gebhart/patrepeval huggingface dataset:
In situ growth of a stoichiometric PEG-like conjugate at a protein's N-terminus with significantly improved pharmacokinetics (2009)

The challenge in the synthesis of protein-polymer conjugates for biological applications is to synthesize a stoichiometric (typically 1:1) conjugate of the protein with a monodisperse polymer, with good retention of protein activity, significantly improved pharmacokinetics and increased bioavailability, and hence improved in vivo efficacy. Here we demonstrate, using myoglobin as an example, a general route to grow a PEG-like polymer, poly(oligo(ethylene glycol) methyl ether methacrylate) [poly(OEGMA)], with low polydispersity and high yield, solely from the N-terminus of the protein by in situ atom transfer radical polymerization (ATRP) under aqueous conditions, to yield a site-specific (N-terminal) and stoichiometric conjugate (1:1). Notably, the myoglobin-poly(OEGMA) conjugate [hydrodynamic radius (R(h)): 13 nm] showed a 41-fold increase in its blood exposure compared to the protein (R(h): 1.7 nm) after IV administration to mice, thereby demonstrating that comb polymers that present short oligo(ethylene glycol) side chains are a class of PEG-like polymers that can significantly improve the pharmacological properties of proteins. We believe that this approach to the synthesis of N-terminal protein conjugates of poly(OEGMA) may be applicable to a large subset of protein and peptide drugs, and thereby provide a general methodology for improvement of their pharmacological profiles.
Two genes, atpC1 and atpC2, for the γ subunit of Arabidopsis thaliana chloroplast ATP synthase (1991)

Arabidopsis thaliana has two genes (atpC1, atpC2) coding for gamma subunits of chloroplast ATP synthase. The atpC1 and atpC2 were cloned and sequenced. They had no introns within the reading frames and coded for proteins of 373 and 386 amino acid residues, respectively, including putative transit sequences (50 and 60 amino acid residues, respectively). In contrast, the spinach gamma subunit gene had two introns within the reading frame. The mature sequences coded by the two genes of A. thaliana (atpC1, 323 residues; atpC2, 326 residues) were homologous with that of spinach (J. Miki, M. Maeda, Y. Mukohata, and M. Futai (1988) FEBS Lett. 232, 221-226): the homologies of gamma subunits coded by atpC1 and atpC2 were 72%, those of the subunits coded by atpC1 and spinach cDNA were 84%, and those of the proteins coded by atpC2 and spinach cDNA were 71%. Like the spinach subunit, the gamma subunits coded by the two genes had unique regulatory domains not found in mitochondrial or bacterial subunits. Poly(A)+ mRNAs corresponding to atpC1 (1.5 kilobases) and atpC2 (2.5 kilobases) were detected in illuminated plants, the amount of the former being at least 140 times that of the latter. The atpC1 mRNA was not found in dark-adapted plants. Nuclear protein(s) specifically bound to the upstream region of atpC1 was detected by gel shift assay and its binding was shown to be inhibited by the GT-1 element of the gene encoding the ribulose-1,5-bisphosphate carboxylase small subunit, which is expressed under illumination (P. J. Green, S. A. Kay, and N. H. Chau (1987) EMBO J. 6, 2543-2549). Consistent with these findings, an increased amount of the gamma subunit was detected immunochemically in illuminated plants.
High field-effect mobility amorphous InGaZnO transistors with aluminum electrodes (2008)

We report on the device characteristics of amorphous indium gallium zinc oxide thin-film transistors (TFTs) with aluminum (Al) electrodes. The TFTs exhibited a high performance with a field-effect mobility of 11.39 cm2/V s, a subthreshold swing of 181 mV/ decade, and an on-off ratio of 107. Further improvement in device performance was achieved by doping the source/drain contact regions, resulting in an enhanced mobility of 16.6 cm2/V s at an operating voltage as low as 5 V.
A simple method for fabrication of highly ordered porous α-alumina ceramic membranes (2012)

