gebhart/patrepeval huggingface dataset:
THE FATE OF PEPTIDES PINOCYTOSED BY MACROPHAGES IN VITRO (1969)

A series of small peptides, such as might arise in the course of intralysosomal protein digestion, were screened for the ability to escape, intact, from mouse peritoneal macrophage lysosomes. Inability to penetrate lysosomal membranes was inferred from a peptide's induction of lysosomal swelling, or vacuolization, in cultured macrophages. Two of the peptides tested, (D-Glu)(2) and (D-Ala)(3), induced vacuolization. Neither peptide was susceptible to hydrolysis by enzymes in macrophages or in the serum-containing culture medium. Their morphological effect was inhibited by parafluorophenylalanine, an inhibitor of pinocytosis. Once formed by either peptide, the vacuoles persisted for several hours in peptide-free medium. Quantitative studies of radioactively labeled (D-Glu)(2) confirmed the morphological evidence that (D-Glu)(2) is taken up by pinocytosis and stored, intact, in macrophage lysosomes. The majority of the peptides which failed to induce vacuolization-(L-Ala)(2), L-Ser.L-Ala, L-Val.L-Ala, L-Ala.L-Thr, Gly.D, L-Phe, L-Ala.D-His, (L-Ala)(3), (L-Glu)(2), and D-Leu.L-Tyr-were found to be susceptible to hydrolysis by cellular or serum peptidases. Their failure to induce vacuolization was attributed to their hydrolysis to subunits capable of penetrating lysosomal membranes. Some of the peptides which had failed to induce vacuolization-(D-Ala)(2), D-Ser.D-Ala, D-Val.D-Ala, Gly-D-Asn, D-Ala.D-Thr, and D-Arg.D-Val-were found to be indigestible. Except for the cytotoxic peptide D-Arg.D-Val, peptides in this category all had lower molecular weights and volumes than (Glu)(2) or (Ala)(3). It is inferred that these peptides are small enough to escape from macrophage lysosomes, while (Glu)(2) and (Ala)(3) are too large to escape intact. The implications of this inference for the mechanism of intracellular digestion of pinocytosed proteins are discussed.
Nanowires for energy generation (2012)

As a result of their morphology, nanowires bring new properties and the promise of performance for a range of electronic devices. This review looks into the properties of nanowires and the multiple ways in which they have been exploited for energy generation, from photovoltaics to piezoelectric generators.
A novel mechanism for switching a neural system from one state to another (2010)

An animal's ability to rapidly adjust to new conditions is essential to its survival. The nervous system, then, must be built with the flexibility to adjust, or shift, its processing capabilities on the fly. To understand how this flexibility comes about, we tracked a well-known behavioral shift, a visual integration shift, down to its underlying circuitry, and found that it is produced by a novel mechanism - a change in gap junction coupling that can turn a cell class on and off. The results showed that the turning on and off of a cell class shifted the circuit's behavior from one state to another, and, likewise, the animal's behavior. The widespread presence of similar gap junction-coupled networks in the brain suggests that this mechanism may underlie other behavioral shifts as well.
Solution structure of the matrix attachment region‐binding domain of chicken MeCP2 (2003)

Methyl-CpG-binding protein 2 (MeCP2) is a multifunctional protein involved in chromatin organization and silencing of methylated DNA. MAR-BD, a 125-amino-acid residue domain of chicken MeCP2 (cMeCP2, originally named ARBP), is the minimal protein fragment required to recognize MAR elements and mouse satellite DNA. Here we report the solution structure of MAR-BD as determined by multidimensional heteronuclear NMR spectroscopy. The global fold of this domain is very similar to that of rat MeCP2 MBD and MBD1 MBD (the methyl-CpG-binding domains of rat MeCP2 and methyl-CpG-binding domain protein 1, respectively), exhibiting a three-stranded antiparallel beta-sheet and an alpha-helix alpha1. We show that the C-terminal portion of MAR-BD also contains an amphipathic helical coil, alpha2/alpha3. The hydrophilic residues of this coil form a surface opposite the DNA interface, available for interactions with other domains of MeCP2 or other proteins. Spectroscopic studies of the complex formed by MAR-BD and a 15-bp fragment of a high-affinity binding site from mouse satellite DNA indicates that the coil is also involved in protein.DNA interactions. These studies provide a basis for discussion of the consequences of six missense mutations within the helical coil found in Rett syndrome cases.
FORMATION OF A THREE-STRANDED POLYNUCLEOTIDE MOLECULE (1957)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFORMATION OF A THREE-STRANDED POLYNUCLEOTIDE MOLECULEG. Felsenfeld, David R. Davies, and Alexander RichCite this: J. Am. Chem. Soc. 1957, 79, 8, 2023–2024Publication Date (Print):April 1, 1957Publication History Published online1 May 2002Published inissue 1 April 1957https://pubs.acs.org/doi/10.1021/ja01565a074https://doi.org/10.1021/ja01565a074research-articleACS PublicationsRequest reuse permissionsArticle Views1719Altmetric-Citations758LEARN 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
'Don't Let the Bastards Beat You' (2006)

