gebhart/patrepeval huggingface dataset:
Cytochrome P450 and Chemical Toxicology (2007)

The field of cytochrome P450 (P450) research has developed considerably over the past 20 years, and many important papers on the roles of P450s in chemical toxicology have appeared in Chemical Research in Toxicology. Today, our basic understanding of many of the human P450s is relatively well-established, in terms of the details of the individual genes, sequences, and basic catalytic mechanisms. Crystal structures of several of the major human P450s are now in hand. The animal P450s are still important in the context of metabolism and safety testing. Many well-defined examples exist for roles of P450s in decreasing the adverse effects of drugs through biotransformation, and an equally interesting field of investigation is the bioactivation of chemicals, including drugs. Unresolved problems include the characterization of the minor "orphan" P450s, ligand cooperativity and kinetic complexity of several P450s, the prediction of metabolism, the overall contribution of bioactivation to drug idiosyncratic problems, the extrapolation of animal test results to humans in drug development, and the contribution of genetic variation in human P450s to cancer incidence.
The morphological lomo filter for multiscale image processing (2003)

Locally monotonic (lomo) images are defined as root signals of a morphological lomo filter. The morphological approach allows a multidimensional generalization of local monotonicity. This generalization is well motivated in that it retains the essential properties of one-dimensional (1D) local monotonicity. Repeated application of the lomo filter produces a lomo root signal of a specified scale. By filtering at multiple scales, a locally monotonic scale-space can be created and used in multiscale image applications such as segmentation, tracking, content based retrieval, and image coding. In contrast to existing linear and nonlinear scale-generating filters, the lomo filter has no spatial or graylevel bias and preserves edge localization through scale-space.
A synthetic receptor for dinucleotides (1991)

Complexation of biorelevant targets with synthetic receptors continues to provide information regarding recognition at the molecular level.2 One tactic involves the concatenation of modular subunits with complementarity to specific domains of the target. Here we apply this means to develop a system (receptor 1) for the complexation of 2'-deoxyadenylyl(3,-&gt;5')-2,-deoxyadenosine (&lt;f(AA)) and give evidence of its success.
Photoacoustic Imaging of Human Mesenchymal Stem Cells Labeled with Prussian Blue–Poly(l-lysine) Nanocomplexes (2017)

Acoustic imaging is affordable and accessible without ionizing radiation. Photoacoustic imaging increases the contrast of traditional ultrasound and can offer good spatial resolution when used at high frequencies with excellent temporal resolution. Prussian blue nanoparticles (PBNPs) are an emerging photoacoustic contrast agent with strong optical absorption in the near-infrared region. In this study, we developed a simple and efficient method to label human mesenchymal stem cells (hMSCs) with PBNPs and imaged them with photoacoustic imaging. First, PBNPs were synthesized by the reaction of FeCl<sub>3</sub> with K<sub>4</sub>[Fe(CN)<sub>6</sub>] in the presence of citric acid and complexed with the cationic transfection agent poly-l-lysine (PLL). The PLL-coated PBNPs (PB-PLL nanocomplexes) have a maximum absorption peak at 715 nm and could efficiently label hMSCs. Cellular uptake of these nanocomplexes was studied using bright field, fluorescence, and transmission electron microscopy. The labeled stem cells were successfully differentiated into two downstream lineages of adipocytes and osteocytes, and they showed positive expression for surface markers of CD73, CD90, and CD105. No changes in viability or proliferation of the labeled cells were observed, and the secretome cytokine analysis indicated that the expression levels of 12 different proteins were not dysregulated by PBNP labeling. The optical properties of PBNPs were preserved postlabeling, suitable for the sensitive and quantitative detection of implanted cells. Labeled hMSCs exhibited strong photoacoustic contrast in vitro and in vivo when imaged at 730 nm, and the detection limit was 200 cells/μL in vivo. The photoacoustic signal increased as a function of cell concentration, indicating that the number of labeled cells can be quantified during and after cell transplantations. In hybrid ultrasound/photoacoustic imaging, this approach offers real-time and image-guided cellular injection even through an intact skull for brain intraparenchymal injections. Our labeling and imaging technique allowed the detection and monitoring of 5 × 10<sup>4</sup> mesenchymal stem cells in living mice over a period of 14 days.
Structural Regions of MD-2 That Determine the Agonist-Antagonist Activity of Lipid IVa (2006)