By taking anodic aluminum oxide membranes as the starting materials and selectively removing the outer layers from the unit cells of anodic aluminum oxide membranes after a proper hydrothermal treatment, highly ordered porous α-alumina ceramic membranes are fabricated successfully. This fabrication method might be a new approach for the preparation of α-alumina ceramic membranes with nanochannel-array architecture not only at the submicron scale but also at the nanometer scale. The obtained membranes are anticipated to become a new generation of filters and supports for catalysts or absorbents, and have wide applications in the fields of nanomaterial synthesis, biology and electronic devices.
Segmentation of document images (1989)

Several methods for segmentation of document images (maps, drawings, etc.) are explored. The segmentation operation is posed as a statistical classification task with two pattern classes: print and background. A number of classification strategies are available. All require some prior information about the distribution of gray levels for the two classes. Training (either supervised or unsupervised) is employed to form these initial density estimates. Automatic updating of the class-conditional densities is performed within subregions in the image to adapt these global density estimates to the local image area. After local class-conditional densities have been obtained, each pixel is classified within the window using several techniques: a noncontextual Bayes classifier, Besag's classifier, relaxation, Owen and Switzer's classifier, and Haslett's classifier. Four test images were processed. In two of these, the relaxation method performed best, and in the other two, the noncontextual method performed best. Automatic updating improved the results for both classifiers.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
THE LOCUS OF EVOLUTION: EVO DEVO AND THE GENETICS OF ADAPTATION (2007)

An important tenet of evolutionary developmental biology ("evo devo") is that adaptive mutations affecting morphology are more likely to occur in the cis-regulatory regions than in the protein-coding regions of genes. This argument rests on two claims: (1) the modular nature of cis-regulatory elements largely frees them from deleterious pleiotropic effects, and (2) a growing body of empirical evidence appears to support the predominant role of gene regulatory change in adaptation, especially morphological adaptation. Here we discuss and critique these assertions. We first show that there is no theoretical or empirical basis for the evo devo contention that adaptations involving morphology evolve by genetic mechanisms different from those involving physiology and other traits. In addition, some forms of protein evolution can avoid the negative consequences of pleiotropy, most notably via gene duplication. In light of evo devo claims, we then examine the substantial data on the genetic basis of adaptation from both genome-wide surveys and single-locus studies. Genomic studies lend little support to the cis-regulatory theory: many of these have detected adaptation in protein-coding regions, including transcription factors, whereas few have examined regulatory regions. Turning to single-locus studies, we note that the most widely cited examples of adaptive cis-regulatory mutations focus on trait loss rather than gain, and none have yet pinpointed an evolved regulatory site. In contrast, there are many studies that have both identified structural mutations and functionally verified their contribution to adaptation and speciation. Neither the theoretical arguments nor the data from nature, then, support the claim for a predominance of cis-regulatory mutations in evolution. Although this claim may be true, it is at best premature. Adaptation and speciation probably proceed through a combination of cis-regulatory and structural mutations, with a substantial contribution of the latter.
Oxidative DNA damage in CD34+ myelodysplastic cells is associated with intracellular redox changes and elevated plasma tumour necrosis factor‐α concentration (1997)