Ian Prior was the Director of the Medical Unit at Wellington Hospital and in the early 1960s he established the Epidemiology Unit. He showed that the life style related diseases were caused by social and environmental changes which produce the changes in individual level risk factors.
Activation Mechanisms of the Urokinase-type Plasminogen Activator Promoter by Hepatocyte Growth Factor/Scatter Factor (1999)

Hepatocyte growth factor/scatter factor (HGF/SF) is a pleiotropic effector inducing invasion and metastasis of tumor cells that express the Met tyrosine kinase receptor. One of the effectors of HGF/SF is the urokinase-type plasminogen activator, a serine protease that facilitates tumor progression and metastasis by controlling the synthesis of the extracellular matrix degrading plasmin. Stimulation of NIH 3T3 cells that were stably transfected with the human Met receptor (NIH 3T3-Methum) with HGF/SF induced a trans-activation of the urokinase promoter and urokinase secretion. Induction of the urokinase promoter by HGF/SF via the Met receptor was blocked by co-expression of a dominant-negative Grb2 and Sos1 expression construct. Further, the expression of the catalytically inactive mutants of Ha-Ras, RhoA, c-Raf, and Erk2 or addition of the Mek1-specific inhibitor PD 098059 abrogated the stimulation of the urokinase promoter by HGF/SF. A sequence residing between -2109 and -1870 base pairs (bp) was critical for stimulation of the urokinase gene by HGF/SF. Mobility shift assays with oligonucleotides spanning an AP-1 site at -1880 bp or a combined PEA3/AP-1 site at -1967 bp showed binding of nuclear factors from NIH 3T3-Methum cells. Expression of an expression plasmid that inhibits DNA binding of AP-1 proteins (A-Fos) abrogated inducible and basal activation of the urokinase promoter. Nuclear extract from unstimulated NIH 3T3-Methum cells contained more JunD and showed a stronger JunD supershift with the AP-1 oligonucleotides, compared with HGF/SF-stimulated cells. Consistent with the levels of JunD expression being functionally important for basal expression of the urokinase promoter, we found that overexpression of wild type JunD inhibited the induction of the urokinase promoter by HGF/SF. These data suggest that the induction of urokinase by HGF/SF is regulated by a Grb2/Sos1/Ha-Ras/c-Raf/RhoA/Mek1/Erk2/c-++ +Jun-dependent mitogen-activated protein kinase pathway.
Degradation of bit-error rate in coherent optical communications due to spectral spread of the transmitter and the local oscillator (1984)

In coherent optical communication schemes, the FM noises of the transmitter and/or the local oscillator seriously deteriorate the receiver sensitivity. A theory is developed describing the effect of the FM noise on the bit-error rate (BER) performance of various heterodyne and homodyne schemes. To verify the theory, the BER of a phase-shift keying (PSK) heterodyne system is measured. The feasibility of the PSK scheme using semiconductor lasers is also discussed on the basis of analysis and experimentation.
Sequence-Dependent DNA Immobilization:  Specific versus Nonspecific Contributions (2004)

