014)

In the present study we investigated the interplay between matrix metalloproteinase 3 (MMP3) and NADPH oxidase 1 (Nox1) in the process of dopamine (DA) neuronal death. We found that MMP3 activation causes the induction of Nox1 via mitochondrial reactive oxygen species (ROS) production and subsequently Rac1 activation, eventually leading to Nox1-derived superoxide generation in a rat DA neuronal N27 cells exposed to 6-OHDA. While a MMP3 inhibitor, NNGH, largely attenuated mitochondrial ROS and subsequent Nox1 induction, both apocynin, a putative Nox inhibitor and GKT137831, a Nox1 selective inhibitor failed to reduce 6-OHDA-induced mitochondrial ROS. However, both inhibitors for MMP3 and Nox1 similarly attenuated 6-OHDA-induced N27 cell death. RNAi-mediated selective inhibition of MMP3 or Nox1 showed that knockdown of either MMP3 or Nox1 significantly reduced 6-OHDA-induced ROS generation in N27 cells. While 6-OHDA-induced Nox1 was abolished by MMP3 knockdown, Nox1 knockdown did not alter MMP3 expression. Direct overexpression of autoactivated MMP3 (actMMP3) in N27 cells or in rat substantia nigra (SN) increased expression of Nox1. Selective knockdown of Nox1 in the SN achieved by adeno-associated virus-mediated overexpression of Nox1-specific shRNA largely attenuated the actMMP3-mediated dopaminergic neuronal loss. Furthermore, Nox1 expression was significantly attenuated in Mmp3 null mice treated with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Together we established novel molecular mechanisms underlying oxidative stress-mediated dopaminergic neuronal death in which MMP3 activation is a key upstream event that leads to mitochondrial ROS, Nox1 induction and eventual dopaminergic neuronal death. Our findings may lead to the development of novel therapeutic approach.
Validation of a Genomic Classifier that Predicts Metastasis Following Radical Prostatectomy in an At Risk Patient Population (2013)

Results indicate that genomic information from the primary tumor can identify patients with adverse pathological features who are most at risk for metastasis and potentially lethal prostate cancer.
Age-related changes in D-aspartic acid of rat teeth. (1995)

In addition to L-aspartic acid, D-aspartic acid was detected in the protein (collagen) of rat teeth. The content of D-aspartic acid in rat molars increased significantly with age, showing a close correlation with age (r = 0.965-0.993), whereas in rat incisors D-aspartic acid did not increase. This suggests that there is little metabolic activity in rat molars after their formation. The amount of D-aspartic acid present in molars of a single rat was in the order first molars > second molars > third molars. This indicates that the amount of D-aspartic acid is higher in teeth formed earlier, corresponding to the time of their formation. The rate of racemization in rat molars was about ten-fold higher than that in human dentin, suggesting the importance of body temperature in the rate of racemization. These findings also suggest that D-aspartic acid is present in the teeth of other animals.
All solid-state GFP sensor (2000)

An all-solid-state green fluorescent protein (GFP) sensor for GFP measurement was developed. It is immune to interference from ambient light and works with standard flow-through cuvettes. The sensor is practically insensitive to the scattered excitation light encountered in microbial suspensions. It has a range of 0.0002-1 g/L (7.4 x 10(-9) - 3.7 x 10(-5) M) with limit of detection 0.00019 g/L (7.0 x 10(-9) M). The sensor could be used with a UV or blue light emitting diode (LED) as a light source, depending on required sensitivity, selectivity, and background levels. Its very low cost makes it useful in a variety of applications. This article describes the construction and validation of the sensor both off- and on-line in fermentation processes.
Exactly Sparse Extended Information Filters for Feature-based SLAM (2007)

Recent research concerning the Gaussian canonical form for Simultaneous Localization and Mapping (SLAM) has given rise to a handful of algorithms that attempt to solve the SLAM scalability problem for arbitrarily large environments. One such estimator that has received due attention is the Sparse Extended Information Filter (SEIF) proposed by Thrun et al., which is reported to be nearly constant time, irrespective of the size of the map. The key to the SEIF's scalability is to prune weak links in what is a dense information (inverse covariance) matrix to achieve a sparse approximation that allows for efficient, scalable SLAM. We demonstrate that the SEIF sparsification strategy yields error estimates that are overconfident when expressed in the global reference frame, while empirical results show that relative map consistency is maintained. In this paper, we propose an alternative scalable estimator based on an information form that maintains sparsity while preserving consistency. The paper describes a method for controlling the population of the information matrix, whereby we track a modified version of the SLAM posterior, essentially by ignoring a small fraction of temporal measurements. In this manner, the Exactly Sparse Extended Information Filter (ESEIF) performs inference over a model that is conservative relative to the standard Gaussian distribution. We compare our algorithm to the SEIF and standard EKF both in simulation as well as on two nonlinear datasets. The results convincingly show that our method yields conservative estimates for the robot pose and map that are nearly identical to those of the EKF.
Properties of Zn3P2Thin Films Grown by Ionized-Cluster Beam Deposition (1983)

