gebhart/patrepeval huggingface dataset:
Complementary advantageous substitutions in the evolution of an antiviral RNase of higher primates (2002)

An improved understanding of the evolution of gene function at the molecular level may provide significant insights into the origin of biological novelty and adaptation. With the approach of ancestral protein reconstruction, we here address the question of how a dramatically enhanced ribonucleolytic activity and the related antiviral activity evolved in a recently duplicated ribonuclease (eosinophil-derived neurotoxin) gene of higher primates. We show that the mother gene of the duplicated genes had already possessed a weak antiviral activity before duplication. After duplication, substitutions at two interacting sites (Arg-64-->Ser and Thr-132-->Arg) resulted in a 13-fold enhancement of the ribonucleolytic activity of eosinophil-derived neurotoxin. These substitutions are also necessary for the potent antiviral activity, with contributions from additional amino acid changes at interacting sites. Our observation that a change in eosinophil-derived neurotoxin function occurs only when both interacting sites are altered indicates the importance of complementary substitutions in protein evolution. Thus, neutral substitutions are not simply "noises" in protein evolution, as many have thought. They may play constructive roles by setting the intramolecular microenvironment for further complementary advantageous substitutions, which can lead to improved or altered function. Overall, our study illustrates the power of the "paleomolecular biochemistry" approach in delineating the complex interplays of amino acid substitutions in evolution and in identifying the molecular basis of biological innovation.
Mouse models of frontotemporal dementia (2012)

The pace of discovery in frontotemporal dementia (FTD) has accelerated dramatically with the discovery of new genetic causes and pathological substrates of the disease. MAPT/tau, GRN/progranulin, and C9ORF72 have emerged as common FTD genes, and TARDBP/TDP-43, VCP, FUS, and CHMP2B have been identified as less common genetic causes. TDP-43 and FUS have joined tau as common neuropathological substrates of the disease. Mouse models provide an important tool for understanding the role of these molecules in FTD pathogenesis. Here, we review recent progress with mouse models based on tau, TDP-43, progranulin, VCP, and CHMP2B. We also consider future prospects for FTD models, including developing new models to address unanswered questions. There are also opportunities for capitalizing on conservation of the salience network, which is selectively vulnerable in FTD, and the availability of FTD-related behavioral paradigms to analyze mouse models of the disease.
Overcoming the Blood–Brain Barrier with an Implantable Ultrasound Device (2019)

Ultrasound-based blood-brain barrier disruption enhances drug delivery. To bypass the human skull, an implantable ultrasound emitter was developed, and proven safe and feasible in a first-in-human trial. Next development steps aim for larger field of disruption, quantification of drug levels, use of various drugs, and ultimately a pivotal trial demonstrating improved outcome.<i>See related article by Idbaih et al., p. 3793</i>.
Fiber-top atomic force microscope: A worthwhile challenge (2008)

Fiber-top technology offers an unprecedented opportunity to bring atomic force microscopy outside research laboratories. In this paper we analyze the challenges this technology-transfer process is facing and we discuss why it is worth addressing them.
Macrophage serum markers in pneumococcal bacteremia: Prediction of survival by soluble CD163* (2006)

Macrophage marker response in pneumococcal bacteremia was compromised in old age. In patients <75 yrs old, sCD163 was superior to other markers, including C-reactive protein, in predicting fatal disease outcome.
Assembly of thin films by means of successive deposition of alternate layers of DNA and poly(allylamine) (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAssembly of thin films by means of successive deposition of alternate layers of DNA and poly(allylamine)Yu. Lvov, G. Decher, and G. SukhorukovCite this: Macromolecules 1993, 26, 20, 5396–5399Publication Date (Print):September 1, 1993Publication History Published online1 May 2002Published inissue 1 September 1993https://pubs.acs.org/doi/10.1021/ma00072a016https://doi.org/10.1021/ma00072a016research-articleACS PublicationsRequest reuse permissionsArticle Views1415Altmetric-Citations432LEARN 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 optionsGet e-Alertsclose Get e-Alerts
Comparison of Lentiviral and Adenoviral Gene Therapy for Spinal Fusion in Rats (2008)