We present results of the first systematic study on in situ sequence-dependent kinetics for short single-strand oligonucleotide surface immobilization. By measuring film coverage for both thiolated and nonthiolated homo-oligomers as a function of adsorption time, we determine the relative contribution of specific thiol-surface and nonspecific DNA-surface interactions to the overall mechanism of DNA-thiol attachment to gold. We find that sequence-dependent nonspecific surface interactions play a significant role in DNA-thiol immobilization, influencing not only the kinetics but also the extent of oligomer adsorption. For example, sequences that initially form strong, rapid nonspecific contacts with the surface hinder long-time thiol adsorption (i.e., poly(dA)-thiol). In contrast, sequences with nucleotides that initially bind slowly and weakly to the surface (i.e., poly(dT)-thiol) do not obstruct further thiol adsorption, resulting in higher film coverage and Langmuir immobilization kinetics. This view of the DNA-thiol immobilization mechanism is further supported by sequence-dependent rinsing losses observed for thiolated DNA strands but not for analogous nonthiolated strands. Nonthiolated strands contact the surface strongly in a more horizontal orientation, whereas thiolated strands attain a more upright orientation that allows vertical DNA-DNA base-stacking. The results clearly illustrate the importance and interplay of competitive specific and nonspecific forces in forming DNA-thiol films. The specific coverage attained and the time dependence of the adsorption process depend on the prevailing sequence composition.
Anti-CD3 monoclonal antibody treatment of patients with CD3-negative tumors: a phase IA/B study. (1992)

Anti-CD3 monoclonal antibodies induce the proliferation of human T-cells in vitro and activate specific and nonspecific cytolysis by human T-cell clones and human peripheral blood lymphocytes. In vivo administration of anti-CD3 prevents tumor growth of a UV-induced mouse fibrosarcoma. We conducted a phase I trial to determine the toxicity and immunomodulatory properties of low doses of anti-CD3 in 36 patients with cancer. In 23 patients, anti-CD3 was given i.v. over 3 h at 1, 10, 30, and 100 mcg/patient. Five other patients received anti-CD3 at 30 mcg by i.v. bolus. Patients were treated every 3 days for a total of four doses. An additional eight patients received anti-CD3 daily for 14 days at 3 mcg by i.v. bolus, 3-h infusion, or 24-h infusion. Dose-limiting toxicity was headache. Headache was often accompanied by signs and symptoms of meningeal irritation leading to performance of a lumbar puncture in nine patients. The opening pressure was usually elevated, and six patients had a cerebrospinal fluid lymphocytosis with an elevated protein. Increased levels of interleukin 6 were identified in the cerebrospinal fluid. The maximum tolerated dose by 3-h infusion was 30 mcg. There were no objective tumor responses. There was a dose-related increase in the number of peripheral blood lymphocytes expressing the T-cell activation antigen CD69 (Leu 23), but no changes were seen in CD25 (interleukin 2 receptor) expression, and no changes were observed in the serum levels of the soluble interleukin 2 receptor. Even at these low doses of anti-CD3, 8 of 16 patients tested developed human anti-mouse antibodies.
Beta-catenin mutation in carcinoma of the uterine endometrium. (1998)

Beta-catenin forms complexes with Tcf and Lef-1 and functions as a transcriptional activator downstream of the Wnt signaling pathway. Activation of the pathway by stabilization of beta-catenin has been shown to be important in the development of colorectal carcinoma, which is mainly caused by inactivating mutations of the adenomatous polyposis coli tumor suppressor gene or by activating mutations in exon 3 of the beta-catenin gene. Here, we analyzed mutations in exon 3 of the beta-catenin gene in endometrial carcinoma cases in which loss of heterozygosity at the adenomatous polyposis coli tumor suppressor gene locus has been rarely reported. We found that 10 of 76 cases had beta-catenin gene mutations. All mutations identified were single-base missense mutations on serine/threonine residues (codons 33, 37, 41, and 45), altering the glycogen synthase kinase-3beta phosphorylation consensus motif, which participates in the degradation of beta-catenin. To determine whether these beta-catenin mutations actually led to stabilization of this protein, expression of beta-catenin was analyzed immunohistochemically, and 9 of 10 cases with the beta-catenin mutation and 20 of 66 cases without it showed accumulation of beta-catenin in the cytoplasm and/or nucleus. In total, 38% of cases showed accumulation of beta-catenin. These data indicate that stabilization of beta-catenin due to mutations in exon 3 of the beta-catenin gene and other mechanisms may have an important role in development of endometrial carcinomas.
Navigation system based on ceiling landmark recognition for autonomous mobile robot-landmark detection based on fuzzy template matching (FTM) (2002)