Ineffective haemopoiesis in the myelodysplastic syndromes (MDS) is mediated, at least in part, by apoptosis, though the mechanisms of apoptotic induction are unclear. Tumour necrosis factor-alpha (TNF-alpha) promotes apoptosis via intracellular oxygen free radical production, oxidation of DNA and proteins, and is increasingly implicated in the pathogenesis of MDS. Using single-cell gel electrophoresis, we have identified oxidized pyrimidine nucleotides in the progenitor-enriched bone marrow CD34+ compartment from MDS patients (P=0.039), which are absent in both CD34- MDS cells (P=0.53) and also CD34+ cells from normal subjects (P=0.55). MDS CD34+ blood cells also showed oxidized pyrimidine nucleotides compared with CD34- cells (P=0.029). Within normal subjects no differences were seen between CD34+ and CD34- bone marrow cell compartments. CD34+ bone marrow cell oxidized pyrimidines were strongly associated with elevated plasma TNF-alpha and low bone marrow mononuclear cell glutathione concentrations (5/6 patients) and the inverse relationship was also found (3/4 patients). This data implies a role for intracellular oxygen free radical production, perhaps mediated by TNF-alpha, in the pathogenesis of ineffective haemopoiesis in MDS and provides a rationale for the bone marrow stimulatory effects of antioxidants such as Amifostine in MDS.
Taxol (paclitaxel): future directions. (1994)

Paclitaxel is the first of a new class of anticancer agents with a novel mechanism of action. Demonstration of the broad activity of this drug and its unusual effects has refocused attention on tubulin as a target for anticancer drug development. Studies are under way to identify the optimal paclitaxel dose and schedule of administration and the effective combination regimens, and to exploit the drug's radiosensitizing properties. Efforts to define pharmacodynamic relationships and clinical mechanisms of resistance and to assess other potential mechanisms for the drug's anticancer activity are also under way. In addition, other compounds that target the microtubule, some more soluble and some more potent, are in various stages of development. Phase III trials in patients with ovarian, breast, and lung cancer are continuing, and adjuvant breast cancer trials will begin soon. Such trials will establish whether paclitaxel increases the cure rate and/or survival in cancer patients.
Judicial Participation in Settlement (1984)

In the following pages, we will briefly delineate the settlement process, enumerate the techniques currently utilized by judges to facilitate settlement, and discuss the perceived ethics of these techniques. Finally, we will consider the circumstances under which judges typically participate in settlement.
Circulating intercellular adhesion molecule-1 as an early predictor of hepatic failure in patients with septic shock (1999)

Because only circulating ICAM-1 was higher in nonsurvivors than in survivors at day 0, circulating ICAM-1 may serve as an early prognostic marker for outcome in septic shock. In addition, measurement of circulating ICAM-1 facilitates identification of those patients with the highest risk of developing liver dysfunction.
Authentication and key management for Advanced Metering Infrastructures utilizing physically unclonable functions (2012)

Conventional utility meters are increasingly being replaced with smart meters as smart meter based AMIs (Advanced Metering Infrastructures) provide many benefits over conventional power infrastrucutures. However, security issues pertaining to the data transmission between smart meters and utility servers have been a major concern. With large scale AMI deployments, addressing these issues is challenging. In particular, as data travels through several networks, secure end-to-end communication based on strong authentication mechanisms and a robust and scalable key management schemes are crucial for assuring the confidentiality and the integrity of this data. In this paper, we propose an approach based on PUF (physically unclonable function) technology for providing strong hardware based authentication of smart meters and efficient key management to assure the confidentiality and integrity of messages exchanged between smart meters and the utility. Our approach does not require modifications to the existing smart meter communication. We have developed a proof-of-concept implementation of the proposed approach which is also briefly discussed in the paper.
A novel high mobility group box 1 neutralizing chimeric antibody attenuates drug‐induced liver injury and postinjury inflammation in mice (2016)

This is the first report describing the generation of a partly humanized HMGB1-neutralizing antibody with validated therapeutic efficacy and with a prolonged therapeutic window, as compared to NAC, in APAP-ALI. The therapeutic effect was mediated by HMGB1 neutralization and attenuation of postinjury inflammation. These results represent important progress toward clinical implementation of HMGB1-specific therapy as a means to treat APAP-ALI and other inflammatory conditions. (Hepatology 2016;64:1699-1710).
Small RNAs: Classification, Biogenesis, and Function (2005)