BMP-2-producing RBMCs developed using lentiviral gene transfer induced more abundant bone within the fusion mass than the RBMCs transduced via adenoviral gene transfer and recombinant protein therapy.
Extrathymic Generation of Tumor-Specific T Cells from Genetically Engineered Human Hematopoietic Stem Cells via Notch Signaling (2007)

Adoptive cell transfer (ACT) of tumor-reactive lymphocytes has been shown to be an effective treatment for cancer patients. Studies in murine models of ACT indicated that antitumor efficacy of adoptively transferred T cells is dependent on the differentiation status of the cells, with lymphocyte differentiation inversely correlated with in vivo antitumor effectiveness. T-cell in vitro development technologies provide a new opportunity to generate naive T cells for the purpose of ACT. In this study, we genetically modified human umbilical cord blood-derived hematopoietic stem cells (HSCs) to express tumor antigen-specific T-cell receptor (TCR) genes and generated T lymphocytes by coculture with a murine cell line expressing Notch-1 ligand, Delta-like-1 (OP9-DL1). Input HSCs were differentiated into T cells as evidenced by the expression of T-cell markers, such as CD7, CD1a, CD4, CD8, and CD3, and by detection of TCR excision circles. We found that such in vitro differentiated T cells expressed the TCR and showed HLA-A2-restricted, specific recognition and killing of tumor antigen peptide-pulsed antigen-presenting cells but manifested additional natural killer cell-like killing of tumor cell lines. The genetic manipulation of HSCs has broad implications for ACT of cancer.
Supplementation of a suboptimal protein dose with leucine or essential amino acids: effects on myofibrillar protein synthesis at rest and following resistance exercise in men (2012)

Leucine is a nutrient regulator of muscle protein synthesis by activating mTOR and possibly other proteins in this pathway. The purpose of this study was to examine the role of leucine in the regulation of human myofibrillar protein synthesis (MPS). Twenty-four males completed an acute bout of unilateral resistance exercise prior to consuming either: a dose (25 g) of whey protein (WHEY); 6.25 g whey protein with total leucine equivalent to WHEY (LEU); or 6.25 g whey protein with total essential amino acids (EAAs) equivalent to WHEY for all EAAs except leucine (EAA-LEU). Measures of MPS, signalling through mTOR, and amino acid transporter (AAT) mRNA abundance were made while fasted (FAST), and following feeding under rested (FED) and post-exercise (EX-FED) conditions. Leucinaemia was equivalent between WHEY and LEU and elevated compared to EAA-LEU (P=0.001). MPS was increased above FAST at 1–3 h post-exercise in both FED (P <0.001) and EX-FED (P <0.001) conditions with no treatment effect.At 3–5 h, only WHEY remained significantly elevated above FAST in EX-FED(WHEY 184% vs. LEU 55% and EAA-LEU 35%; P =0.036). AAT mRNA abundance was increased above FAST after feeding and exercise with no effect of leucinaemia. In summary, a low dose of whey protein supplemented with leucine or all other essential amino acids was as effective as a complete protein (WHEY) in stimulating postprandial MPS; however only WHEY was able to sustain increased rates of MPS post-exercise and may therefore be most suited to increase exercise-induced muscle protein accretion.
Induction of fat apoptosis by a non‐thermal device: Mechanism of action of non‐invasive high‐intensity electromagnetic technology in a porcine model (2018)

Application of a high-intensity electromagnetic field in a porcine model results in adipocyte apoptosis. The analysis of serum levels suggests that HIFEM treatment influences fat and muscle metabolism. Lasers Surg. Med. 51:47-53, 2019. © 2018 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.
Selective abrogation of the uPA-uPAR interaction in vivo reveals a novel role in suppression of fibrin-associated inflammation (2010)