A cell surface receptor complex consisting of CD14, Toll-like receptor (TLR4), and MD-2 recognizes lipid A, the active moiety of lipopolysaccharide (LPS). Escherichia coli-type lipid A, a typical lipid A molecule, potently activates both human and mouse macrophage cells, whereas the lipid A precursor, lipid IVa, activates mouse macrophages but is inactive and acts as an LPS antagonist in human macrophages. This animal species-specific activity of lipid IVa involves the species differences in MD-2 structure. We explored the structural region of MD-2 that determines the agonistic and antagonistic activities of lipid IVa to induce nuclear factor-kappaB activation. By expressing human/mouse chimeric MD-2 together with mouse CD14 and TLR4 in human embryonic kidney 293 cells, we found that amino acid regions 57-79 and 108-135 of MD-2 determine the species-specific activity of lipid IVa. We also showed that the replacement of Thr(57), Val(61), and Glu(122) of mouse MD-2 with corresponding human MD-2 sequence or alanines impaired the agonistic activity of lipid IVa, and antagonistic activity became evident. These mutations did not affect the activation of nuclear factor-kappaB, TLR4 oligomerization, and inducible phosphorylation of IkappaBalpha in response to E. coli-type lipid A. These results indicate that amino acid residues 57, 61, and 122 of mouse MD-2 are critical to determine the agonist-antagonist activity of lipid IVa and suggest that these amino acid residues may be involved in the discrimination of lipid A structure.
Some biological properties and an in vivo evaluation of tyrosine phenol-lyase on growth of B-16 melanoma. (1976)

Tyrosine phenol-lyase from Erwinia herbicola was purified with the goal of assessing its effect on growth of malignant melanoma. Ammonium sulfate-sodium citrate fractionation and diethylaminoethyl cellulose-hydroxylapatite chromatography were used. The purified enzyme was shown to reduce plasma tyrosine levels when administered to normal C57BL x DBA/2 F1 mice. The plasma half-life value of the enzyme was found to be 6 to 7 hr. Unlike results reported with glutaminase and asparaginase preparations, the lactate dehydrogenase-elevating virus had no significant influence on plasma clearance of tyrosine phenol-lyase. The enzyme significantly inhibited growth of established B-16 melanoma tumors.
Use of riboprobes for northern blotting analysis. (1991)

We compared cDNA and riboprobes for their use in Northern blotting analysis and found that higher hybridization signal can be obtained using riboprobes. Comparison of five nylon membranes for Northern blotting using riboprobe revealed that each nylon membrane differed in their performance. Background noise was minimal for all five membranes for two riboprobes. However, because of the higher thermal stability of RNA.RNA hybrids, the riboprobes could not be stripped out from the membrane even after five hours of treatment at 80 degrees C.
Contextual String Embeddings for Sequence Labeling (2018)

Recent advances in language modeling using recurrent neural networks have made it viable to model language as distributions over characters. By learning to predict the next character on the basis of previous characters, such models have been shown to automatically internalize linguistic concepts such as words, sentences, subclauses and even sentiment. In this paper, we propose to leverage the internal states of a trained character language model to produce a novel type of word embedding which we refer to as contextual string embeddings. Our proposed embeddings have the distinct properties that they (a) are trained without any explicit notion of words and thus fundamentally model words as sequences of characters, and (b) are contextualized by their surrounding text, meaning that the same word will have different embeddings depending on its contextual use. We conduct a comparative evaluation against previous embeddings and find that our embeddings are highly useful for downstream tasks: across four classic sequence labeling tasks we consistently outperform the previous state-of-the-art. In particular, we significantly outperform previous work on English and German named entity recognition (NER), allowing us to report new state-of-the-art F1-scores on the CoNLL03 shared task. We release all code and pre-trained language models in a simple-to-use framework to the research community, to enable reproduction of these experiments and application of our proposed embeddings to other tasks: https://github.com/zalandoresearch/flair
Eradication of glioblastoma, and breast and colon carcinoma xenografts by Hsp70 depletion. (2002)