We propose a vision based navigation system for autonomous mobile robots that recognizes outlets of air conditioning system (anemo) located on the ceiling as landmarks. Because landmarks on the ceiling are not obstructed by other objects, robots can find them easier than landmarks on the floor. To detect the landmark, we applied the fuzzy template matching (FTM) method. Based on FTM, a fuzzy template (FT) is modeled based on the edge information of landmarks in the image. In addition, we use neural network (NN) to detect landmarks quickly. Inputs of NN are the grades of fuzzy memberships and the learned NN directs FT to the landmark in the image. Because FTM does not use image processing, except edge extraction, it does not make processing error and the landmark can be detected precisely. The navigation system can calculate the distance and the angle of the anemo from the map information. As a result, the navigation system can identify the present robot's position and orientation. By the proposed algorithm, precise and fast landmark detection become possible even if the landmark follows the shadow.
N-Alpha-Acetylation of α-Synuclein Increases Its Helical Folding Propensity, GM1 Binding Specificity and Resistance to Aggregation (2014)

A switch in the conformational properties of α-synuclein (αS) is hypothesized to be a key step in the pathogenic mechanism of Parkinson's disease (PD). Whereas the beta-sheet-rich state of αS has long been associated with its pathological aggregation in PD, a partially alpha-helical state was found to be related to physiological lipid binding; this suggests a potential role of the alpha-helical state in controlling synaptic vesicle cycling and resistance to β-sheet rich aggregation. N-terminal acetylation is the predominant post-translational modification of mammalian αS. Using circular dichroism, isothermal titration calorimetry, and fluorescence spectroscopy, we have analyzed the effects of N-terminal acetylation on the propensity of recombinant human αS to form the two conformational states in interaction with lipid membranes. Small unilamellar vesicles of negatively charged lipids served as model membranes. Consistent with previous NMR studies using phosphatidylserine, we found that membrane-induced α-helical folding was enhanced by N-terminal acetylation and that greater exothermic heat could be measured upon vesicle binding of the modified protein. Interestingly, the folding and lipid binding enhancements with phosphatidylserine in vitro were weak when compared to that of αS with GM1, a lipid enriched in presynaptic membranes. The resultant increase in helical folding propensity of N-acetylated αS enhanced its resistance to aggregation. Our findings demonstrate the significance of the extreme N-terminus for folding nucleation, for relative GM1 specificity of αS-membrane interaction, and for a protective function of N-terminal-acetylation against αS aggregation mediated by GM1.
Securing electronic mail systems (2003)

It is pointed out that security at the network layer cannot provide application-specific services associated with electronic mail such as signed receipts and digital signatures. These deficiencies can be remedied by providing end user to end user security where mail messages are black (protected/encrypted) at all intermediate points. The authors describe the approach and implementation taken in building such a mail security device. Mail messages are protected along the entire path from originator to recipient. The messages are protected during storage and processing at all intermediate points. the security can be implemented independently of the network layer architecture or a network layer security device. The key distribution technique is suitable for client-server architectures such as electronic mail, where the number of users is large and connectivity is diverse.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
RettBASE: Rett syndrome database update (2017)

Rett syndrome (RTT) is an X-linked progressive neurodevelopmental disorder that primarily affects females. Mutations in the MECP2 gene have been attributed as the major genetic cause of RTT. Recently, mutations in CDKL5 and FOXG1 genes have also been suggested to give rise to RTT, although subsequent more extensive studies suggest that diseases resulting from mutations in these two genes should be considered as distinct clinical entities. While the genetic basis for the RTT has been recognized, so far there is no effective cure for the disease and the treatments available are mainly aimed at ameliorating clinical problems associated with the disorder. The swift identification of the mutations in children is crucial for pursuing the best therapeutic care. RettBASE was created in 2002 as a MECP2 variant database and has grown to become a comprehensive variant database for RTT and related clinical phenotypes, containing a curated collection of variants for MECP2, CDKL5, and FOXG1 genes. Here, we describe the development and growth of RettBASE after its inception in 2001. Currently, RettBASE holds a total of 4,668 variants in MECP2, 498 variants in CDKL5, and 64 variants in FOXG1.
Characterization of a monoclonal antibody as the first specific inhibitor of human NTP diphosphohydrolase‐3 (2008)