The urokinase plasminogen activator receptor (uPAR) has emerged as a potential regulator of cell adhesion, cell migration, proliferation, differentiation, and cell survival in multiple physiologic and pathologic contexts. The urokinase plasminogen activator (uPA) was the first identified ligand for uPAR, but elucidation of the specific functions of the uPA-uPAR interaction in vivo has been difficult because uPA has important physiologic functions that are independent of binding to uPAR and because uPAR engages multiple ligands. Here, we developed a new mouse strain (Plau(GFDhu/GFDhu)) in which the interaction between endogenous uPA and uPAR is selectively abrogated, whereas other functions of both the protease and its receptor are retained. Specifically, we introduced 4 amino acid substitutions into the growth factor domain (GFD) of uPA that abrogate uPAR binding while preserving the overall structure of the domain. Analysis of Plau(GFDhu/GFDhu) mice revealed an unanticipated role of the uPA-uPAR interaction in suppressing inflammation secondary to fibrin deposition. In contrast, leukocyte recruitment and tissue regeneration were unaffected by the loss of uPA binding to uPAR. This study identifies a principal in vivo role of the uPA-uPAR interaction in cell-associated fibrinolysis critical for suppression of fibrin accumulation and fibrin-associated inflammation and provides a valuable model for further exploration of this multifunctional receptor.
Radical Scavenging Activities of Peels and Pulps from cv. Golden Delicious Apples as Related to Their Phenolic Composition (2004)

The relationship between phenolic composition and radical scavenging activity of apple peel and pulp was investigated in fruit produced according to both organic and integrated agricultural methods. Apple tissue extracts were subjected to high-performance liquid chromatography separation, which showed that as compared with pulps, peels are richer in almost all of the quantified phenolics. Flavonols, flavanols, procyanidins, dihydrochalcones, and hydroxycinnamates were the identified phenolic classes in peel tissue, and the most abundant compounds were epicatechin, procyanidin B2, and phloridzin. Pulps were poorer in phytochemicals. Their major phenolics were procyanidins and hydroxycinnamates. Flavonols in amounts <20 mg kg(-1) fresh weight (fw) were also found. In both peels and pulps, integrated production samples were richer in polyphenols. Among the 14 compounds identified, only phloridzin had a tendency to appear higher in organic peels. The total antioxidant capacities (TAC) of extracts were evaluated using the 1,1-diphenyl-2-picrylhydrazyl radical assay and were expressed as Trolox equivalents. Integrated peels gave the highest TAC (18.56 mM kg(-1) fw), followed by organic peels (TAC = 14.96), integrated pulps (TAC = 7.12), and organic pulps (TAC = 6.28). In peels, the top contributors to the antioxidant activity were found to be flavonols, flavanols, and procyanidins, which accounted for about 90% of the total calculated activity whereas in pulps, the TAC was primarily derived from flavanols (monomers and polymers) together with hydroxycinnamates. A good correlation between the sum of polyphenols and the radical scavenging activities was found. Among the single classes of compounds, procyanidins (in peels and pulps) and flavonols (in peels) were statistically correlated to the TAC.
Local Aggregation for Unsupervised Learning of Visual Embeddings (2019)

Unsupervised approaches to learning in neural networks are of substantial interest for furthering artificial intelligence, both because they would enable the training of networks without the need for large numbers of expensive annotations, and because they would be better models of the kind of general-purpose learning deployed by humans. However, unsupervised networks have long lagged behind the performance of their supervised counterparts, especially in the domain of large-scale visual recognition. Recent developments in training deep convolutional embeddings to maximize non-parametric instance separation and clustering objectives have shown promise in closing this gap. Here, we describe a method that trains an embedding function to maximize a metric of local aggregation, causing similar data instances to move together in the embedding space, while allowing dissimilar instances to separate. This aggregation metric is dynamic, allowing soft clusters of different scales to emerge. We evaluate our procedure on several large-scale visual recognition datasets, achieving state-of-the-art unsupervised transfer learning performance on object recognition in ImageNet, scene recognition in Places 205, and object detection in PASCAL VOC.
Genes Expressed in Human Tumor Endothelium (2000)

To gain a molecular understanding of tumor angiogenesis, we compared gene expression patterns of endothelial cells derived from blood vessels of normal and malignant colorectal tissues. Of over 170 transcripts predominantly expressed in the endothelium, 79 were differentially expressed, including 46 that were specifically elevated in tumor-associated endothelium. Several of these genes encode extracellular matrix proteins, but most are of unknown function. Most of these tumor endothelial markers were expressed in a wide range of tumor types, as well as in normal vessels associated with wound healing and corpus luteum formation. These studies demonstrate that tumor and normal endothelium are distinct at the molecular level, a finding that may have significant implications for the development of anti-angiogenic therapies.
Numerical methods for mathematics, science and engineering (1992)