Zinc phosphide (Zn 3 P 2 ) thin films have been fabricated by ionized-cluster beam (ICB) deposition on glass substrates. Highly crystalline Zn 3 P 2 films are obtained with a strong preferred orientation along the c-axis by optimizing the acceleration voltage and substrate temperature. The Zn 3 P 2 films have extremely good stoichiometry compared with those by conventional vacuum evaporation: fluorescent X-ray spectroscopy indicates Zn 3 P 2.05 for the Zn 3 P 2 films deposited at an acceleration voltage of 2 kV and substrate temperature of 300°C. The absorption coefficient is deduced from the optical transmission and reflectivity data; the fundamental absorption edge is obtained as 1.55 eV at 300 K.
Chronic Cocaine Treatment Decreases Levels of the G Protein Subunits Giα and Goα in Discrete Regions of Rat Brain (1990)

A possible role for G proteins in contributing to the chronic actions of cocaine was investigated in three rat brain regions known to exhibit electrophysiological responses to chronic cocaine: the ventral tegmental area, nucleus accumbens, and locus coeruleus. It was found that chronic, but not acute, treatment of rats with cocaine produced a small (approximately 15%), but statistically significant, decrease in levels of pertussis toxin-mediated ADP-ribosylation of Gi alpha and Go alpha in each of these three brain regions. The decreased ADP-ribosylation levels of the G protein subunits were shown to be associated with 20-30% decreases in levels of their immunoreactivity. In contrast, chronic cocaine had no effect on levels of G protein ADP-ribosylation or immunoreactivity in other brain regions studied for comparison. Chronic cocaine also had no effect on levels of Gs alpha or G beta immunoreactivity in the ventral tegmental area and nucleus accumbens. Specific decreases in Gi alpha and Go alpha levels observed in response to chronic cocaine in the ventral tegmental area, nucleus accumbens, and locus coeruleus are consistent with the known electrophysiological actions of chronic cocaine on these neurons, raising the possibility that regulation of G proteins represents part of the biochemical changes that underlie chronic cocaine action in these brain regions.
Regularization of Neural Networks using DropConnect (2013)

We introduce DropConnect, a generalization of Dropout (Hinton et al., 2012), for regular-izing large fully-connected layers within neu-ral networks. When training with Dropout, a randomly selected subset of activations are set to zero within each layer. DropCon-nect instead sets a randomly selected sub-set of weights within the network to zero. Each unit thus receives input from a ran-dom subset of units in the previous layer. We derive a bound on the generalization per-formance of both Dropout and DropCon-nect. We then evaluate DropConnect on a range of datasets, comparing to Dropout, and show state-of-the-art results on several image recognition benchmarks by aggregating mul-tiple DropConnect-trained models. 1.
Polyspecific pyrrolysyl-tRNA synthetases from directed evolution (2014)

Pyrrolysyl-tRNA synthetase (PylRS) and its cognate tRNA(Pyl) have emerged as ideal translation components for genetic code innovation. Variants of the enzyme facilitate the incorporation >100 noncanonical amino acids (ncAAs) into proteins. PylRS variants were previously selected to acylate N(ε)-acetyl-Lys (AcK) onto tRNA(Pyl). Here, we examine an N(ε)-acetyl-lysyl-tRNA synthetase (AcKRS), which is polyspecific (i.e., active with a broad range of ncAAs) and 30-fold more efficient with Phe derivatives than it is with AcK. Structural and biochemical data reveal the molecular basis of polyspecificity in AcKRS and in a PylRS variant [iodo-phenylalanyl-tRNA synthetase (IFRS)] that displays both enhanced activity and substrate promiscuity over a chemical library of 313 ncAAs. IFRS, a product of directed evolution, has distinct binding modes for different ncAAs. These data indicate that in vivo selections do not produce optimally specific tRNA synthetases and suggest that translation fidelity will become an increasingly dominant factor in expanding the genetic code far beyond 20 amino acids.
Wave field synthesis and analysis using array technology (2003)

The concept of wave field synthesis (WFS) was introduced by Betkhout in 1988. It enables the generation of sound fields with natural temporal and spatial properties within a volume or area bounded by arrays of loudspeakers. Applications are found in real time performances as well as in reproduction of multitrack recordings. A logic next step was the formulation of a new wave field analysis (WFA) concept by Berkhout in 1997, where sound fields in enclosures are recorded with arrays of microphones and analyzed with postprocessing techniques commonly used in acoustical imaging. This way, both the temporal and spatial properties of the sound field can be investigated and understood. WFS and WFA meet in auralization applications: sound fields measured (or modeled) along arrays of microphone positions can be generated by arrays of loudspeakers for perceptual evaluation.