Eukaryotes produce various types of small RNAs of 19-28 nt in length. With rapidly increasing numbers of small RNAs listed in recent years, we have come to realize how widespread their functions are and how diverse the biogenesis pathways have evolved. At the same time, we are beginning to grasp the common features and rules governing the key steps in small RNA pathways. In this review, I will summarize the current classification, biogenesis, action mechanism and function of these fascinating molecules.
Effect of P to A Mutation of the N-Terminal Residue Adjacent to the Rgd Motif on Rhodostomin: Importance of Dynamics in Integrin Recognition (2012)

Rhodostomin (Rho) is an RGD protein that specifically inhibits integrins. We found that Rho mutants with the P48A mutation 4.4-11.5 times more actively inhibited integrin α5β1. Structural analysis showed that they have a similar 3D conformation for the RGD loop. Docking analysis also showed no difference between their interactions with integrin α5β1. However, the backbone dynamics of RGD residues were different. The values of the R(2) relaxation parameter for Rho residues R49 and D51 were 39% and 54% higher than those of the P48A mutant, which caused differences in S(2), R(ex), and τ(e). The S(2) values of the P48A mutant residues R49, G50, and D51 were 29%, 14%, and 28% lower than those of Rho. The R(ex) values of Rho residues R49 and D51 were 0.91 s(-1) and 1.42 s(-1); however, no R(ex) was found for those of the P48A mutant. The τ(e) values of Rho residues R49 and D51 were 9.5 and 5.1 times lower than those of P48A mutant. Mutational study showed that integrin α5β1 prefers its ligands to contain (G/A)RGD but not PRGD sequences for binding. These results demonstrate that the N-terminal proline residue adjacent to the RGD motif affect its function and dynamics, which suggests that the dynamic properties of the RGD motif may be important in Rho's interaction with integrin α5β1.
High-performance assays of small molecules: enhanced sensitivity, rapidity, and convenience demonstrated with a noncompetitive immunometric anti-immune complex assay system for digoxin (1994)

We report the first clinical application of a noncompetitive immunometric assay system that provides advantages for the rapid and robust assay of small molecules similar to those realized for larger molecules with two-site immunometric assays. This anti-immune complex assay is based on the interaction of a receptor such as a primary antibody with its ligand, such that new binding sites, recognizable by a secondary antibody, are formed. In this report the system is applied to the measurement of digoxin in serum. Utilizing an anti-complex antibody that recognizes a digoxin-bound primary antibody with affinity > 2000-fold over its binding to the primary antibody alone, we show that this anti-complex assay system provides a high-performance assay for serum samples, being conveniently simple (immobilized primary antibody binds digoxin and then labeled secondary antibody so that when excess unbound label is washed away the immunometric readout reflects the digoxin concentration), rapid (incubation time 1-10 min), sensitive (detection limit 30 ng/L), precise (3-4% within-run CV, 1-8% total CV), and free from interference from digoxin-like immunoreactive factors.
Augmenting Connectivity Information by Compound Name Parsing: Automatic Assignment of Stereochemistry and Isotope Labeling (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAugmenting Connectivity Information by Compound Name Parsing: Automatic Assignment of Stereochemistry and Isotope LabelingWolf-Dietrich Ihlenfeldt and Johann GasteigerCite this: J. Chem. Inf. Comput. Sci. 1995, 35, 4, 663–674Publication Date (Print):July 1, 1995Publication History Published online1 May 2002Published inissue 1 July 1995https://pubs.acs.org/doi/10.1021/ci00026a002https://doi.org/10.1021/ci00026a002research-articleACS PublicationsRequest reuse permissionsArticle Views66Altmetric-Citations9LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options Get e-Alerts
Emendation of Acetivibrio and Description of Acetivibrio ethanolgignens, a New Species from the Colons of Pigs with Dysentery (1981)