The book (paperback edition) is the second edition of the work
published under the title ``Numerical methods for computer
science, engineering, and mathematics'' (1987). The intention
of the author is to give an introduction to numerical methods
for undergraduate students in computer science, engineering,
and mathematics. On more than 600 pages, the book provides an
ample material in different fields of numerical analysis such
as the solution of nonlinear equations and linear systems of
equations, interpolation and polynomial approximation, curve
fitting, numerical differentiation, numerical integration,
numerical optimization, solution of ordinary and partial
differential equations, and calculation of eigenvalues as well
as eigenvectors.\par It is assumed that the reader is familiar
with calculus and basic aspects of structured programming
languages. The book contains a well-balanced minimum of the
theory of numerical analysis and takes care to provide a good
understanding of the essential ideas of numerical methods.
Otherwise, special emphasis is placed on the presentation of
algorithms for various numerical processes. Some algorithms are
described by pseudo-code and are easy to translate into BASIC,
C, FORTRAN, or Pascal. Computer calculations given in the form
of tables and graphs, and many examples as well as figures
improve the readability of the text. Numerous exercises and the
computer-oriented presentation of numerical methods are special
features of this book.
Characterization of Actinobacillus pleuropneumoniae riboflavin biosynthesis genes (1995)

In this paper, we report the identification, cloning, and complete nucleotide sequence of four genes from Actinobacillus pleuropneumoniae that are involved in riboflavin biosynthesis. The cloned genes can specify production of large amounts of riboflavin in Escherichia coli, can complement several defined genetic mutations in riboflavin biosynthesis in E. coli, and are homologous to riboflavin biosynthetic genes from E. coli, Haemophilus influenzae, and Bacillus subtilis. The genes have been designated A. pleuropneumoniae ribGBAH because of their similarity in both sequence and arrangement to the B. subtilis ribGBAH operon.
In Vitro Activities of Daptomycin against 2,789 Clinical Isolates from 11 North American Medical Centers (2001)

The in vitro activity of daptomycin is affected by the concentration of calcium cations in the test medium. Mueller-Hinton broth is currently adjusted to contain 10 to 12.5 mg of magnesium per liter and 20 to 25 mg of calcium per liter, but for testing of daptomycin, greater concentrations of calcium (50 mg/liter) are recommended to better resemble the normal concentration of ionized calcium in human serum. Two levels of calcium were used for broth microdilution tests of 2,789 recent clinical isolates of gram-positive bacterial pathogens. MICs of daptomycin were two- to fourfold lower when the broth contained additional calcium. For most species, however, the percentages of strains that were inhibited by 2.0 microg of daptomycin per ml were essentially identical with the two broth media. Enterococci were the important exception; i.e., 92% were inhibited when tested in calcium-supplemented broth but only 35% were inhibited by 2.0 microg/ml without the additional calcium. This type of information should be considered when selecting criteria for defining in vitro susceptibility to daptomycin.
EFFECTS OF LOAD DISTRIBUTION AND INTERFACE SLIPPAGE ON BACKCALCULATED YOUNG'S MODULUS (1992)

舗装の非破壊試験法として, FWD試験機を用いて舗装表面のたわみ形状を測定し, その結果から層弾性係数を推定することが行われている. この時, 荷重を等分布とし, また層間には相対的な滑りが起こらないと仮定している. この仮定の妥当性を確認する必要があるかどうかを判断するため, 本研究では, 載荷荷重の分布状態と相接する2つの層の境界面の付着が, 逆解析弾性係数に及ぼす影響を調べている. 解析にはBISARを, また逆解析にはガウス・ニュートン法を用いた.
Differential potentiation of alkylating and platinating agent cytotoxicity in human ovarian carcinoma cells by glutathione depletion. (1985)