The study and therapeutic modulation of purinergic signaling is hindered by a lack of specific inhibitors for NTP diphosphohydrolases (NTPDases),which are the terminating enzymes for these processes. In addition, little is known of the NTPDase protein structural elements that affect enzymatic activity and which could be used as targets for inhibitor design. In the present study, we report the first inhibitory monoclonal antibodies specific for an NTPDase, namely human NTPDase3 (EC 3.6.1.5), as assessed by ELISA, western blotting, flow cytometry, immunohistochemistry and inhibition assays. Antibody recognition of NTPDase3 is greatly attenuated by denaturation with SDS, and abolished by reducing agents, indicating the significance of the native conformation and the disulfide bonds for epitope recognition. Using site-directed chemical cleavage, the SDS-resistant parts of the epitope were located in two fragments of the C-terminal lobe ofNTPDase3 (i.e. Leu220-Cys347 and Cys347-Pro485), which are both required for antibody binding. Additional site-directed mutagenesis revealed the importance of Ser297 and the fifth disulfide bond (Cys399-Cys422) for antibody binding, indicating that the discontinuous inhibitory epitope is located on the extracellular C-terminal lobe of NTPDase3. These antibodies inhibit recombinant NTPDase3 by 60-90%, depending on the conditions. More importantly, they also efficiently inhibit the NTPDase3expressed in insulin secreting human pancreatic islet cells in situ. Because insulin secretion is modulated by extracellular ATP and purinergic receptors, this finding suggests the potential application of these inhibitory antibodies for the study and control of insulin secretion.
Automatic ID Photos Matting Based on Improved CNN (2019)

Image matting that aims to estimate the foreground from the mixed pixels is key to ID photos processing. Recently, deep convolutional neural network (CNN) has shown competitiveness for image segmentation, but not achieved good accuracy in practical matting. In this paper, we propose an improved light network for ID photos matting. The model adopts the MobileNetV2 as backbone and leverages the densely connected blocks to predict a high-accuracy binary mask for K-nearest neighbor (KNN) matting. In addition, an automatic portrait matting system based on L-UNet is built, which is very fast without any interaction. Experimental results on a large scale real-world dataset verify the effectiveness of the proposed method on ID photos matting task.
Characterization of (+) Strand Initiation and Termination Sequences Located at the Center of the Equine Infectious Anemia Virus Genome (1999)

Permeabilized preparations of equine infectious anemia virus (EIAV) are shown here to support efficient and accurate synthesis of full-length double-stranded proviral DNA. When (-) and (+) strand products were analyzed by Southern blotting, a discontinuity, mapping approximately to the center of the EIAV genome, could be demonstrated for the (+) strand, predicting a second site for initiation of DNA synthesis and a specific mechanism of (+) strand termination. Precise localization of this (+) strand origin within the integrase (IN) coding region was achieved through its in vitro selection and extension into, and excision from, nascent DNA by purified recombinant p66/p51 EIAV reverse transcriptase (RT), suggesting that the EIAV genome harbors a central polypurine tract (cPPT). In addition, a model system was developed for evaluating whether sequences immediately downstream of the cPPT would terminate (+) strand synthesis in the context of strand displacement. Such a sequence was indeed discovered which functions in a manner analogous to that of the central termination sequence (CTS) of HIV, where A-tract-induced minor groove compression has been suggested to induce localized distortion of the nucleic acid duplex and termination of (+) strand synthesis. This interpretation is reinforced by experiments indicating that read-through of the CTS can be efficiently promoted by substituting 2,6-diaminopurine for adenine, thereby relieving minor groove compression. The nucleotide substitution can also shift the site of termination in strand displacement (+) strand synthesis. Collectively, our data support proposals that lentiviruses may have evolved specialized mechanisms for initiating and terminating (+) strand DNA synthesis at the center of their genomes.