We describe an organism that constituted 20% or more of the bacterial population in the colons of pigs experimentally infected with Treponema hyodysenteriae. This organism was not found in clinically normal pigs. Because this organism had properties different from those of any previously described taxon, we propose that it be regarded as a new species, Acetivibrio ethanolgignens. The isolates of A. ethanolgignens were obligately anaerobic, gram-negative, nonsporeforming, motile, slightly curved rods with lateral flagella that emanated from the concave sides of the cells and formed fascicles. A. ethanolgignens differs from other species in the genus Acetivibrio principally in its inability to degrade cellulose or ferment cellobiose, its production of ethanol as a major fermentation product, and its possession of multiple flagella. The guanine-plus-cytosine content of its deoxyribonucleic acid is 40 mol%. The type strain is 77-6, a culture of which has been deposited in the American Type Culture Collection under the number ATCC 33324. We also emend the description of the genus Acetivibrio to include bacteria with multiple flagella.
Rate Limiting Steps of AAV Transduction and Implications for Human Gene Therapy (2001)

Despite the fact that adeno-associated virus type 2 (AAV2) is an extremely attractive gene therapy vector, its application has been limited to certain tissues such as muscle and the brain. In an attempt to broaden the array of target organs for this vector, molecular studies on the mechanism(s) of AAV transduction have expanded over the past several years. These studies have led to the development of innovative strategies capable of overcoming intracellular barriers to AAV2 transduction. The basis of these technologic breakthroughs has stemmed from a better understanding of the molecular processes that control AAV entry and intracellular trafficking to the nucleus. This review will focus on the identification of molecular components important for recombinant AAV (rAAV) transduction while highlighting the techniques used to discover them and potential clinical application of research findings.
Antitumor immune response of human peripheral blood lymphocytes coengrafted with tumor into severe combined immunodeficient mice. (1997)

Here, it is established that human peripheral blood lymphocytes (HuPBLs), injected s.c. with a human lung tumor into severe combined immunodeficient (SCID) mice, engraft and display antitumor cytotoxic activity. Initial studies used HuPBLs from normal donors and an allogeneic tumor cell line derived from biopsy tissue of a patient with a squamous cell carcinoma of the lung. Evidence of HuPBL antitumor activity was revealed by a cell dose-dependent suppression of the tumor xenograft. Tumor suppression was shown to be dependent upon both CD8+ T cells and CD56+ natural killer cells in the donor HuPBLs. By titrating the antitumor activity of HuPBLs in SCID mice with and without cytokines, it was established that interleukin (IL)-12 enhanced the HuPBL-mediated tumor suppression and that IL-2 had a synergistic effect upon the IL-12 enhancement of cytotoxicity. Subsequent studies revealed that a lung cancer patient's PBLs also suppress the growth of the patient's (autologous) tumor when coinjected s.c. with the tumor cells into SCID mice. The patient's antitumor immunity was shown to be mediated by CD8+ T cells and CD56+ natural killer cells. The data presented here indicate that the s.c. coengraftment of HuPBLs and tumor into SCID mice represents a viable model with which to study (and to periodically monitor) patients' immune responses to their tumors for extended periods of time and suggest that this SCID/Winn assay could be used to evaluate novel immunotherapeutic approaches, such as bolus injections of cytokines, cytokine gene therapy, or vaccination strategies for the treatment of human cancer.
Fast pose estimation with parameter-sensitive hashing (2003)

Example-based methods are effective for parameter estimation problems when the underlying system is simple or the dimensionality of the input is low. For complex and high-dimensional problems such as pose estimation, the number of required examples and the computational complexity rapidly become prohibitively high. We introduce a new algorithm that learns a set of hashing functions that efficiently index examples relevant to a particular estimation task. Our algorithm extends locality-sensitive hashing, a recently developed method to find approximate neighbors in time sublinear in the number of examples. This method depends critically on the choice of hash functions that are optimally relevant to a particular estimation problem. Experiments demonstrate that the resulting algorithm, which we call parameter-sensitive hashing, can rapidly and accurately estimate the articulated pose of human figures from a large database of example images.