We have determined the effect of glutathione (GSH) depletion on the cytotoxicity of three nitrogen mustards, six platinum complexes, and mitomycin C in a human ovarian carcinoma cell line. GSH levels in COLO 316 cells were depleted by exposure of cell monolayers to 0.5 mM D,L-buthionine-S,R-sulfoximine. GSH depletion significantly potentiated the cytotoxicity of L-phenylalanine mustard, chlorambucil, and mechlorethamine as determined by clonogenic assay on plastic plates. The dose modification factors were 2.6, 2.6, and 1.9, respectively. The same level of GSH depletion had a minimal effect on the cytotoxicity of cis-diamminedichloroplatinum(II) (cis-DDP), carboplatin, dichloro(ethylenediamine)platinum(II), 1,2-diaminocyclohexylplatinum(II) malonate, and iproplatin. The dose modification factors of GSH depletion for these drugs were 1.4 or less. trans-Diamminedichloroplatinum(II) was, however, markedly potentiated by GSH depletion with a dose modification factor of 2.7. Mitomycin C was minimally potentiated by GSH depletion. We have also generated cis-DDP-resistant cells from COLO 316 and 2008 human ovarian carcinoma cells by in vitro selection with cis-DDP. These cis-DDP-resistant cells had identical levels of GSH as the parental cells. GSH depletion sensitized these cells only to the same degree as the parental cells and did not reverse the resistant phenotype. Our results indicate that intracellular GSH levels are not an important determinant of the cytotoxicity of cis-platinum(II) or cis-platinum(IV) complexes in COLO 316 and 2008 cells. In addition, altered GSH metabolism does not appear to be a component of the cis-DDP-resistant phenotype in these cells.
Experiences Using Chloramine-T and 1, 3, 4, 6-Tetrachloro-3α, 6α-diphenylglycoluril (lodogen®) for Radioiodination of Materials for Radioimmunoassay (1981)

A comparison of labelling compounds with chloramine-T and with 1, 3, 4, 6-tetrachloro-3 alpha, 6 alpha-diphenylglycoluril (Iodogen) has been carried out. For human transferrin, human calcitonin, 1-84 bovine parathyrin, fibrinopeptide-A, human thyrotropin and F-CB3, a cyanogen bromide cleavage peptide of human fibrinogen, the quality of tracer produced by the Iodogen method was better. For rat lutropin, human growth hormone and human prolactin, labelling with Iodogen produced a tracer of unsatisfactory quality. For a further 13 peptides, the results from both methods were comparable. Optimal reaction times using Iodogen were of the magnitude of two to three times longer than when using chloramine-T. Reduction of the volume of radioactive waste by up to 90% could be achieved when the Iodogen method was coupled with a short cation-exchange column to separate unreacted iodide from the labelled compound. Data is presented on the quality of tracer, expressed in terms of elution profiles and radioimmunoassay standard curves. A novel "combi-method" of labelling proteins without tyrosine or histidine moieties is presented where N-succinimidyl-3-(4-hydroxyphenyl)-propionate is labelled at pH 7.5 using Iodogen to give "Bolton-Hunter" reagent, which is then transferred to a vessel containing the peptide to be labelled at ph 8.6.
The DDF1 transcriptional activator upregulates expression of a gibberellin‐deactivating gene, GA2ox7, under high‐salinity stress in Arabidopsis (2008)

High-salinity stress affects plant growth and development. We have previously reported that overexpression of the salinity-responsive DWARF AND DELAYED FLOWERING 1 (DDF1) gene, encoding an AP2 transcription factor of the DREB1/CBF subfamily, causes dwarfism mainly by levels of reducing bioactive gibberellin (GA) in transgenic Arabidopsis. Here, we found that the GA 2-oxidase 7 gene (GA2ox7), which encodes a C20-GA deactivation enzyme, is strongly upregulated in DDF1-overexpressing transgenic plants. A loss-of-function mutation of GA2ox7 (ga2ox7-2) suppressed the dwarf phenotype of DDF1-overexpressing plants, indicating that their GA deficiency is due to overexpression of GA2ox7. Transient overexpression of DDF1 activated the promoter of GA2ox7 in Arabidopsis leaves. A gel shift assay showed that DDF1 binds DRE-like motifs (GCCGAC and ATCGAC) in the GA2ox7 promoter. In Arabidopsis under high-salinity stress, six GA2ox genes, including GA2ox7, were upregulated. Furthermore, the ga2ox7-2 mutant was less growth retarded than wild-type Col under high-salinity stress. These results demonstrate that, under salinity stress, Arabidopsis plants actively reduce endogenous GA levels via the induction of GA 2-oxidase, with the result that growth is repressed for stress adaptation.