Heat shock protein 70 (Hsp70) is an antiapoptotic chaperone protein highly expressed in human tumors. Here we demonstrate that locoregional application of adenovirus expressing antisense Hsp70 cDNA (Ad.asHsp70) eradicates orthotopic xenografts of glioblastoma and breast carcinoma, as well as s.c. xenografts of colon carcinoma in immunodeficient mice. Ad.asHsp70-treated tumors showed massive apoptosis-like cell death and recruitment of macrophages. Human monocyte-derived macrophages effectively removed the corpses of Ad.asHsp70-treated tumor cells in vitro. Interestingly, both tumor cell death and phagocytosis were caspase-independent. Thus, Hsp70 appears as a promising target for the treatment of cancers resistant to classic caspase-mediated apoptosis.
Protein A Affinity Chromatography for Capture and Purification of Monoclonal Antibodies and Fc-Fusion Proteins: Practical Considerations for Process Development (2006)

Monoclonal antibodies and Fc-fusion proteins form the largest and most rapidly
expanding category of biopharmaceuticals today with annual sales exceeding
$8 billion and applications across a wide range of diseases [1]. With the growth
of this class of biomolecules, significant attention is now being focused on
reducing manufacturing costs and streamlining process development activities
to enable the rapid progression of these therapeutic candidates through clinical
development. Protein A affinity chromatography has come to be used as the
industry-wide standard for capture and purification of antibodies and Fc-fusion
proteins. This chapter will provide a brief introduction to antibodies and Fcfusion proteins, describe the basics of Protein A chromatography and discuss
practical considerations for the development of this process step in an industrial
context.
Replicase-Mediated Resistance To Potato Virus Y in Transgenic Tobacco Plants (1994)

Nicotiana tabacum 'Turkish Samsun NN' plants were transformed with nuclear inclusion b (NIb) gene sequences of potato virus Y, O strain (PVYO). The full-length construct included an additional in-frame initiation codon contiguous to the putative N-terminal amino acid codon and a stop codon replacing the C-terminal amino acid codon. Of 13 independently transformed lines, four yielded 37 (out of 100) plants in the R1 generation that were resistant to PVYO infection. Progeny of 13 out of 15 of R1 plants tested expressed resistance in the R2 generation. Conversely, 30 independently transformed tobacco lines expressing essentially the same sequence but deleted for the Gly-Asp-Asp (GDD) motif were not resistant. Two other constructs encoding either the 5'-deleted or 3'-truncated NIb gene, but harboring the GDD motif, conferred resistance to PVYO in some tobacco plants. Despite the high level of nucleotide and amino acid identity shared by strains PVYO and PVYN for the NIb gene, PVYN replication was found in all PVYO-resistant plants. However, plants of one R2 line showed reduced PVYN replication.
Fast-switching frequency synthesizer with a discriminator-aided phase detector (2000)

A phase-locked loop (PLL) with a fast-locked discriminator-aided phase detector (DAPD) is presented. Compared with the conventional phase detector (PD), the proposed fast-locked PD reduces the PLL pull-in time and enhances the switching speed, while maintaining better noise bandwidth. The synthesizer has been implemented in a 0.35-/spl mu/m CMOS process, and the output phase noise is -99 dBc/Hz at 100-kHz offset. Under the supply voltage of 3.3 V, its power consumption is 120 mW.
Clinical Course and Prediction of Survival in Idiopathic Pulmonary Fibrosis (2010)

Idiopathic pulmonary fibrosis (IPF) is a progressive, life-threatening, interstitial lung disease of unknown etiology. The median survival of patients with IPF is only 2 to 3 years, yet some patients live much longer. Respiratory failure resulting from disease progression is the most frequent cause of death. To date we have limited information as to predictors of mortality in patients with IPF, and research in this area has failed to yield prediction models that can be reliably used in clinical practice to predict individual risk of mortality. The goal of this concise clinical review is to examine and summarize the current data on the clinical course, individual predictors of survival, and proposed clinical prediction models in IPF. Finally, we will discuss challenges and future directions related to predicting survival in IPF.
Visualizing locations of off-screen objects on mobile devices (2006)

Browsing large information spaces such as maps on the limited&#13;\nscreen of mobile devices often requires people to perform panning&#13;\nand zooming operations that move relevant display content offscreen.&#13;\nThis makes it difficult to perform spatial tasks such as&#13;\nfinding the location of Points Of Interest (POIs) in a city.&#13;\nVisualizing the location of off-screen objects can mitigate this&#13;\nproblem: in this paper, we present a user study comparing the&#13;\nHalo [2] approach with two other techniques based on arrows.&#13;\nHalo surrounds off-screen objects with circles that reach the&#13;\ndisplay window, so that users can derive the location and distance&#13;\nof objects by observing the visible portion of the corresponding&#13;\ncircles. In the two arrow-based techniques, arrows point at objects&#13;\nand their size and body length, respectively, inform about the&#13;\ndistance of objects. Our study involved four tasks requiring users&#13;\nto identify and compare off-screen objects locations, and also&#13;\ninvestigated the effectiveness of the three techniques with respect&#13;\nto the number of off-screen objects. Arrows allowed users to&#13;\norder off-screen objects faster and more accurately according to&#13;\ntheir distance, while Halo allowed users to better identify the&#13;\ncorrect location of off-screen objects. Implications of these results&#13;\nfor mobile map-based applications are also discussed.
Targeting of adenovirus penton base to new receptors through replacement of its RGD motif with other receptor-specific peptide motifs. (1995)

The adenovirus coat protein, penton base, contains the peptide motif RGD which mediates binding to the integrin cell surface receptors alpha v beta 3 and alpha v beta 5. These integrins then mediate adenovirus internalization. We have developed penton base chimeras that recognize tissue-specific integrin receptors by replacing the wild-type RGD peptide motif with alpha v beta 3- or alpha 4 beta 1-specific peptide motifs. In one chimera the original haiRGDtfa motif was replaced with the peptide motif eiLDVpst which mediated chimera binding to the integrin alpha 4 beta 1. This integrin is expressed at high levels on lymphocytes and monocytes but is not expressed on epithelial or endothelial cells. In a second chimera the wild-type sequences flanking the RGD motif were altered to abrogate its interaction with alpha v beta 5 while retaining its specificity for alpha v beta 3. The integrin alpha v beta 5 is expressed primarily on epithelial cells whereas the integrin alpha v beta 3 is normally expressed on endothelial cells. The integrin alpha v beta 3 is also aberrantly expressed on certain metastatic melanomas and glioblastomas. A deletion mutant lacking the RGD sequence did not bind to any integrins. Such chimeras incorporated into adenovirus virions may be useful in targeting specific tissues in adenovirus-mediated gene delivery.
Single Molecule Detection Using Surface-Enhanced Raman Scattering (SERS) (1997)

By exploiting the extremely large effective cross sections ( ${10}^{\ensuremath{-}17}--{10}^{\ensuremath{-}16}{\mathrm{cm}}^{2}/\mathrm{molecule}$) available from surface-enhanced Raman scattering (SERS), we achieved the first observation of single molecule Raman scattering. Measured spectra of a single crystal violet molecule in aqueous colloidal silver solution using one second collection time and about $2\ifmmode\times\else\texttimes\fi{}{10}^{5}\mathrm{W}/{\mathrm{cm}}^{2}$ nonresonant near-infrared excitation show a clear ``fingerprint'' of its Raman features between 700 and $1700{\mathrm{cm}}^{\ensuremath{-}1}$. Spectra observed in a time sequence for an average of 0.6 dye molecule in the probed volume exhibited the expected Poisson distribution for actually measuring 0, 1, 2, or 3 molecules.
Construction of a high-affinity receptor site for dihydropyridine agonists and antagonists by single amino acid substitutions in a non- l -type Ca 2+  channel (1997)

The activity of L-type Ca2+ channels is increased by dihydropyridine (DHP) agonists and inhibited by DHP antagonists, which are widely used in the therapy of cardiovascular disease. These drugs bind to the pore-forming alpha1 subunits of L-type Ca2+ channels. To define the minimal requirements for DHP binding and action, we constructed a high-affinity DHP receptor site by substituting a total of nine amino acid residues from DHP-sensitive L-type alpha1 subunits into the S5 and S6 transmembrane segments of domain III and the S6 transmembrane segment of domain IV of the DHP-insensitive P/Q-type alpha1A subunit. The resulting chimeric alpha1A/DHPS subunit bound DHP antagonists with high affinity in radioligand binding assays and was inhibited by DHP antagonists with high affinity in voltage clamp experiments. Substitution of these nine amino acid residues yielded 86% of the binding energy of the L-type alpha1C subunit and 92% of the binding energy of the L-type alpha1S subunit for the high-affinity DHP antagonist PN200-110. The activity of chimeric Ca2+ channels containing alpha1A/DHPS was increased 3.5 +/- 0.7-fold by the DHP agonist (-)Bay K8644. The effect of this agonist was stereoselective as in L-type Ca2+ channels since (+) Bay K8644 inhibited the activity of alpha1A/DHPS. The results show conclusively that DHP agonists and antagonists bind to a single receptor site at which they have opposite effects on Ca2+ channel activity. This site contains essential components from both domains III and IV, consistent with a domain interface model for binding and allosteric modulation of Ca2+ channel activity by DHPs.
Design of Hard Water Stable Emulsifier Systems for Petroleum- and Bio-based Semi-synthetic Metalworking Fluids (2003)

Metalworking fluids (MWFs) increase productivity and the quality of manufacturing operations by cooling and lubricating during metal forming and cutting processes. Despite their widespread use, they pose significant health and environmental hazards throughout their life cycle. An obvious environmental improvement to MWF technology would be to improve the lifetime of the fluid while utilizing more environmentally friendly and less energy-consuming materials without compromising existing performance levels. This investigation focuses on the design of mixed anionionc:nonionic emulsifier systems for petroleum and bio-based MWFs that improve fluid lifetime by providing emulsion stability under hard water conditions, a common cause of emulsion destabilization leading to MWF disposal. Experimental conditions were designed to evaluate the impact of emulsifier structural characteristics (straight chain, branched tail, branched head) and the molar ratios of anionic to nonionic surfactant and oil to total surfactant. Results from the 2500 formulations generated indicate that the use of a twin-headed anionic surfactant can provide improved hard water stability for both mineral oil- and vegetable oil-based formulations, even in the absence of a chelating agent and a coupler. Results also suggest that an oil:total surfactant molar ratio of 0.5 or less is necessary for particle size stability in hard water conditions for these systems. The newly developed petroleum and bio-based formulations with improved hard water stability are competitive with commercially available MWFs in performance evaluations for tramp oil rejection, contact angle, and tapping torque efficiency. These results can be used to design MWF formulations with fewer components and extended lifetime under hard water conditions, both of which would lead to a reduction in the life cycle environmental impact of MWFs.
The thermal pulse decay technique for measuring ultrasonic absorption coefficients (1983)

The classic method for measuring absorption coefficients of materials requires a determination of the temperature rise within a medium during ultrasonic irradiation. Serious errors may result from a viscous heating effect around the required thermocouple probe, and from heat lost by conduction to surrounding, cooler regions. A thermal pulse-decay technique is proposed and evaluated which allows for the separation, in time and space, of the viscous heating artifact and the true absorptive heating of a medium. In addition, the pulse-decay method explicitly accounts for heat conduction and the ultrasonic beam patterns used in experiments. The inherent advantages of the new technique allow for an extension of absorption measurements to smaller beamwidths and higher frequencies and intensities than were previously possible.